1 100 30 http://exhibits.library.stonybrook.edu/mfp/files/original/4b34d77a93adfdf543aae63a1ead5831.pdf 9a3d77013a79d7057f02f224ed583aa6 PDF Text Text 42.5.3. gm Standin- of tho ‘ alteration in mum the focus or mufﬁns 1 laboratory for olmtmnmphllompm studying A or the Dona-“mm. of Manley during eh. ambuahod, and ”min manta]. oyndma m. introduced. grasp Band», dapreuivu m mm ammmud with unplug“ illmaua, men-u, man-hm. We: m method- for on, The tha change in pal-cerium in and following alactrocomulaivo therapy. “fact. at barbiturate”, ”mun um um intentiuly studied. “new of the Wan. put you. invents;pmimWe“ 51113393“ to alwltmm stimulation buts, hogan at tinted study gationa or the raspame of by Dr. w with changu in brain funeum wan and 1.780er acid (181345) on such The mammal latter part or the year, a corn-3.1M in brain function during data-woman“. thump: m In tho m psychologists. Dr. march assistants to the Imam Robert him and In; R. Karin worn uppointod «Mt, tad Dr. in: link a fellow of the ﬁatiml for Infmtiln Fanlyain mu appoinm to mum” the laboratory work. oi: Databa- 1, 1953 am charmmloganQ laboratory was cmbliahod with a Man. 8 clam}. instrumnt. In the mum. mm month. 65 mount. are taken. 01' than 19 um emulation muons m M in the ovum of th. integrated study an altered bran functian. [mung tn. year. 55 consultation mum matured. ﬁgure than half of mania mental am.» “mated with amt-"sin 111m“, were far or mhtod to duotmnhook thonw‘ 301m awn». neuritic types of pain, 1nd abnoml involunm menu and. up the bulk of mum. 81.: patients with «ism «11:0er um mum and controlled with anaemia to the neurologiml service of mi. Sinai amen. Thu. patient. are fie-pita?! m further ima’oiauogu for nmlogim conditions chums»! at tho m mum: We mm haapi talc �~2- m pmodural chm m introdum by an dmﬂunﬁ. u an Ad to evaluating thu uremic mum sum, tn. «ma “but” no introduood m Ivar round tbu 1m thin m1: «as worming an m put yaw, mum. ' folio-“mg the am of ehktrolhm mutant” and the In part of the in maid». mu m at mmimlmholim inugrltod study an olectrwhaoh in (month) A: In Want chlorich new“ mmmm mum; as mutated. and at «Iv m tho no! emu)“ m1- want. 1: mm «amnion: in indumn; roux-Man mum cum mining agent: 50mm. 121 Mates! m: or thetroﬂmck wanmu. 3.. at 4:1: The damn“ an at maharhiul ”dim in Mam” m. Jaw. Psych. zommm. (Jump) 1953. Eu- 31131108.» (1953) Mr. 11.8.! Kit.“ of link, I!" Harm, 9.3., Bath-awn, I. and on Perception, Trans. Amer. Hm. used... Jun- 1953. m, it" Green, )1- and Binder, Simultaneous 3.3.x Perception of & Malta, am. mm mu. m». mm» 5: A ma a. sum-um. study m: a ﬁnk. Tmhw, w mummy Jour. 31mm. Hosp. 236%71 (Ha-ch) 1953. 117th34¢9 m I thtu M11. um.) emu 1953. momma mamas, �October h , 195“ Interin Report Dear Dr. Miller, requested I wish to report that the following projects have been in progress this summer in this department. 1. Effect of electroshock on memory func» tion tests. Twenty-four patients are now fully studied; the data is beingA collected; and a report is planned for the 1955 A P meetings. 2. Effect of Lysergic Acid on perceptual functions, including Rorschach; and on blood chemistry. These experiments are now in progress and will be completed by the end of the year. ‘E3iy Under the terms of the U.S.P.H.S. grant a continuing study of perceptual changes in insuli n, and EST patients is now in planning. a. A psychiatric rating scale, modified after Malamud, is in use. As soon as it is standardized in this population, it will be presented to the Research Eonmittee. £5. The Funkenstein test (Hecholyl) in EST and insulin therapy is being checked in our pop— As you ulation. Sincerely, HF33RB �Obtober Projects in Progress as. 1954 / ,2-\ Relation of mental changes to behavior f‘ 1' (1) Effect of organic mental syndrOme on results of EST. (3) Changes in perception with I92. \ (3) Can ACTH. cortisone alter brain function and thereby (a) l ; i results of (b) EC! or ICT? \ \ Psychophysical measurements of Psychiatric terms - an operational approach to terms of diagnosis. (1) Denial: Relation to improvement in electroshock Relation of premorbid character to change in behavior in electroshock. (2) Ambivalence: Is it possible to measure ambivalence by psychophysicel menad and relate to the past history of the patient in choice of neurosis? Relation of chemical agents to psychoses. psychological. (o) biochemical and behavioral aspects. (d) 9 Rating Scale' �October 1?, 195b Dear Dr. Rachlin, requested I wish to report the following projects have been i n progress this summer. (1) Effect of electroshock on memory f unction, FRO, Amytal tests and nerceptual tests. Twenty four patients have been fully shielded. The first revert on the relation between the response to treatment and the occonotal test is being submitted to the A E A. The observat ion support As you the thesis that there is a relation between t development of an organ. he Mental syndrome and improvement. Effect of lysergiv acid on perce ptual functions. Rorschack and blood chemistry. The psychiatric and psychologic tests are being prepared for presentetnion at the American Psychopathological Association. (3) Under the terms of the U.S.P.H.S. gr ant a continuing study of perceptual changes in insulin and EST patient a is now i n planning. (3) A psychiatric re.ing scale, modified after Halemud, is i n use. As soon as it is standardized in this population, it will be presented to the (2) Research Committee. (5) The Punkenetein test (neohom) in EST and __ �nsulin the rapy population. 1 18 being checked Since rely, 1 n our � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Progress and annual reports; research activities (folder title). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-001 Date A point or period of time associated with an event in the lifecycle of the resource 1953-1954 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Annual report - department of neurology; Interim report to Dr. Miller; Progress Report; Letter to Dr. Rachlin; Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/e5d103cbe3dc9cd93159ddec488b3ecc.pdf 022eaace568b7d0816980adc5ccaa74c PDF Text Text �nau- mmmmtmw.mumntwmsm Mmammmmawmatmmmummm mmmwmmawmmwmmmamuwum uwmmummmmmm. mammmmipwh umummonm. mwwumwamm vamwwmhym.mmm. mmuummmmmmmmww mmmmmmwmmuormmmm 1. Wanna-m mmmummwummwtw wommwmmmumzmmmmmm mamawaum. itmhmmummum wm.mmm1mmmwm.mm,mmmm Wm W W M as th- an M: to» Manama. at Bra. 13.311.313.31, a «mud mam-1. m mgm.mmmmmmmﬁam.mmmruuw u1wmmmamwmmmtmmmm. M mmwmmmgmmwummmuzmw. m W‘M‘MWMWmmwMWMMdm msMMMmMmm-cmaammm.m 1mm». smu‘mmmmuwmmmmmm umwmmmwmdmmwwnmmm mwumwmuwmwmamummuum. ' mmummmmmmmwuammmm ammmmam~mummdummum mwummnmmmm. �03¢ unmmmumswummmammau wthmquduWMuMdehu-W atmwmummthummmu-mum ﬂat “mm. ”mum, mum... 'm man-om. mm: mmmummmmmmpmnymm and a; W13M.Wﬂ a. WWW mimnmmtmmmatﬁmmm W(mm)maamum. Wmmmmm minituamtmﬂtmmlymmsum. mmmmmmmmmtmmanm M 1(th m.w.muammmmammuumm ﬂaw. maem,nnmmwgmnhmtmnmu Madmanhdtnmmmm. nmmmm,mm Mmtmm)mmlwwm.nm,mmmnum nu mm“ m madam ( mm mm. 31WCW319511}. in. thWWWMtWWthqu man up man. um), mum m by the (at... P. mm um), WMWWW‘WuM): Wmmmtzmm mﬁmleohtaM (mu. 3» a.» scam mum (in. A. mm) m: mm mm mm m afﬁrm! 1*» the mama about»: mlmumtomammumwmmmm mmmuwmmumdmm mommamm mwmmmmammmm �ah- m.nmmmmtm.amahmummm mammwmmwmmumarmmmwnmwmm ww-wwmmumzwmmmmdm- mummmmmmm Ammaomwmt . mumermmmmmmd. mammalian ”wind to: m :mm mm, W Wm m1 momma-g. Wammmmormmmw mmmmmmmuma,mmmm wuunmmu.m«smmormum. mummm monarwmm,wmm9r£mgmtmrormwa Wcmmummmuamumwm. nmmuumymawwwmm W..1tmwmtm‘uitr1nhmdmhm mmmammmm. Mmmmemdin mommmum. num-mmmummmu immiwﬂmmmmg nmwmmm.m.mmmwwm mmwmmmotmummmmmmmm PM!» mmmmimhﬁmotuMMiﬂthmhm wmmummmwmmmmnww wwwmmtawmummwmwm. Pu WW hammmwmamummmaaw WWhmamﬁSﬁmmmnu-ammnh «ma-W'mmmwmmhnmmmwmm hmuuaummumMmmwrm-um unmmmm,m.m,wmmummm ��.ﬁ‘ V mum mum. mm am-ammummmrmmmam ummmmmmmnmw hr mum iii. W mumt WM AM}. 1955. www.mmmmarumwanm mnmwmmmwmmumummuw mmmu‘mummm‘ WW. 8. mMMMMWWWhNWW‘ mu m in nan-mm m :15 7.» WW Mmemm 3» mm .mumwmummmwbmmmmwm «mmgmumﬂormwmwmmwu mummuuwotmmumm 9'9me”. mammmmdmuuatmummmmum murwmwmuwuwmmmnr ammmxmysa. ��Dr. Fink January 18, 1955 To: All Department Heads 'Re: Annual Report Please prepare Report all - l95h of your data for the 195h Annual at the earliest possible date. All tables and other information should be turned in to Mrs. Bailey, Office Manager, on or before February 10. uith your statistical data, Dr. Miller requests that in addition to any tables or general statistics which you will furnish, that you write a succinct out— line of the'work of your department for the calendar which comments in appeared the to similar l9Sh, year Along the last Annual Report for your department. Please submit all data in three copies. I think that will be Report in.March of this With everyone's cooperation, able to publish the Annual year. a report of I vities of the hospital similar to the would like you to Janua RY 19 meeting. make all research'acti— one given Maurice Bachrach Administrator. Mled at the �(33L Biochemical Research Material assistance was offered the laboratories during 1954 in the form of enlarged quarters, and by the award of a two-year grant from the National Institutes of Health. The program initiated the previous year by Dr. Harry Goldenberg, Director of Laboratories, was continued along the following lines: Clinical Methodoloww It has become abundantly clear that the clinical laboratory can no longer cope with the special problems of mental disease using ther standard chemical tests carried out in general hospitals. Consequently increased attention has been directed towards providing the clinical laboratory with procedures for testing adrenal and carbohydrate metabolic function as well as for determining the course of drug and shock therapy. Reference has previously been made to ketosteroid and corticoid analyses. A new direct colorimetric test for hormone conjugates is nearing completion. Rapid micromethods have alib been perfected for two standard analyses, viz. blood phosphorus and which have hitherto been subject to large experimental phosphatase, A simple technique is also being investigated for following errors. the course of chlorpromazine excretion in urine. Metabolism of Steroid Sulfate Conjugates Impetus to our earlier studies on the metabolism of sulfuric acid—bound steroid hormones has been furnished by an InStitute of Health Grant which makes provision for much needed equipment and simple personnel. At the outset of the grant period a remarkably method was discovered for the colorimetric assay of steroid sulfates, based on the use of basic dyes. Further inquiry shows that, aside from its use in enzyme research, the method offers great promise for the assay of bound steroids in blood and urine as an index of these lines. Studies along continuing are stress. physiological Mechanism of Action of Lysergic Acid Diethylamide and from drawn have been vitro conclusions inc preliminary ig which induces LSD mode 25, a of of drug action on the vivo studies in a—transient psychotic state: (l) LSD 25 is a powerful inhibitor of human serum cholinesterase. (2) Parallel with a definitive response by the individual receiving LSD 25 there is a rise 11),..38rum alpha keto acids. Hormone Assay with Enzyme Systems There appears to be little doubt but that hormones are implicated The in establishing deterrent prime mental aberrations. and emotional in of for of assay suitable procedures this relationship is the lack . �function. Were such procedures available it should be possible to catalog mental illness on a chemical basis and suggest corrective action as an adjunct to the psychiatric services. Since the effect of hormones on various organs is mediated via enzyme systems, an extended study has been undertaken into the The hormone for systems isolated enzyme of‘using assay. possibilitywould involve incubating the test fluid with the appropriate procedure enzyme system in a test tube, and then determining the degree to which the enzymes are altered by the hormone in question by measuring conditions the release of a colored product. To determine the choice of makuxx been necessary to for carrying out these measurements it has The on two mathematical studies. papers out detailed first carry in Several manuScripts are more been have published. this'subject of preparation. various stages hormone Bibliography Goldenberg, Harry "Rectification of Nonlinear Beer's 690 (1954). Goldenberg, Harry Law Plots”, Anal. Chem., gg, "Rectification of Nonlinear Enzyme Activity Curves. Arch. Ricchem. and Biophys., §§, 288 (1954). I. Preliminary" �.; and Research of the of Publications Department Psychology ;/ Research in the Department of Psychology was oriented around several themes including: Refinement of psychological tests, the persis— tent problem of schizophrenia, and the effect of maturation and agang as measured by objective criteria. Certain aspects of the Rorschach test were dealt with more objectively by a series of papers by Dr. Gurvitz and Mr. Eichler and Mr. Feinberg. These set up for the first time objective adult standards for evaluating many Rorschach criteria which were not available previously. Further data was made available to experimenters illustrating the normal process of aging and maturation to further extend the cancept that if people grow older there are decrements in intellectual functioning and personality ingegration. In two new papers to be presented at the Eastern Psychological Association meeting, further progress was made in diagnosing schizophrenia by teens of psychological tests. The past and current research in psychology at Hillside has continued to attract attention both in terms of the acceptability of papers in both scientific meetings and professional journals, and also in terms of the many hundreds of requests for reprints sent in by psychiatrists, psychologists and social workers. These papers and research projects have also served as a training medium for psychological internes in the Department of Psychology and the past year was noteworthy for the fact that each one of the psychological internes or staff members presented at least once at a psychological convention or participated in some published research.project. ��RESEARCH During the calendar year l9Sh two projects were in process. their families pay for hospitalization a) Study of rates which patients and as correlated with time Spent in the hospital. b) The adjustment of applicants referred by psychiatrists found unsuitable for admission to Hillside Hospital during period 1951/1953. This latter study is a series of studies which is being done to determine the adjustments in the community and the use of community resources for applicants who have applied for admission to Hillside HOSpital but were found unsuitable. It is planned to continue this series during the year 1955. In addition, the joint project with the Jewish Community Services of long Island concerning the placement of discharged patients in private residence continues. W3 research project is being set up at the Altro'work Shop to which patients discharged from Hillside Hespital go in order to learn work habits. A Publications: )/ <3'“>( '21” ,~ 63‘” 7 s====r ;) Vocational Adjustment for the Emotionally Disturbed Authors: Roland Baxt, Abraham.Lurie, and Joseph .A. Miller, . - M.D. Presentations at conferences: a) [pulse Pinsky presented a paper at the National Conference of Jewish Communal Service in May, 1951;, called, "The Impact of Medical Crisis on the Family". b) AL:hd ‘ Abraham Lurie Spoke at the National Conference of Social‘Wbrk in may, 195h, "The Implications for Psychiatric Social‘work of Team‘work Relationship Between Social'workers and Psychologists". �MEMORANDUM FROM THE CREATIVE THERAPY DEPARTMENT WWW 1955 Study on the constructive and/or destructive use of passive and active aggression as a differential test for determining schizophrenic responses. Data for this research project had been gathered for the past three years. Their sifting and clinical evaluation is planned in the near future. The test is carried out within the C.T. program and consists of 16 specific proand number of jects EZ/r #290 a sub-tests. “a 707 Ernest Zierer �Fsbmary 2, 1955 Memorandum from: Dr. To: Subject: Fink M. Bondsr, M. D. 24.1). Anmsl Report of Hillsids Hospitals and medical services with other Coordination md cooperation with the psydxiatrio staff past you. With in. slsotmoncsphalogmm, for the of laboratory sstsblishnsnt tho crossed use of this facility and of the consultation faoilitin m was incrsssed during the: ands by members of the resident and attsndim staff. the answered attending by 19 consultations ssrs the yes“: hiring neurology oer-vies, and 1:0 consultations in addition vsrs anmrsd by the rssidaxt neurologist. In the slootrosnoophahgramio laboratory 111:8 this nun":- 75 constituted consultstion taken rsoords wars the 0! records. maindsr, follow-up ”cords vars taken. rsqnssts and 01' in tho oourss of two invsstigations - one in tho effects of electro- shosk on brain function; and the second on the relationship between treatinsulin the of and the rssults can function brain in changes mt. Evaluation of the organic mental mamas provided the major with three Thurs were patients consultations. nourologio Icons for the clinic. followed in sud who controlled wars disordsrs leisurs Four logic nonrafurther for another institution to transfsrod sore pstiants work—up and troatmnt. when direction another in The neurologic service nto consultation prior for aimissions olinis nods tbs tron qussts ms was extended hospital admission. your and Sm such oomltstions were dons during the svnlustion butts:for s an upper-unity ssrvioo providsd this �of the patients problems before autumn“. introduced to you in 1953 to evaluate organic m natal The " mail test" which was mm richly used during the put year, syndmmlg . �Fobmary 15', 1955 modem Annual Report of Wt of Neurology, 11111:“. Hospital — moperation with the psychiatric star! and other mdical gen-ion by when of the neurology was increased during the year. 63th Fortyunino «nomination: by the attending neurologists, and «agitation: 1:0 additionﬂ were answered by the supervising neuropaychiatriut. the eiootroenmphalographie laboratory 111:8 ream-ch mm m. In this 01' lumber, 75 constim‘bod consultation requests and follow-up rewards. Evaluation of the organic mantel syndrome provided the major focus for ammlog‘io consultations. more were three patients with mime disorders who were controlled and followed in the patients mm tranatemd to work-up and treatment. Hillsido in 1953 was The «3111116. Four guard hospitals for further nonmlogie «um»; ﬁrst“ which to: introduced at mm widely used to evaluate organic mental and» must. {the mmlogic service uni also extended when rogue“; worn man from the admissions clinic for consultation prior to hospital admission. such consultations were answer-ad during the your and Sm this service provided boron admission. Under tom an opporhnity for a batter evaluation of patients of a U.S.P.H.S. grant, the electroencephalographic laboratory was swarmed for taohirboscopy, and a number of basic nouns. physiological problems were smdiod. f ’13:“ ��_ my}- 1955 Neurology hmommmwumammmwumh mes in the visiting a... was noon almond by mm. Wynn». tndmtharrﬁ m supervising mailman In th. metro-n mphdographic laboratory, 210 mom an am, of which 7!; war; consultaticn "quests. For the most put, the consultations in!" on)» momentum (6); pain syndma (3) and axiom cum tit-onion (7); men-1 wt: >nenrnlng1c mum (10). 'th wk). test for organic bran dim” Wmtinﬂpt’dnnu. activities mar-aura: ”sued mm... «momma-mt uﬂmofuorganicmtalayﬁmﬂﬂ ingpmmo. mmormmmmommsmemzm “Wmtmmmum var. mammotmmpaum fonmddnringthairtmmtﬂth aerial Wanndawmtem. numﬂtamsoam.tunmnn¢mdnmmm ammunmummmmmmmmamm mummiﬁufornm �"... u. p.-.. “N... . . N, ~ mm .mu—mww." wwmmw’mwm. ., W, .vnx— “‘Wn" .7 m as: u.- momma! Dr. H1110? TO: Dr. H. Fink RESEARCH SERVICE, smcrmmmya-pm-m. Dummmtharmmhthemmamanumwmume . in organizing an mom nhctmshook 2mm, the and the mam, the mm m Scrpuil project. Considerable mm electron-Museum laboratczy, and sum Public Health Bunion for adds! lamb Grant “97. penis“ w mm in project with Dr. spout in letting up WMar by the equipment mud thu no , Fonoving discussion with Dr. Embers and Dr. known, Dr. LnQuor Wimudtoviaitiﬂllgidumdmmmm..Dr.LIQm15mchup of the Luann unit at Grandma: State Hospital. a: March 9th, Dr's. numbers, mum and melt mum cm:- to as Dr. hQuor'I mam unit. m intended in his that. Vinita, the use or split mm mm: to induce com. mm. This '11]. be mm RobertluhnandnvaeuvisiudDr. hulﬂoehandnr. thhtric Imtituto chitin-$133M. Wﬂaittonr. WWW Dr. undue for the nut Following Med research emanate. at. Dr. Blmbarga suggestion din- mud a similar project ban, and the protocol was prumtod at the nut numb can-dun mating. nth» w. purponoracqmmuthmmaentnumh with Dr. Ismail m most helpful as m. second Our b. has had dmidunbla experience in psychoplvaicq. tachniquu. SW8 ut his ham and dime.“ withhmthemdforimmudmndsforthocmmm. Iupmssodtohiu (h March 17th I Visited Dr. Ismail thodllinbﬂityofhlvingmummeo that Dr. ﬁlmmldbo thoDuunPoundntionorthoPnaidcntamifm Public mppomw ‘19de that ��mm: Glon om, no: Ia-k KEPITAI. April 28, 1955 to, Dr. Josoph S.A.Hillor,llodioal Dix-sates M8 Dr. Kl! Pink 8i: subJoot: ' hospital, Honth Promos Ropu-t and Room-noun". Atthsondstthofirstsixnouthsasbirootorotnosoomhatth 1 should libs to dosoribo tho prosont stoto of our rosoaroh program, thhnsfathoﬂuturo,anitonkowonoouasndationsforsrosm asparagus. I: Prosoat m dotinitivo report of tho rosooroh aotivitioo of tho dspsrtnsnts of tho hospital was prooontod to tho nsdioal Board on April It, 1955. by tho chairman of tho Itososroh Omittoo. A tho prosont tins, tho staff assisting tho Dirootor inoludos two it psychologists and a part-tins sscrotary ( supportod by norm and Dausn Foundation grants); and o half-tins no toohnioian. Port-tins roooorch ootivitios aro cox-riot! out in tho various sorvicod sports-onto. In tho Doportuont at Ioborotorios, two toohnioians oro assisting Dr.Goldonborg, undo:- tho tons of a noon-oh grant of tho USPRS. Of tho psychiatric staff, two supss‘visim psyohiatrists and two rosidonts aro ootivoly oncogod in part-tins rosoaroh. Of tho ottonding staff, tour labors of tho Hodicol Board as in diroct collaboration with hospital psrsonnol in spocitio projects. is octivo in tho following projootst a. Following on tho sumoay of tho 1951; proJoot on thorolotion of altsrod brain mnotion to following olootroohook thorapy, a oooond projoot has boon undsrtoksn to asaosa tho chorootomlogioal and bioehonioal factors in impromnt. b. An snluotion of sorposil so a thoropoutio ogont hao boon undortakon as an intomopsrtaontal projsot, with tho sotivo oooporotion of tho .diool dopu-tmnt, onporvisim psychiatrist and a rosidont psychiatrist. has Dinotor imam. o. dosslopuont of moan-so of abivolonoo, both as a chorootonologiosl factor and a symptom of psychiatric choc-ponsation. “his study is in conjunction with a lambs: of tho Hodiool Board. d. and taoMstoooopio ”physiological of tho new, is now noaring oonplotian. Dnﬁont Tho 'l'ho laboratory, built with funds Tho hm m'ass stimlata's, nocosoary for tachis- mt. mublod. oscilloooops, and roloy and lons tosoopy havo boon dolivorsd, on?! are being boon outlinoo and will begin by slid-Mu. Projects hovs �4-2Bimltonoomly with thou motto, I havo boon participant in a nunbor of tho dopartnontol projocto at the hoopitalp oooporatod with tho ﬁbcultun Study Omittoo in tho dmlop-ont of its protocol; and havo mlnatod throo protocola which uoro oubnittod to tho Roaoaroh Conittoo from outoido loot-coo, and out. opooifio roommdationa on oooh. now mum problou of mohiatry involvo all aopooto of tho moo, oonroo, for thoo'pocitio tonic tron-int and provontion of tho Nor poyohoooo. an! innmatory poychoooo, nothing is known of tho otioloy of ochioophronia, involutional paycheck or antic-domain illnooo. Itch duoription of tho oouroo of thooo illnooooo io availablo, but thio haa boon of littlo bola": in troatnont or promotion moot in ioolatod inotonooo. mutant io omit-idol; and W at boot, poi-ital". ' " control roam for hospitalisation in loot pationto in tho dmlomontvo! owning tonsion and anxiow, and pmhotio thoughto. lutorporoonal rolaticnohipo havo boom diotortod, culmination blurrod, and otfootivo activity oo to throotod oolf-prooorvation. rho vat-1m porchiotric thorapioo oo availablo today attack difforont aopoota of thooo problouo. A prion-y goal io tho doovoaoo in tonoion and musty, and tho ovum-o of mohotio idoation. hob offal-t in «pound ot chaining intorporoonalxolatimohipo and oodoo of omnioation; and nontual ”education and oupport d tho pationt in dirootim his ootivitioo along «room ohannolo that lood to on! meiot- prooorvotim. Tho m1 alto 0'thMom. “ti-toot“: intho njority or ma‘ont nothoda portion.- in at loaot town-11y atomim tho poyohotio rollovine tonnion and indnoim a roturn to non offoctivo In this prooooo, tho following nothodo are pennant at tho hoopitoln Ont 1. W. By 2. By 3. By hoopitolilation, thoe pationt ' is ”poo-om pm, and ioolatod ' tron bio » .diootion, barbitnratoo, oorpooil, and chlorpronaoino, and by olootz-oohook and ubnlatory insulin trootnonto, ton-ion and anxioty are roduood. dmg W oo olootroohock, olootz-onaroooio and inmlin cola thorapy pontwtio idoation in omod by altoring brain function. It. 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W. ’ neopo, ' ' 06.000 to 10,000. on twmpuyeholoyuﬂanm mammal. mmwamm,mummmpommwrortu nothoda and smut-hum at thbut Newt. smart. duign ' with tho soul- of thy . ‘ 'thryrumn-Sﬁﬁoommhwo «Wotan. ”mam Mat-311W W, build can. mmuw “Wham cm; with tho parallel-exist inc m maul-d) mat: MW ”Wham cup-rd..in ohmic“ magnum" mum m. b. mum: a); 1ft!» hbontcry u asp-aloe to m. manna-n whatnot-chain studio’s. Wlmmmmtdﬂummool con-urn. Salary to 30,900. mg. Mtg ",3‘ an an -, o :7 . sup-n13. abducts-Inna; Ia and: null-1 than“ 1‘0 and Wm a- 85,200 W 1mm wWad cum W We m, um ”hum 1M www.mmupmdmwmmw mum mm: rem um mm mm Wwamn‘tarofthu “hm; wtocmmmumumhmungmmm unioapnjocum toba-Iunhyﬂu ”Mummhmm; alum d. And-mt - Social WI 3.5. (Seaman-k) with yum work. on use-sing funny nhtiennhipu. Pinon-1 ambit: 11' pmiou mun-ch «pox-hm. with or mum-nu it should be Muﬂy might-d. Aid-tut. u to napouihdhty for on binary tad to obtain {tantalum ad to the only you. of durum] to with tho mm of f1” 1- in amusing mum, m1 new mammal Ihichhcwmoorgwuththnpm «mammal-am follow up contact. undo. For :11 fellow-up touting an! thc 1:111 like tin mos-cry contact- tad arrangunufor Hindu-actor. “0mm Tho wot-hr to th- aws-Itch amo- I111. 11‘ t1.- 13 mm]... cooperate with the Dix-actor 3350:3111 8mm. in ﬂint prawn 5% WtuWNIIMMWtMDMrMMIWO. aim-Monongooor WmomMmuwW-innm �hme-mlmm,aw0uommmwm anuslupus. alum; m “not. In. "can!”mum «a! £11m; “parts WM mmmegaMnmmp—m. ”00 I;thMtum-mhmmutbm. ‘9 ”‘mo “’m‘ 1 .“ ”m m1. PM W, 2. Gallop M00, WW1. m.mehw. huststthubmmm” uthmmmnngarmm mamwmmusimmmm.mmmmwnm «.memgmummmmmormgwmua mmmpamgmw,mnmmm1mm. mrmdwmmmmmuémm. ﬁmmmﬁmgmmmw 81 1'' m.ummumniymowu‘mumma bmmamtimingfumtimmdukolomm mum-norm. plmning haiblo, it is mud-d 0h“ W stummmormmmmmuwaecmmm of . nun-buds» of 060,000 870,000; and with . 3 luau-uh 1955-56 by Ommhﬂl] ﬂat 836.100. mmnwwmmmbmm-uﬂ, lab-1M. Wily We!” lam, 3.0. I955. �HILLSIDE HOSPITAL Glen Oaks, New York April 28, 1955 Tb: Dr. Joseph S.A. Miller, Medical Director From: Dr. Max Fink Six Month Progress Report and Recommendations. Subject: At the end of the first six months as Director of Research at the hospital, I should like to describe the present state of our research program, our plans for the future, and to make specific recommendations for a research department. I: Present 'A Proggam definitive report of the research activities of the departments of the hospital was presented to the Medical Board on April h, 1955, by the chairman of the Research Committee. At the present time, the staff assisting the Director includes two psychologists and a part-time secretary (supported by USPHS and Dazian Foundation grants); and a half~time EEG technician. Part-time research activities are carried out in the various service departments. In the Department of Laboratories, two technicians are assisting Dr. Goldenberg, under the terms of a research grant of the USPHS. Of the psychiatric staff, two supervising psychiatrists and two residents are actively engaged in part-time research. Of the attending staff, four members of the medical Board are in direct collaboration with hospital personnel in Specific projects. The Director is active in the following projects: a. Following on the summary of the l95h project on the relation of altered brain function to improvement following electroshock therapy, a second project has been undertaken to assess the characterological and biochemical factors in improvement. evaluation of serpasil as a therapeutic agent has been undertaken as an interdepartmental project, with the active cooperation of the medical department, supervising psychiatrist and a resident psychiatrist. b. An c. development of measures of ambivalence, both as a characterological factor and a symptom of psychiatric decompensation. This study is in conjunction with a member of the Medical Board. d. neurophysiological and-tachistoscopic laboratory, built with funds of the USPHS, is now nearing completion. The two Grass stimulators, DuMont oscilloscope, and relay and lens systems necessary for tachistoscopy have been delivered, and are being assembled. Projects have been outlined and will begin by mid-May. The The v' / �-2... Simultaneously with these efforts, I have been a participant in a number of the departmental projects at the hospital; cooperated with the Subculture Study Committee in the development of its protocol; and have evaluated three protocols which were submitted to the Research Committee from outside sources, and made specific recommendations on each. II. Future Programs Present problems of psychiatry involve all aspects of the cause, course, treatment and prevention of the major psychoses. Except for the specific toxic and inflammatory psychoses, nothing is known of the etiology of schizophrenia, involutional psychosis or manic-depressive illness. Much description of the course of these illnesses is available, but this has been of little help in treatment or prevention except in isolated instances. Treatment is empirical, and at best, primitive. central reason for hospitalization in most patients is the devel~ opment of overwhelming tension and anxiety, and psychotic thoughts. Interpersonal relationships have become distorted, communication blurred, and effective activity so minimal as to threaten self-preservation. The various psychiatric therapies available today attack different aspects of these problems. A primary goal is the decrease in tension and anxiety, and the erasure of psychotic ideation. Much effort is expended at clarifying interpersonal relationships and modes of communication; and eventual reeducation and support of the patient in directing his activities along effective channels that lead to self- and social- preservation. The present methods are apparently satisfactory in the majority of patients in at least temporarily stemming the psychotic process, relieving tension and inducing a return to more effective functioning. In this process, the following methods are prominent at the hospital: Our 1. By hospitalization, the patient is separated environment. and isolated from his 2. By drug medication, as barbiturates, serpasil, and chlorpromaline, and by electroshock and ambulatory insulin treatments, tension and anxiety symptoms are reduced. 3. By electroshock, electronarcosis and insulin coma therapy psychotic ideation is erased by altering brain function. b. By group and 5. By social activities, environment, better and group therapy communication is fostered. in a permissive individual psychotherapy interpersonal relationships are fostered along realistic lines. 6. By environmental manipulation, job reeducation, and help, effective functioning is strengthened. Our social service research program is devoted to studying these processes. A. To Understand the'ﬂay Therapy'Horks: disciplines are constructively applied at the hospital, the effectiveness of any has not been sufficiently assessed, nor has the mode While these �.3mode of of the lhe study evaluated.r present been adequately of operation has Electroshock of our interest. example an electroshock of is operation By assessing in many from patients. depression psychotic resulted in improvement be works will electroshock the various possibilities it understood. If this is accomplished, then some ideas about the mental and The understanding of become clear. may in depression physiological processes A plan for a of service. research the electroshock treatment is the first goal similar study of insulin coma therapy is now in preparation; and others at the environment as a therapeutic of the hospital a study planning hospital are is hoped that the way mechanism. B. Relationship of Character Structure to Diagnosis: child— of the the demonstrate importance to devoted been study has hood environment in the development of character, behaviour patterns under stress conditions and the neuroses. Other investigators are actively involved in assess— of adult in the variety result that childhood relationships the in the factors ing behaviour patterns. It is not possible to carry out such studies at Hillside, but the important relationship between character and the type of mental illness of behavioural to of the character patterns the relation the patient shows; change which we call 'improvement'; and the aspects of character that resist treatment methods can be assessed. A prototype of such studies is now in progresselectroshock in therapy. improvement to basic of character the in aspects much C. Biochemical and Physiological Factors in Mental Illness: ill for long periods, appear to take on a stereoPersons who have been and chemistry in their reflected which is ultimately typed behaviour pattern, by neurologic, 'non—reactor' and patterns such of 'reactor' Study physiology. the failures in assessing methods important and are drug biochemical physiologic, and physical illness between psychiatric the relations of present therapies; Such and a improvement. between therapies 'organic' and the relation illness; to drugs EST and reaction where second project, the in incorporated study is and of long short terms in be assessed will electroencephalogram changes in the term improvement rates. (Follow—up): Results Treatment of D. Continuing Evaluations suffer treatment of generally of present the results studies Follow-up of the evaluation done an without are only; one therapy because they assess control to standard and compared not are improvement; for subject‘s potentialities followcontinuing a be to organize possible With may active support, it groups. evaluated on admission; assessed are the in hospital which patients up program, in followed a and over then methods at discharge; and psychiatric by psychologic number of years with an evaluation as to sustained change and reasons for failure. much would have at discharge, the to predictions Such an evaluation, if compared base—line for and a provide of choice therapies, present merit in assessing the the evaluation of any future therapeutic methods. III. Recommendation of problems the methods in attacking of suggested In this outline the treatment best; as one made to specific specify no effort have I psychiatry, is that fragmentary so it knowledge is Present the specific. or one etiology as of psychoses. the major to the eticlogy make as only a to poor guess possible A multidisciplinary approach with full freedom to follow many leads is the best of a establishment recommend the would For I be this offered. reason, that can �- u - Research Service, with full-time personnel devoted to such studies. I would suggest that such a service have "research" as its function; that it be independent of the service departments of the hospital; and that it have a basic budget which would assure continuation regardless of the availability of outside research funds. A. The Research Service should have the following organization: 1. Director of Research -- Responsible to the Medical Director. 2. Research Associates in Psychiatry and Psychology. 3. Research Assistants: a. b. c. d. Psychology Neurophysiology Psychiatry Social Service h. Secretarial and clinical personnel. 5. Technicians. B. Annual Budget recommendations for the Research Service: 1. Director 2. Associate in Psychiatry " in Psychology b. Assistant in Psychiatry " 5. in Psychology “ 6. in Neurophysiology " 7. in Social Service 8. Secretary 9. Technician n 10. - Lab EEG (1/2 time) $20,000 12,000 8,000 6,000 5,200 5,200 h,000 2,760 h,000 1,300 Equipment: As warranted Consumable Supplies Travel Overhead: As decided by Administrator. - $25,000. - 20,000. - 10,000. - 10,000. — - - 8,h00. 10,000. 6,000. 3,300. 6,000. 1,800. 2,h00. 1,000. available as a continuing commitment to the Medical Director for long range planning of the Research Service. These funds should be made For the budget year 1955-1956. I should like to make the specific recommendation that the following are the minimum requirements: 1. 2. 3. h. 5. Director Research Assistant " " Secretary Consumable Supplies 6. Travel 7. Overhead 8. EEG - Psychiatry - Psychology & Equipment Technician (in Operating budget) $15,000. 7,500. 7,200. 3,000. 2,h00. 1,0000 - $36,100. 1,600. $37,700. �0. Space: Problems of space at the hospital are acute, and will provide an increasing measure of difficulty as the service is developed. It is suggested that in the next capital outlay by the hospital for construction, some allowances be made. for the Research Service ‘ D. Relation with Other Departments: activities of the Research Service are to be those designated by the Director. Interdepartmental projects will be carried out by the Research Service, or in those instances where approval of the Research Committee is obtained, by the departments involved. Supervision of such interdepartmental projects will lie with the Research Director. The Interdepartmental projects are to be fostered by the Director. Prior approval by the Research Committee and the Medical Director is required. Such projects as are consistent with the service functions of the departments involved W111 be fostered. Presentations and reports are to be approved by the Research Committee prior to publication. E. Job Description: 1. Director of Research: objectives of the Director of Research will be to: (l) Organize and maintain an active program of research and a Research Service; (2) Promote, supervise and integrate research activities at the Hospital; (3) Educate hospital personnel in research methods and progress; and (h) Administer research funds. The The director of research will: a. Organize a central project or series of projects appropriate to the unique character of the Hospital and integrate this into the activities (therapeutic) of the Hospital. Progress reports will be submitted to the Medical Director and to each meeting of the Research Committee of the Medical Board; and such data as is approved for presentation will be submitted by the Director or his delegate at the appropriate scientific society. all staff to plan and carry out individual research projects. Third year residents in psychiatry are to be specifically encouraged to undertake research projects under his direct supervision, or that of an attending psychiatrist. For these residents, and any other professional members of the staff, the director of research is to assist in the planning of b. Encourage members of the the project; in its integration into the hospital program; and in both technically and financially. its support 0. Carry on such educational activities as the supervision of third year residents in research; monthly seminars in research problems and progress; and periodical reports of important psychiatric meetings. The director will maintain a calendar of meetings and lectures; stimulate attendance thereto; and foster the He such of is also to invite such meetings. at Hospital activities presentation guest lecturers and seminar leaders as are available. d. Administer all research funds with the approval of the Medical Director. This includes the stimulation of fund sources; the application for funds; and their allocation to hospital projects. �2. Research Associate: Director in all projects at the hospital; to assume responsibility for specified projects; and to carry on such independent investigations as his training and experience dictate. Tb work with the Associate in Psychiatry is to be a qualified diplomats in psychiatry, with extensive experience both in psychoanalytic psychiatry and in descriptive psychiatry. By training or experience, the associate should have teaching qualifications; and some training in research methods. A. Such an assume responsibility for that portion of the functions of the service assigned to him by the director; assume responsibility in the director's absence; attend conferences, meetings and assume teaching functions as recommended by the director. He range — will Salary to be determined by qualification and experience. Probable $12,000 to 20,000. B. Such an Associate in Psychology is to be a qualified psychologist with at least 10 years experience. Psychoanalytic experience is preferable. The equivalent in academic standing of Associate Professor is the guide line. research associate in psychology is to assume responsibility for those functions of the Research Service assigned to him by the director. An evaluation of testing methods. statistical evaluation of results. and a of the research of of aspects contr0l the.functioning procedure in all rigorous service are his responsibility. The research associate in psychology may be chosen from the research assistants. Salary range - $8,000 to 10,000. The will: organize and supervise projects in the department; supervise projects of the resident psychiatric staff; assist such department heads as request aid in organizing departmental projects; advise the director of new research possibilities; attend conferences, write reports and papers, and carry on such administrative activities as the Director may require. Both Research Associates Board at Appointments to Research Associate are to be made by the Medical the recommendation of the Medical Director and the Director of Research. 3. Research Assistants: assist the director in his research activities and carry on the work of the department. Each assistant is to be responsible to the director, and will carry on such tests, procedures, write such reports, and present those To papers designated by the Director. Assistants are to be qualified by training and experience for the specified jobs named. They are to be appointed by the Medical Director at the nomination of the Director of Research. a. Assistant in Psychiatry: For such psychiatristswho have had three or more years of formal psychiatric training but not yet certified, the opportunity to work for one or more years on a Research Service may provide the stimulation for continuation in research and also provide the director with the assistance of personnel intermediate in experience between the resident and the associate. The assistant in psychiatry can assume responsibility for the selection �-7of the patients for the various projects; evaluate changes in behaviour with treatment; assess the importance of intrapsychic and environmental factors in the present behaviour of the patient. the assistant.vill assume responsibility for those aspects of the problems under investigation as are within his scope, and assigned by the director. He will write such reports, papers and make such presentations as the director may suggest. He will make such tests, learn such technics and work with those members of the research service or the service departments of the hospital as his projects permit. Salary is dependent on experience. Probable range $6,000 to 1C,000. b. Assistant in Psychology: Graduate in psychology with a minimum of doctorate. Preferable experience in research methods and publication experience with some specialization in laboratory methods. Equivalent academic status of assistant professor. The assistant in psychology is to carry on such psychologic and laboratory tests, and make such statistical and methodological evaluations as the projects of the service require; and to make such reports and presentations as the director may suggest. He is to direct the laboratory technicians, organize their work and assume responsibility for the maintenance of all testing equipment and materials. In the design of projects, he is to assume responsibility for the application of the best methods and design commensurate with the goals of the project. Salary range ~ $5,200 to 8,h00. c. Assistant in Neurophysiology: M.D. or Ph.D., with a minimum of three years experience in electroencephalography or neurophysiology. To supervise and coordinate all neurophysiological studies, now being organized; develop and build electrophysiological equipment; assume responsibility fer such animal studies as are organized; cooperate with the psychologist in coordinated neuropsychological investigations; and supervise technicians in electrical methods. This position can be filled only if the laboratory is expanded to include more basic studies. Personnel can then be recruited from medical school training centers. Salary range - $5,200 to 10,000. d. Assistant ~ Social Service: B.S. (Soc. Work) with minimum of five years experience in field or administrative work. Emphasis on interviewing technics and assessing family relationships. Personal analysis recommended. If previous research experience with psychiatrists or psychiatric clinics is noted, it should be heavily weighted. Assistant is to assume responsibility for interviewing relatives of patients and develop technics of assessing premorbid characteristics based on history and interview; to obtain histories from relatives and patient relevant to the early years of development; to cooperate with the psychologist in assessing the personality of the subjects; and to coordinate research testing in the various projects. Patients seen during their hospitalization in any of the research service projects are to be seen by the social worker prior to discharge, and eVery effort at follow up contact made. For all follOWbup testing and evaluation, the assistant will make the necessary contacts and arrangements for the director. The social worker assigned to the research service will, if time is available, cooperate with the Director of Social Service in those interdepartmental projects which he may have organized with the approval of the director of research. Assistant is to be selected by the Director of Social Service. Salary range proportionate to experience in research. Range - $h,000 to 6,000. �e. Technicians: EEG -~ High l. fundamentals school graduate, although two years college preferred. To learn the of electroencephalography; make the necessary measurements and place electrodes; obtain artefact free records; maintain card files; type reports; keep records in systematic way; and maintain equipment. Technician is to be responsible to the assistant in neurophysiology or the director. Salary -- if untrained, $52,600; if trained, $33,060 to 353,600. 2. Lab. Technicianp-Neurophysiology. College graduate, preferably with some engineering or physics experience. To assist the assistant in neurophysiology and/or the assistant in psychology, in the development and maintenance of electrical equipment; to assist in the handling of animals; to cooperate in the experimental procedures; to build, adjust and design special equipment. Salary range dependent on training-- Rangeﬁ .000 to 6,000. IV. Summary: Research Director is actively involved in a number of studies of the mechanism of treatment. To maintain a continuing function and make long term planning feasible, it is recommended that a Research Service be established; that be an integral part of hospital organization with a continuing annual budget. it A proposed organization is included in this report, with a projected annual budget of $60,000 ~ $70,000; and with a minimum budget 1955-56 of $36,100. The This report approved by the Research Committee April 27, 1955. Respectfully submitted, Max Fink, MoDo Director of Research �HILLSIDE HOSPITAL Glen Oaks, New York April 28, 1955 Th: Dr. Joseph S.A. Miller, Medical Director From: Dr. Max subject: Six Fink Month Progress Report and Recommendations. first six months as Director of Research at the hospital, I should like to describe the present state of our research program, our plans for the future, and to make specific recommendations for a research At the end of the department. I: Present A Program definitive report of the research activities of the departments of the hospital was presented to the Medical Board on April 5, 1955, by the chairman of the Research Committee. At the present time, the staff assisting the Director includes two psychologists and a part-time secretary (supported by USPHS and Dazian Foundation grants); and a half-time EEG technician. Part-time research activities are carried out in the various service departments. In the Department of Laboratories, two technicians are assisting Dr. Goldenberg, under the terms of a research grant of the USPHS. Of the psychiatric staff, two supervising psychiatrists and two residents are actively engaged in part—time research. Of the attending staff, four members of the l"ledical Board are in direct collaboration with hospital personnel in specific projects. The Director is active in the following projects: a. Following on the summary of the l9Sh project on the relation of altered brain function to improvement following electroshock therapy, a second project has been undertaken to assess the characterological and biochemical factors in improvement. b. evaluation of serpasil as a therapeutic agent has been undertaken as an interdepartmental project, with the active cooperation of the medical department, supervising psychiatrist and a resident psychiatrist. c. development of measures of ambivalence, both as a characterological factor and a symptom of psychiatric decompensation. This study is in Dmedical member of the with Board. a conjunction d. neurophysiological and tachistoscopic laboratory, built with funds of the USPHS, is now nearing completion. The two Grass stimulators, DuMont oscilloscope, and relay and lens systems necessary for tachistoscopy have been delivered, and are being assembled. Projects have been outlined and will begin by mid-May. An The The �-2... Simultaneously with these efforts, I have been a participant in a number of the departmental projects at the hospital; cooperated with the Subculture Study Committee in the development of its protocol; and have evaluated three protocols which were submitted to the Research Committee from outside sources, and made specific recommendations on each. II. Future Programs Present problems of psychiatry involve all aspects of the cause, course, treatment and prevention of the major psychoses. Except for the specific toxic and inflammatory psychoses, nothing is known of the etiology of schizophrenia, involutional psychosis or manic-depressive illness. Much description of the course of these illnesses is available, but this has been of little help in treatment or prevention except in isolated instances. Treatment is empirical, and at best, primitive. The central reason for hospitalization in most patients is the devel- opment of overwhelming tension and anxiety, and psychotic thoughts. Interpersonal relationships have become distorted, communication blurred, and effective activity so minimal as to threaten self-preservation. The various psychiatric therapies available today attack different aspects of these problems. A primary goal is the decrease in tension and anxiety, and the erasure of psychotic ideation. Much effort is expended at clarifying interpersonal relationships and modes of commun— ication; and eventual reeducation and support of the patient in directing his activities along effective channels that lead to self- and social- preservation. present methods are apparently satisfactory in the majority of patients in at least temporarily stemming the psychotic process, relieving tension and inducing a return to more effective functioning. In this process, the following methods are prominent at the hospital: Our 1. By hOSpitalization, the patient is separated and isolated from his environment. 2. By drug medication, as barbiturates, serpasil, and chlorpromaaine, and by electroshock and ambulatory insulin treatments, tension and anxiety symptoms are reduced. ' 3. By electroshock, electronarcosis and insulin coma therapy psychotic ideation is erased by altering brain function. ' b. By group and social activities, and group therapy in a permissive environment, better communication is fostered. 5. By individual psychotherapy interpersonal relationships are fostered along realistic lines. 6. By environmental manipulation, job reeducation, and social service help, effective functioning is strengthened. Our A. To research program is devoted to studying these processes. Understand the Hay Therapy Vorks: disciplines are constructively applied at the hospital, the effectiveness of any has not been sufficiently assessed; nor has the mode While these �.3mode of of The the study evaluated. present been adequately of operation has Electroshock of interest. our example an electroshock of is operation By assessing in many from patients. depression psychotic improvement resulted in be works will electroshock the way that hoped is the various possibilities and mental about the ideas some then accomplished, understood. If this is it The of become understanding clear. may in depression physiological processes A plan for a of service. the research electroshock treatment is the first goal similar study of insulin coma therapy is now in preparation; and others at the environment as a therapeutic of the hospital study a planning hospital are mechanism. B. Relationship of Character Structure to Diagnosis: study has been devoted to demonstrate the importance of the childhood environment in the development of character, behaviour patterns under stress involved in assessOther actively are and investigators the neuroses. conditions of adult the in variety result that childhood relationships the in factors the ing behaviour patterns. It is not pOSSible to carry out such studies at Hillside, mental of illness and the between type character the but important relationship of behavioural to of the patterns character the relation shows; the patient of character that resist and the aspects 'improvement‘; we which call change A be prototype of such studies is now in progressmethods assessed. can treatment electroshock therapy. in improvement to basic of character the in aspects Much C. Biochemical and Physiological Factors in Mental Illness: ill for long periods, appear to take on a stereoPersons who have been and chemistry in their reflected which is ultimately typed behaviour pattern, by 'non—reactor‘ neurologic, and patterns of such 'reactor' Study physiology. the failures in assessing methods important and are drug biochemical physiologic, and physical illness between psychiatric the relations of present therapies; Such a and improvement. between therapies 'organic' and the relation illness; and to drugs EST reaction where second project, study is incorporated in the and of long short terms in be assessed will electroencephalogram the changes in term improvement rates. D. Continuing Evaluations of Treatment Results (Follow~up): suffer treatment generally of of present the results studies Follow-up of the evaluation done an without because they assess one therapy only; are control standard to compared and not are improvement; subject's potentialities for followa continuing be to organize possible may With active support, it groups. evaluated on admission; assessed the are in which hospital patients up program, in followed a and over then methods at discharge; and psychiatric by psychologic number of years with an evaluation as to sustained change and reasons for failure. much would have at discharge, Such an evaluation, if compared to the predictions for base-line and a provide of therapies, choice present merit in assessing the the evaluation of any future therapeutic methods. III. Recommendation of problems the methods in attacking of suggested In this outline the treatment best; as one made to specific specify no effort have I psychiatry, is that fragmentary so it knowledge is Present the specific. or one etiology as of the psychoses. major to the etiology make as only a to guess poor possible A multidisciplinary approach with full freedom to follow many leads is the best of a establishment recommend the would For I this reason, that can be offered. �- h - Research Service, with full-time personnel devoted to such studies. I would be indesuggest that such a service have "research" as its function; that have a basic pendent of the service departments of the hospital; and that budget which would assure continuation regardless of the availability of outside it it research funds. A. The Research Service should have the following organization: 1. Director of Research -- Responsible to the Medical Director. 2. Research Associates in Psychiatry and Psychology. 3. Research Assistants: a. Psychology b. Neurophysiology c. Psychiatry d. Social Service h. Secretarial and clinical personnel. 5. Technicians. B. Annual Budget recommendations for the Research Service: 1. Director 2. Associate in Psychiatry " 3. in Psychology b. Assistant in Psychiatry " 5. in Psychology " 6. in Neurophysiology " 7. in Social Service 8. Secretary 9. Technician " 10. — Lab EEG $20,000 - $25,000. 12,000 - 20,000. 8,000 - 10,000. 6,000 - 10,000. 5,200 - 8,h00. 5,200 - 10,000. h,000 - 6,000. 2,760 - 3,300. h,000 - 6,000. 1,300 - 1,800. (1/2 time) warranted Consumable Supplies Travel Overhead: As decided by Administrator. Equipment: As 2,h00. 1,000. available as a continuing commitment to the Medical Director for long range planning of the Research Service. For the budget year 1955-1956. I should like to make the specific These funds should be made recommendation 1. 2. 3. h. 5. 6. that the following are the Director Research Assistant " " Secretary Consumable Supplies Travel minimum - Psychiatry Psychology ~ & Equipment 7. Overhead 8. EEG Technician (in Operating budget) requirements: $15,000. 7,500. 7,200. 3,000. 2,h00. 1,000. - $36,100. 1,600. $37,700. �C. Space: Problems of space at the hospital are acute, and will provide an increasing measure of difficulty as the service is developed. It is suggested that in the next capital outlay by the hospital for construction, some allowances be made. for the Research Service ' D. Relation with Other Departments: activities of the Research Service are to be those designated by the Director. Interdepartmental projects will be carried out by the Research Service, or in those instances where approval of the Research Committee is obtained, by the departments involved. Supervision of such interdepartmental projects will lie with the Research Director. The Interdepartmental projects are to be fostered by the Director. Prior approval by the Research Committee and the Medical Director is required. Such projects as are consistent with the service functions of the departments involved will be fostered. Presentations and reports are to be approved by the Research Committee prior to publication. E. Job Description: 1. Director of Research: objectives of the Director of Research will be to: (l) Organize and maintain an active program of research and a Research Service; (2) Promote, supervise and integrate research activities at the Hospital; (3) Educate hospital personnel in research methods and progress; and (h) Administer research funds. The The director of research will: a. Organize a central project or series of projects appropriate to the unique character of the Hospital and integrate this into the activities (therapeutic) of the Hospital. Progress reports will be submitted to the Medical Director and to each meeting of the Research Committee of the Medical Board; and such data as is approved for presentation will be submitted by the Director or his delegate at the appropriate scientific society. staff to plan and carry out individual research projects. Third year residents in psychiatry are to be specifically encouraged to undertake research projects under his direct supervision, or that of an attending psychiatrist. For these residents, and any other professional members of the staff, the director of research is to assist in the planning of b. Encourage all members of the the project; in its integration into the hospital program; and in both technically and financially. its support c. Carry on such educational activities as the supervision of third year residents in research; monthly seminars in research problems and progress; and The director will maintain of meetings. important psychiatric periodical reports a calendar of meetings and lectures; stimulate attendance thereto; and foster the He such of is also to invite such meetings. at Hospital activities presentation guest lecturers and seminar leaders as are available. d. Administer all research funds with the approval of the Medical Director. This includes the stimulation of fund sources; the application for funds; and their allocation to hospital projects. �2. Research Associate: Director in all projects at the hospital; to assume responsibility for specified projects; and to carry on such independent investigations as his training and experience dictate. Tb work with the Associate in Psychiatry is to be a qualified diplomats in psychiatry, with extensive experience both in psychoanalytic psychiatry and in descriptive psychiatry. By training or experience, the associate should have teaching qualifications; and some training in research methods. A. Such an assume responsibility for that portion of the functions of the service assigned to him by the director; assume responsibility in the director‘s absence; attend conferences, meetings and assume teaching functions as recommended by the director. will He Salary to be determined by qualification and experience. Probable range - $12,000 to 20,000. ‘ B. Such an Associate in Psychology is to be a qualified psychologist with at least 10 years experience. Psychoanalytic experience is preferable. The equivalent in academic standing of Associate Professor is the guide line. research associate in psychology is to assume responsibility for those functions of the Research Service assigned to him by the director. An evaluation of testing methods, statistical evaluation of results. and a rigorous control of procedure in all aspects of the functioning of the research service are his responsibility. The research associate in psychology may be chosen from the research assistants. Salary range - b8,000 to 10,000. The will: organize and supervise projects in the department; supervise projects of the resident psychiatric staff; assist such department heads as request aid in organizing departmental projects; advise the director of new research possibilities; attend conferences, write reports and papers, and carry on such administrative activities as the Director may require. Both Research Associates Board at Appointments to Research Associate are to be made by the Medical the recommendation of the Medical Director and the Director of Research. 3. Research Assistants: assist the director in his research activities and carry on the work of the department. Each assistant is to be responsible to the director, and will carry on such tests, procedures, write such reports, and present those To papers designated by the Director. Assistants are to be qualified by training and experience for the specified jobs named. They are to be appointed by the Medical Director at the nomination of the Director of Research. a. Assistant in Psychiatry: For such psychiatristswho have had three or more years of formal psychiatric training but not yet certified, the opportunity to work for one or more years on a Research Service may provide the stimulation for continuation in research and also provide the director with the assistance of personnel intermediate in experience between the resident and the associate. The assistant in psychiatry can assume responsibility for the selection �-7of the patients for the various projects; evaluate changes in behaviour with treatment; assess the importance of intrapsychic and environmental factors in the present behaviour of the patient. the assistant will assume responsibility for those aspects of the problems under investigation as are within his scope, and assigned by the director. He will write such reports, papers and make such presentations as the director may suggest. He will make such tests, learn such technics and work with those members of the research service or the service departments of the hospital as his projects permit. Salary is dependent on experience. Probable range $6,000 to 10,000. b. Assistant in Psychology: Graduate in psychology with a minimum of doctorate. Preferable experience in research methods and publication experience with some specialization in laboratory methods. Equivalent academic status of assistant professor. The assistant in psychology is to carry on such psychologic and laboratory tests, and make such statistical and methodological evaluations as the projects of the service require; and to make such reports and presentations as the director may suggest. He is to direct the laboratory technicians, organize their work and assume responsibility for the maintenance of all testing equipment and materials. In the design of projects, he is to assume responsibility for the application of the best methods and design commensurate with the goals of the project. Salary range - $5,200 to 8,hOO. minimum M.D. of with a Ph.D., or Assistant in Neurophvsiology: c. three years experience in electroencephalography or neurophysiology. To supervise and coordinate all neurophysiological studies, now being organized; develop and build electrophysiological equipment; assume responsibility for such animal studies as are organized; cooperate with the psychologist in coordinated neuropsychological investigations; and supervise technicians in electrical methods. This position can be filled only if the laboratory is expanded to include more basic studies. Personnel can then be recruited from medical school training centers. Salary range - $5,200 to 10,000. d. Assistant - Social Service: B.S. (Soc. Work) with minimum of five years experience in field or administrative work. Emphasis on interviewing technics and assessing family relationships. Personal analysis recommended. If previous research experience with psychiatrists or psychiatric clinics is noted, it should be heavily weighted. Assistant is to assume reaponsibility for interviewing relatives of patients and develop technics of assessing premorbid characteristics based on history and interview; to obtain histories from relatives and patient relevant to the early years of development; to cooparate with the psychologist in assessing the personality of the subjects; and to coordinate research testing in the various projects, Patients seen during their hospitalization in any of the research service projects are to be seen by the social worker prior to discharge, and every effort at follow up contact made. For all followbup testing and evaluation, the assistant will make the necessary contacts and arrangements for the director. The social worker assigned to the research service will, if time is available, cooperate with the Director of Social Service in those interdepartmental projects which he may have organized with the approval of the director of research. Assistant is to be selected by the Director of Social Service. Salary range proportionate to experience in research. Range - th,000 to 6,000. �e. Technicians: l. EEG -- High school graduate, although two years college preferred. learn the fundamentals of electroencephalography; make the necessary measure— ments and place electrodes; obtain artefact free records; maintain card files; type reports; keep records in systematic way; and maintain equipment. Technician is to be responsible to the assistant in neurophysiology or the director. To Salary -- if untrained, $2,600; if trained, $3,000 to $3,600. 2. Lab. Technician--Neurophysiology. College graduate, preferably with some engineering or physics experience. To assist the assistant in neurophysiology and/or the assistant in psychology, in the development and maintenance of electrical equipment; to assist in the handling of animals; to cooperate in the experimental procedures; to build, adjust and design special equipment. Salary range dependent on training-~ Range$h,000 to 6,000. IV. Summary: Research Director is actively involved in a number of studies of the mechanism of treatment. To maintain a continuing function and make long term planning feasible, it is recommended that a Research Service be established; that be an integral part of hospital organization with a continuing annual budget. it A proposed organization is included in this report, with a projected annual budget of 3,560,000 - $570,000; and with a minimum budget 1955—56 of $536,100. The This report approved by the Research Committee April 27, 1955. Respectfully submitted, Max Fink, M.D. Director of Research �Viva—v Wu'I-v-r “IV 11; 1955 mom DR. M. FINE SUBJECT: MOW REPORT, RESEARCH SERVICE «- APRIL 1. My louder ectiviw this month has been the planning and preeentim to the Director, the Research Committee end to the Medical Affairs a plan for a research department. This was discussed at length at the hoepdtel. and then presented to the Research Omittee, April 27th and approved. It was later presented on May 3rd to the Medical Affairs Oomittee. 2. Research pro cots underm: a. BM 2: theetndy ienowinmllewingendueam followingconoeoutive patients with all our indiciee of change. (30th " b. Ambivilence: Our equipment for techietoecopy hue been set up. Correlations between clinical evaluations between embivilunce made by Dr. Tmohow and tween, and the laboratory studies using the techietoecope and the TAT test, are new in pmgmee. \ electrouetimuletore and oscilloscope have been coordineted and preliminary measurements are being made in the alteration in tactile perception in electnoehock patients. (I. Serpaeil project continues despite some difficulties in the choice of patients. c. The ' e. Subculture: This comittee has continued ite work despite a number of hwering developments. This eppointment of Dr. Navarro to the adolescent pavilion hue limited the amount or time available for this project. Simlteneouely, Dr. Outwits announced that because of the pressure of other activities, he would be unable to devote the mountﬂ‘ time previously outin- eted to the project. For the meanwhile, the committee elucidating a protocol. is continuing and in Projects begun: Dr's Ledemn end Emberg have begun a study or the use of divided insulin doses and their effect on come levels. 3‘. attended: Dr. Knhn attended the Eastern Psychological Asediction nee e in Philedelphin, Ind participated in a panel and presented a paper based npm his work at the hunt Sinai Hoepital. I attended the April meeting of the New York Neurologic Society. 1;. ' p 3 " 5. Pipers published: In the Joumel or the Hillside Hospital, the ”th1 Test in Mental Petientc' by Dr. Kuhn, Weinetein and myself. . �MEMORANDUM Dr. Joseph so A. Miller, Mono FROM: Dr. Max Fink SUBJECT; Monthly report, Reaearoh Service T08 1. Activities of - Boy of the Research Service during the month have been attendance at various psychiatric matings; the presentation of papers; and tho continuation of ongoing projects. members 2. Papers Presented: (c) The paper entitled "RelatiOn of want in Eleotroshockﬂ was read, ~ Kwalwasser. To . and Learning to Improve» the Electroahcck Rosearoh Association Changes in Memory hy title, by Mr. Karin, Dr. Fink, and Dr. This paper received the Annual Prize Award of the association. (b) To the American Psychiatric Association, the paper entitled "Relationship Betucon Altered Brain Function and Denial in Electroshook Therapy“ was presented by Dr. Kahn and Dr. ?ink. ‘(c) the resident's meeting of tho New York Neurologic Socioty, Dr. Grnubert road the paper 'Daluaional Rodnplication of Parts of the Body After Insulin Coma Thorapygﬁ To final manuscripts of these three paperc Committee, at the end of the month. The 3. Meetings uttendod: were sent to the Resoarch or the Research Service attended the following meetings: Amorican Psychosomatic Society, American Psychiatric Association, Electroshock Ecuooroh Association - all at Atlantic City. Also the Nowhers York Neurologic Society and the American Psychopathological Association in New York City. ‘ How h. Notes regarding ongoing projects: a. Further data has been con llected for the two projects - EST # 2 and Ambivalence. b. Serposil: Some difficulties in the selection were cleared in conferences with Dr. Loderman and Dr; Blumberg. Later on in the month Dr. Laderman requcsted that he be relieved of working on this project except in the aupervisony role since he has to many other activities. The project will continue with Dr; chhspress assuming the major psychiatric role. 0. Subculture: Furthor work in preparing a protocol has continued during the month despite the hampering difficulty of the nooignaticn of Dr. Gurvito and the increased activities of Dr. Navarre. It is my anticipaticn that a satisfactony protocol may be available by the and of the month. up �S. New Projects: Following an initial meeting with Dr. Loon Helium: of the Sloan Kettering Institute on April 25th further dismsions were held at the hospital between Dr. Goldenberg and myself and a second visit to the institute was made on May 23rd. With the elucidation of their program, our own protocol is being prepared and will be submitted to the Research Committee and Medical Dimctor within the next few days. ‘ The Annual Prim Award of $100.00 was donated to the the Electmshock Research urea]. Strauss Research Fund, Association for also renewal mquest for tho grant. of the 0.3. Public Health Service were submitted on May 3rd. 6. Funds: 7. Papers Published: None. �DOW 0! 310011-131.” eeeeeeseeeeeeeeeeeeeeeeeeeeeeee Dr. 8. mm MW 1. PROGRESS mom, m Gold“ 19” WtionctchlorpromeineendSeryuilinSem,Urineend embroepdnel Fluid. Wire inthodhesbemdevelopedrorthe detemiutionor drugesnd rented elheloidel compounds in blood end urine. The procedure involves extinction orthe buiriedi‘luidwith heptsneendreextraetionottheecupoundfromthe heptsne leyer with hydrochloric acid. an mixing the acid solution with methyl orange e complex is formed which dissolved in ethyl.” dichloride to give I: soln. whose color in directly proportionel to the amount of chlorpromssine, eerpcsil, or other elkeloid origindqureeent intheteettluid. Adeteiled etudyhes eleo bean nude or the specificity of the melytiecl method. Prelim-:7 results obtained with serum of petiente indicate an «trench rapid rate of dieeppesrsnee or the mister-ed meterinl. Studies are being mderteken to determine whether this 1e due to repid elimination, detonticetion, or both, and whether the degree or retention of the drugs can be correlated in em we: with their clinical effectiveneee. 2. Inhibition of Sena Cholinestereee by Hallucinogen» stub wee reemd or en intereeting observation that had been made in our lobe. lest Sept... 195:. but not subsequmtly followed up became of leek of personnel. it that time it was noted that LSD 25 is e potmt inhibitor of mm 11;. The cholinesterese. question eroee as to whether thie phenomenon correlates in may we; with the echisogenic ection of LSD 25, end whether hallucinogenic in general have 1 eimer effect on cholineetereee from serum, cells, end brain. serum Prelilinery results with serum cholineetereee indicate a perelleliem between hallucinogenic eetivity of the 3 druge teeted, listed in the order or decreasing activity, '13., lysergic acid diethylenide > lyeergie seid monoethylamide > mecsline, end their ability to inhibit the anyone. 3. Steroid 3mm. Conjugate Studies. einple method hec been found for eliminating the protein and alkaloid interference with steroid sulfate cnelyeis or biological fluids. Procedure involves eddition of alkali to diesoeiete steroid sulfate bound to protein, followed by extraction with lipid oolvente end treatment with e eulronie eeid resin to remove excess bees as well a: tree alkaloid. Progreee along theee lines has been extremely rapid and fruitful. It hes also been discovered that the home sulfates ere synthesized by the liver. Chromtomphic end paper electrophoretio methods are being adopted ee companion tools to our dye teehnie in order to establish the identity or the component hormone conjugates. A �mm .1..qu MW “mm.o 1. Papa of biological fluids to Maniac tho 1nd alkaloidol drugo, prosciu- in mm... Italics “mid on 2. Preparation for following out. to ho conduct-d on blood and urino or tor urinary “mid studios hy Slow-Kauai.“ mend opp-oval): steroid sum». uhloido, phosphorus, plating ' fum- W151" chemo-two, ma poooihly total War; of 1W Wm. W, 2.xuuam1cmmmmmmummnmidmum; 1. K. Board with! ham Education “pm to orients." 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Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Progress and annual reports; research activities (folder title 1/2). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-002 Date A point or period of time associated with an event in the lifecycle of the resource 1955 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Annual report - research; Biochemical research; Research and pUblications of the Department of Psychology; Annual Report of Department of Neurology, Hillside Hospital; Letters to Dr. Miller (Budget); Research Progress Report Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/6d5d109f552158de5a99360da32ba4a2.pdf cbe6f09f352080376a08471f0e47212a PDF Text Text HILLSIDE HOSPITAL FOR PSYCHIATRIC TREATMENT. TRAINING AND RESEARCH 75-59 263RD GLEN OAKS. N. Y. STREET FIELDSTONE 3-7300 JOSEPH S. A. MILLER. M. D. MAURICE BACHRACH MEDICAL DIRECTOR ADMINISTRATOR SIMON KWALWASSER. M. D. Assoc. June 27’ 1955 MEDICAL DIR. Dear Dr. Fink: This is to I sure that there acknowledge, with thanks, the receipt of $100 for the Research Fund, from yourself and your Associates, Hyman Karin and Simon Kwalwasser. no need am for us to tell you is of the importance of our research program. The Directors are appreciative of the sentiment underlying your gift of this $100. to Hillside Hospital. Very sincerely yours Maurice Bachrach MBzhm cc: Dr. Kwalwasser Dr. Miller Mr. Korin AN AFFILIATE OF FEDERATION OF JEWISH PHILANTHROPIES OF NEW YORK �June 30, 1955 Somatic Therapy'fbsearch Program 1955-57 From the Research Service of the Hillside Hospital mode of action the to investigate A. AIMS: It is the purpose of this study We do by this to plan mental illness. of somatic therapies in and personality behavioral of physiological, the systematic investigation factors which B. may be involved. mechanism conc‘eming the therapeutic Although many theories BACKGROUND: been have they advanced, been have of the somatic therapies cannot validity their that either empirically disproved, or, are so vague be and hypothesis, meaningful more of a development the More recently, tested. new methods of study have provided the opportunity ion. In l952,'ﬂeinstein and Kahn (Amer. for a fruitful investigat- Journal Psychiatry l923 22-26) sug- of milieu a creating by improvement to gested that the somatic therapies lead Some could of denial operate. anisms mec in.which function brain altered support for this hypothesis has been found in the literature. Carter (Am. earlier work of Janis, unpleasant life memories after the of some confirmed 1953) has §5 330, Psychologist of selective forgetting there is showing that electroshock. non—emotional and emotional of Using tachistoscopic presentation demonstrated 1953) hhS, §5 (Am. Psychologist words, Teicher that of repression" to emotional stimuli occur in the post-shock state. For the past year and a half preliminary studies "mechanisms investigating this done been have hypothesis at these laboratories at Hillside Hospital. results to date striking. have been patients were followed.with serial taneous tactile Twenty—four The consecutive electroshock electroencephalograms and amytal, simul- perceptual and memory tests. A marked correlation between �.02. improvement and early, persistent alogram, and in the amytal tests was observed. appear, improvement did not occur. sistent and severe changes on the electroenceph- It is If such changes did not our conclusion that early and per- sufficient, prepossible to predict changes in these indices are a necessary, though not make These observations improvement. for it requisite the short term response to therapy during the second and third week of treat- ment. A report on the amytal test results was presented at the recent meet- ing of the American Psychiatric Association (May 1955) and submitted fer public- Electroshock the At of of meeting American Journal a Psychiatry. the to ation Research Association on May 8th, a report of the changes in memory and learn- This was treatment presented. electroshock of the course ing occurring during he Award citation Association. the of Annual Prize awarded the was report noted the methodology as exemplary, and offering a fruitful method of study- ing electroshock. Concomitant with these studies,t7e have followed patients on insulin therapy. Recent reports onthe value of prolonged coma as the basis for improvement (Kwalwasser and Caplan: J. Hillside Hospital l; 1&5, 1952; Revitch, coma E. : Neurol. Arch A.M.A. Rowsell: and 195h; shagass 72, Quart. ﬁg; Psychiat. and Psychiat. 225 705, l95h; and Yeager 195h) In one gt 3;; J. Nerv. & Ment. Dis. llgg h35, 2 the over studies past in years. in our patients unusual case report the direct relationship between altered brain fun- have been confirmed (Delusional demonstrated Reduplication been has and improvement denial ction, of Parts of the Body After Insulin Coma Therapy, J. Hillside Hospital, 1955, in press). C. METHOD: 1. we plan to verify and amplify our preliminary observations on the relation of changes in behavior to altered brain function after somatic treatment. �-3” E.A. and Kahn, sease, Am. electroshock will be given amytal tests (heinstein, DiBrain Sodium In Organic Use Amobarbital of Diagnostic Patients (a) 3.: on J. Psychiatlggf Test" for Brain Disease: 889—89h, 1953; Its Serial Administration of the "Amytal Arch A.M.A. Value, and Prognostic Diagnostic and before and electroencephalograms l95h) Neurol. and Psychiat. 1;; 217-226, treatment. make be a used to This will data preat stated intervals during diction of the short term response to treatment. (b) Double simultaneous tactile perceptual tests will using threshold electrical stimulation. be carried out Using two Grass Sh-B stimulators, to be his for tested ability the will patient monitored by an oscillograph, of his body. different parts to simultaneously two stimuli applied perceive shown to been previously has stimulation simultaneous double of technique hé-SB, g} Neurology, (Fink function 3}, be a good index of altered brain at The January, 1952). By applying this highly refined technique it is hoped that elicited. be will patients tests, changes in brain function which are not otherwise apparent will be and amytal of electroencephalognmn the case in tested before and at stated intervals during treatment. As 2. Other Physiological procedures will be carried out in con- junction with the tests above. (a) Each patient will be given the mecholyl-epinephrine cribed by Funkenstein and associates The results will (J. Nerv. (b) sulin coma as des- Ment. Dis. Egg: h09, Nov. 19h8). be compared with the work of previous as with the results of our other physiological test investigators as well tests. and electroshock of undergoing Biochemical testing patients treatment have been in progress for some time in- in these laboratories. In this series of patients, estimates of urinary ketosteroid excretionxates Simultaneously esexcretion rate. be post-treatment to compared their will timates of steroid sulphates; phosphatase; and blood levels of steroid sulphate, �«hphosphorus, phosphatase and total alkaloid will be done. of many that investigation 3. It has been evident in our preliminary months. within six treatment somatic relapse the patients tm.t improve after imp of duration the to involved in regard The critical problem of the factors provement is also to be studied. One hypothesis now under investigation is related to the premorbid personality. denial" verbal of the "explicit characteristics the with patients Specifically, Denial Factors in Personality R.L.: and Kahn, personality (Mainstein, E.A. that sustained improvement may be 1953) March, 1-13, ﬁg: Psychiat. Illness, A.H.A. Arch. Neurol. more likely to maintain improvement, than patients & of who do will be not have this pre- morbid personality makeup. (a) two with interviews by personality of premorbid the Evaluation close relatives will airre will be used to be made elicit dictive value such as need to for each patient. A standardized question- characterological factors, which be at least may have pre- right, prestige-consciousness, sensitivity toczﬁticismand compulsive drive. words: and of pictures (b) Tachistoscopic presentation The threshold material be compared.with will illness to related levels of subject matter characterological for be evaluated data This will of more indifferent nature. assessed be as quantwill in response alterations In addition, indications. itative indices of denial. (c) and be Rorschach given will and the Test The Thematic Appereeption evaluated for the same factors as the personality interviews. to of response predictions material, the of personality (d) the basis of treatment the to start Prior made at different periods.. treatment will be 1) those unthree to possibilities: according be classified patients will On and temporarily; moderately or to improve 2) those likely to improve; likely 3) those improvement and sustained marked maintain to likely (for at least 6 �.5. Prediction will also be months). made during the course of treatment (the third weekfbr the electroshock patients) taking into account the physiological At the of factors. the premorbid personality well analysis indices as as conclusion of treatment patients will be evaluated for actual immediate response to the treatment. Those who showed some improvement ified again according to whether or not improvement will will then be be class- sustained. h. Evaluation of the change in behavior of patients undergoing treatment will Such ratings will be be made on the basis of a modification of the made independently of all Malamud the other rating scales. test results by a supervising psychiatrist. D. FACILITIES AVAILABLE: l. Hillside Hospital is a 200 bed voluntary hospital for psychiatric care. All patients subjected to phy— siological therapies are available for study. Periods of hospitalization.are 2-8 months; and a h-6 week observation period is generally available prior to the institution A of physical therapy. Research Service has been established, with a full time professional staff of a Director (neuropsychiatrist); assistant in psychiatry; biochemist EEG and technician (Ph.D.) research and assistant chemist; neurophysiologist and secretary. A full time psychologist and two chemists are associated on a project basis. Laboratory a Medcraft D-8, two S—hB 8 facilities include: (a) Electroencephalographic unit with channel instrument; (b) Neurophysiological laboratory with Grass stimulators, Du Mont # 3&0 R oscillograph; two synchronized tach- Biochemical (0) laband equipment; electronic auxiliary projectors istoscopic the followwith and of equipped 1000 with feet laboratory space square oratory ing major items: Beckman spectrophotometer,'Warburg respirator, Coleman Spect- rophotometer, and radioisotope unit following the basic specifications of the A.E.C. �2. Personnel: (a) Dr. Max Fink, M.D., Director of Research: After undergrad- uate studies at the University College of his D-A. New York University where he received cunllaude with Honors in Biology in l9h2, he attended the New York University College of Medicine, graduating in 19h5. After a rotating interneship he served in the U.SL Army, where he attended the School of Military Neuropsychiatry. training Formal neurologic York (19h8-l9h9) and was received at Montefiore Hospital in at Bellevue Hospital ( l9h9-1951). Formal psychiatric training received at Bellevue Psychiatric HOSpital (6 Hillside Hospital (1952). and During 1951, again in 1953, New at months 1950) and then he was a research fellow of the Nat- ional Foundation for Infantile Paralysis, first at of Medicine and then at Mount Sinai Hospital in New New York University College York. Both periods of study were under the supervision of Dr. Iorris B. Bender. In 1952 he was certified in Neurology by the Amer. Board of Psychiatry and Neurology, and was granted complementary May certification in Psychiatry in l95h. Simultaneously he attended and.gsunnﬁndfrom the William Alanson Institute of Psychoanalysis, Psychiatry Certificate for Physicians in January 1953. White and Psychology, receiving (b) Dr. Jeseph Jeffe, M.D., Assistant in Psychiatry: undergraduate studies at their Following Columbia College (B.A., l9hh), Dr. Jaffe attended the New York University College of Medicine, and was granted was elected to Alpha Omega Alpha. He was an interne his M.D. in 19h7. He at the Morrisania City Hospital, and then began three years intensive study at the Bellevue Psychiatric Hospital. First as a resident in psychiatry, theniizneurology, and he com» pleted his studies as a U.S.P.H.3. post-doctoral research fellow under the supervision of Dr. Morris B. Bender. �~7— From 1951 to 1953 he was in the United States Air Force. He graduated from the School of Aviation Medicine and was Chief Psychiatrist at the Mitchell Air Force Base Hospital. Since discharge from the military service he has been in the private practice of psychiatry. He was certified in psychiatry by the American Board of Psychiatry and Neurology in 1953. Since 19h? he has been a candidate in White Psyof Psychoanalysis, Alanson Institute William the at psychoanalysis in Research Assistant two and the and for past years Peychology; chiatry Neurology at the Mount Sinai Hospital of (0) New York. Dr. Robert L. Kahn, Fh.D.: Assistant in Neurophysiology: After graduation from Brooklyn College Columbia University which was United States Army. in l9h0, he started graduate interrupted by work at four years of service in the In the army he went to Clinical Psychology School and served as psychologist in various hOSpitals within this country and overseas. On leaving the army he became a Research Psychologist in the Department of Neurology of the Mount Sinai Hospital in the supervision of Dr. time. To date, M. B. New York, where he has worked under Bender and Dr. E. A. Weinstein up to the present he has been an author of more than twenty co-author of the monograph. "Denial of Illness: ASpects" which was published in Symbolic and Physiological May, 1955. received his Ph. D. from the He publications, and is New York University School of Graduate Arts and Sciences in 1953, and was an instructor of psychology and Hunter Colleges sultant to the New for York at Brooklyn For the past two years he has been a con- years. State Department of Mental Hygiene and has conducted two training programs in several of thé mental hospitals. (d) Chemist: A Dr. Harry Goldenberg, Ph.D.: Director of Laboratories and Chief Trethe of he where was a C.C.N.Y. l9hh, of recipient in graduate maine Scholarship and graduated cum laude, Dr. Goldenberg received his Ph.D. in �~8l9h9 from the Polytechnic Institute of Brooklyn. (who-ll?) Institute the Polytechnic at biochemistry He (1951 to date).' In l9h7-h9 National Institute U.S.P.H.S. project he was a Research Fellow an been has and in instructor in at Brooklyn College enzymology of the of Health, and from 1950 to 1952 he was a chemist to a at Jewish Hospital of Broeklyn studying enzyme methods in clinical chemistry. (e) Mr. Hyman Korin, Research Assistant (Psychology): Following four College of the City of military service, he matriculated at and received his B.S. in 19h? and his M.S. in 1950. During years of New York 1951-52 he was Ph.D. his for and matriculated Sinai Hospital psychology interns at the in Research Assistant been 1953 has he June Since New York University. at thesis doctoral his completed and has recently Psychology at Hillside Hospital Mount on "The Effects of Electroshock on Retroactive Inhibaticn." 3. Publications: Recent publications of the Research Service include: The Amytal Test in Patients with Mental Illness, 1955. 3-13, ii: Hospital, Hillside J. Electroshock, in Improvement and to Memory Learning of in Changes Relation press). Conf. Neurologica, 1955 (In Delusional reduplication of Parts of the Body After Insulin J. Hillside Hospital, 1955 ( Therapy, In press). Relation Between Altered Brain Function and Denial Amer. Coma in Electroshock Therapy, J. Psychiatry (submitted). Rectification of Nonlinear Beer's Law Plots, Anal. Chem. gé: 690, l9Sh. Bioand Biochem. Arch Curves, Enzyme Non-Linear Activity Rectification on phys., ﬁg; 288, l95h. �July 1, 1955 BUDGET l. -. RESEARCH SERVICE, PERSOM'EL 1955-56 EFF—ES. Director of Research 15,000 - BD OF DIRECTORS 15,000 in Psychiatry 7,200 Research Assistant in Neurophys. 7,500 Chief Chemist 8,200 Assistant Chemist 2,800 Research Assistant in Psychology h,000 h,000 - Assistant Chemist h,000 h,000 ~ Assistant Chemist 1,800 1,800 - 2,520 960 150 150 3,810 2,1uo 1,670 1,000 200 800 $ 57,980 $20,750 $37,230 Research Assistant Secretary - EEG Technician 2. EQUIPMENT 3. CONSUMABLE )4. TMWBL-CONFERENCES TOTAL SUPPLIES 7,200 7,500 - 8,200 2,800 1,560 ��your grant for the biochemm and neuroplvsiologiul approved. A mpplamuzy grunt request fer $7992.00 apprum! by the Public Health Serum for the 24—927 pmaeem This may will amt thsalary or Dr. R. him. 6. grants were A. , 3 The ascend In sdditionk protoccla were submitted thmgh Hr. medatim. m Calm ta the Hofheimr �Department of Biochemistry ................................. RESEARCH PROGRESS REPORT, JULY-AUGUST A. Major work Dr. H. Goldenberg 1955 in Progress 1. Determination of Chlorpromazine in Blood and Urine procedure for the colorimetric estimation of chlorpromazine and related alkaloids, described in the June 1955 progress report, has been further refined to permit detection of the extremely small amounts of drug circulating in blood. The method is based on two new features: (1) The finding that drugs can be quantitatively extracted from biological fluids with a single portion of an ethylene dichloride-ether solvent mixture, and (2) The use of a three—phase solvent dye partition system of analysis. The Clinical data are also being obtained on bound as well as free circulating promazine, based on the use of hot acid to liberate the conjugated drug. 2. Inhibition of Cholinesterase by Hallucinogens These studies are being continued as indicated in the prior report. 3. Steroid Sulfate Conjugates All but one of the major problems involved in the assay of steroid sulfate metabolism.in mental disease have now been solved. A novel device has been introduced for eliminating the interference with our test due to phenol sulfates in blood and urine. A two-phase system incorporating dicyclohexylamine (DCHA) as a complexing agent effectively separates the steroid from the phenol sulfates, permitting their unequivocal determination. The procedure for serum is now as follows: is treated with alkali to release the hormone conjugates. b. A lipid solvent is added to precipitate the proteins and simultaneously extract the hormones. DCHA The and between to brought is dryness supernate partitioned c. lipid a. Serum and chloroform. free steroid sulfates are released by shaking the chloroform extracts with acidic resin. e. Final assay of the sulfate conjugates is effected by adding dye and reading the color. d. The considerable amount of clinical data have already been obtained on normal people and on patients selected for independent studies by the Sloan-Kettering Institute. An immediate correlation has been established in our laboratory between urinary conjugate levels and sex, males excreting about twice as much conjugate as females. This ties in well with what is known of steroid metabolism A �and tends to confirm the validity of the method. Attention is now being devoted to fractionation of the steroid hormones in conjugate form. Paper electrophoresis has proven inadequate for the purpose. Paper chromatography is more successful and is under continuing study. B. Papers, Lectures and Conferences following papers are in preparation: (1) "Colorimetric Determination of Alkaloids, with Particular Reference to Chlorpromazine", and (2) "Steroid Sulfate Conjugates. II. Colorimetric Microestimation". The C. Funds and Personnel Changes 1. Research Grant #A-675 from the National Institutes of Health the fiscal period Sept. 1955 - Aug. 1956. 2. Messrs. Michael Miller and Spencer Parness terminated in the laboratory at the end of August. cc. to: Dr. Fink Dr. Miller their was renewed for summer employment �Department of Biochemistry ................................. RESEARCH PROGRESS REPORTI SEPTEMBER - A. Major werk Dr. H. Goldenberg 12§§ in Progress 1. Determination of Chlorpromazine in Biological Fluids As a result of repeated analyses of blood drawn from patients receiving chlorpromazine, the circulating blood level has been established as less than 1 microgram per ml. serum. The three-phase solvent dye partition scheme of analysis mentioned in the previous report has therefore been adopted as the only method capable of detecting the extremely minute amounts of drug in peripheral blood. A new shaking machine has just been obtained from the A.H. Thomas 60., Philadelphia, to permit application of the method on a broad scale. question naturally arises as to the metabolic fate of chlorpromazine in humans. We have recently detected in patients! urine an ether-soluble carboxylic acid which reacts with ferric chloride and appears to be an oxidative byhproduct of chlorpromazine metabolism. The 2. Inhibition of Cholinesterase by Hallucinogens three-phase system mentioned above has been found applicable to the analysis of LSD 25 as well as chlorpromazine and serpasil. By combining this observation with the earlier discovery of the inhibitory effect of LSD 25 on human serum cholinesterase, it is now possible to relate the enzyme inhibitory action to the alkaloid concentration in "unknown" samples of fluid and so deter— mine the specific molar inhibitory action at the 0.1 microgram level. This amounts, in effectI to the first sensitive chemical test ever reported for the detection of LSD 25 and related hallucinogens. The 3. Steroid Sulfate Conjugates work progressing cc. to: Dr. essentially as described in JulyhAugust report. Fink Dr. Joe. S.A. Miller M. �TJ'M‘ W10,” kW!“ mmMume mmﬁmmmam.mu¢wmtbmmmm dﬁltﬂdmﬁord’pﬁiﬁﬁd‘ﬂ. 7 mauummm �WW Wmmtmmmunmmngmpm. 3.) nmmmm Wamwmm‘m M.anummt.mk mmmwmmummmm.w. mmrpmhmmmmdmdt “Wumm Mnuwhmwmmmmmmmunm �.3. «W. wammnwunm-Wmum. 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Dr. mmnuuudatwrmnummmmmhmmm �mum-mu. n.) nun-rum WWII-luminous mummmnmummmwmm. mum Wummmmomumsnnamw-m www.mum.mmummmma: ’mmuem‘mwmrvwgm W m&% 11.:an . �\ﬂ October 20, 1955 MEMORAEDUM TO: Dr. Joseph S. A. Miller mom: Max Fink, 14.1). SUBJECT: Six Months Report of Research Activities at Hillside Hospital At the request of the Chairman of the Medical Affairs Committee, I am submitting this six month report of the activities of the Research Service and associated research activities at the hospital. During this period, numerous projects have been under investigation, our staff has expanded, and our space requirements were met. Two projects are being completed, and one project has just been instituted. A. PROGRESS l. hmw2: In ONGOIﬁG PROJECTS: ELECT§9§§QQK # Our second electroshock project was undertaken in March project had clearly demon- in September. Our first strated that cerebral changes were essential to improvement and that these 1955, and completed could be measured by the electroencephalogram and by amytal tests. 'Ue also concluded that memory tests were a poor index of improvement and believed that there were specific psychological patterns indicative of denial which were more prominent in the improved group than in the unimproved. Following this study, the second project was undertaken and was designed to demonstrate the reliability of the electroencephalogram and the amytal tests for prognostic purposes; and to ascertain the characterological as‘ﬂe term be term the short which and in results. long factors might pects have studied.twenty-seven patients to date. The data of this project is now being processed, and will be available following our six month follow up period, (which is from November to January). data from the first study was pres nted at various meetings, including the American Psychiatric Association, the Electroshock Research Association, and the Eastern Association of Electroencephalographers. The memory data, presented by Mr. Korin at the Electroshocx Research Association The in May, was awarded The their annual prize. electroshock project # 3 is below), and will be instituted November 15. now in the planning stage (see This project, which has been undertaken with Dr. Sidney Tarachow of the Medical Board, has accomplished a considerable amount of its basic work. Three approaches to the problem of measuring ambivalence have been accepted. These include an interview evaluation; the thematic apperception test, and tachistoscopic presentation of pictures. During this period of evaluating methods, twenty-three patients have been studied. Dr. Tarachow has been attending to this work, and the testing has been undertaken by dr. Korin. 2. AMBIVALcNCE: ‘ �~2- Serpasil evaluation study, undertaken at the end of last year, is com~ double blind a by been have studied intensively Seventeen patients pleted. Blumberg Drs. andeachspress. evaluated by The now data being is technique. To date, the clinical results are disappointing. Patients who were depressed, who were over-active Patients symptom. of this manifested an eﬁag ration disturbed/EnogIIeviation of this activity but the psychotic ideation genand of secondary induced a The variety intramuscular dosages erally persisted. complaints. In the evaluation of'the mecholyl responses following serpasil, The blood in pressure response all subjects. effect consistent was a there of this presentation considering Dr. and Blumberg is lower was significantly data at the next meeting of the American Psychosomatic Society. 3. SQRPASLL: The } Preliminary studies by Dr. Laderman in 20 patients in a series of clinical not was but significant this alterations and behavioral showed symptom studies of Shaw evaluation undertook an Dr. In mid-September, in the doses used. A protocol coma therapy. Thorazine as a possible substitute for insulin French and Kline submitted Smith, to was The Research Committee, approved by and approved, assuring us of adequate supplies for the duration of our proof 8,to a medication for period receive will In this study, patients ject. 12 weeks, comparable to the insulin coma period. During this time, very have been To be used. patients eight date, will thorazine of doses large The obser3600 1500 initial from to The daily. mg. dosages range studied. three had clinical response; a show significant three the patients vations h. THORAZINE: and one symptoms, toxic developed one minimal had patient changes; patients medthe of Cohen and Blumberg Drs. medication. the patient has just begun our using to permit controls the have contributed necessary ical department such large doses of this potent drug. Since June, Drs. Goldenberg and Royce have been coopof a in study Sloan—Kettering Institute the chemists the at with erating the possible alteration in the keto-steroid excretion patterns in our patSince June. Committee Research in by our This was approved study ients. then five patients have been under investigation. The initial data is not in Dr. Goldenberg by studied Each of being the is patients available. yet his laboratory as well as by the chemists at the Institute. 5. SLOAN KETTERIDG STUDY: Dr. Goldenberg has been occupied in studies measurand acid of devising the effects lysergic estimating ing chlorpromazine, methods to measure steroid sulphate conjugates. This basic research is to which to we apply measurement plan of methods the to provide necessary our patients. (a) Chlorpromazine: An ultra~sensitive technics has been of amounts this drug. microgram) minute (0.1 which measure can developed Golden— Dr. Thorazine, of number By applying this to a patients receiving bloodstream. the amounts in small appear demonstrated only that has very berg LSD has been by cholinesterase The LSD: of serum (b) inhibition A compounds. demonstrated, and this test applied to other hallucinogenic correlation between hallucinogenic activity and cholestestcrase inhibition was found. 6. BIOCHEMICAL RESEARCH: �*3“ a (c) Steroid Sulphate Conjugates: ‘Nith the grant support from the USIHS, methods to estimate these compounds have been devised. By studying hormone demonstrated sulphates are synthat Dr. Goldenberg liver slices, of the level in difference and a there sex is that the thesized by liver, steroid excretion. Both these observations are of fundamental significance, and will be presented to various societies this winter. In the Department of Medicine, hrs. Cohen and Blumberg have continued Durand the electroshock of the patients. serpasil studies their Mocholyl and than more been have studied to additional an patients this period ing half have had more than one such evaluation. The serpasil group demonstrated a significant alteration in their blood pressure patterns following this done be and been will has The correlated not data electroshock yet drug. as soon .8 our electroshock # 2 data is available. 7. MECHOLYL: Following the approval of this project by the Research Committee last spring, Drs. Navarre and Graubert had a number of meetings with members of the Medical Board. Following these discussions, they have begun a pilot study of one patient, and intend to evaluate those factors in the hospital environment which may be contributory to the patient's improvement. This satisfactory pilot study was udertaken in an effort to clarify a protocol to the Ibsearch Conmittee and of sufficient quality to be submitted for 8. SUBCULTURE: To some extent, this project outside to organizations. financial support was hampered by the multiple duties of members of the committee and by the resignation of Dr. Gurvitz. Since September, however, the committee has been working very actively and it is anticipated that a satisfactory protocol will be available by the end of the year. In June, following some discussions concerning the Laderman and Drs. coma of insulin doses for insulin treatment, correct doses between the multiple relation into undertook an Blumberg investigation 05 insulin and the blood glucose level. lt was anticipated that multiple small doses of insulin might reduce blood sugar significantly earlier and large dose. It was quickly determined, for longer periods than a single .) however, that multiple small doses, even if the sum total was equal to a This and of depth. coma degree a not did satisfactory produce dose, single project is now being prepared for publication. 9. B. DIVERE' I SULIN D SE8: PROJECTS PLANI‘IED: November # the third Electroshock 3: Beginning let, l. electroshock project will be undertaken. This study is designed to extend our experience with the factors which may be relevant in both the long and short term clinical reSponses following electroshock. Also, in this study specific emphasis is placed on the psychiatric and language changes which follow electroshock treatment and which we have been accustomed to calling "improvement." Dr. Joseph Jaffe has prepared a number of specific studies, including detailed interviews with patients prior to and during treatment, in which specific aspects of behavior and language will be assessed. �a... In this study, also, a basic problem in the perception of multiple simultaneous tacti e stimuli will be undertaken. Under our original grant from the United States Public Health Service, we were given funds to study the problem of Satisfactorily delivering single and multiple independent and The completed was designed equipment wave impulses. electrical square in Septemler and for the past few weeks has been undergoing rigorous clindur« be and will applied found been has satisfactory highly ical tests. It between changes the of relation the with question specific ing this project the in and in behavior, changes stimulation tests simultaneous double in electroencephalogram and in amytal tests following electroshock. 2. EIOC ‘thAL APPLICATION OF HEM TESTS: ’ Dr. Golden— berg has completed.the pilot studies necessary to devise measures of Specific compounds. He believes these should be applied to our clinical population over the next year. A specific protocol for this application is being prepared. 3. For more than a year, has been interested in form- EEQQNOSTIC IdDIGATQE§ﬂIﬂ ELECTROSHOCK: ' ‘ Dr. Karliner of the attending psychiatric staff electroshock. would be in which helpful factors some prognostic ulating Discussions were held in June and at the suggestion of Dr. Miller, Dr. Karlbe This scale will evaluate scale to prognosis. iner prepared a special months. next the six and Committee assessed over Research the to presented C. STAFF CHANGES: Dr. Joseph daffe, a practicing peychoanalyst, was and in research psychiatry, assistant Service Research as appointed to the behavioral the in is Dr. interest Jaffe's work on September began lst. induced altered brain function and the by and language changes which are relation between such changes and premorbid personality. were resolved effectively Lowenstein of the floor the on the of first extension the laboratory by The reduced. been tachistoscopic have also Our problems equipment building. be able now to works and well. are into alignment was brought equipment During this period our space problem simultaneously. two or individually pictures tachistoscopically present The electric stimulatorsale functioning satisfactoraly so that we are now able to produce isolated simultaneous square wave stimuli with the ability to vary any of the essential parameters. D. FUNDS: In May, we submitted an application to the United Sept— In of Dr. Jaffe's Service Health program. for support Public States an in the and staff interviewed the Frank Jerome came to hospital Dr. ember, USPHS the from in we anticipate a response evaluation of our program. mid—December. In June, we also submitted the necessary forms for second renewals and both and Dr. Goldenberg myself, both renewal for grants year the these both renewals, note for that to were approved. It is important overhead allowances were increased to 15%. At the suggestion of Mr. Coleman, specific protocols of our re» search program were submitted to the Kaufman, hoffheimer, and lttleson Foundations during this period. �-5the been for has Service writing Research the which The protocol of Committee Research the submitted to was Ford Foundation grant pr gram was the protocol that the consensus was the Medical Board in September. It suggestions, their Following be submitted. not and that it unsatisfactory of Drs. the with cooperation Service Research made the by changes are being Lenzer and Luttrell. another submit application to am planning I present time, re— March for meetings their to the USth in January for consideration at to an application am contemplating also I newal of our present program. ambivalence study, the for for Fund support for Psychiatry Foundation the as soon as the basic work is completed. At the E. Q?HER.ACTIJITIES: l. ISRAEL 5T3§p?§nF9§E§Ei9F THE JOURNLL QEWEELEEERE HOSPITAL: Following diScussion with Dr. Tarachow, the Research Service has undertaken the Tarachow issuin Dr. work in and ssisting editorial necessary secretarial Journal. Volume of Hillside the Commemorative the special ing 2. ISRAEL STRAUSS LECTURE: Consideration is being given by members of the at Discussion is next the lecture. Committee for Lecture Strauss Israel should decision and a final candidates of number present centered about a be available by the end of November. Respectfully submitted, . i "’ -," ’- 4 H7 ”.51 ‘ ‘) {I 1 «I g.“ ,--‘or ,. ‘ j . If ‘f‘ \ Fink, M.D. Director of Research Max . . �Department of Biochemistry ................................. Research Pro ress Re Major werk l. rt, Dr. H. Goldenberg November l9§§ in Pregress Chlorpromazine Studies previous work has been summarized in the report for the 6 month period ending Oct. 1955. We have subsequently learned from two representatives of the Smith, Kline and French Laboratories that Drs. Salzman and Brodie, working at the National Institutes_of Health, have identified chlorpromazine sulfoxide in the urine of dogs and men after treatment with chlorpromazine. A sample of the sulfoxide was requested from Smith, Kline and French and arrived the end of Nov. Our ultraviolet absorption spectrum of the sulfoxide was determined in aqueous solution and compared to the Spectrum obtained with extracts from patients! urine. A remarkable similarity was noted. On the basis of this and other data accumulated in our lab., there can be no doubt but that urine from mental patients receiving chlorpromazine contains: (1) chlorpromazine, (2) the sulfoxide, (3) one or two other alkaloids of related structure, and (A) at least one break-down product which yields a violet color with sulfuric acid, as contrasted to the pink colors typical of chlorpromazine and its sulfoxide. The Using our dye—partition scheme, the sulfoxide yields a color which is roughly 1/5 the value given by chlorpromazine in equimolar concentrations. Hence our dye scheme is not applicable as such to the analysis of fluids con~ taining both derivatives, unless some additional information is available on the relative amounts present.‘ Fortunately the relative proportions can be estimated from the extent to which the color is depressed by the addition of ether. Nonetheless, we are withholding a manuscript dealing with chlorpromazine analysis until this question is completely resolved. Ultraviolet and chromatographic studies are to be undertaken soon to establish the various chlorpromazine derivatives in urine and their clinical significance. 2. Role of Toxic Agents in Mental Diseas : An Enzyme Test for LSD first draft of a manuscript entitled "Inhibition of Serum Cholinesterase by Lysergic Acid Derivatives. Submicro Detection of LSD 25" has been completed. Copies are to be forwarded to the Research Committee on Dec. 8th. The 3. Steroid Hormone Conjugates Little progress has been made in this area in the last 6 weeks because of a delay in construction of our chromatography cabinet and unavailability of electrical parts needed for the circuit. This situation should be remedied by the middle of December. cc. to: Dr. M. Fink Dr. Jos. S.A. Miller �ELECTROSHOCK THERAPY EVALUATION PROGRAM from the Research Service of the Hillside Hospital Glen Oaks, New York December 20, 1955 Alvin E. Coleman, President Joseph S.A. Miller, M. D. Iiedical Director �Electroshock Therapy Evaluation Program em I. Aim II. Background III. Previous Studies Development and Progress in Studies IV. Tests of Altered Brain Function Premorbid Personality of Adaptation Patterns NonAVerbal Verbal, Evaluation of Improvement Steroid Excretion Studies Autonomic Studies V. Program Summary Method Significance VI. Facilities Available Laboratories Personnel VII. Budget Present Budget Requested Support VIII. Appendix References Bibliography of Personnel Page �I. E: During the past few decades there has been an of various new somatic intensified development therapies for mental illness. Jhile some have even- been an has established as electroshock therapy into fallen disrepute, tually important and successful method for both immediate and long term results (1). Despite its empirical usefulness, the many theories concerning the mechanism of this therapy have been either disproven or are so vague that their validity tested. In a comprehensive review, Kalinowsky and Koch (2) emphasize the lack of information in this regard stating: ".......the theoretical cannot be aspects of the various somatic treatments in the case of the shock treatments, still ..... are poorly understood, or, as entirely obscure in their mode of action." The aim of this program is to study the therapeutic mechanisms in electro- convulsive therapy by the systematic investigation of behavioral, personality, physiological and biochemical factors. Thile the program has electroconvulsive therapy as its focus, considerable theoretical and experimental information can be derived to relate the phenomena observed in this therapy to other somatic treatments such as lobotomy, electronarcosis and insulin coma. �II. BACKGROUND: of abundance has stimulated an electroconvulsive therapy of use and the Both kind theories of the much and research. exper(3) hypotheses The of interest the reflect however, particular undertaken, imental investigations the origin frame reference of regarding and theoretical his the investigator of mental disorders. Thus, each has been usually limited to one aspect of the problem. In general, these theories may be differentiated between those that emphasize physiological, biochemical, or psychological constructs. A who classical physiological construct is exemplified suggests that the various by Gellhorn (h) forms of shock therapy "act on the centers of the autonomic system, produce intensive and prolonged sympathetico-adrenal mental activity, hypothalamic-cortical augmented and alter, through discharges processes and behavior." psychogalvanic reflex, The varying responses of blood pressure, heart rate, and other physiological indices to chemical stresses are obtained been has data huch of sympathetic reactivity. interpreted as indices to and Show autonomic reactivity, in this induces change a electroshock therapy that (5) coaworkers and support this his Funkenstein by studies recent conclusion. Much illness and biochemical study has been devoted to the relation between mental steroid metabolism. between ketosteroid excretion Numerous rates instances (6) in which a relation and change in mental state following electroshock therapy are reported, but the clinical difficulties in the measurement of steroids have left this issue unresolved. Kore recent studies excretion to the total steroids between individual the relationship exploring rate (7) utilize elaborate chromatographic separation technics. �In a good review of the biochemical and neurophysiological hypotheses, mode the view the that evidence to justify Ashby (8) presents experimental of action of electroconvulsive therapy is through effects on the adrenal cortex mediated by direct stimulation of the hypothysis. Psychologic constructs generally fall into three designs - studies of the psychic significance of the loss of consciousness; the relative importance of ities memory loss; and an estimate of the subject's re-integrating abil- the Numerous unemphasize studies of confusion. following a period conscious significance of the treatment as a “rebirth which eliminates reand exneed punishment for of a satisfaction narcissism" a (9); or gressed piation for committed sins (10). Amnesic effects are a common concomitant of treatment but most studies of these The significance of impairment. the nature emphasize the temporary defects for therapeutic results is emphasized by numerous authors. Data is the on emotional charge patreduces the treatment that presented to emotionallyfor of induces familiarity loss a associations (ll), ient's show toned associations (12), or a selective forgetting of unpleasant life memories (13). These constructs are further elaborated by authors who believe that the as behavioral responses confusionalemate including of an organic induction im» electroshock the for basis is over-reacting euphoria, impulsiveness or provement (1h). A more umerated by Weinstein & recent elaboration of this explanation is that enKahn (15), described subsequently. �-h- adaptive in changes proregard explanations of psychologic Another group describe (16) and Frosch Impastato mechanism. cesses as the basic therapeutic on a which then re-integrates the of ego electroshock as causing a dissolution suggestopinion similar has a Alexander of adaptation. previous or higher level ing that defensive operations. enhances active and electroshock arouses For this in'whii1 conditions those in effective such is therapy that he asserts reason conp in ineffective but are low ebb, as in depressions, such operations are at a (17). alerted highly already ditions in which defensive operations are most two in.which Kahn (15) and Another hypothesis was developed by weinstein were the process of therapeutic aspects related. They asserted that the thera- of altered milieu of a creation the in convulsions lay induced of action peutic is of problems his expression symbolic brain function in which the patient's Their them. studies, denying of form the explicitly altered, particularly in cerebral with with patients documented by an extensive neurologic experience behavior. in adaptive of changes a function, amply demonstrate great variety dys— attention (l9), orientation (18), They describe altered patterns in language manifestations (21) as defect of and awareness (15b) (20), sexual behavior the patient's constitute mechanisms these conclude that and of adaptive behavior attempt to deny his illness or striking and enduring in those its meanings. patients Such who had most were denial at attempts habitually used the defenses with their of coping means a as and rationalization of verbal denial of indicative these patterns that problems (22). They also demonstrated administraintravenous the following interview "denial" could be elicited in an interview the clinical manifest in not when were they tion of sodium amytal (23)-* followdenial and explicit disorientation of * This appearance of patterns with associated so clearly sodium is amytal ing the administration of authors these by described been has diffuse cerebral dysfunction, that it test." named "amytal the been has This (23). as a test for such dysfunction �-5of denial between a patient's noted direct relationship a they cere— of the of and signs the electroshock appearance therapy pain following test) of mechanism the that suggested they amytal bral dysfunction (positive Thus, when electroshock therapy may be the facilitation of patterns of denial by altered brain function (15). and psychophysiological at integrating This hypothesis is an attempt which terms in View it of the and As operational in such, factors. logical have which studies base our theoretical upon a has provided is stated, it been elaborated. �III PREVIOUS STUDIES: of altered manifestations studies investigating For the past three years, cerebral function in psychiatric patients, have been in progress at Hillside Hospital. In 1952, the application of the amytal was asseSSed (2h). test to psychiatric subjects Positive responses were found only in patients who had had electroshock therapy or had other indications of organic brain disease. in order to test the relationship between altered brain referred consecutive patients electroshock to therapy, and the function response electroencephalograms, with serial intervals weekly at tested treatment were for During 1953-195h% amytal tests, simultaneous tactile perception%% tests, and tests of recall function. A marked correlation was found between improvement therapy and early, persistent the electroencephalograms. following electroshock and severe changes in both the amytal If no such tests such changes did not appear, improvement and failed correlations were manifest between improvement to occur. In contrast, and tests of recall function or changes in simultaneous tactile tests. WM TWenty—four subjects were tested in this first study, and were classified improved markedly as psychiatrist the supervising by independently ately improved (6) and unimproved (7) at the (ll), moder- end of one month post-treatment. Paralysis Infantile for Foundation National from the Aided Fellowship a by * (Dr. Fink, 1953) and Grant K—927, National Institute of Fental Health, National Institutes of Health lQSh-Sé. stimuli two simultaneous tactile of the of perception as Previous studies one localize to or of perceive failure demonstrated characteristic patterns of the stimuli in patients with diffuse cerebral dysfunction (25). �-7Of the markedly improved patients, every one had at least one positive amytal reaction during treatment. Of the 50 tests given to this group, 38 (765) were positive. In contrast, of the unimproved patients, five of the seven never showed a positive result, positive. 6 (13%) were and of the The LS tests administered to this group, only moderately improved group showed more positive re- sponses than the unimproved patients, but fell far short of the much improved group. In addition, there were consistent changes in language and non-verbal as- pects of behavior indicating alterations in adaptive mechanisms in the in interviews not employing amytal. These alterations improved group, even were much either minimally or only transiently manifest in the unimproved group and then only under the influence of sodium amytal.* Concomitant studies of the electroencephalograms taken on a day pre- ceding the amytal first measured test indicate for per~cent time a similar 31 w wave relationship. The 160 records were (delta) activity, the extent of burst activity and the amplitude and frequency of the slowest waves present. They were then placed in a rank serial order. Those falling in the upper third were labelled "high abnormality" abnormality." ality after Of the and those in the lower much improved patients, one week of treatment; 80% after 25% showed third as "low a high degree abnormp two weeks and over 90% after three In the unimproved patients, however, none had a high degree abnormality record during the first three weeks and only one had such a record by the fourth weeks. week of treatment. The records of the moderately improved patients fell between these two groups.*% * Presented at the Annual Meeting of the American Psychiatric Association, Kay 10, 1955. ** Presented at the joint meeting of the Eastern and Southern Electroencephalographic Societies, Bethesda, September 30, 1955. �Changes in memory and learning were tested in these subjects by using the principle of retroactive inhibition. 3-letter originally learned By the serial testing of recall of words following the interpolated learning of nonsense syllables, patterns of decrement in learning and recall were elicited. As a week of treatthe showed to third impairment the increasing up patients group, ment, and a rapid improvement after the cessation of treatment. No relation- ship, however, could be established between impairment and reSponse to treatment.* The responses of these subjects to simultaneous tactile tests using touch stimuli were also assessed. While an increasing impairment in the ability to be two demonstrated with increasing could and stimuli the localize identify treatment, no relation to improvement was noted. however, and in anticipation that more meaningful The tests were extremely gross, correlation for this index of altered brain function could be obtained, a study using threshold electrical stimuli has been undertaken (pg. 10). As ent and result of these studies, it was our conclusion that early, persistsevere changes in both the electroencephalogram and in the amytal tests a are a necessary, though not sufficient pre—requisite for improvement following electroshock therapy. These observations make it possible to predict the short term response to electroshock, and such a study was undertaken earlier this year (pg.ll). Concomitant with these studies, we have made some preliminary observations in patients undergoing insulin coma therapy. Recent reports of the value of prolonged coma as the basis for improvement (26) have been confirmed in our patients. In one unusual case report we noted a direct relationship between * Presented before the Electroshock Research Association,1;ay 8, 1955 and awarded their Annual Prize award for excellence in research design. �altered brain function, altered patterns of adaptation in language and behavior, clinical and improvement (27). Concurrent with these psychologic investigations, basic studies have been done in in biochemistry. 1950* with an The initial biochemical research laboratory was established program of study of the relationship between steroid excretion patterns and states of mental illness. studies, utilizing alumina column chromatography, demonstrated atypical The number excretion of a levels in psychotic ketosteroid patients. urinary The of B—steroids (particularly dehydroisoandrosterone) was found to be elevated, and the etiocholanolone was depressed (7a). The ll-ketoetiocholanolone values appeared to be sex-dependent: male patients excreted the steroid metabolite in normal amounts, while the several female patients studied had markedly elevated values. During the past year, a collaborative study was chemical department of the Sloan-Lettering initiated with the Institute of new York. bio~ Similar steroid excretion pattern studies were undertaken utilizing paper chromatographic technics. In the first phase of the study recently completed, the elevated excretion of ll-ketoetiocholanolone was confirmed, with a severe reduction in the excretion of this when compound prior to discharge, at a time the patient had shown considerable improvement from her * Supported by grants from the Dazian Foundation illness. for Hedical Research. �.10... IV. §EUDIES IN PROGRESS 1. Relation 2f AND Tests IN DEVEILEEENT: Improvement: Function Brain 33 Altered 3; altered between relationship direct Our earlier studies this that however, apparent, is treatment. It to and function response brain and not only function brain altered of indices certain holds for relationship and elabconfirm to undertaken been has for others. Further study, therefore, have shown a methods of measuring orate these findings, as well as to investigate improvement. clinical to related function which are more reliably a. cerebral Amytal Test and Electroencephalogram: Amytal tests and electroencephalograms are done and second the and during subjects before, third in all weeks of electroshock treat— make a used predicto data is the findings ment. On the basis of our earlier those that predicted is treatment. It to term short response the of tion and with positive abnormality electroencephalographic patients with a high degree amytal test findings will be most likely to show improvement; while those with amytal and with negative abnormality a low degree electroencephalographic results are considered unlikely to improve. b. Tactile Perceptual Tests: perceptual tactile simultaneous the As described before, was planned inconclusive. It were of test results in our first series patients conditions under stimulation, electrical to repeat this study using threshold terms Under controlled. be could rigidly wherein the various stimulus parameters two of consisting assembly instrument (M—927) an USPHS grant of an existing dewhich can devised was oscillograph monitored by an Grass Sh-B stimulators the assembly, this Using stimuli. electrical wave independent square liver stimuli applied simul- to perceive their ability for tested patients are technique refined this By applying body. taneously to different parts of the two �.11be may otherwise not apparent function brain in it is anticipated that changes and of improvement the be to degree compared will observations These elicited. to our other test~results. As in the case of the electroencephalogram and the and intervals during stated before at tested are amytal tests, patients course of treatment. c. Hemory Tests: imp and loss of memory of relation the Numerous theories provement have been described. Our own data to date shows no significant re- and words and simple nonsense syllables for lationship forselective a there is evidence that considerable But there is improvement. For memories. and situations of life significant getting, during treatment, between the memory loss a record this purpose, may be is made of events during the preceding six months which of emotional significance to the patient. During treatment, inquiries records verbatim of these events, recollection patient's are and these compared to the pre-treatment reports. made of the 2. Relation gf’Premorbid Personality to Duration 3; made, Response: has also been apparent that the relationship between altered It brain function and clinical response is valid only for the short term response When six followed a for treatment. weeks several after to treatment, ite., return a had showing relapsed, the of improved several patients period, of their former symptoms, and in some instances requiring further hospital- month ization. thesis To account for the varying duration of was advanced that the difference personality patterns. Specifically, it was clinical response, the hypo- related to differences in premorbid was suggested that patients who showed would (22) denial verbal personality" the of "explicit the characteristics likely to maintain improvement. premorbid personality of each patient is assessed be those more The an interview with family members, psychologic and psychiatric interviews. by four procedures tests, tachistoscopic tests - �a. Family Interviews: At least two close relatives are seen in independent interviews. A standardized questionnaire has been devised to elicit characterological factors indicative of the "explicit verbal denial" personality. For this study fifteen characteristics defined as typically present or absent in conscious— Such include items prestige selected. were of this type personality and and to sex attitudes temper to imagination, criticism, ness, sensitivity illness. Each patient is rated on a scale of 0 to 2 for each item - the higher score signifying a greater tendency to denial. b. Psychologic Tests: Each patient is tested on a standard psychologic eval- uation battery including the Rorschach and Thematic Apperception TEStS. These adap— defense of and usual or types structure character assessed for tests are tation. Such tests are repeated at the termination of the treatment program and again prior to discharge, to obtain additional information as to changes in behavior in the course of treatment. - c. Tachistoscopic Tests: tachistoscopic study has been devised; in which pairs of emotional and non-emotional words are flashed on a screen at 10, 20, 50, 100, and 250 millisecond periods. The patient's ability to identify the words, A the reaction time, and the distortions are ascertained. This pre-treatment data is now being explored as to defense patterns. The its ability to clarify the patient's usual tests are repeated at the end of greatment and again prior to discharge for the possibility that characteristic changes in perception develop with altered modes of adaptation.. �-13.. d. Psychiatric Interviews: In the course of estimating changes in behavior, patients are seen prior to treatment, and at intervals during treatment. In a clinical interview setting, an assessment is made of the patient's symptoms, and usual of adaptation. Changes in symptoms, behavior, language and modes of adap- modes tation are noted. By interviews with the patient's therapist, judgment as to the significance of such changes and bral states can ment their relation to treatment, or altered cere- be made. On the basis of the data in a-d above a prediction of response to is made. treat- Prior to the start of treatment the patients are classified as: 1) those unlikely to improve; 2) those likely to improve moderately or temporarily; 3) those likely to maintain marked and sustained improvement (for at least six months). During the third week of treatment, (after the patients have had ments), a second prediction of the short term response change is made 7—9 treat- according to the in the physiological indices. 3. Altered Patterns g£.Adaptation Kanifested in‘Verbal and NonéVerbal Behavior: In the earlier study on the amytal test it had been noted that specific changes in language and behavior indicative of altered adaptive responses occurred in the improved patients to a significantly greater degree than in the unimproved patients. Further experimental procedures were necessary to clarify the nature and significance of these changes. deemed �alb- a. The is a highly structured interview of the patterns of language. made ients who show language will in émytgl Tests: amytal test procedure is recorded. This Language Changes Induced situation, The and systematic observations are hypothesis tested is that those pat- consistent, increasing use of the following types of adaptive be more likely improve: 1) The use of the second or to third person. In such instances the patient reports his main trouble as "the Doctors say I'm depressed", or state the wish that "my family should be well." 2) The selective response to questions, as answering readily questions about date and location but failing to answer, illness. tive mumbling or using neologisms when asked about 3) The use of conditional or qualifying expressions, or the subjunc- mood which has the effect of vitiating the patientis committment to the is I feel kind of dBpressed", in w hich "sometimes" qualifies the temporal degree of illness, and "feel" and "kind of" statement. An example "sometimes ‘qualify the intensity of the illness. Committment would be indicated by the direct, unconditional statement of "I am depressed". h) or stereotyped expressions in discussing illness, as "to or "well, in a manner of speaking..." or "I didn't keep wheel". 5) Language antic statements. 6) problems. tell my The use of cliches you the shoulder to the filled with nonpsequiturs, circumlocution, ornate The use or pedp of humor when talking about their illness or other 7) The use of metonymy or paraphasia, as Dr. as a "recorder". 8 )The various forms of ulation about the main problem truth..." referring to the examining explicit denial including confab- and temporal displacement. 9) changing the sym- bolic frame of reference in response to questions, as replying to the question, feel?", by stating, "with my hands." 10) The use of hyperbole, as "you're the best Dr. in the whole eastern Atlantic seaboard area." "how do you �.15- State: Confusional the PostaShock b. Language Changes in Each orientation for tested is patient and awareness of treatment. a following immediately awakening of the period in his main problem such At intervals. weekly and then at treatment the initial done after @his is most severe, and a defects are cerebral neurologic the times, These of language appear. tive changes in the pattern variety of may be comparable adap— to the records are and the situations, interview other the in noted changes language and changes language the later to both as indications assessed for prognostic the degree of improvement. Study: Sentence Completion 0. in language in and changes A way of studying the patterns technique. completion sentence a devised using been has fashion a quantitative accordstructured been have which complete, to sentences to given The patient is the in first been have put sentences the of Ten different patterns. ing to four when....", criticized am "I Wish that......", such "I as unconditional, person, the in expressed are they that except meaning in identical Ten others are etc. sometimes "people as aspect, qualifying or conditional third person and with a the In reetc. When.....," criticized wish that.....", "people are usually these of senten In indicated. maining twenty items no person is specifically or occurrence exact an to refers or direct is sentence the tences, however, event as "every time....", ”when the doctor comes in.....", etc. The remainp "at times....", as aspect, indefinite or qualifying conditional, have a ten ing etc. when.....", better "things usually seem a little for analyzed not in sentences The response of patients to the incomplete rated is each response Instead, manner. psychologic content in the traditional �16 the whether include ratings for its grammatical or syntactical structure. or conditional, direct or is second third person, or response is in the first, The 1h). (page above described of language manifests aspects 1) assumptions: following the on This study is based begins in the to most obviously applicable a manner A sentence which patient (e.g., first person, adaptive reto elicit likely unconditional) creates conditional is or the third in person A sentence which is expressed 2) sponses. and least minimal is stress creates is less applicable to the patient. It complete used to The 3) person syntactical likely to elicit adaptive responses. maximum stress and is most of indicative is to person in regard indeterminate is whose beginning sentence a shows less of the person first the use the degree of stress experienced (e.g., third second or the of the use defensiveness, person shows greater defensive— ness). d. Attitude Interviews: In this part of the study an attempt the of mechanisms ego. adaptive the tionally Two is made to define opera— structured interviews followed. The attitude of the questionnaire is interone In next. the to interview from one examiner, however, is reversed and the in concerned, view the examiner is empathetic, pessimistic, minimize to and tends insensitive non-empathetic, he brusque, is other interview are held, in which the the patient's same difficulties. In general, the first attitude produces good a in grossly results latter the while rapport with these disturbed patients, each asked in are non-communicative situation. Although the same questions to be appropriate to the examiner‘s attitude. interview, the wording is altered "YOu must today?", poorly "feeling as such he questions asks In one interview worse?.“ been getting "has and it consider your condition pretty serious?", don't "you today?", well While in another interview he asks, "feeling pretty consider your condition serious, do you?" and "have you been improving?". �.11.: The two structured.interviews are performed just prior to electroshock interviews All are treatment. of treatment and repeated following the course of the patient's 1) alteration the study: in recorded. There are two variables The four attitude. examiner's the in behavior by treatment, and 2) alteration recordings are studied for and changes. language vocal changes, content, The it defensive mechanisms of the patient both out be carried can that transactions of the of terms range in ationally, and any changes in can be defined, oper- be commmay patient depressed For a example, very treatment. and after before he whereas interview, empathetic concerned, the in treatment before unicative jovial, mood is the when latter examiner's the in will be unable to participate of one is treatment to his response However, if and minimizing. bantering becomes he sustreatment Following reversed. be euphoria, the situation may and empathetic, concerned examiner is when the anxious or hostile, picious, Thus the interview. the optimistic in stressful less communication is whereas terms, objective in be stated the defensive system of the patient can change i.e., in of interpersonal standardized range to a in terms of his reactions uations. in sit- M h. Clinical Ratings 2: "Improvement": changes evaluating of methods and test These various experimental ratthe psychiatric in significance further have may and behavior language considerable experienced we studies revious In our : rovement." "im of P ing Or, be guide? the to relief symptomatic Is our patients. difficulty in rating to recovery Is be the goal?. to improvement" "social recovery" or is a "social relief? Agreement by symptomatic well as as of insight be judged by the degree "unimproved" and improved" "much "recovered", of definition the in psychiatrists is not available, investigations, to further crucial is issue and yet, this We �they terms as these of assessing task further the undertaken have therefore apply to the electroshock population. of incapacity and type the degree are Central to this problem of evaluation and the the of therapist, the goal personality, of the patient, his premorbid capacity events, intercurrent as Other aspects, therapy. to attitudes patient's environmental the patient's of therapy, suitability of the therapist, temporal present. at encompassed not but are assessment, to important also assets are To are studies evaluation following the "improvement", of meaning clarify the in progress. Evaluation: Pre-treatment a. the by therapy electroshock Patients are referred for and resident therapist. supervising psychiatrist evaluation is made by the research psychiatrist. An Two independent psychiatric aspects are specifically decompensation of signs clinical encompassed in this study: of sympdegree for and rated mental status descriptive a recorded in which are of the patient‘s estimate 2) an (28); scale tomatology on a Kalamrd rating 1) the symptoms and operations. defensive usual his of with description a develOpment of ego level Relationship: Therapist—Patient the in Changes b. to held prior therapist resident the with interviews In and the therapist between relationship the therapy, electroshock of the onset recomp the for the reason on emphasis with specific explored the patient are and the patient's treatment, the of the goals mendation for this form of therapy, mental of treatment of method Since the primary attitude to the treatment. electroshock for recommendation the disorders at this hospital is psychotherapy, the between patient communication that assumption the with carries it generally deis the exploration For this reason, meaningful. no longer was and therapist and recommendation, the led to that relationship the in voted to those changes �19 and symptoms that it is behavior of of those aspects statement a definitive We the in interested also therapist's affect. treatment are may the anticipated attitude to this may form of treatment, and attempt to assess the role this attitude play in the eventual results. of the the results theories relating numerous there are Furthermore, made being are attempts and in our inquiries, therapy to its punitive aspects, to assess the significance of this factor in the outcome. During the interviews with the resident therapist and with the patient, the patient's attitude behavior) and against (both language defensive operations to the treatment, his his in and alterations the electroshock represents, the reality threat that attitude during the weeks of treatment are studied. Further information regard— of our the in course be ascertained will of factor this ing the significance control study (page 21). c. Follow—up Study: Crucial to the evaluation of "improvement" is the oppor— treatment of the period following various periods tunity to repeat evaluations at from hosthis discharged of the patients follow—up report Recently, a four-year between customary the disparity indicated and (1) this pital was made available of inthis the In course illness. discharge ratings at out carried being observers is same the vestigation, repeat evaluations by As check a treatment. months after and six various times during hospitalization and eventual course of the and the physiological of the personality basis the on the predictions two—week the for recorded factors studied, specific follow—up evaluations are (long-term months period and the result) six post-treatment period (short-term made on ther— the resident of the to ratings result). These evaluations are compared each In instance, medical director. and the apist, supervising psychiatrist and the of terms projected formulated in the ratings made in this study are and interpersonal language of behavior, those noted aspects in actual changes �Excretion 23 Improvement: 5. Relation of Steroid and their reof steroids excretion patterns of The studies of the More recently continuing. is 9, on described page mental to states, lation of measurement the for of techniques development the on been has emphasis colorimetric and * new separative steroid conjugates. During the past year sulfate steroid measure to (29) devised techniques have been these for patterns excretion blood and urine. Daily urinary compounds in compounds are and prior again electroshock of the course assayed prior to treatment, during resolve to is of this program The object selected patients. in to discharge individual total the with values these and compare bound steroids, the sulfate excretion hormone between relationship the elucidating Besides hormone levels. which to extent the indicate of mental illness, such studies and rates states hormones. steroid of metabolism the the liver (30) participates in Electroshock Therapy: Results Functions of on 6. Effect of Autonomic behas studies, it electroencephalographic of our In the course alterations the typical fail of number patients that a apparent come to also fail These patients treatment. extensive in cerebral rhythms despite and frequently tactile tests, in the amytal tests, simultaneous to show show changes reactivity the studies, these with Simultaneous periods. confusional evince no mecholyl of administration the to rate and the pulse blood of the pressure to done was prior too, This, out. carried been have "Funkenstein—test") (the Marked ended. had treatment of the course after immediately treatment and two test these found in were medication this to variations in the responses the of earlier the reports way general a in followed observations These periods. between relationship the of exploration the undertaking workers, but we are now tests. physiological and these function brain altered of tests in the alteration * Aided by a grant (A-6YSC) Public Health Service. States United Health, of from the National Institutes �v. THE PROJECTED PROGRAM: SUMMARY 1. 3 21 - Method: the along and development continuation The projected program is a Our ultimate of this two report. sections lines indicated in the preceding the systematic by therapy electroshock of mechanism goal is to clarify the of behavioral, inter-relationship the of and integrated investigation biochemical factors. and physiological sonality, This program is per— rev interdisciplinary full-time a by undertaken being neurophysiolpgist, psychoanalyst, of psychiatrists, search staff consisting help. technical and allied biochemist physiologist, experimental psychologist, Some in scope clear already are the in program of the specific studies and new continues the program as become apparent Others will and outline. Two new basic develop. leads promising further or problems appear critical decided been upon. already have methodological aspects date work to our in 1. Control group:0ne of the major deficiencies starting Accordingly, control group. has been the absence of an adequate two into divided be will electroshock for referred January 1, 1956, patients of conusual course the receive will One group fashion. random a in groups treatments. sub-convulsive be given vulsive therapy; the other group will Ulett of study instructive recommendation follows the recently reported This et a1. (31). In other respects the two groups will be treated in the same will each group in are patients who will The only person fashion. of The purpose treatments. the administering be the supervising psychiatrist in— of the effects physiological the differentiate to is such a control group know which outcome. therapeutic the affecting Some duced convulsions from other factors disease process, the of particular 1) nature the of these factors might include 2) the attitude and symbolic etc.; depression, involutional or as schizophrenia of a large attention 3) the special the patient; to treatment of the meaning �~22: numbers of observers h) the incident to being placed on the treatment program; attitude of the patient's therapist toward the patient and toward electroshock therapy, including the expected goals in each case; and S) the relative effectiveness of other forms of therapy provided for these patients in the hospital milieu. The use of a control group will also clarify the nature of "Spontaneous recovery" and may aid in the understanding of "atypical" results in the patients actually receiving convulsive therapy. 2. Insulin Coma: It is planned to extend the present methods of study to an investigation of those patients receiving insulin coma therapy. �~23.- 2. Significance This program of study has both applied and theoretical significance. there since electroshock of therapy use clinical It can lead to the improved be mechanism. will It the of therapeutic will be a greater understanding to who better improve, will those patients more skillfully select to possible and to predict the involved therapeutic in process, factors other manipulate more accurately future management problems. of the psychounderstanding to a greater however, also This study leads, pathology of mental picture which illness. Through the various methods of study a clearer will be obtained meaningful criteria for of the mechanism of defense and modes of communication may contribute more operationally accurate and "improvement". of determination the for diagnostic classification techtherapeutic other on throw light may Finally, the investigation and and obserthe function cerebral in niques. The studies of the alteration have signifi— damage and cerebral behavior between vations on the relationship also is It electrocoagulation. and cerebral cance for the studies in Ibbotomy modes of and in language the changes into here gained the insights that likely of psychotherapy. study eventual significant make an possible adaptation may �VI. FACILITIES AVAILABLE: 1. Hillside Hespital is a 200 bed non-profit psychiatric hospital. All admissions are voluntary, with periods of hospitalization varying from h-lZ months. All patients are available for study. The hospital was established in 1927, for the purpose of treating ulatory psychiatric patients. A amb- residency training program.was instituted earxy, under the supervision of an active staff of psychoanalytic psychiatrists. In 1950 the research biochemical laboratory was established, to be followed in 1953 by the neurophysiological research laboratory. In 19Sh these laboratories were combined and expanded, and a Research Service established as a:full-time operation of the hospital. Research Director was appointed to integrate program. At this time, the staff consists all A full-time the studies into a basic of the Director, research assis— tants in psychiatry and psychology, biochemist and assistant biochemist, siologist, and EEG technician. In addition, a psychologist and phyb two chemists are associated on a project basis. Laboratory Medcraft D-8, two S-hB Grass 8 facilities include: (a) Electroencephalographic unit with a channel instrument; (b) Neurophysiological laboratory with stimulators, tachistoscopic projectors ical laboratory with Du Mont # 3&0 R and feet of laboratory space Beckman Coleman Spectrophotometer, and ifications of the A.E.C. two synchronized auxiliary electronic equipment; (c) 1000 square the following major items: oscillograph; Biochemp and equipped with Spectrophotometer,'Warburg respirator, radioisotope unit following the basic spec- �£2 5.. ﬂ 2. Personnel:* studies Undergraduate Research: of (a) Dr. Max Fink, H.D., Director the and degree New Yorn College University, of Universitv were undertaken at the {e the attended l9h2. in was granted of B.A. cum laude with Honors in Biology New l9h5. in graduating of Hedicine, York University College interneship he served in School of the from he where graduated U.S. Army, the Military Heuropsychiatry in Knox After a rotating 19h7, and was Chief of the Psychiatric Section, Fort Station Hospital during 1947. Formal neurologic training was received at hontefiore Hospital in York New Formal psychiatric (l9h9«1951). Hosoital Bellevue Dsychiatric and at (l9h8-l9h9) and than (1950) at Hospital Bellevue ?svchiatric undertaken at training was Hillside Hoscital (1952). During 1951, and again in 1953, he and then at Mount In 1952, he was American Board of first at Sinai Hospital in a research fellow of the Hational Both periods of study were under the Foundation for Infantile Paralysis. ection of Ur. horris 3. Bender, Was ﬂew York dir- University College of ﬂedicine ﬂew York. the by in l95h, and Psychiatry, in Feurology, in certified ‘sychiatry and Neurology. Simultaneously he attended and gradof Psychoanalysis, Psychiatry and Institute 1953. In January, in Physicians for Psychology, receiving their Certificate Mental of Institute National the of June, l9Sh, he was granted a research grant uated from the ”illiam Alanson Fhite Health for a 2-vear study of electroshock processes. In September, l95h, he was Fink Dr. Hillside Hospital. Service at Research appointed Director of the is 33, married and has one son. _____._.__.___.___________.___.____________.._._____._______._____________.______. 38. apaended, page of is personnel * Bibliography �7-20Collowing Psvcuiatry: in Assistant (b) Dr. Joseph Jaffe, h.D., the attended Jaffe Dr. l9hh), (B.A., Columbia College at studies undergraduate Then 19b7. M.D. in his and.was granted of hedicine, College New vorlr. University he began interneship, rotating a he was elected to Alpha Omega Alpha. Followinr resident a as First Hospital. DelleVue Psychiatric the at of study three years U.S.P.H.S. posta as studies his he completed in psychiatry, then in neurology, lender. 3. Morris Dr. of doctoral research fellow under the supervision from graduating Air Force, States United the in he was 1953, From 1951, to Air Eitchell the at Psychiatrist Chief He was ﬁedicine. Aviation the School of Force Base Hospital. prac— the private been in has he service Since discharge from the military of Board American the by psychiatry in He certified was tice of psychiatry. psychoin candidate been he a has Since l9h9, 1953. in and Neurology Psychiatry Psychiatry Psychoanalysis, of Institute 'hite Alanson analysis at the William the at Assistant Research been has a two years the and past for and Psychology in position present to his He was appointed Mount Sinai Hospital of New York. September, 1955. Chemist: Chief Ph.D., Goldenberg, (0) Dr. Harry A graduate of the Tremaine of a recipient York New in of the City of College D. in ”h. his received Goldenberg Dr. Scholarship and graduated cum laude. in instructor He been has an Brooklyn. of Institute from ‘olytechnic the l9h9 l9hh, he was the College Brooklyn and at (l9h6-h7) biochemistry at the Dolytechnic Institute Natthe of enzymology Fellow in Research he l9h7~h9 was a In (1951 to date). ional Institute of Health, and from 1950 the to chemist he was a 1952, to methods enzyme studying of Brooklyn Hospital Jewish the at U.S.D.H.S. project in clinical chemistry. �...27.. Dr. Robert L. Iahn, Ph.D., Assistant in Psychology: (d) After graduation from Brooklyn College in l9h0, he undertook graduate studies at Columbia University. These studies were interrupted by four years of service and School Dsyc‘hology went he Clinical to where United Army, States in the On and overseas. country in this various hospitals served as psychologist in of Neurology the Department in Research T’syc‘iologist became he the army leaving of the Mount of Dr. horris Sinai Hospital in New York, where he wormed under the supervision B. Bender and Dr. E. A. "einstein until January, 1955. is He of monograph, the and co-author is studies, experimental of numerous the author "Denial of Illness: He Symbolic and Physiological Aspects" published received his Ph.D. from the New in May, 1955. York University School of Graduate Arts instructor of psychology at Brooklyn and Huntto been he a.consultant has two two For the past fbr years years. er Colleges conducted and has training proMental of Hygiene New York Department State the and Sciences in 1953, and was an he been has 1955, a Since January, mental the of several hospitals. in grams member of this staff. (e) Dr. Hyman years of military service, received his 3.8. in ogy interns at York four Following Psychology: in Assistant Ph.D., Korin, he matriculated l9h9, and at College of the City of his H.S. in 1950. During 1951-52 he the Hount Sinai Hospital and University. New was York and psychol- matriculated for his Ph.D. at New Since June, 1953, he has been Research Assistant in Psychology at Hillside Hospital. He recently completed his doctoral thesis on "The Effects of ﬁlectroshock on Retroactive Inhibition," and received his Ph.D. in October, 1955. his'L. F. (f) Dr. Arnold Blumberg, H.D., Internist: Dr. Blumberg received from the University of Pennsylvania in l9h2, for studies in physiology, and in l9h5, received his E.D. from the Mew York University College of Medicine. continued he two of and service, military years interneship Following a rotating 1952. l9h8 First from to Memorial Goldwater Hospital at his residency training �-28he completed Fellow Medicine, in then a as as a resident in neuropsychiatry, He has 1950-1952. Division Research the his studies as a Research Fellow in been a Fellow in Medicine at the New York University College of Medicine, 1951-Sh. He was is an certified Internal Medicine in l95h and of Physicians. He is the associate by the American Board of associate of the American Attending Internist at Hillside Academy Hospital and has'been directly responsible fa' of coordinator well as as Research Service, the physiological studies of the the biochemical programs. 3. Function of Research Service: the Research Service, the of research programs In addition to the with actively They cooperate functions. staff is active in two additional research who on part-time carrying are those members of the hospital staff In such instances, aid nature. of clinical a chiefly projects, the planning of goals, project clarification the is given in and design of programs, and is needed. and during in is progress, program Secondly, an active resident training independon an to opportunity carry an given is the third year, each resident been have two service projects of this ent project. Since the development such technical assistance as the include projects completed, and three are testosterone of and the use states anxiety in of reserpine clinical evaluation include resident At projects present, coma therapy. insulin to adjuvant an as now active. The completed a factor, therapeutic milieu a as the of hospital a study clinical evaluation and clinical, coma therapy insulin for substitute a of chlorpromazine as aMbivalence. of measures and tachistoscopic psychologic �-29In May, 1955, the Research Service established a. liason with the Sloan- York of steroid New out study to cooperative a of Institute carry Kettering excretion rates in psychotic patients, with emphasis on the patterns altered during and following electroshock thefapy. �-30.. VII, M PRESENT BUDGET AND REQUESTED SUPYOR : Budget and Present Support: 1. Present anus—“u The following is the full budget of the Research Service for the fiscal year l9SSmS6. The major Share of the program is supported by the Board of Directors, supplemented by grants of the United States Public Health Service. Under Grant M—927 of the National Institute of Mental Health, $1h,807 of direct costs and $2221 of overhead costs was granted for the year September 1, 1955 to August 31, 1956. This grant is the second year of a 2-year grant for neurophysiological studies including the present Electroshock Evaluation Study. awarded $6500 The National Institute of Arthritis has for the second year of a twoayear grant for biochemical studies. �~31- 1. w.- ' Board of Directors U.S.P.H.S. 15,000‘ 15,000 -——- Psychiatry* 7,200 7,200 --— Research Assistant in Psychology 8,000 -——-— 8,000 Research Assistant in Psychology 5,000 -—-—- 5,000 2,520 2,520 -———— Chief Chemist 8,600 8,600 -—-—- Assistant Chemist h,000 __—- h,000 Assistant Chemist 2,800 2,800 -——- Assistant in Chemistry 1,800 -——- 1,800 h50 -—-— h50 3,810 2,253 1,557 1,200 1,000 200 Personnel Director of Research Psychiatgz: Research Assistant in 7E0 Technician - Secretary Biochemistgz: 2. Equipment 3. Consumable supplies h. Travel - Conferences Total Overhead TOTAL * 3/5 time to September 1956. 60,380 39,373 21,007 2,521 ______ 2,521 62,901 39,373 23,528 �.32.. 2. Requestegjg‘udgetagr Support: A. include requirements of the Electroshock Therapy Evaluation Project The two two of other modification the to professional staff, additions specific allocations of equipment funds. (1) Psychiatrist: The cooperation of an additional full time psycoma insulin include of to the study the needed to enlarge scope chiatrist is positions, and of evaluations the in to assist control the study; therapy; to supervise diange in patients and carry out follow-up studies. For this position, an- alytic experience is essential. (2) Physiologist or Heurophysiologist: Present physiological studies of Further physiostudy and the Internist. Director the out by carried are by full-time a of studies these coordination the changes requires logical physiologist, (3) M.D. or Ph.D. Equipment: and physiology. For Present needs are focused in two areas - biochemistry further refined studies of the steroid sulfate patterns mechanical and a Beckman.Spectrophotometer the attachment for a recording carry out the anticipated physiological studies modifications and attachments to the electroencephalograph are shaker (Dubnoff) are requested. To suggested. following budget is one suggested to continue the present proneeded completo the of 1956 personnel addition the with July 1, gnmn after ment the present staff. The budget is divided into three categories, followB. The Research Serthe coordinated in which divisions are the three laboratory ing and five period, a for the for year Estimates listed first year, are vice. including projected salary increments. �M First 1. Psvchiatqz: a. Director Secretary Conferences 13 Year Five Year Total (20,-25,000) 20,000 112,500 (2,6-3,100) 2,600 1,200 11,220 (15,-18,000) (15,-18,000) 15,000 15,000 9,000 5,500 82,500 82,500 52,500 35,000 1,200 3,600 . Personnel 1. Psychiatrist 2. Psychiatrist 3. Eeychologist 13.. Psychologist c. Supplies Subtotal - & ( 9"12:OOO) (5’5' 8,500) Equipment 388,820 69,500 Psychiatry 2. Neurophysiologx: a. Personnel 9,000 3,600 52,500 12,000 b. Equipment 1,000 1,000 c. Supplies 1,200 6,000 1. Physiologist 2. Technician (9,-12,000) (3 : 641-31400) 71,500 10,800 Subtotal - Neurophysiology 3. Biochemistry: a. Personnel Chief Chemist (9,-11,000) 9,000 6,000 0,000 1,800 36,000 25,000 11,200 b . Equipment 7,000 7,000 0. Supplies 1,500 7,500 1. 2. 3. h. Chemist Chemist issistant Subtotal - Biochemistry (6,-8,h00) (bu-6,000) (1,8—2,600) 29,300 137,700 �Total First - All Programs .. All Programs 113,600 598,020 17,0h0 89,700 130,6h0 687,720 Overhead Allowance\(15%) TOTAL Five Year Total Year C. Budget Reconciliation: 1. Salaries: The salary range for each item is consistent with pre- sent positions established at the hospital, or for new positions, with neighbor- for supervising psychiatrists is $12,-15,000, with a projected revision to the stated scale in 1956. ing institutions. Present salary 2. Equipment: ment expenditure ance range For psychiatry, the initial year includes the equip- for tape recording system (#600) and an annual for expenses. The $600 allow— physiological equipment expense (51000) is to allow modification of present electroencephalographic equipment to record other physiological indices. The expenditure for supplies includes allowances for consumable items and the provision for the building of specialIized equipment. In biochemistry, the a recording attachment for the Beckman intiial expenditure includes $7,200 for spectrophotometer and 9800 for a Dubnoff shaker. 3. Conferences: Present budgetary items include this of the Director or members of the sum for the use staff to attend appropriate scientific meet- ings. h. Overhead: Consistent with hospital policy and recent administrative changes in other grants, a 15% allowance is requested. This amount includes hospital allocations for Social Security coverage; and for such contingencies in the expenses of the program as not reg iring a significant alteration in the budget. 5. Subtotals and Total: The budget is presented in three sections, representing natural subdivisions of the program, thereby allowing for modifications in support. �VII. APPENDIX A. REFERENCES: from Discharged 317 Patients of Study Follow-up H.L. RACHLIN, 2E.§i: 1. in Hosp., Hillside press. l?50, J. in Hillside Hospital and other Psychosurgery Shock Treatment, 2. KALINOWSKY, L.B. and HOCH, P.H.: New York, Grune Stratton, (2nd a ed.), Somatic Treatment in Psychiatry 1952. 19h8. 397, Mil. Surg. $92: Theories, Shock Therapy Fifth GORDON, H.L.: 3. and Dsvchiatry, Neurology of Foundations h. GELLHORN, E.' Physiological 1953. Minneopblis, Hinnesota Press, University of Nervous Autonomic H.C.: S.a FNNKENSTEIN, D.H., Ment. 3 Nerv. J. Shock Treatment, System Changes Following Electric GREENBLATT, M. Dis. 329%.: 2109, and SOLOMON, 19,480 Which PreA Test H.C.: 5.b FUNKENSTEIN, D.H., GREENBLATT, M., Schizophrenic on Treatment Shock Electric of dicts the Clinical Effects 1950. 889, Am. 199: Psychiat. J. Patients, AND SOLOMON, 5.0. Autonomic Changes H.C.: SOLOMON, and M., FUNKENSTEIN, D.H., & Nerv. J. Patients, in Mentally Changes Psychologic Paralleling GREENBLATT, Ment. Dis. 6.a. 11;: 1, 1951. Ill Exthe and in HOAGLAND, H. et al: Changes in the Electroencephalogram of AgitTherapy Electro-shock Accompanying cretion of T7-Ketosteroids 19h6. Med. §32h6, Psychosom. ated Depression, Excretion on Treatment of Effect B.H.: 6.b. ALTSCHULE, N.D. and & Neurol. Arch. Mental Disease, with Patients in of l7-Ketosteroids 1950. 516, éﬁ: Psychiat. Cortins of Excretion the on Convulsive Therapy 6.c. ASHBY,‘W. 1.: Effects of 19h9. 275, Ment. Sci. 23: and Ketosteroids, J. PARKHURST, Excretl7-Ketosteroid the of Studies Chromatographic H. WERBIN, 7.a. gt El: Hosp., Hillside Normal J. Individuals, and ion Datterns of Psychotic 195,40 2011, 2: l7~ Neutral of Urinary The Fractionation S. R.: M. STITCH, and REISS, 7.b. Ment. $99: Sci., J. Male Schizophrenics, Chronic from Ketosteroids 7011, 195,40 8. ASHBY, W. R.: Mode 22: 202, 1952. of Action of Electro-Convulsive Therapy, J. Ment. Sci. �.36... 9. Shock Therapy, Hypoglycemic and JELLIFFE, S. E.: Discussion on Insulin 1937. 200, & 2Q: Psychiat. Arch. Neurol. of Aspects Psychologic Certain 0n E. MOSSE, 9.: and J.A.B. 10. MILLETT, l9hh. 226, Med. 6: Electroshock Therapy, Psychosom. Shock Electric with Treated Patients in Functioning Memory ZUBIN, J.: lla. l9h8. 33, Dersonality Therapy, J. ll: on Therapy Convulsive Electric of Effect S.E.: BARRERA, and ZUBIN, 11b. J., 596, l9hl. ﬁg: Biol. Soc. Exper. Hemory, Proc. Assoword the on Performance on Shock Therapy of : Effects ZEAEAN, J. 12, 19h7. Association, Psychological Eastern the at Presented ciation Test. J. Treatments, Convulsive Electric Following Loss Memory JANIS, I.L.: 13. 191.18. Personality 1.1: 29, der mit Erfabrungen Psychopathologische GROBE,’W.: and W. BAEYER, von, lha. l9h7. 163, Psychiat. $12: Elektrokrampfmethode, Arch. f. after Patients Mental on Observations E. STAINBROOK, J.: H. and LOWENBACH, lhbg l9h2. 828, Am. 2g: Psychiat. J. Electroshock, Post—Convulsive of Immediate Description Rorschach STAINBROOK, E.J.: Ibo. 19AM. 302, & Personality'lg: Mental Function, Char. Electroshock During Psychosis KAHN, and R.L.: LIEN, L., WEIWSTFIN, E.A., 15a. Am. Psychiat. J. Shock Therapy, of the Theory to Relation Its Therapy: 1952. 22, $92: and PhysioSymbolic of Illness: Denial KAI-1H, R.L.: 15b. mnrsmm, F..A and 1955. Illinois, C. Springfield, Thomas, Charles Aspects, logical Ego, the on Treatment Shock of Effects D.: IMPASTATO, and FROSCH, J. 16. Psychoan. Quart. I]; 226, l9h8. l7. 18. 19. 20. Recent Under "Normal" Person of Electroshock on a L.: Effect 1953. 696, Am. J. Psychiat. $92: Stress, in (Paraphasia) Misnaming Non—aphasic UEINSTEIN, E.A. and KAHN, R.L.: 1959. 72, 61: a Psychiat. Neurol. Arch. A.M.A. Brain Disease, Organic Organic in Disorientation of Patterns KAHN, R.L.: WEINSTEIN, E. A. and 1951. 21h, & Neurol. I: Brain Disease, J. Neuropath. Clin. "47.1%.: 7-iithdrawal, Inattention, 310133, and mms'mm, E.A., ram-I, R.L., 1955. 235, & IA: Psychiat. and Pain Asymbolia, A.M.A. Arch. Neurol. ALEXANDER, �-3721. T‘JEII‘YST‘EIN, & E. nsychiat. A. _6_L_l: and mm, 772, 1950. D. Neurol. Arch. Anosognosia, of L.: Syndrome " of Denial Illness, in Factors Personality R.L.: MEN, and 22. IEINSTEIN, E.A. 1953. §_9_: 355, & T.‘Ieurol. Psychiat. 11.14.11. Arch. 23. L.A. and LINN, R.L., SUGABI'JIAN, Brain Disease, Sodium Organic in Amobarbital of “IEINS'I'Em, 33.11., MEN, Am. Use Diagnostic 1.: J. Psychiat. 112: 889, 1953. 21;. Test" "Amytal E.A.: H. and vmmsmm, KAI-1N, R.L., PINK, 1955. 3, Hosp. 3: Hillside Mental Illness, J. in Patients with Differential the in Tests Perceptual NJ: Tactile 25a. DEF-HER, MB. and 1952. 21, Hosp., Hillside 1: J. Disorders, Psvchiatric of Diagnosis Sign 8. Diagnostic Test as Face-Hand 1.1.3.: 25b. PINK, M. GREEN, M. and BINDER, 1952. h6, 2: Neurology, of Organic Mental Syndrome, ImproveClinical and Damage Brain 26a. REVITCE-I, 13.: Observations on Organic 195h. §_8_: 72, Quart. ment Following Protracted Insulin Coma, Psychiat. Coma: TreatInsulin A Prolonged Case of M.: 26b. IC-“IALEJASSER, S. and CAPLAN, 1952. 1115, Hosp. 1: ment, J. Hillside and ClinicElectroencephalographic 26c. SHAGASS, C. and ROFSML, P."T.: Serial & Neurol. A.Z"T.A. Arch. Coma, Insulin Prolonged of Case al Studies in a 195b,. 705, Psychiat. 12.: Posthypoglycemic in Studies 26d. TRACER, C.L. at £1: Electroencephalographic 19530 1135, 1.32%: Dis. l‘ient. Coma, Jo NerV. Parts of 1-5.: Reduplication Delusional and N. FINE, 27. KAHN, R. L., GRAUBTE’ET, D. 1955. 13h, Hosp. g: Hillside Coma Therapy, J. Insulin After 1Jody the of Scale, Rating the A Psychiatric of Revision 28. MALAI‘EUD, 'T. and SANDS, S.L.: Am. J. Psychiat. _l_9_l_l: 231, ram. Colorimetric Quantitative the for Dyes Basic Use of 29. GOLDENBERG, H.: Chemical Society American Conjugates, Sulfate Estimation of Steroid 1955. 'Iarch 31, 200, Abstract, Highspeed by Synthesis Sulfate Steriod : T4.. REIL’IANN, J. and 30. GOLDEHBERG, Chem. Soc. in Am. press. J. , Liver Supernates, Convulof Evaluation the in Matched Groups Use The of G. A. 313 31.: 31. ULE'IT, 195h. 128.: 138, July, Menn. Clin. Bull. Photoshock, Subconvulsive and sive F11 K, (31‘. �B. Publications of Personnel: Dr. N l. x Fink: Subdural Hematoma Developing during Hospitalization, Amer. J. Psychiat., 191: 381-383, 1950 (with Dr. M. Green). 2. Patterns in Perception of Simultaneous Tests of Face and Hand, Trans. Amer. Neurol. Assoc., 22; 250, 1950 (with Drs. M.B. Bender and M. ..., Green). ibid, Arch. Neurol. & Psychiat., éé: 355-362, 1951. Test as a Diagnostic Sign of Organic Mental Syndrome, Neurology, 2: hé-58, 1952 (with Drs. M. B. Bender and M. Green). The Face-Hand Tactile Perceptual Tests in the Differential IJiagnosis of Psychiatric Disorders, J. Hillside Hosp., 1; 21—31, 1952 (with Dr. M. B. Bender). A Clinical Evaluation of Carotid Angiography, Conf. Neurol., 13: Exosomesthesia, or Displacement of Cutaneous Sensation into Extrapersonal Space, Trans. Amer. Neurol. Assoc., lg; 1952 (with Drs. M. F. Shapiro and M. B. Bender). .... ibid, Arch. Neurol. & Psychiat., éﬁ: h8l-h90 1952. 9. Order of Dominance in Cutaneous Perception, Trans. Amer. Neurol. Assoc. 2E3 238~h0, 1952 (with Drs. M.B. Bender and M. Green). 10. Development of Perception of Simultaneous Tactile Stimuli in Normal Uhildren, Neurology, 2; 27-3h, 1953 (with Dr. M. B. Bender). 11. Perception of Simultaneous Tactile Stimuli by Mentally Retarded Adults, J. Nerv. Ment. Dis. 111; h3-h9, 1953 (with Drs. M. B. Bender and M. Green). l2. Spinal Fluid Findings 2: 137, 1953 (I-rit‘n Dr. 13. Following Cerebral Angiography, Neurology, M. Stein). Statistical Study of a Psychoanalytic Hypothesis; Absence of a Parent as a Specific Factor Determining Choice of Neurosis, J. Hillside Hospital, a; 67-71, 1953 (with Dr. S. Tarachow). A Effects of Barbiturates 15: 1953 (with Drs. on Perception, Trans. Amer. M. B. Bender, P. Bergman and M. Neurol. Assoc., Nathanson). Homosexuality with Panic and Paranoid States (Case Report) Hillside Hosp., _2_: 16h-9o, 1953. J. 16. Standardization of the Face-Hand Test, Neurology a; 211-217, 195h (with Dr. M. Green). �.3917. Patterns of Perceptual Organization with Simultaneous Stimuli, Arch. Neurol. & Psychiat., 12: 233-255, 195A (with Drs. M. B. Bender and H. Green). 18. The Amytal Test in Patients with Mental Illness, J. Hillside Hospital, g; 3-13, 1955 (with R. L. Kahn and E. A. Heinstein). l9. Delusional Reduplication of Parts of Body After Insulin Coma Therapy, Dr. Joseeh Jaﬁig: 1. Perceptual Patterns During Recovery From General Anesthesia, Jour. of Neurol. Neurosurg. & Psychiat., 1%; 316-321, 195l (with M. B. Bender). 2. Factor of Symmetry in Tests of Double Simultaneous Stimulation, Brain, 15: 167-176, 1952 (with M.B. Bender). Dr. Rdbert Kahn: 1. Toxicity of Quinacrine (atabrine) for Central Nervous System: Experimental & Human Neurol. Arch. on Psychiat., 5g: 28h—299, l9h6 Study Subjects, (with Dr. T. Lidz). 2. After-Imagery in Defective Fields of Vision, J. Neurol., Neurosurg. and Psychiat., lg: 196-20h, l9h9 (with Dr. M. B. Bender). 3. A Hereditary Syndrome Characterized by Mirror Movements, Left Handedness and Organic Mental Defect, Trans. Am. Neurol. A., ZS? 22h—226, 1919 (with Drs. I. Freiman and L. Michaels). Tumors and Vascular 15: 277-278, 1950 (with h. Correlation of Clinical and EEG-Abnormalities in Disease of the Brain, Trans. Am. Neurol. A., Drs. E. A. ieinstein and H. Strauss). 5. Syndrome of Anosognosia, Arch. Neurol. (with Dr. E. A. Heinstein). & Psychiat., ég: 772-791, 1950 6. Patterns of Disorientation in Organic Brain Bisease, J. Neuropath. Clin. Neurol. 1; 21h-226, 1951 (with Dr. E. A. heinstein) & 7. Nonaphasic Misnaming (Paraphasia) in Organic Brain Disease, A.M.A. Arch. Neurol. & Psychiat., él: 72-79, 1952 (with Dr. E. A. Neinstein). 8. Preoperative and Postoperative Personality Changes Accompanying Frontal Lobe Heningioma, B. Schlesinger). 9. J. Nerv. & Hent. Bis., llh; h92-510, 1952 (with Dr. Phenomena of Reduplication, A.M.A. Arch. Neurol. & Psychiat., 81h, 1952 (with Drs. E. A.'Heinstein and L. A. Sugarman). él: 808- �uhO- Shock Therapy, Am. J. Psychiat., heinstein and L. Linn). Its Relation to the Theory of 222; 22-26, 1952 (with Drs. E. A. 10. IBychosis During Electroshock Therhpy: ' Brain Sodium") Sodium ("Amytal Organic in Amobarbital of Diagnostic Disease, Am. J. Psychiat., 109: 12, 889-89h, 1953 (with Drs. E. A. Ueinstein, L. A. Sugarman and L. Linn). Use Neurol. Arch. of Denial Factors in Illness, Personality Q2: 355—367, 1953 (with E. A. Heinstein, M.D.). & Psychiat., Behavior Disturbances Following Cataract Extraction, Am. J. Psychiat., and L. Linn). E. 1953 A.‘ einstein (with Drs. 281—289, 219} Delusional Reduplication of Parts of the Body, Brain, 7?: h5-60, l95h (with Drs. s. A. deinstein, s. Halitz, and J. hozanshiT: Serial Administration of the "Amytal Test" for Brain Disease: Its Diag195h & 217-226, Neurol. Arch. and Psychiat., Value, Prognostic nostic ll: (with Drs. E. A. Heinstein and S. Malitz). 16. Ludic Behavior in Patients with :rain Disease, J. Hillside Hospital, A. Sugarman). and L. B. A.'Heinstein l95h (with Drs. 98-106, 2: 17. Test in Mental Illness, J. Hillsiﬁe Hospital., (with Drs. M. Fink and E. A. ﬂeinstein). The Amytal Q; 3-13, 1955 Amer. "Irritative" Lesions, in of Functioning Intellectual Patterns 18. PSychologist, 25 h02, l95h (with Dr. E. A. Meinstein). 19. "Spatial inattention" in Patients with Localized Lesions of the CereN. S. l95h (with 327-328, Drs. Psychologist, 2: Pollack and M. B. Bender). brum, Amer. M. Batteery, 20. The Adaptive Role of Behavior Accompanying Brain Disease as Exemplified by the Phenomena of Reduplication, Amer. Peychologist, 2; h90, l95h (with Dr. E. A. ieinstein). 21. Denial of Illness: Symbolic and Physiological ASpects, Springfield, I11., Charles C. Thomas, 1955 (with Dr. E. A. ;einstein). 22. Coma Therapy, Insulin Body After of of Parts the Jelusional [@dnplication M. and Fink). D. Graubert 1955 (with lBh—lh7, Drs. J. Hillside Hosp., g: and Pain Asymbolia, A.M.A. Arch. Neurol. 23. ’kithdrawal, Inattention, Psychiat., 1h: 235—2h8, 1955 (with Drs. s. A. neinstein ana'h. H. & Slote). Spatial Inattention in Focal Cerebral Lesions, Brain, in press (with Drs. C. S. Battersby, M. B. Bender and.M. Pollack). �25. Autokinetic Movement in Patients with Sensory and.Motor Disturbances, J. M. M. and B. Pollack S. (with Drs. H. Battersby, Exp. Psychol., in press Bender). 26. Relation Between Altered Brain thction and Denial in Electroshock Ther& Peychiat., in press (with Drs. M. Fink and A.M.A. Meurol. Arch. apy, E. A. heinstein). 27. Mount Sinai of J. With Picture Schizophrenia, Clinical a Encephalitis Hosp., a1; 1955 (with Drs. E. A. Heinstein and L. Linn). Korin: Dr. .1. The New Effects of Electroshock York University, 1955. on Retroactive Inhibition, Ph.D. Thesis, Dr. Hargz Goldenberg: and of Amino Acid Esterase Trypsin Activities of the 1. Chymotrypsin, Arch. Biochem., 22; 15h, 1950 (with V. Goldenberg). pH Depenﬁence 2. Several Derivatives of Acetyl-dl-phenylalanine, J. 5317, 1950 (with V. Goldenberg and A. McLaren). Am. Chem. Soc., lg: 3. Effect of Ultraviolet Light on the Specific Activity of Chymotrypsin and Trypsin, J. Am. Chem. Soc., 72: 1131, 1951 (with A. D. McLaren). h. An Ester Leucine of Ethyl Hydrolysis the Enzyme-Catalyzed Into Inquiry Gold1951 V. (with Biochem. 110, Acta, Biophys. 1; et Chymotrypsin, by enberg and A. D. McLaren). 5. Report D-12, April 1, l9h6; cf. pp. 117-119, concerning 8-Hydroxyquinoline Method (Alcohol Extraction), in C.J. Rodden's "Analytical Chemistry of the Manhattan Project", (with J. Greenspan, M. J. Sohuler, D. Taub, and A. S. Carlson). 6. Calcification. V. Influence of Fluoride and Cyanide Ions in the Presence and Absence of Magnesium, Proc. Soc. Exp. A. L. Sobel). Biol., 19: 719, 1951 (with kaline Earths on Survival of the Calcify1952 (with A. E. Sobel). 695, Exp. Soc. Proc. g1: Mechanism, Biol., ing 7. Calcification. IX.Inf1uence of A 8. Calcification. IV. Influence of Strontium and Magnesium Ions on Calcification in vitro, Proc. Soc. Exp. Biol., IQ: 716, 1951 (with A. E. Sobel and A. Hanok5. 9. Calcification. XI. Studies of the Incorporation of Citrate in Calcification in vitro J. Dent. Res., 3;: L97, 19Sh (with A. E. Sobel and E. Schmeriler). �~h2§ Ions and Cyanide Fluride by Inhibition 10. Calcification. XII. Cation-Linked & Hed., éé: 27S, Biol. Soc. Exp. Proc. in B-GlycerophOSphate Medium, l9Sh (with A. E. Sobel). 19Sh. 26: 690, Chem., Anal. Plots, ll. Rectification of Nonlinear Beer's 12. Curves. Nonlinear Activity of Rectification Biochem. & Biophys., ég; 288, 195h. Enzyme Law I. Preliminary, Arch. �Studs.“ '1 tho room. L 01‘ 91‘ the “mum Width. 01‘ tn: 1:: Win A man}: Wm Wtm «mum, 01’ khanm tar claatraoncophﬂampw W! «mum “W studying 01-min manta]. with WW in brain during tin mmmd. m and Wm M wt yaw. W method. for YMMMW mmmmno at Madam ta stimulation mm W m,mmmmuhhmmmmmmmmpumm thew. m Wu. Mitmun. mental W «mum int-mm: um M m huts, ham gatima or tho hymn dam-uni" affect: of inn-ms, and human um cum-a. tannin; haloahraaanmkin acid (mp-was) an anal: and In tho mm- 5: yaw, a my at tho was in brain function during mmmuw mm «I Mpmholamu. Dre WWW”. Kmmlwomm and the Pink to Dr. fellow of tha a «mm. m mum «mm. Mutilation tar Inna“): Win an imam to sup-mu that kbonhary work. “W. Ha rm on with a Main: 1. W 1953 In a alumni ultimatum immut- In tbs Ané’t‘tmwmu aluminum tantalum tho integrator! “My an laboratory was «unnamed mam than math! Wamhéin 11W brain mum. the 1mm ammo: 65 m W of {w with maul mania 111mm, dwmatu ”mum 3W m mm mum to mmm mime. Mam dim, mun WI ef pain; mwnwmmmmumwmmotmmmmm» mtkm; with «13m (litmus-I m tuna-Id ma amtralkd with anal-put: drugs. may ammu- m ta m mammal mm a: am: 1m1uuoha During tho yaw, $5 mutton tum-Ind. More than half. aw 85.1: mm}. hospi'alk m- mmr M m mammal «mum at... am an. an. �4-» mmmaohmmmmwmwmmmm ”mutate ermg than thﬂu Ina 1mm yum, ”we“. macaw «:1th at mum. mmmwmnmmsunmmmmumm :Mz‘mmwmmmmnwdwumﬂoftb W. «ammuﬁmmnsmmmmmmmuuumma mm m In addition. tan on m at mammalian!!- mmmmm McMithmmmmmmngnmm_ mmammmomrmmmammmmmammm uttkﬂhoapim. . wmmm, s. A. at .1: The mm, M. am PM o: mama: mm in m damn IWtSMﬂs (Jam) Bibltoﬂ (1953) 1953:» m. mm. m. tau-m, 9.5.. Ramon. n. m mm on Pmopum, Mm... Jam 1953. il'ink. K... m m, M; m. u. and Bond», 11.3.: remap-um a: w man-11y mm: m mm at mm.“- 51mm mm. Stimuli Now. a m. nu. mam-w (Jar-u) 1953. am. mm, 3. m: m, m A sumac-1 away ’or a mummm mom-m, am. swam no». 2167*?! (March) 1953. rm, � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Progress and annual reports; research activities (folder title 2/2). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-003 Date A point or period of time associated with an event in the lifecycle of the resource 1955 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Letter to Fink; Somatic Therapy Research Program; Monthly report; Research Progress reports - Department of Biochemistry; Letters to Dr. Miller; Electroshock Therapy Evaluation Program; Annual Report - Department of Neurology; Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/5fddf7ec4456da255de4e0d4b1d4c29a.pdf e18d9957071a91ab8e65015c0fde8e69 PDF Text Text January 15, 1956 Perceptual Changes Induced M Prorress Report Maximilian Fink, Director of Research M. D. 927 By Drugs and Electroshock (c) September 1, 1954—January 1, 1956 ' Hillside Hospital Glen Oaks, New York aHEMRY: Beginning with a study of perceptual changes induced by electroshock, emphasis has shifted to a study of the mechanism of electroshock therapy. A marked relationship was demonstrated between clinical improve- ment and certain indices of altered cerebral function. Early, persistent and severe changes in amytal tests and the electroencephalograms were ob- served; but no correlation was demonstrated for memory double simultaneous stimulation. tests or tests of clinical improvement did not alvays persist, further studies to elucidate the relationship of premorbid personality to both short and long term improvement were devised. Preliminary data demonstrate a relationship between persistent improvement and a specific character pattern. Since suprathreshold simultaneous tactile stimulation techniques failed to discriminate in terms of clinical response, threshold studies utilizing square—wave electrical stimuli were undertaken. This technique elicits patterns of altered function not clinically apiarent, and the relation of these patterns to clinical improvement is under study. As �PROGREeS REPORT The inception of M~927 in September 1954 permitted an expansion of studies previously undertaken as a Fellow of the National Fbundation for Infantile Paralysis. Three studies were in progress: (a) evaluation of the amytal test(l) in psychiatric subjects; (b) relation between al~ tered cerebral function and tests of simultaneous tactile stimulation; (c) effect of lysergic acid diethylamide, pervitin, and amytal on visual perception. and In the amytal test, the patient is asked questions concerning his illness, orientation, and recall before and immediately after the intravenous administration of amytal to the point of nystagmus and slurred speech. In the original studies at the Nount Sinai Hospital, the development of disorientation and explicit denial of illness was clearly associated with diffuse cerebral dysfunction(1). As a admissions to Hillside Hospital were tested. patients control study, consecutive Of 68 interviews essayed a- not had recent electroshock therapy, 56 were adequately completed. Of these, 51 were "negative" for brain dysfunction; and of the five " positive" results, hree showed other evidence of brain mong damage. who had In addition to further defining the scope of this test as an in- dex of cerebral dysfunction, the study demonstrated other differences from a group of patients with physical disabilities but without brain disease. There was more transient disorientation and denial, more withdrawal and ludic behavior and more changes in the syntactical aspects of language in the psychiatric population.‘ ._____.________________________..____.______________________________________ *Kahn, R.L., Fink, M., & Heinstein, E.A.: The "Amytal Test" in Patients with mental Illness, J. Hillside Hospital ﬂzﬁ-lj, January 1955. �2. When such tests were applied in patients who had recently under- gone electroshock therapy, "positive" amytal reSponses were elicited. This aberration had previously been reported by Weinstein, Linn, and Kahn(2), and formed the basis for their explanation of the mode of action of electroshock therapy. In a second study, patients undergoing electroshock therapy tested by simultaneous tactile stimulation methods(5). With were increasing amounts of electroshock therapy, patients demonstrated consistent alterations in the perception of the two stimuli. Failure to report one stimulus and mislocalization of one or both stimuli in predictable patterns were demonstrated. These patterns were transient, however. Electroence- phalographic records were also obtained in these subjects at weekly vals. progressive appearance of delta activity, The first inter- as random, low voltage activity, and later as symmetric, high voltage bursts, previously described by numerous authors(4) was confirmed. Attempts at this time to correlate changes in the electroencephalogram tests and the simultaneous tactile unsuccessful. were third group of studies, of the effects of d~lysergic acid die— thylamide and pervitin on visual perception were inconclusive. A variety of ill~defined subjective perceptual alterations which failed of objec— tive verification were observed and the study was discontinued. A The experiences with amytal tests and simultaneous tactile tests formed the background for the studies undertaken since September 1954 un- der H—927. To determine the relationship between various indices of a1- tered brain function (the amytal test, the electroencephalogram, and �5. tactile tests) simultaneous a correlated study was undertaken. Conse— cutive patients referred for electroshock therapy were studied. Treatment was administered three times a week. Electroencephalograms were done weekly on a day following a treatment. tests Simultaneous tactile stimulation tests were done once a week immediately preceding a treatment and 48 hours after a previous treatment. In addition, special tests of memory and recall utilizing the technique of retroactive inhibition were carried out at weekly intervals. and amytal In addition to intercorrelations between these indices, we were anxious to determine the relation between such changes and clinical alteration in behavior. For this purpose a clinical evaluation of improvement at weekly intervals during treatment was made ing therapy. and the These patients and unimproved. showed by the ratings were The symptoms their therapists; and up to one month follow~ were made independently classified as markedly of the other indices, improved, moderately improved, markedly improved patients were those that brought and the who no longer to the hospital; were rated improved them nurses' notes confirmed such aspects as being able to sleep without medication, better appetite and improved capacity to participate in hospital activities. showed no change The unimproved or only transient changes. were those who had some imtrovement in The patients were those who moderately improved patients symptoms, but in whom severe dis- turbances as obsessional thinking, paranoid ideas or somatic preoccupation persisted. A marked correlation was found between clinical improvement and early, persistent and severe changes in both the amytal tests and the �4. electroencephalogramx to occur. No If such changes did not appear, improvement failed such correlations were manifest between improvement and the tests of recall function or changes in simultaneous tactile tests. Thirty patients were essayed in this study, but 24 were success- fully concluded. At one month post-treatment, eleven were classified by the supervising psychiatrist as markedly improved; six as moderately improved; and seven as unimproved. the markedly improved patients, every one had at least one positive amytal test during treatment. Of the 50 tests given to this group, 58 (76%) were positive. In contrast, of the unimproved of the 45 Of patients, five of the seven never showed a positive result, and tests administered to this group, only 6 (15%) were positive. The moderately improved group showed more positive responses than the unimproved patients, but fell far short of the much improved group. In addition, there were consistent'changes in language and non- verbal aspects of behavior indicating alterations in adaptive mechanisms in the much improved group, even in interviews not employing amytal. These alterations were either minimally or only transiently manifest in the unimproved group and then only under the influence of sodium amytal.* Concomitant studies of the electroencephalograms taken on a day preceding the amytal cords were first test indicate M a similar relationship. measured for per-cent time slow wave The 160 re- (delta) activity, frequency of the the duration of burst activity and the amplitude and slowest waves present. The records were then placed in a rank serial order. Presented at the annual meeting of the American Psychiatric Association, May 10, 1955; and submitted to the Archives of Neurology & Psychiatry for * publication. �5. falling in the upoer third were labelled "high abnormality" and those in the lower third as " low abnormality". Of the much improved Those patients, 25% showed a ment; 80% after two weeks and 90% patients, iowever, first after three weeks. The treat- In the unimproved none had a high degree abnormality record during the three weeks and only one had such a record by the fourth treatment. these high degree abnormality after one week of records of the moderately improved patients week fell of between two groupsc* Changes in memory and learning were tested in these subjects by using the principle of retroactive inhibition. recall of three-letter originally learned By the serial testing of words following the interpola- ted learning of nonsense syllables, patterns of decrement in learning and recall ment up elicited. As a group, the patients showed increasing impairto the third week of treatment, and a rapid inorovement after the were cessation of treatment. No relationship, however, could be established between impairment and resnonse to treatment.** The responses of these subjects to simultaneous touch stimuli were also assessed. ability to identify and While an localize the two tactile tests using increasing impairment in the stimuli could be demonstrated with increasing treatment, no relation to improvement was noted. By tent the spring of 1955, and severe changes tal tests it was our conclusion that early, persis- in both the electroencephalogram and in the amy- are a necessary, though not sufficient, pre~requisite for ..___....-—_. m---_—. » Presented at the joint meeting of the Eastern and Southern E1ectroence~ phalographic Societies, Bethesda, September 50, 1955. * Presented before the Electroshock Research Association, May 8, 1955, and awarded their Annual Prize Award and cited for excellence in research design. ** �6. improvement following electroshock therapy. initial part of the This obserVation confirmed the hypothesis of weinstein, Linn and Kahn(2) ascribing the therapeutic results of electroshock to the facilitation of patterns of denial by altered brain function. But was it true that the patient's improvement resulted from denial of illness or denial of other a- More symptoms? daptive mechanisms manifest? Also, within a few months a number of the markedly improved patients had relapsed. At this time, a second Why? electroshock population was studied. First, to confirm our previous observations on the relation between improvement and changes in the amytal tests and the electroencephalogram. if exnlicit denial is a mechanism in improvement, it post—treatment and directly related to improvement. advanced that those patients who showed cit verbal denial" personality Secondly, should be manifest The hypothesis the characteristics of the would be those more was “eXpli— likely to maintain im— provement. Between April and August, were studied. Satisfactory data electroencephalograms and amytal and again d ring the second and thirty consecutive electroshock patients was obtained in twenty-five subjects. The tests were carried out before treatment, third week of treatment. The patients were again independently rated for improvement by a supervising psychiatrist du- ring treatment, and one month following treatment. These patients are also now being seen in six month follow-up visits to assess the " long-term" changes. In addition to these of subjects was tests, the premorbid personality of this group assessed by an interview with family members, psychologic �7. tests and a tachistoscopic study. in independent interviews. to A At least two close relatives were seen standardized questionnaire has been devised den verbal "explicit the of indicative factors characterological elicit this study fifteen characteristics defined as typiSuch in selected. were of absent in this personality tyne or cally present tons include prestige consciousness, sensitivity to criticism, imagination, temper and attitudes to sex and illness. Each patient is rated on a scale nial" personality. of 0 to denial 2 For for each item - the higher score signifying a greater tendency to o l Each patient vas also tested by a standard psychologic evaluation These Thematic and Tests. Rorschach the Apperception including battery tests were assessed for character structure and the usual tynes of defense or adaptation. tional A tachistoscopic study was devised, in which pairs of emo- and non-emotional words were flashed on a screen at 10, 20, 50, 100 patient's ability to identify the words, the reaction time, and the distortions were ascertained. This pre-treat~ nent data is now being studied as to its ability to clarify the patient's and 250 millisecond periods. The usual defense patterns. Only the short term group nine uatients were results of this study are available. Of this rated as showing marked improvement; twelve as mo- derate inprovement; and four as unimproved. Of the physiological indices assessed in these patients, a signi- ficant difference was again noted in the anytal tests and the electroence— phalograms between the markedly improved and unimproved groups. no There was difference between the markedly and moderately improved groups. �8. relation of personality ratings and improvement, an indefinite correlation was manifest in this small group. Lcores expressive of tendency to "oxalicit verbal denial" ranged from O to 25 in a scale of O Asgarding the to 50. The following table describes the natterns of each grouw when "high" and "low" scores are compared. (10 and Below) Low ﬁarked Improvement (9) Hoderate " " Uninproved High (Above 10) 2 7 (12) 7 5 (4) e 0 Because the scores were unusually low in this group, a sample of consecutive private electroshock estients were studied. lity ratings and clinical evaluations were made. To Similar persona- date, ten patients have this study is continuing. This study is still in progress. The six month follouaup is now being undertaken and further correlations will be done. Kcanwhile, certain conclusions can be entertained. The relationship between alteration in the been studied and physiological tests and improvement It became apvarent that the patients manifesting clinical exolicit denial of illness post-electro— was confirmed. shock did not have the best long—term response. Lesser degrees of adaptive better prognostic value. This observation led to an analysis of the only verbatim recorded data for this series - the language changes changes may have in the amytal interviews. The data is now being analyzed for a variety of adaptive language changes and correlations with clinical assessment are to be made. �9. Chile these studies of the ohenbmena underlying improvement in electroshock therapy have been under investigation, the tual studies have run concurrently. group studied, the lack of In the first (1954) electroshock correlation between simultaneous tactile sti- mulation tests and improvement was nuzsling. The tactile tests tremely gross, hovever, and this might be a factor. a more meaningful was developed. anticipation that be obtained from Previous exteriences with von Frey hairs for such threshold stimulation had convinced mulus In were ex- this index if threshused, equisnent for threshold electrical correlation could old stimulation techniques were stimulation tactile percen- me that the variation in the sti- often exceeded the fluctuations in hreshold, and the studies were inconclusive. Reports by Segal(5) on the perception of square-wave elec- trical stinuli led to our development of similar equipment. 84~B stimulators and isolation units monitored by a deliver independent stimuli. A Dnnont Two Grass oscillograph switch box and l centimeter steel disc e- Difficulties in isolating the stimuli precluded this testing being carried out satisfactorily until septenber. A continuation of the second electroshock group has been in prolectrodes corolete the assembly. gress since September. The same nhysiological tests and personality assess~ patient's responses to simultaneous hreshold electrical stimuli is tested before treatrent and at weekly intervals. To date, 18 patients have been studied. The same phenomena of exments are undertaken. In addition, the tinction, displacenent, nerseveration, and confabulrtion described in patients with organic mental syndrome with suprathreshold stimuli by Fink, 4. �10. Green, and Bender(6) are apparent technique elicits these patterns in these natients during treatment. This clinically manifest. while extinction is also manifest in yrs-treatment testing, displacement and perseveration are related to the extent of treatment. This study is now though they are not in progress. Concomitant with these studies, preliminary observations of a milar nature have been made in patients undergoing insulin coma si— therapy. Recent reports of the value of prolonged come as the basis for improvement by Revitch, Kwalvasse? and Caplan, Sharass and Rowsell, and Yeager gt al<7> have been confirmed in our patients. In reported a direct relationship between altered brain function, altered patand imnrovement.* and behavior terns of adantation in lan mace clinical t: . ' - one unusual case we r R.L., Graubert, D.H. and Fink, N.: Delusional Reduplication of Parts of the Body After Insulin Coma Therapy, J. Hillside Hbsnital ﬂ;154v147, 1955. * Kahn, �11‘ Summary of Our Work to Date and Plans for the Future: studies of perceptual changes induced by electroshock are pro- is in elucidating the factors underlying improvement following electroshock therapy: changes in shysiologiccl indices; adaptive changes in language and behavior in resnonse ceeding in two concurrent and related courses. One to altered brain function; and the factor of personality. study of the watterns of threshold tactile perception The second is a under conditions of altered cerebral function; their relation to "inprovenent" following elec— troshock; and the relation to other indices of altered cerebral function. The problems before this study are conylex. The rating of "improve- is primitive and further vork alcnf this line is mandat ry. The delineution of the explicit verbal denial character is a gross anprOfination of this problem. FUrther study of the role of personality and a descrip- went" tion of defensive operations other than denial which may significance is in progress. To clarify in our data the have therapeutic 203 beneficial be which ascribed to "general interest", electroshock can of therany result "spontaneous cure" or "placebo" effect, a control study is being instituted on February 1. Titb the concurrence of the Sedical Board of Hillside Yos- be will electroshock referred for therauy treated, by ranpital, pitients dom selection, by either pentotbal-convulsive electroshock or jentothal— subconvulsive stimulation. The cerebral chmnjcs induced by pentothal- subcenvulsive stimulation are miniwal and result in a minimal inprovenent rate(8) o �M References l. einstein, E.A., Lahn, R.L., Sugarman, L.A., & Linn, L.: Diagnostic Use of Amobarbital sodium in Organic Brain Disease, Am. J. Tsychiat. 112: 889—894, 1955. 2. Heinstein, E.A., Linn, L. & Kahn, R.L.: Psychosis During Electroshock Therapy: Its Relation to a Theory of Shock Therapy, Am. J. Psychiat. 102:22-26, 1952. 5. Bender, H.B., Fink, H., & Green, N.: Patterns in Perception of Simultaneous Tests of Face and Hand, Arch. Neurol. & Psychiat. §§3555-362, 1951- , ~ 4. Pacella, B.L., Barrera, o.”., a Kalinowsky, L.: Variations in the Electroencephalogram Associated with Electric Shock Therapy of Patients with Mental Disorders, Arch. Neurol. & Psychiat., ﬂl:567~58#, 1942. f‘! 5. Segal, Harry: Prick Threshold stimulation with Square ‘ave Current: A New Heasure of Skin Sensibility, Yale Jour. Biol. & Med., g§:145-154 1955. A 6. Fink, 3., Green, D. & Bender, U.B.: Face-Hand Test as a Diagnostic Sign of Organic Mental Syndrome, Eeurology.g:46-58, 1952. , 7. (a) Revitch, E.: Observations on Organic Brain Damage and Clinical Improvement Folloring rotracted Insulin Coma, Psychiat. auart. gé: 72, 1954. (b) Kualwasser, S. and Caplan, M.: A Case_of Prolonged Insulin Treatment, J. Hillside Hospital 35145, 1952. Coma: (c) Shagass, C. and Rowsell, P.W.: Serial Electroencephalographic and Clinical Studies in a Case of Prolonged Insulin Coma, .M.A. Arch. Neurol. & Psychiat. 13:7059 1954. (d) Yeager, C.L. 33 El: glycemic Coma, 8. Ulett, Electroencephalogranhic studies in PosthypoJ. Harv. & Ment. Dis. 118:455, 1955. of Matched Grougs in the Evaluation of Convulsive and Subconvulsive Photoshock, Bull, Kenn. Olin. l§:158, G. A. gt_al: The Use �m 30, 1956 mama Ammm m mm m - 3.955 FollwingthsamﬂmdﬁnﬁamtheMamm,msmstyw mrked by integratim at um. 38mm with ongoing 15h. mdnpamimotthsntaff. Maddiﬁmlgrantsm wise rewind its first prize award. Wk left Ht. 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' 1wmmm.m195§.wuamwupotpatmumemu mmmmwmmatMuatmmmmmm his mmumsm‘sgmwmsmmammuuamm appumummbyumlam. ﬂﬂ.mmmps,mthommt stMmmmmwmamunu-ammmw :mwmnwm,mdmnrmwuobmmmmﬁmm themﬂﬁergm. mmw,rmmeMmmdu-m,bymu"mm «wmxmmdwuam mmnawmm fermdbyplvaicima otherthmpsycmmtu. £130,312 Immammnmmmmm. “Wham; . ��y‘ﬁ-WWWAMV'VUM amp" Husky, 1min: from in “night and Roasttlmt‘ by H. 3.8nw “3%; 3.3.3.3.c.o., 6.4. MAL, Imam, Shit!” 5. The Childm, ' Putter, Mm sown. Gsoop Hark st. Killuidn Haunt-1, Amer. at 151.161.19553mw Glam; lam,1955. W, J. WM Hosp. g: Orbhopaychiatric Ame... �I April 2, 1956 Corrected Copy RESEARCH ACTIVITIES ANNUAL REPORT SAME AS ORIGINAL - 1955 �IDENTICAI. UP TO END OF PARAGRAPH 1. Research Programs were actively carried out by the Research Service, resident and attending psychiatrists, and by departments at the hospital. (a) Research Service: With the two additions to the expand staff, Dr. Fink was able to continue and his studies of the changes in behavior'widch fallowed electroshock therapy. These studies were directed to understanding the effects of the treatment on the brain, as well as trying to understand the changes in the patients behavior, language,and memory which might result from such changes in brain function. There were three different tests that were used. The changes that occured in the brain patterns (electroencephalogram) were studied and it was shown that it was necessary to have some changes in the brain wave patterns before patients be- wave came better from electroshock. Secondly, by giving the patients injections of who have that patients it changes in brain function show certain specific changes in language after the drug. Thirdly, by special tests of the ability of the patients to perceive two touches simultaneously applied to different body parts, it is possible to get a seditive drug (sodium amytal) is possible to show another index of brain function. These three indices, together, form the best way available today to demonstrate changes in brain function. One way of showing changes in a patient is to study his language. We have continued our studies of language following the administration of sodium amytal. In addition, Dr. Jaffe has begun a study of the changes in language which follow changes in the doctors attitude to the patient. For this purpose interviews between himself and the patient during which he changes is recording his own attitude he to the patient and then measures and examines the type of responses the patient has to this change. �-3- interest has Much been aroused in the newer drugs in psychiatry. A pre- vious study at Iﬂllside Hospital had shown that small doses of reserpine had very little effect on our controlled study and the patients. When purified reserpine was undertaken by one of internist, Dr. was made available, a the resident physicians, Dr. Wachspress Blumberg, to determine whether high doses of reserpine eleviate anxiety in our patients. It was the impression of the observers that the reserpine failed to relieve anxiety symptoms regardless of dosage and, would that it increased the depressive symptoms. These observations will reported in a forthcoming issue of the Journal of the Hillside Heepital. moreover, be In the biochemical program, under the direction of Dr. Harry Goldenberg, three projects were undertaken. In one study of the effects of chlorpromazine, Dr. Goldenberé carried out fundamental studies azine to under-Stand where and how this on drug might the metabolism of chlorprcm- act. In this study he was us- ing special techniques that he had developed. In a study of the effect of some new drugs in inducing disturbed behavior like schizophrenia, Dr. Goldenberg had studied a variety of alkaloids for their ability to affect a special enzyme system (serum cholinesterase) he reported that the most powerful of the new compounds (hallucinogens) known as which looks to be a very potent enzyme inhibitor as well. the development of a very refined technique so that he can lysergic acid diethylamide Most remarkable was measure very minute was quantities of drugs in the body. Thirdly, fundamental studies on the function of the liver in the he made some metabolism of hormones. (b) Psychiatric Staff : (1) Ambivalence Study: This study was continued by Dr. 3. Tarachow, H. Karin and 5. Freidman. In this study, an effort is patients develop the kind of neurosis that they do. psychologic measured. tests as well as made to understnad Emphasis is made by why some special clinical interview, the degree of ambivalence is This study attempts to prove a hypothesis that there is a relation bea �tween the loss of a parent early in life and the type or neurosis that developes in adulthood. (2) Subculture 5tugy: Under the directian of Dr. R. Navarre, supervising Graubert D. Dr. of (resident therapist), psychiatrist, an interdisciplinary staff Dr. H. Korin (psychology), Mr; A. Lurie (social service) and.Miss Z. Putter (group activities) have studied the hospital environment as a therapeutic agent. They are emphasizing the fact that just coming to a hospital has therapeutic value. Also, that there are many agencies at the hospital which affect a patients change, besides the specific psychiatric treatment that they are receiving from the phy- sicians. In a pilot study, they demonstrated the value of a diary of patients activities in clarifying the communications between patient and therapist, and also to explain unusual changes in patients behavior. The staff has devoted a good part of its time to understanding some of the aspects in thenhospital which motivate changes in the patient. In September, following our preliminary exper- (3) Chlogprcmazine Study: iences with chlorpromazine, one of the newer psychiatric drugs, two of the res- ident psychiatrists Drs. a potential substitute for insulin coma coma undertook a study of are divided into two groups in a randem fashion insulin It is this drug as therapy. Patients referred for insulin R. Shaw and G. Gross, coma hoped - one receiving routine therapy; and the other receiving chlorpromazine for three months. that this study will make a little bit clearer the usefulness of this new drug. (h) Prognostic creteria in Electroshock Therapy: PARAGRAPH REMAINS UNCHANGED �-5(0) Departmental Research Programs: In addition to the cooperation between various hospital services, the following projects were in progress or jndere taken during 1955. (1) Medical Demrtment: In addition to the medical and physiologic observations of the patients undergoing treatment with the newer drugs, reserb pine and chlorpromazine, Dr. A. Blumberg has investigated a new test-the test has Funkenstein Test. This been described as being able to a patient will improve following electroshock or insulin coma tell whether treatment. There- fore, to find out whether this is true at Hillside Hospital, Dr. Blumberg has been seeing all the patients prior to physical treatments. The test is harms less and so far, the results are not available. Dr. Blumberg also studied the possibility that insulin a number of hours. He dosage could be made smaller showed, both by clinical if it were and laboratory divided over studies, that divided doses were not as good as single large dosages of insulin. (2) Social Service: Student affiliates in Social Service have been studying the inter-relations of various factors in patient care. For the most part these studies relate the length of hospital stay, discharge evaluation, fee paying, and.a follow-up of patients who were unsuitable for Hillside HOSpital. These studies show great promise because they help us understand the social factors in mental illness. �Department of Biochemistry .............................. April 30, 1956 Progress Report, MarchpApril 1256 A. Active Projects 1. Steroid Sulfate Conjugates It that high speed liver supernates catalyze sulfate conjugation with the following sterols: deso corticosterone, androsterone, and cholesterol, as well as dehydroisoandrosterone, estrone, and testosterone. The underlined sterols conjugate most readily. Considering the various positions in which the hydroxyl functions are located in these molecules, it may be concluded that the conjugase(s) is nonspecific and can act at C 17, 21, 3a, 38, has been established and on phenolic compounds. least four steroid sulfates have been separated from urine using paper chromatography. The major conjugate has been identified as dehydroisoandroster— one sulfate. The other conjugates are under investigation. At 2. Chlogpromazine Study of a hitherto unidentified metabolite of chlorpromazine have been isolated from 9 liters of a pooled urine collected on the wards. The compound crystallizes in beautiful colorless needles, m.p. 190°C. It has been sent out for an element analysis. We suspect it is chlorpromazine mercapturic acid; the analysis will reveal whether our hunch is correct. Another metabolite has been separated electrophoretically and is believed to be an hydroxy derivative. 270 mg. B. Projects Planned to study the metabolism of mescaline this Summer, provided funds are forthcoming from the Dazian Foundation (see below). The investigation would throw light on the mode of detoxication of hallucinogens in the body and facilitate follow~up work dealing with trace endogenous alkaloid excretion in mental disease. We C hope . Funds grant application was submitted to the Dazian Foundation fer personnel support and for the purchase of a spectrofluorometer. We were infonned that funds are not available for instrumentation, but that personnel coverage may be forthcoming. Further information is not available at this time. A — cc. to: Dr. Fink Dr. Jos. S.A. Miller Max H. Goldenberg, Ph.D. �HILLSIDE HOSPITAL GLEN OAKS, N.Y. geptember h, 1956. Mr. George W. Galinger 170 East 79 Street New York, New York Dear ﬁr. Galinger: is Facilities". a copy of the "Recommendations for Expansion of Research Space and This data has been compiled by Dr. Max Fink, who prepared an original outline on the basis of the needs of the Department of Neurophysiology and Neuropsychiatry, and on the basis also of a discussion with myself and with the heads of the Departments of medicine and Biochemistry. The present draft also was discussed in some detail at a special meeting of the Research Committee held on Tuesday, August 28th. Enclosed I understand that will refer these outlines, which include the main functional uses to which thisnnew building will be put, to the architect. The current plans are based on three floors of space (a basement and two floors) with an approximate area of hO' x 100‘ for each floar. The data includes the expected expansion during the next few years of the current projects of the Department of Neurophysiology, the set-up and inclusion of a clinical laboratory, projected space for dynamic and psychological research. The building plan should include the possibility of establishing 12-20 interviewing or psychotherapy rooms which would be housed on the first floor, either at the beginning of construction or sometime later. Such space would be valuable in offering a replacement for the present psychotherapy rooms used for in-patient psychotherapy and housed currently on you the second floor of the Elizabeth Sloman Lowenstein Clinic Building. where Our it present plans are to leave the research and biochemistry department presently is located, but to move the clinical laboratory into the new research facilities. If there is any other data or clarification that you would 11g; from.n§; the Research Committee or Dr. Fink, please feel free to communicate With me.~ Yours JSAl-‘I:1b encl. sincerely, Joseph S.A.Miller, M.D. Medical Director �TO: DR. 1v .. 8-31-56 J.S.A.Miller gear-1: Max Fink, q§UBJECT: RECOMMENDﬁTIONS F R EXPANSIOT OF RESEARCB;§?ACE. M.D. “u.- following recommendations for the development of facilities for research summarize the consensus of meetings held by me with my staff; Dr. Miller, Dr. ReCohen and the to Blumberg; Dr. Mr. as presented Dr. Bachrach, Goldenberg, search Committee of the Medical Board, at its meeting August 28, 1956, and apBoard of Directors. the committees of the them to for appropriate referral by proved The I, INTRODUCTION: A.) Eggatiggi - The major share of the work in the recommended facilities who and are in the acute be with patients the chiefly population, will in-patient services. For this reason, the research building should be in close proximity, recommended Lowenstein for consideraBuilding. Sites Morris the to attached or a3 LowenThe Morris between the include order area the in ofusefulness, tion, stein Building and 76th Avenue;.b) The smaller area lying between the Morris Loqenstein and Elizabeth Sloman Lowenstein Buildings, the connecting tunnel and 76th Avenue; and c) The field east of the Morris Lowenstein Building, and north of the Israel Strauss Pavilion. W 3.) Facilities: 1.) In the development of the Research Service, during the past two Anamet have been various by measures. temporary the space.requirements years, needs the for reasonable well work expansion as the as of present program, lysis next five years, has resulted in the following recommendations. The character of the research program, at present, is along the lines of experimental psychiatry and neurophysiology. Such a program requires neurophysiology laboratory space, sound recording rooms, and special laboratory equipment as the first objective. logical expansion of the research program.as outlined by the Research Committee, by the development of a section in Clinical Psychodynamic Psychiatry, the next need is for facilities for interviewing patients and relatives; offices for staff members; and space for the observation of the psychoﬂierapeutic interview. The latter should be capable both for the observation of single patients and, also, groups. 3.) For the cooperation of staff members, conference rooms are needed. These should be so placed and equipped that much of the interaction between staff members will occur in that area. b.) Another need lies in facilities for the 2h-hour physiologic observation of patients. A four-bed unit, next to the thSiOlogy laboratories, will serve both as a recovery room for physiologic studies, as well as an observation unit for physiologic and biochemical studies. 2.) Keeping in mind the 5.) Another recommendation is with regard to the potential growth and utilization of the medical library. During the past few months, in which we have had a librarian on a full-time basis, space in the library has beCome �-2 '9 overtaxed. A major portion of the librarian's time is devoted to work in conjunction with the Research Service. It would be advisable that pro— vision be made in the same area of research expansion for the medical library. Facilities for an adequate reprint file, and facilities for microfilm reading are recommended. 6.) For time, the present separation of the Medical Clinic (in.Morris Lowenstein Building), the X—ray laboratories (in the Littauer Building), and the @linical Chemistry Laboratories (in the Sloman Lowenstein Building), has made adequate service cumbersome. It is recommended that the Clinical Chemistry Laboratory be relocated in the Research Building, in close proximity to the physiologic observation ward. some With the moving of the present neurophysiology offices from their present position, on the first floor of the Morris Lowenstein Building to the Research Building, three rooms adjacent to the present Medical Clinic will be vacated. It is recommended that these rooms be converted to the x-ray, fluoroscopy and radio~isotope laboratories of the Department of Medicine. With the Research Building attached or in proximity to the Morris Lonenstein Building, the present separated facilities will be in close proximity. Relocation of the Clinical Chemistry Laboratory, from the Sloman Lowenstein to the Research Building, will free an additional 300 ft. of laboratory space for the expansion of the Research Biochemistry Laboratories. 7.) In the history of the growth of this hospital, it is ap— parent that the growth rapidly outstrips the projected allowances. In the development of this building, it is recommended that provisions for expansion be provided in the initial designs, by ind.uding a foundation strong enough for the addition of 100% of the Space; space for elevators; and utility resources adequate for this type of expansion. Also storage space rapidly outstrips the needs of the laboratories. For this reason, a recommendation is made that a basement storage, equal to 15% of the initial floor area, be provided. 0.) Name: is inadvisable 'It"Laboratories" to apply to this building or wing the name or "Experimental". To follow the traditions "Research", of the hospital, the name of a benefactor may he applied, or other non- specific designation. D.) Research Beds: item of research need is not recommended. That item is a To ward. research provide facilities for the continual observaspecial tion of a large number of patients, separated, even in name only, from the rest of the hospital group, would dilute to potentialities for the utilization of all other patients, as well as provide a psychologic barrier to the experimental program. For the present, it is inadvisable to admit One patients for "research.". �.3. II. . GENERAL OUTIINE 0F SPACE RELOCATIQE: Taking into account the available fUnds and the potentiality of additional Public Health Service support, a three-story building, approximately of the size 100 ft. x no ft. is projected. A.) Basement: To include space for the following: 1.; 2. 3.) h.) Library stacks. Storage Space. Clinical Chemistry laboratory and offices. Space for expansion of Chemistry Research laboratories. include utilities, enlarged to 5,000 sq. ft.). (To it may be advisable to have the basement area B.) Egret Floor: l.) waiting room - receptionist. 2. Medical library. 3. Large conference room. Small conference room. h.) 5. Offices and interviewing rooms - 12. 6.) Secretaryfs office and filing room. C.) Second Floor: 1.) 2.) 3.) h.) 5.) 6.) III. Neurophysiology laboratories - 2 - and central recording room. Physiology observation ward. Psychophysical laboratory. Psychotherapy experimental laboratories - 2 - and central sound recording room. Four offices. Small conference room. SPECIFICATIOIB: A.)‘.Taboratories: l.) Physiologic and Neurophysiologic Laboratory: Two rooms for the simultaneous observation of two subjects should be placed about a central third room, which will contain the physiologic recording equipment. In such a system, single pieces of recording equipment can serve dual functions. Such rooms should have independent facilities for temperature and humidity control. Initially, the central equipment room will contain a single EEG unit; but space for a second unit and a frequency analyzer should be allowed. The equipment room should contain recording equipment capable of continuous, simultaneous observation of a number of physiologic variables, such as blood pressure, pulse rate, respiratory rate, and galvanic skin reflex. The position of these three rooms should be in close proximity to the physiologic observation ward. a.) Location - Second floor. b.) Approximate size: each experimental sq. ft., the equipment room of 180 sq. ft., with an adjoining smaller repair laboratory of 120 sq. ft. room of 150 �.h. c.) Relationship access to and access: Each experimental room to have the phySiology ward; and to the equipment room. Equipment room to have large glass port into experimental room. Port to slide into wall to allow direct communication between equipment and experimental rooms. d.) Special construction: (1) Individual temperature and humidity control for experimental rooms. (2) Sliding port. (3) Double walls and ceiling for sound-proofing. (h) water piping and sink in each experimental room. 2.) - Physiological Observation War ‘ Attached to the physiological laboratory, there should be a four-bed observation unit. Such a unit should be equipped for the 2b hour study of patients for biochemical and hormonal studies. A nursing unit should be provided, as well as storage space for the medical equipment needed to protect patients who are under investigation. a.) Location: second floor. 800 sq. ft. Size: b.) c. Relationship and access: access from the main hall and offices; as well as the two physiology laboratories. d.) Special construction: (1) Two two-bed units. (2) Two lavatcries and one shower. (3) opace for storage of clothes of patients; and nursing equipment. (h) Nurses station of desk, storage space, reirigerator and 3 1m 0 (5) Doors wide enough for stretchers or bed. 3.) - Esychophysical Laboratory: This laboratory should be equipped for visual and tactile studies. he room should have windows with built-in light- proof shutters, and the doors should be such that complete darkness can be achieved. For a visual laboratory, the length should be at least 2h to 26 feet. This room should have individual temperature and humidity control. a.) Location: second floor. 250 Size: Length sq. ft. b.) and c. Relationship should be 2h access: access to the logy equipment room and an office. d.) Special construction: El) Light-proof shutters ft. hall, the and doors. 2) Individual temperature and humidity control. physio— �-5h. Psychotherapy Experimental Laboratory: Sound Recording Unit. For the proper observation of patient and therapist, two experimental rooms about a central observation equipment room, should be provided. These rooms should be sound-proof and isolated, preferably at the end of a hall, away from traffic . Lighting should be provided in experimental rooms so that filming of the procedure can be done without additional lights. The central equipment room should contain sound recording equipment which can be controlled either remotely from inside the observation room or from the equipment room itself. A port should be provided from the equipment room into each of the experimental rooms for filming. It would be advisable that at least one of the two experimental rooms be of sufficient size to permit a group of six or eight patients to be under continuous observation. Observation will go on from the central equipment room through one-way vision.windows. should be possible to accommodate a large By adjustable, one-nay vision mirrors, group of observers in the large experimental room, to study the procedures in the smaller experimental room, while recording is accomplished for the separate recording it room. a.) Location‘ second floor (this facility may be placed the first floor in exchange for officeS.) b.) Size: three rooms: (1) Experimental room, large - ZhO sq. ft. on (é) Experimental room, small - 100 sq. ft. (3) Recording-observation room 150 sq. ft. 0.) Relationship and Access: (1) Both experimental rooms are to have one-way ports from the recording room. (2) The large experimental room should have a one-way port into the small experimental room. (3) Access to hall from each experimental room and recording ' room. (h) Access from recording room into large experimental room. d.) Special Construction: (1) Double walls, ceiling for soundproofing. (2) One-way mirrors as in (c) each into filming Special room. experimental port (3; (A Cable connections from each experimental room to recording room. (5) Loudspeaker connections from small experimental room to large. (6) Microphone location and outlets placed in original wall brackets and fixtures. 5, Clinical Laboratory: Relocation of the Laboratories for Clinical Chemistry in close proximity to the physiology ward is advisable. The Clinical Laboratories should heprovided with adequate benches for routine and special test procedures. In View of the space recommendation for Research Biochemical Laboratories, it is advisable to locate the Chemical Laboratories in the basement, with access bv open stairway to the first floor reception room. a.) Location: basement near stairwell. b.) Size: 750 sq. ft. c.) Access: from hallway in basement; to first floor reception room and second floor laboratories through stairwell and elevator. �u6u d.) Special construction: (1) High ceiling to allow for hanging pipes and "false" ceiling. (2)'work benches, sinks, electrical, compressed air, hot and cold water, gas outlets according to detailed specifications of biochemist. 6. Allowance for Expansion of Research Biochemistry: 1500-2000 recommended that is allowances of the this In building, it expansion. biochemistry future be for basement incomplete, of left area sq. ft. Such area should have higher than average ceiling to allow for the installation of necessary piping. B. foice Space: Individual work space for each of the members of the research service inpsychiatry in experimental The requirement staff be present should provided. and two provision psychologists, clﬁles two psychiatrists, a neurophysiologist, and additional psychologist. an of a physiologist addition the by for expansion into would requirements I space picture Clinical Psychiatry, In the section for (anthropologist scientist social two a psychologists, clude three psychiatrists, of staff makes This professional a total worker. and a social or sociologist), One three persons. 1h. In addition, the secretarial services will require in she act also receptionist as a can such that be in a position secretary should secretarial Additional of offices. section the of entrance the a waiting room at adv In be where records will kept. section and filing help should be in an office pre-docresearch fellows, for be aside set two additional officesashould dition, research the with who become associated medical students may toral psychologists or nrqgram. be the on to first floor, largely is office Location: space a.) with some on the second. b.) Size: 1.) Offices of 2.) 3.) c.) Access 1.) 2.) 3.) ft. are recommended. Sixteen are required for the fourteen provisional personnel and two additions. A waiting roomplSO sq. ft. A large secretarial office for two secretaries and filing space - 150 sq. ft. and Relationship: Twelve offices on the first floor, each with access to. two of sets leave advisable be to may a hallway. It offices with an inter-connecting door for the administration heads of the two psychiatric sections. The reception room should be at the entrance to the and staircommand the hallway through and access unit case with the basement, second floor and all offices. The 10x12 or 120 sq. secretarial office should be located close to the reception room. d.) §pggial construction: Double walls and ceiling to establish privacy for the patients under observation. �C.) - Conference Room: important element in any research unit is a place where various A conference room so and discuss activities. their workers can get together This would be workers most the of be would for ideal. central placed that it would prevent the use of one office, the lihary or a laboratory for group disand slides films; blackThere be for should projecting provisions cussions. boards for discussions; and space for exhibits of projects under study. An A second small conference room should be provided for similar purpose on the second floor. a.) Location: first floor for large small. room; second floor for 180 sq. ft. and 120 sq. ft. Access and Relationship} (1) The large room should have access from the b.)Size: c.) library. (2) The small room needs access only from the hall and hall. centrally located on floor. d.) Special construction: facilities for slide-projection, blackboards, and exhibition space allocated on two walls Both should be of the room. D.) - Medical Library! present Medical Library contains one thousand volumes. In Committee has been aware that the library the the Library assessing collection, be obtained during volumes thousand will that one approximately by deficient is the next two years. In addition, considering the number of journals now in subadded and texts are that number neurologic of and the psychiatric scription, hundred hundred four to of three the rate at of a the expansion library annually, volumes per year is anticipated. In addition, the Library Committee anticipates For and these micro-cards. micro-film both the use recommending that library removed of the is location library the the that present well fact as reasons, as from the main activities of both the resident and research staffs, it is recommended that space for the library be provided; the Space to be divided into a main reading room; small librarian’s work room; and library stacks. The a.) Location: 1.) The main reading room to be on the first floor, The preferably near the entrance to the building. librarian's work room to be off the main reading room. 2.) Library stacks to be in the basement, preferably under the main library. b.) Size: c.) Main reading room Librarian work room Basement stacks: 900 sq. 100 sq. 750 sq. ft. ft. ft. Access and Relationship: The main reading room to have access from the hall and from the large conference room. The work room is to come off the main.reading room. The stacks to have access from the basement hallway. �.8d.) Special construction: In the main reading room, bookcases for current books, journal racks for current journals; special equipment for microfilm reading. Also a mechanical dumb-waiter to connect library and the stacks. E.) -;§nimal Laboratories: Present studies on steroid metabolism, the role of cholinesterase and acetylcholine, and the need for some experimental work on the threshholds of convulsions,hsve made me feel that facilities for animal studies diould be provided. The space presently allocated in the Sloman Lowenstein Building is satisfactory; and part of the funds allocated for this expansion should be utilized to equip that space. F.) ~ Storage Space: Storage space for patient records, laboratory data and equipment, should be provided. Such space should be considered in the basement. Minimal allocation of 500 sq. ft. for the laboratories is suggested. G.) - Egpansion: ._ Allowance should be made in the planning of this building, for the addition of a third and fourth floors. For this reason, an elevator well should be included in the original designs, as well as boiler and other facilities with expansion possibilities to accommodate doubling the original ﬂoor space. an Furthermore, to accommodate laboratories on the basement floor, extra-high ceiling is recommended. Also, construction of the foundation and supporting structures should be such as to accommodate the increase in floor space. �ham”. nus-an 1. \ um. um. ”a. “it. W 1.. Ida. nun. mu m u: hm, mm. may M. 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Miller Subject: Report of Research Service, Second Year - To September 1, 1956 At the request of the Medical Affairs Committee Chairman, I am sub. mitting this report of the Research Service, describing its activity during its second year. During this year, the staff has increased; we renewed our grants with the U.5.J.H.S. and through the efforts of members of the Board of Directors, received grants from the Kaufmann and Dazian Fbundations; and we were encouraged by the results in our electroshock evaluation, reserpine and chlorpromazineinsulin, and anbivalence studies. distressing feature of the year was the denigratration of the Research Service to separate services without a Director. As of September 1, 1956, the Research Service is divided into a Section of Experimental Peychiatry (under my direction); a Section of Clinical (Psychodynamic) Psychiatry, to be created; a section of Biochemistry headed by Dr. H. Geldenberg; and a section of Internal Medicine unfer Dr. Cohen's direction. 'Uhile there is some theoretical justification for such a development in a large institution, the development here has led to a diapersicn of activities and a lack of adequate supervision of ongoing One activities. high note at the end of this year has been the recommendation by the Board of Directors that the Ford Foundation funds be allocated to relieving the space problems of the Research tervice. Following this recommendation, and after discussion with interested members of the hospital staff, I drew up a basic program for the Research Building. This program was approved by the Research Committee of the Medical Board at its meeting on August 28, 1956, and is now in the hands of the hospital architect. A A. PROGREjs l§*9HGOING PROJECTS l. Electroshock.Evaluation.Proaec : We have completed Electroshock Project # 3 which demonstrated the dependence of the rating of improvement following electroshock on the patient‘s personality; as well as elicited definite measures of language changes which were correlated with improvement. result of these studies, we instituted a "control" study, designed to validate our hypotheses. we are new in the midst of this study, which will continue until spring, 1957. As a believe that we now understand the neurophysiologic, personality and psychologic factors in electroshock therapy. Our data has both prognostic and theoretical significance; and I plan to present a definitive report before the American Psychiatric Association in may,.1957. We presented the language changes in electroshock to the American Psychopathological Association; the EEG changes to the Eastern LEG Society; and will present a report entitled "Relation of Tests of Altered Brain Function we have �92- to Behavioral Change lolloning Electroshock" to the Divisional A.P.A. meeting in November, 1956. Reports of the memory changes, amobarbital test and EEG changes in electroshock have already appeared in press. T? Meanwhile, as part of the resident training program, we have encouraged a senior resident, Dr. Harold Esecover, to undertake a study of the type of psychotherapy which is best suited to different types of electroshock patients. Furthermore, as a consequence of data presented at the American ELG Society in June, I have devoted considerable time to an elucidation of the biochemical changes underlying electroshock. Such reading has led me to elaborate a theory of the relationship of acetylcholine and cholinesterase in blood and spinal fluid to electroshock results. nith the cooperation of Dr. Goldenberg, this study will be added to the ongoing control electroshock study. (a) Thorazine - Insulin: The control study instituted a year ago has continued with dramatic results. To date hS patients have been studied, 22 on Thorazine and 23 on insulin. All were insulin coma condidates. The thorazine group has demonstrated a higher improvement rate, and a lower refusal and complication rate than the insulin patients. we are impressed by this data and plan to complete the study by the end of the year, for presentation to the staff. 2. Drug Evaluation ﬁfudies: (b) Reserpine: See "com. pleted projects." (c) Anectine- Electroshock: Continuing our studies of paralytic agents in electroshock, we utilized a technic for administration of anectine devised by ur. William Karliner of the Attend. ing staff. ’Ue found it most useful and safe and the results prompted us to recommend the adoption of this technic for our unit.‘ This study, undertaken by Dr. Tarachow, has been successful in defining enmivalence in operational terms, i.e., by the tests used to measure A summary of the two years work is being presented to the staff on Octit. ober 7th. 3. émhiyalence Study: In addition to Dr. Tarachow, Dr. H. Korin has beenzactive in this project; and recently, under the resident training program, a senior resident, Dr. Stanley Friedman, has been assigned to the project. h. Commlication Studies: Aided by the grant from the Foundation, Dr. J. Jaffe has devoted this year to developing ways of measuring the verbal interaction between doctor and patient. To do this, he records his interviews with patient before and after periods in which he modifies his attitude to the patient. At one time he says little, later he may re-enforce the patient's positive (or negative) comments. By noting changes in language, rate of speech and in mood, Dr. Jaffe has developed an index of communication change. Kaufmann �-3... present, he is testing the validity of his scoring methods, and plans to apply them to doctor-patient interviews in the near future. At In addition, with Dr. Kahn, 3r; Jaffe has explored the possibility of other technics, as sentence completion tests and the reading of'a standard parab graph under conditions of immediate feed-back as measures of changes in commun- ication patterns. 5. Autonomic Reactivity: In his initial studies, Dr. Blum» berg demonstrated that the class; ification of patients according to their blood pressure response to mecholyl was meaningful for our population. He then applied the test to the patients on the reserpine study, and noted a consistent and persistent lowering of blood pressure 11th an a-.. increase in the mecholyl response Iuring the period of reserpine action. w“. Host significant, however, has been his studies of the electroshock He has studied 100 patients, and established celrelations of their mechgroup. olyl reactivity with age, diagnosis, and therapeutic result. He concluded that the mecholyl responsivity is directly related to age - and that this is the determining factor, more than the primary illness. He is describing his observations in the forthcoming Israel Strauss Volume of the Journals a consequence of these studies, he has recommended, and the Research Committee has approved, a study of better ways of measuring blood pressure; and a collaborative biochemical venture (with Goldenberg) inDC the chanes As . r. in adrenalinenoradrenalin in the blood. 6. Biochemistgy: (a) Steroid Sulfate Coniugates: As indicated earlier, the steroid studies were undertaken because these hormones are known to be implicated both in the physiological response to stress as well as in the sexual processes. Three impartand observations have been made in the Hillside Hospital Laboratory. First, has been noted that the steroids, which are manufactured by the adrenal and it sex glands, are converted in the liver to water-soluble steroid sulfate conjugu ates. Since this is one of the major forms whereby the sex hormones are elim» inated from the body (via urine), the liver evidently plays an important role in maintaining hormonal balance. A second discovery in this area was made by comparin“ male and female rat liver activity. Female rat liver was found to be remarkably active in conjugating the steroids, particularly the male hormnnes. This means that the female animal possess- a regulatory device whereby she maintains her ielaleness by preierentic.lly excreting the male hormone which, incidentally, are present in both senes. s Finally, in the first group of 18 normal human observed that urinary steroid sulfate output is a) so::-linked, being tnice as high in males as b) appears to be low in value for calm people, whoare innately tense, excitable, prone to controls it has been in females, and but rises in subjects anxiety. (b) Psvchotomimetic and szchotherapeutic Dru;s“ : Thesecond preject in the laboratory involves a study of the possible role of hallucinogens in the development of mental disease. It has been hypothesized that indole-like compounds, comparable to LSD, acrenochrome, or a.crenolutine may be formed in vivo as a result of faulty metabolism and give rise to the $3.rmptoms commonly.associated with the psychoses. Initial studies in Our laboratory have failed to detect these alkalw , �.u. oidal products in patient's urine. Ebssibly this is due to a poor choice of patients, since none were actively hallucinating. it of the the most proportion that greater likely appears suSpected alkaloids would be excreted in changed form, and very likely via the feces. r‘his is suggested by metabolic studies which we have carried out to is administered in known quantity. determine shat happens to mescaline when unaccounted The 5% the rest is urine. in unchanged comes about through Only carbon diobe A as of expired course carbon residues might of the portion for. LSD the isotope the drug. in would account not nitrogen for xide, but this hence excretion the of in drug accumulation gut, this indicate studios in Jurope studies For subsequent these reasons our here. seems also feces the likely in However, it will involve isotopically—labelled hallucinogens to determine their ultimate decould more then we intelligently these at our facts disposal, Having fate. termine the excretion of related compounds by psychotics. (c) 92lorpromazine project; Studies on the metabolism of chlorpromazine by psychotics were reported earlier, at which time chlorpromazine, chlorpromazine were derivative alkaloidal and unidentified an chromogen, the purple sulf Xide, demonstrated in urine. A sufficient quantity of the last compound could not be and the project conventional methods, by identification from for urine isolated was held up in April pending receipt of a continuous flow electrophoresis unit. This item has been on order for h months but has not yet come in. 7. Tactile Perception: Following the technics devised by Dr, Bender, Dr. Green and myself, we have, with U.S.P.H.S. support, set up studies of tactile perception using simultaneous threshold electrical stimuli. Patients have been studied before and during electroshock. To date, the data amply demonstrates that the phenom! ena of extinction, displacement and confabulation, noted clinically in childin all elicited readily are cerebral with dysfunction, and organic ren patients induced the organ— with electroshock, Furthermore, threshold levels. at subjects ic cerebral changes exaggerate the perceptual errors in identifiable patterns. This study is continuing and it is planned to present the data before the appropriate neurologic societies. ' 8. Prognostic EngiCatorg g: glectrgshgggg This study, designed by Dr. Karliner to elucidate the relation between presenting symptoms and the results of electroshock therapy, is continuing. Forty-five patients have been studied, and it is anticipated that the results will be determined in the coming weeks. �.5. B. COMPLETED PROJECTS: collaborative study of the urinary steroid pattern changes with electroshock has been discontinued. The initial findings demonstrated a significant alteration in the steroid patterns after electroshock in improved patients. After studying these results, Dr. Hellman of the SKI and I prepared a protocol of experimental drug administration designed to clarify these findings. 1. Sloan Ketterinr Study: The presentation of this protocol to the Research Committee, it was their recommendation that, despite the merits of the research design, it not be approved for this hospital. The chief criticism was one of the risk to the pat. Upon ient of the procedure. these studies could not be meaningfully carried out at the hospital, the program.has been transferred to Creedmcor State Hospital, where the cooperation of the Medical Director and the Commissioner of Mental Hygiene of New York has been assured. As 2. subculture: project has been discontinued following the initial reports of the study group. hour observation of a patient, islaeing prepared The primary study, that of a 2h for the Research Committee by Dr. R. Navarre. The 3. Reserpine Egalyation: The high-dose reserpine evaluation study was completed in harsh. The results demonstrated a limited usefulness of this drug in our population. Hhile it occasionally controlled overactivity, it did not reduce the symptom of anxiety; and did increase existing feelings and states of depression. The results were reported in the April issue of the Journal and summarized for the administrator and staff in memoranda and meetings in April. As a result, reserpine was made part of the hospital formulary, with specific recommendations for its limited use. C . PROJECTS Fulﬁl-ED: 0*.“ 1. Cerebral Reactivity: In the course of our studies cf electroshock, we have been imp pressed by the differences in brain responsivity to electroshock. Some patients show a quick and intense change in behavior and on our tests; while others require more frequent treatments, higher voltages, etc. to induce any change. u developed a series of hypotheses which ascribe the differences in reactivity to (a) biochemical differences in acetylcholine-cholinesterase metabolism; (b) personality differences; and (c) generalized hypo-responsivity to all stresses. For this purpose, we are now elaborating protocols to test these hypotheses. As developed, they will be submitted to appropriate granting agencies for support. we have 2. Autonomic Reactivity: See "Ongoing ProjectS." �3. Digghemistrv: Following the present studies it is planned to continue the studies of bio- chemical changes in mental steroifs sulfate excretion illness along the following lines. end a) Comprehensive survey of urinary its relation to anxiety. b) Circulating steroid sulfate levels in blood and spinal fluid. c) Enzymic and fluorometric evaluation of alkaloids excreted in feces, with particular reference to patients who are hallucinating. Cholinesterase and acetylcholine levels in spinal fluid of patients undergoing electroshock therapy (as part of the electroshock evaluation study). d) D. STAFF CHANGES essential change during this period has been the reorganization of the hospital‘s research activities. As of SepteMber, 1956, the Section of Experimental Psychiatry, which is one of the surviving sections of the Research Service, consists of the following: The Dr. N. Fink D?, - J, Jaffe Dr. R. Kahn Dr. H. Karin Dr. H. Green Research Associate Research Assistant~Psychiatry Sr. Research Assistant-Psychology Research Assistantufsychology Research Assistant-Neurophysiology and a full (Mrs. H. Hosquera). time secretary (Miss Gayle Iankel) and 2/5 - time EEG technician chief addition has been the addition of the EEG technician and the part time appointment of Dr. M. Green. For the present, and until December 1957 As of January somatic the 1, Green ﬁlerapies. Dr. 1956, supervising is 31, he will devote all his time at Hillside to experimental work. The E. FUNDS: for 1956-57 have been received from the U.S.P.H.S. From the National Institute of Mental Health, support for Dre. Kahn and Karin, in the electroshock evaluation study, and for biochemical studies in the relation of alkaloids to mental disease. Also, from the National Institute of Arthritis, funds for the study of steroid sulphates, now used to support one research Grants chemist (Hrs. Ruth Foley). Also, a small grant from the Dazian Foundation supported the summer employment of a chemist; while the Kaufmann Foundation has been supporting the studies of Dr. J. Jaffe. �I are planning to submit an application for support of the studies in cerebral reactivity; while Hrs. Blumberg and Miller are submitting one for their studies in autonomic reactivity. Both reAt present, Dr. H. Green and quests are to go to the U.S.P.H.S. before F. OTHER November 1, 1956. ACTIVITIES l. hedical Library: In mic-1955, the hospital obtaineo the services of a part-time 1110(l0a1 librarian. By the year's end, it was apparent that the acecuate utilization of our library required a full time librarian, anc as of March 1956, miss Rosalind Lazarus was apppointed. I was appointed chairman of the Library Committee, and through our joint efiorts, the medical library was activated. A definitive budget was prepareC and approved; rules for library use established; and more recently, a 2000 volume addition to the library was recommended to bring this library up to the standard as the most complete psychiatric library in the North Shore area. of the Journal of the Hillsidee“ 2. Israel gtreuﬁg_folune S ervice Research* m<.1d3ers o;t of the the By active aith Dr. cooperation HosEital: S. Tarachov 3 the volume was orranized and editec. It is new in the hence of the printer and fill appear in November, 1956. 3 3. Isreal Strauss hemorial Lecture: The appointment of the second lecturer, Dr. Hilliam Halamud, an” the detailed arrangements for the lecture were made by the Committee headed by Dr. Bender, with the active cooperation of members of the Research Service. Research Builcing: Following the recommendation of the Board of Directors, the members of the Research Service were most active in planninf the new structure; describA. The and the for architect. relationships descriptive ing its uses; establishing first blueprints were submitted and after considerable discussion, were returned with corrections. Continued liason with the architect is planned. 5. Resident Training: During the past year, members of the Research Service gave bimonthly seminars on recent advances in psychiatric research. Two special lectures were arranged; and the local Research Conference of the Nassau Heuropsychiatric Society'nas held at Hillside Hospital. Respectfully submitted, Mfﬁgw Fink, M.D. Research Associate (bxperimental Psychiatry) Max �ﬁ— - Methods New Reports .For Evaluating Electroshock Hosﬁpifali W . . thropies, is engaged in a number of investigations into the basic causes and treatment of mental ailments. Dr. Maximilian Fink, research associate at Hillside, said that electroshock actual1y Fan change the way the braln functions, and that these Changes can be observed and measured by electroencePhalography. The change' in the brain also, shows itself in the response to dru es, M s cholo gical testin e and the weakening of unpleasant memories. The Hillside researchers report new and definite methods for measuring the extent of these changes. In the successfully treated electroshock patient, these brain changes enable the person to maintain better control over his emotions and behave more like a normal person. An' important clue to how'to identify patients less likely electric shock therapy affects to benefit from electroshock the human brain has been un- so that they can be treated covered by researchers at Hill- earlier by other methods. side Hospital, Glen Oaks, it The electrOShock developwas announced today. ment was described in the Hillisannual report side Hospital is It expected that this discovery will increase the ability sued todayvto select patients most likely Hillside, a non-profit mental to benefit from electroshock. hospital affiliated with the This development also will help Federation of Jewish Philan‘ ll llIlllllllllllllllllllllllllllllllllllllllllllllllllllll . For Free. 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SP'“*" 8" Pr°°£ ‘ i V ‘ 3 QUARTS—‘l 1.75 0 CASE or 12—4650 . r nolh§§§£§§ZXt°£atlt°2§§§i§ 31;: HEAR-OLD "MITCHELL" MARYLAND RYE patient to benefit more readily from psychotherapy administered during and after the . tcourse of electroshock. .tElectroshock therapy will continue to be used in the treatment of depressions occurring in patients in the 30 -to 60-year age groups, and also in younger schezophrenics showing mainly excitement or stupor as symptoms. In issuing the report, Dr. Joseph s. A. Miller, medical director, also presented the following data about the year’s activities at the hospital. Among 575 patients treated during the year, the average length of hospitalization was 176 days. Of_ these, 32 patients were admittﬂd t0 the Israel Strauss Adolescent Pavilion, a facility for adolescent girls; which was founded in October, 1954. The out-patient service treated 224 patients. ‘ ——~— �. following day- BERNETHY—Elnia 1... on October 30, 1956. wife of the late Richard 3.. beloved mother at Gertrude Tobias and 1Estelie Abcrnethy. ervices Thursday, November lst. 8:30 P. M. at the Clarence F. Simonson Funeral gall-[EL 1119-04 Hillside avenue. Richmond ntermeni‘ Friday. 1]. A. M. Maple Grove Cemetery.lALICCHlO—Raifaele, on October 30. 1956. of 101-28 99 stret, Ozone Park, beloved husband of Marianna, dear father of .Vincent and Florence. dear brother of Carmine. also survived by eight grand— l children. Leposmg at the Cassese .Funeral‘ Home, Inc.. 101-07 101 avenue, Ozone Park. Funeral Saturday, 9:15 A. M. Solemn requiem high mass St. Mary Gate of Heaven aterment St. John’s Cemetery. IHRISTENSEN—Chauncy J., on October 30, 1956, after a long illness, belov‘ed husband of Amelia.‘ devoted father of the late Dorothea C. Herold. loving grandfather of Barbara and Richard Herold. ‘uneral from the Walter B. Cooke Funeral Home. 158-14‘ Northern boulevard. Flushing L. 1. Friday, 3 P. M. nterment Cedar Grove Cemetery. URClo—Lena. on October 28. 1956, of 73-11 Metropolitan avenue. Middle Village. devoted wile of Carl. loving mother oi Salvatore and Joseph. Leposing at the Phillips Funeral Home. 79-02 Metropolitan avenue. Middle Village. Funeral Friday at 10 A. M. Solemu mass of requiem at st. Margaret's R. C. Church at 10:30 A. M. nterment st. John's Cemetery. “NAN—Elizabeth. on October 29. 1956. beloved wife of William. mother oi Lulu Harrington and Mary Mattoe; also survived by two great-grandchildren. teposing at the Walsh Funerar Home. 94-08 118th street. Richmond Hill. Services Friday. 1 P. M. nterment Mount Olivet Cemetery. HEDGE—Catherine V.. of 585 Seneca avenue. Ridgewood. on October 30. 1956.-age 66 years, beloved mother of Walter. Joseph, Madeline, Frances Connell, Mary Jo. (Dolly) Connell. devoted sister of Ellen O'Loughlin, also survived by four grandchildren. ’uneral Saturday. 9 A. M. from Charles Morton Funeral Home. 578 Onderdonk avenue, Ridgewood. Solemn requiem mass St. Brigid’s R. C. Church. 9:30 A. M. e nterment St. John’s Cemetery. lAY—Laurance X, Staff Sgt. U.S.A.F.. suddenly at Carlisle. Mass. on Saturday. October 27, 1956. beloved husband of Patricia A. (nee Joerger). devoted father of Donna Patricia. Laurance and Kevin Gay, dear son of Lorraine and Margaret ,Gay. loving brother of James. Jere. Patricia Papscun. Marguerite Clay. Jeanne-Marie Dalessandro. and the late Lorraine Edwina Gay. uneral from the Gleason Funeral Home. 10-25 150th street. Whitestone. N. Y. on Friday. November 2nd. at 10:30 A. M. Solemn requiem mass st. Luke’s R. C. Church at 11 A. M. utennent United States National Cemetery, Pinelawn. L. I. lATCH—Helen Frances. on October 29. 1956. beloved wife of the late Lewis. devoted mother of Ruth E. ervices at Walter B. Cooke Mineral Home. goaOSrgdena avenue. Brooklyn, Wednesday, ' , . ' , :iterment Walkill Valley Cemetery. Walden. New York. lAVERLY—Joseph. of 60-27 78 avenue. Ridgewood. on October 28. 1956. age 76 years. beloved father of Joseph. Jr.. Henry and Robert Haverly. Catherine Anastasia. Lucy Corrado. Lillian Caverler. Marie Roethel: also survived by 28 grandchildren and nine great-grandchildren. uneral Friday. 9:30 A. M. from Charles Morton Funeral Home. 578 Onderddnk avenue. Ridgewood. Solemn requiem mass. 10 A. M at st. Matthias R. C: Church. nterment St. Charles Cemetery. Pinelawn. Long Island. sum": non Until 5:39 in «m... or I. IL Satori-y llliib‘S—Mai‘ie (nee Gademann). on Octoher 30, 1956. beloved wife of Edward Heiss. devoted mother of Carol Elizabeth. Nancy Edwina and Bruce Edward G. Heiss..deai sister of Frances. of Regen— burg, Germany, loving daughter of Reinhold and Francisca Koob of Munich. Reposing at the Leo F. Kearns Funeral Home. 61-40 Woodhaven boulevard at Dry Harbor road, Rego Park. Funeral Friday, 9:30 A. M. Solemn requiem mass at our Lady of Perpetual Help R. C. Church. Richmond Hill, 10 A. M. Interment St. Charles Cemetery. Please omit ﬂowers. ., .. , HOFFMAN—Augusta E., on October 29, 1956. beloved mother of Fhillip Pflug, dear grandmother of William Pflug, sister of Anna Uphoff and William Warnke. Services. at the Stutzmann Funeral'Home, 224-39 Jamaica avenue. Queens Village, L. I., on Thursday. 8 P. M. Funeral Friday, 1:30 P. M. Interment Lutheran Cemetery. Jun—Wilhelmina M.. on October 30. 1956. Beloved wife of Ernest. dear mother of Jr.. and grandmother of Leona Ergest u . SerVices at the Stutzmann Funeral Home. 224-39 Jamaica avenue. Queens Village. L.‘ 1.. on Thursday. 8:30 PM. Funeral a,_ ~ Friday. 10 AM. BAECH’I‘OLD—Emil Albert.‘on October 30. 1956. beloved husband of Anna '1‘. (nee Pfei er). dear father of Mrs. Ruth H. Will and Elmer A. Baechtold. brother 01 Christian A. and Walter 0. Baechotld. also survived by two grandchildren. Reposing ,at the Floral Park Chapel of Thomas F. Dalton. 29 Atlantic avenue. Religious serVices Thursday. 8 P. M. followed by Masonic services, Eureka Lodge No. 243, F. a. A. M.. Machinists Lodge, F. 8: A. M'., Interment Friday, 2 P. M._ Lutheran Cemetery. . BURNS—Samuel J., of 84 New York avenue. Baldwin. formerly of Brooklyn, on October 29, 1956, son of the late George J: Alice O’Keefe Burns; dear brother of. Belle Burns. Reposing at the Fullerton Funeral Home, 131 Merrick road. Baldwm. Solemn R. C. Eeguiegl Firiiiaiss €5.00C1Arilatopher'l urc r ay : . . 2312 Third Street. KOLLlNS—John S., of East Meadow, L. I.. suddenly, on Monday, October 29 1956 in his 45th Year. beloved husband of Angela. devoted ratherr of Adrienne. dear brother of Mrs. Bertha Bowers, Stanley and Tony Kollins. R'posing at‘ the Catholic Chapel. 2100 3e11more avenue, Bellmore. L. I. Notice of funeral later. Under direction of John J. Mlchalek. ' Interment Maple Grove Memorial Park. KENNEDY—Thomas F.. 116-30 221 street, FUNERAL HOME. BELMORE Cambria Heights, L. .I. Beloved husband of Ethel (nee Huxley), father of Eileen CAROW—Edward, of Malverne. suddenly Devlin. Kathleen Wilson.» Ethel Albert. October 30. 1956. beloved brother of Loretta McGivney. Adeline on Tuesday. of Rayhusband of Jennie. dear father Doyle.. Ethel Casey. Seven grandchildren. ' of Dorothy Koenig and Reposing at the Funeral Home of Lawrence mond. brother survived by four grand" Eldred. also D. Rouse Inc. 191.02 Linden boulevard, children, St. Albans. L. I. Solemn requiem mass. Reposing at the Flinch a. Bruns Funeral .Friday. 10 A.M.. Sacred Heart R.C. Home. 34 Hempstead avenue. Lynbrook. Church. Cambria Heights. L. I. Interment st. John's Cemetery. Middle The family will receive friends between the hours of 3 to 5 P. M. 8: 7:30 to Village. L. I. 10 P. ,M. Masonic services on Thursday. [ALLY—Philip E., on October 27. 156. 8:30 P. M. Religious services on Friday. dea; uncle of William F. Lawkins. 10 A. M. Funeral from the Queens Village Chapel Interment Knolls Memorial Park. Nassau at Thomas M. Quinn a Sons, 214-65 Port Washington. Jamaica. avenue. Queens Village. L. I..‘ on Friday, 9:30 A. M. Solemn requiem FLORENCE—John W.. on October 30. 1956. ﬁes: Olﬁ Lady of Lourdes R. C. Church, of 315 Locust avenue. Unlondale. Beloved husband of Frances. and loving father Interment St. John’s Cemetery. of John W. Jr.. Jeanne and Diane. SurLOMBARDO—Teresa vived by one brother and two sisters. (Rommanelli) , on October 29, 1956, beloved wife of Angelo Reposing at the Martin Funeral Home. 412 Willis avenue. ,Williston Park. Solemn Lombardo, devoted mother of Mary requiem mass at St. Martha R.C. Church Strollo, Anne Carro, Sue Cremona, John Frank and Edmund Lombardo, dear sis- on Friday. 10 A.M. ter of Rafiaela Genovese and Carmela Interment Holy.,Rood Cemetery. Impci'ato, also survived by seven grand~ children. KOLLINS—John S.. of 2312 {rm (1 street. Reposing at the Leo F. Kearns Funeral East Meadow, L.I.. suddenly n MonHome, 103-33 Lefierts boulevard near day, October 29, 1956. in his 45th year. Liberty avenue. Richmond Hil Funeral Beloved husband of Angela. devoted Thursday. 10 A. M. Seryice at the father of Mrs. Sophie Kincinski AdriChristian Pentacostal Church 'of God, enne, dear brother of Mrs. Bertha Bowers. Mrs. Ann Mankowskl. Stanley and Tony 10:30 A. M. Also surviving are two Interment “The Evergreensz” Kalirdohlisllgi en. ran c ._ Regiaosing 1956. 29 BellOctober 2100 BeMAYER—Bertha. on Catholic Chapel. the at loved wrfe of Otto Mayer, active member Bellmore. L. 1. Salem avenue. more ‘ of Ridgewood Heights Maenner Cbor. high requiem mass on Friday Noyember Memorial services at Buss-Avenius Funeral 2 at 11:15 A.M. at St. Rap leis R.C. Home. 63-32 Forest avenue. gewood. Newbrldge road. East Meadow. Church. L. 1.. Wednesday. 8:30 P. Funeral L. I. Thursday, 11 AM. Mt. Calvary Cemetery, Linden. Inger-merit Cremation Fresh Pond. ew ersey. Under direction of John J. Michalek MEYER—George F., on Tuesday. October l BELLMORE FUNERAL HOME 30. 1956. of 111~21 198 street. st. Albana. L. I. Beloved husband of Florence Meyer. 149 w. Stanton of E. and devoted father of Mrs. Florence McCRAI Victoria Combes. grandfather of Dorothy Combes. ,avenueltulaaldwin, on Monday. October 29. SerVices at the Fairchild Chapel, 220-05 1956. beloved wife of Morton C. McHillside avenue. Queens Village on FriGraime; devoted mother of Douglaomnd Kenneth: dear daughter of Eugenie and _day at 8 PM. Victor Fernandez. NIGRl—Lucia. beloved mother of Edmund Reposlng Funeral Brother: Weigand at oi” the ngl‘l Nigrl Furniture House. Home. 24 South Grand avenue, Baldwin. Orstehnydia Mancino: in Italy. Gaetano. Services Wednesday. 8:30 P.M. Elena. Dorotea, Teresna and Nicoletta. Interment Thursday. Milford Cemetery. Reposmg at Robert Giordano Funeral Milford Connecticut. Home. 2346 Pacific street. Brooklyn un-. til Friday, 9:30 A. M. solemn requiem QUAGLIATo—Anita Hill). on October (nee Our of Lady Loretta Church. 29. 1956. of 678 Franklin avenue. Massaf0“: alt/I pequa. L. I. beloved wife of Ferdinando: Interment St. John's Cemetery. devoted mother of Mrs. Lucille Rubusto. oasrﬁtLE—Aiwma. on-October 28, 1956. Mrs. Blanche Burns, Richard, Joseph. Services Wednesday. October Slst. at and Ferdinand Quagliato; dear sister of 8 P. M. at the Clarence F. Simonson Mrs. Rose Brandt. Mrs. Isabelle Snediker Funeral Iﬂome, 119-04 Hillside and William Hill; also: survived h- “-1-“ ‘ ___.__,_______———. - - _ . . . ‘ �Wham”. ”mi”: mashing”. mm”; ' WW W W W wmummwmmmw,w WWatt-bMMuﬁ-mtdw ww.nmmmumwm¢t:wum mammwmm (W)M murmugmmmdmmam wwummawmmm mamam'mmmwmnmu Whuumumwmmu mam “anmmmmthWu-m «mama-ammuuwmmuworbw WW‘OM . manuumnbuwm. ramming-ma. mamammaum.mmmm~p mmmwummww m mummmcmpmwum. 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Wu..m.h¢~mx.mmsu.mmmm H. m) I mum mumamnmumm.m. 396. 3.956. 15) (um mummy. m a. . «Whammwm‘mmnmma.mmm Wpiiﬂ'ﬂgm �,v .7. vie .._.,.._..,-,_ "W ’3"“W". m. .. a":r-x—z var Aﬁv DCK TERA?! or one administered third in electroshock therapy we in previous years the adult patients. For the meet pert, it was prescribed for peuente in the As forties and fifties who electroshock was used manifested depressive symptoms. (21: To a lesser extent, patients) in schisophrenic patients to modify ms- active, essenltin er delusional behavior. the studies the of earlier results of that was in this group pstients It Psychietry were applied and extended. Patients of the Departmnt or W received series a the electroshock psychiatrist by supervising for mmmded encberbital test These included electroencepmlogren, of neurophysiologic tests. for organic brain disease, and pemeptusl tests, tactile. During per week, the tests were both visual and the course of treatmentﬁhieh ms adminstered three times periodically repeated. with clinical Based upon changes "alustiens in these mumplwsiologic tests ceabined psMiatx-ist, the extent «amines; In these instances in which the neuro- by the resident and supervising of electroshock tmmpy was treatment bed been not behavior obtrdned, in alteration for basis physiologie intensively. week and acre occasionally times modified five to per regimes were Ch this basis, the usual com-es of tmmnt m the patients meshing between 6 me lo batsmen 11 and 19 with m percent of the patients received more than 20 of mtients rescind less an incomplete series. Twenty-five treehnen’os .. The number of tmtnnnts tmtmsnts. than 5 treatments, which in each instmee 10% Four and to reference with diswosie therapy results at in chart is condition at time at discharge is seen in chart #9. The original studies relating the alteration in brain function indueed by electroshock to the short term clinical results, were confirmed in this series amounts-sud of and his Fink staff Dr. where study. of patients in a predictive shown #10 and the I that only these patients in when alteration in the electroencephalogram and �#2 mbarbikl taste had bean to warrant the rating of a umber 031‘ reports have mud, had mm D. clung. in behavior sufficient uprated or momma. A: a Insult. of these studies, been presented before nation]. psychiatric societies. much �#3 During 1953 there had been considerable experience at the hospital with of the newer chemotherapeutic agents, chlorprousine and reserpine. It decided to evaluate ohlorpronasim as a potential substitute for insulin tVo was em therapy. The use of chlorpronnzine we suggested by the many reports thst mlcrpronasinc had been successful in schisophrenio psychoses. Also, the specie; report of the Medical Board noting the course of patients disohnrged roam dmonstnted that the poorest long tom results were found in the insulin cone population. For this reason, a control study was instituted. Beginning Septenber, 1955, and continuing until Deomber 31, 1956, :11 patients in 1950 had referred for insulin coma therapy by the supervising psychintriste were divided into tee groups: one group received insulin coma therapy in the established doses received in and second therapy the urge chlorprmsine group newer; over a four month period. Insulin coma therapy was given for a course of 50 comes in most instances. treatedlcsees. The results Chart #llxoﬂects the number of cones in insulin of insulin some therapy is noted in Chart #12 and it is seen that of the 15 much of inproved or recovered. were a four rating given patients ,. In the patients who were given chlorpronesine, dosage ranged betueen daily with a 800 600 of milligrams. to mge Treatment was oontimed for a period or shut four months. In this group 200 and 3600 tailligrsms of patients, who were median unselected except for having been candidates for insulin of the insulin to that were of improvement equivalent the ratings moment, cone population. 01' 21: patients discharged during 1956, one was discharged as riftem miinprored. and much as improved, as em recovered, three as inpmd, some Guptring the complication rates of both treatments, it was noted that prolonged of nine tones and in were insulin resis cmplications reactions ledondary ems, the insulin some patients. Wtansion airfioient to cause fainting and severe demtitis were complications in five of the chlorpronasine group. Agitation �#h and penis, seizures and numbers It refusal of further therapy were seen in muivalent of patients in both groups. was the opinion of the numbers of the Deparhuent of peydtiatry ami Manual the resident physicians, Doétora Robert Shaw, George Gross Mean for this study, that in to insulin coma therapy, chlorpromasine was safer, easier to ldminater, more controllable in its effects, and had fewer aid: effects. It was their recommendation that chlorpmmine therapy would be warranted as the initial and Fred Coleman, who had hem responsible treatment for patients in the younger age group who were suffering with schizophrenic disorders. In such cmditions, they anticipated that chlorpromuino would be most behavior. effective in modifying overactive, as saultive and delusional �#5 cogg sagx rmmr 01' the ﬁfteen patients treated by insulin com therapy, the modification of behavior was inadequate in ﬁve, loading to a be combined with insulin come. nemudntion that. electroshock of these, four patients were suffering fm a schizophrenic disorder and one from a manic-depressive not one of the patients were mach improved illness. In each instance, or recovered after combined mutant. Similarly, there were four patients or the insulin com group who had had metroshock therapy either prior to the insulin com or subsequent to the insulin con moment. Here too, the mtinga or immemnt were in the lower 4 two categories. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Progress and annual reports; research activities (folder title). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-004 Date A point or period of time associated with an event in the lifecycle of the resource 1956 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1954-1965 Relation A related resource The Max Fink Collection Description An account of the resource Perceptual Changes Induced by Drugs and Electroshock - Progress Report; Research Activities - Annual report; Letters; Annual Reports - Department of Experimental Psychiatry; Newspaper clipping, Hospital reports new methods for evaluating electroshock, Long Island Daily Press, 1956-11-31; Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/c825cf38265f35eaf923d1fdede27f5a.pdf 8e37b7104043290b0428aed652df73e2 PDF Text Text Manhasseit Medical Center Hospital 4CZ54@/¢/;ﬁé€rn.2%éui%§C}¢%;lﬂéd536/ c<lgeyi N ]E W Y O R K PEARL A.KLICK ADMINISTRATOR 35K TELEPHONE MANHASSET 7-4000 1: "VINE February 25, 1957 Dear Doctor: Quarterly Medical Staff Meeting of the Manhasset Medical Center Hospital will be held on Thursday, March 7, 1957, at 8:h5 P.M., promptly at THE ALLISON, 1583 Northern Boulevard, almost directly opposite the hospital. The PART faRT 1. Review and analysis of Clinical werk in the Surgical and Medical Sections for the month of December 1956, and the months of January, February 1957 inclusive. 2. A. Surgical Section - Ralph S. Emerson, M.D., Chairman B. Medical Section - 3 ‘§~ “ Lawrence S. Kryle, M.D., Chairman Tissue Committee Report - Howard L. walker, M.D., Chairman SCIENTIFIC PROGRAM - Arnold G. Blumberg, M.D., Chairman "THE TRANQUILIZERS IN PSYCHIATRIC PRACTICE AND THEIR APPLICATION TO GENERAL PRACTICE." Dr. Maximilian Fink Director of Research in Experimental Psychiatry Hillside Hospital, Glen Oaks, N. Y. COLLNTION. Respectfully yours, John G. Connell, M.D. President - Medical Board Telephone number The MA 0 Allison is 7"558’4v at Harry H. Abrahams, M.D. Secretary - Medical Board ~ﬁg ��mmmwm,wmpmmmmmmmm at then obs-mum, w an both» that m. WW WMMwnwmmoma-pmiwhcwnmmw Mx «811.1% unit-(unmask mmmumtmwumatmimummmmm ”demhmlm,wmm mummmmmmmaMaummmmwm m Intact. 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Mﬂty Ml . ummmwmummekam. wmamuamum mammnmammlma. nmlamamwuu W dummiom W whom. manummuumuhmormmmmuméapmrmwm mt: or or induced by mammm: Wmhhymmlﬁuut marmmmw,wuw Wmuhtiam the, response to tin «mm mama to 3551mm m boa umwwmmummmm(mmm Win In, itumuipum thutmlmntarywmmmmsumhm mmmuutnnmmmMmpmummum,mmtm ”munm'mummmw. Gum the the alumna-hip mm «Mmmad anmmmmamlmmummmnmwmw mat of 01 tramway. we may in mum." concurrently, Dr. ~ -- has - w na- 3. am, hu mm and ten W 3.“ 4 aw, under as: 013an have a: Dr. 31am mmbut: museum hero-m tho In Mmmmmmmmm manmummmmmu ammmchunamammmma‘nmsmwmawmm chum. ' 4* m: mmwmxmmmmmmmmmuor . , magma... mmnwmmuwummmmamwm maxim/:31“. hmm,‘§9‘pﬁmunhmdtwmmmm 1957. ﬂammmmnmwmmmmwmmw «Mammal!» It cmluim ”was M. «human ”mom” ﬂammable Warpatumulmmmtham. mm that. as �.5. mm m be the for diseharge to better for the claim-pren— ratings team uino group than for tho um group. H. emclmd that, in to 111M131: new therapy, ehloxpmine m mar, easier to aura contmlhbla in its effects. and had fmr $5.60 attach. We 3190 amended tint n9 evidame had appear“ in the fiftm math: a! the study that. either than” had altered thy basic. schiaaphmie process, nor did my real that either tom of therapy had a greater speciﬁcity far schizophnnie illnesses. At the concluaim of the stndy, the ladies). Biroctur placed in tin for» ulary and a um 13¢th a. its use 13m IV smut: mm”, the maidont staff. W: @10me During this” period Dr. Green has evaluﬂd magma, for its ability to bring out debuts in brain mum. The "port. at his findings mm meant-ad at. the aid-winter muting of the Eutem lasaeiation of Bleetroancephalographam. dials :6. Pro «aka 8: It. is anticipated that tha mark now in prams: in we will continue for the remainder of the year. The aleetmshock evaluation study will be cmletod this spring and the next few months will ha spent in a new agent in ulcetrooncepmlographg, M ' «muting biannual: chained and writing the reports. As indicated in the ongoing pmgraaa not”, a. War of development: have grown out. at these studies and it. is anticipated that than will he immoramd in the mum n— the W aeamh pmgrlm 1. been «aloud by Diffomma 3.3; Wen}. Romam pmtocol has Dr. “a: Franck, which incorporates than pmblem or panama 11 dictating individual rosponsivity to abattoshoek. By entertaining than subject‘ 8 patterns of perception in awfully devolopod arianhatim and visual 1uy tasks, in hope to demonstrate O. “hump batman: those pater-nu and the bov- both havioral under the. special conditim of altered brain funcuun. and the general condition of hospitalisation and plywothompy. 8min a study ream, has bearing on tha problems of the personality upset: of resume to change �«6. in behavior wider stressful maniacs (us in forceful indactrimum, isolatim. atarmtim); a3 well as an «imam at mimic madame fer various W“ chntric therapies. ma mamwwwm me mums“ W w: 2. with elootmahock have led us to Em- theua mute personality factors in the patient and which ing the chain of treatment. a workabla hypothasia. We He of a. hypo— the tharapi‘at affect» am in the process of developing our ideas into antiéipate mdertnking such Mt I stuck by the and of the last report this section has been mdeaigna‘bed an the of Men-1mm thiatry. In addition to the panama]. listed 31am the Department the timofﬂwwtmport,mhmappointad, maparttimbasis, mm at. mm assistant in psychalngy. Dr. Pomek, who has his 111.11. from Kw York: University in 1955, has bean a mum-oh psychologist at tho Haunt Sinai Hospital and the 145mm rmdaum for emu Research for the past six Ha is experienced in both pamanauty and perceptual ”pants in march. years. It. in anticipatod that he will be appoint“ an 2. m1 tin basis on My 131:. A the individual differences in bahavior with specific ambush to study pram Pamela, as on tho perceptual and ation has been made pemmnty sweats has teen «“10de by his and applic- to various foundations for support. mauve April 131:, than will be appeintod to the Duparfanent, a Assistant for linguistic analyses. Under the hem of the E) funds warn and: mm“ x. devised ‘by m: 21:: «:1th Firm.” far a technical assistant he carry Dr. Jane. manna»! 1mm Grant (see out. Senna the language for Renaud: in Psyuhutry has gxmtad Dr. Jute sun or [26,919 plml $5,700 overhud far continuum Fund support for two years in than of the study “Language of the Dyna“ which has been dmlopod during hm past year. �ﬂan MMMMmWVWWrmum. mama-mm «mumspm 1st. 3957 unmmmt. 1959. mmmmmummmmuwudmmwm mararmmawmmmwmam £100»,me mumwmmmxmm-mwmmwmzwnmm ammwmnmmummmsumw,wmmmm InWr,;mawrthammkqu atmmwmammmmmtmummm mummuuwnhumamunumsmmumwwm nmr,nr.ammmmnm mmmmw. inmwmmmmmwhgmwnwnmemum mm‘dWomx-l. kWawﬂmWﬁs dWWWWMMmmmmmammm in m Widv mom 153mm my. autism “MW tho Em MWMWtWamrdmmawvmmmuMmr ﬂammmrmmu»hpoumha1umtorpnmumu an Week mum}: mama. th- smosy or Mom-1 WW, tho Inumhiml Wan of RM and the Imam-Mom}. 0mm! fer WW.‘ hmumnmmmmwwwumwunmmm ma for humﬁml Puma? ”W4. Mm: WM: mum mummnnmmmmmammwnam thrmthMme,uthw-omcmmmmm summeodmga. Womanhmmmmmwupummmma mmwwm.hﬂo,umupmmungmormm mum»“momwmdummotmmrdmwmmmm Chum; �vammamwmmmmmmamw fowlmm. unnaommmwanmnmmum or J. Mt. 1: in Manny mm}. m 3mm mm: Dr. anti-u”. main mum” at. an mum Alma: mu mum means with an W Wthmmuthortmmmmho- W, matmwmmmmumum. of Dr. a mmmamnmsmvm‘mmmm Morn a: thin-Baum: an «an in an «Mama and m... other 19%. numtatmthm; WW: mwmmwmm. DnlgmmbmnmngtMpmbhmof smwwmmmmuhmm 0 Wm wmwammmw‘mﬂammwhmmm. mm puma pm: mm mm is um We Wm mmuwappmuwmmumm. hummmpmaaar with acumen ”mm. Elam during typu of no bu been mpcmm ﬂu «mm-hock maniacal... 69min supports.“ an! that. and In thin new: be mmmwumum. Dr. 3. Fri-mm contributed mun-My to mmamm mm. mmmmmmwwmw. In WWmnodWMme,mmofmmmtmm mm m a may mm“ mm: m- m on at .m u» mam mm: mmmmmmmuw. Manama, WM” W 1913!! a: tum-3mm Mammary: Wm Max Pink. 11.13. �March 1957 Personality Factors in Behavioral Beeponse to Electroshock Therapy Robert L. Kahn, Ph. D. andMax Pink, From New 14. D. the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, York. Aided by grant 14-927 of the National Institute of Mental Health, l“aﬁcional Institutes of Health, APublic Health Service. Presented a the Electroshock Research Association, Chicago, May 1957. �INTRODUCTION The behavioral response of patients receiving electroshock therapy is variable. In previous studies of the factors related to this variability we that patients who showed early, persistent and relatively marked degrees of altered brain function, as measured by the e1ectroencephalogram.and the amobarbital test for brain disease (10), were most likely to show a clinical The (h) (6) which (7). improved rated was present study is an as response investigation of the role of personality in the behavioral reSponse. An explicit hypothesis concerning this relationship has been derived noted from previous studies of the patterns of behavioral change occurring with EST. In an analysis of language changes after electroshock (7), that patients who we reported develop such language patterns as explicit denial of ill- and of and symptoms; displacement qualifitemporal Spatial personal, ness; cation, evasion and minimization are rated as improved. These language patterns are similar to those previously described by Weinstein and Kahn (13) in their studies of neurological patients with cerebral dysfunction. They characteru ized this behavior as the "language of denial" and demonstrated a relationship to personality. In particular they described the characteristics of the "ex€M)On the of these the denial" basis verbal observations, personalit plicit hypothesis was advanced that those patients who most closely approximated this "explicit verbal denial" personality type would be more likely to havioral changes after The purpose EST show the be- which are rated as improved. of the present study, therefore, was to determine: 1) whether personality characteristics related to the behavioral reaponse to electroshock therapy show proved. differentiated; and patients with greater "denial" tendencies are more likely behavioral changes after electroshock therapy which are rated as imp 2) whether to can be �.2POPULATION Sixty-three consecutive patients referred for electroshock therapy were studied. staff, The selection of patients for treatment was made by the psychiatric independent of the judgment of the authors. The patients ranged in age from 20 to 66 with a mean of I47, and included 21 men and 142 women. METHOD Prior to treatment each patient was evaluated according to the following methods : l. Structured EM Interviews: Personality was evaluated in inter- patient' 3 family. At the opening of the interview, the relative was asked to describe, in his own words, the patient's usual interests and attitudes. The relatives were encouraged to talk about any aspect they wished, and the interviewer followed the trend of their talk, rather thm proceeding in a serial fashion. The interviewer asked questions, however, to been 15 obtain information in m described as charspecific areas which have views with members of the acteristic of the "explicit verbal denial" personality,“. The number and withgibrelative varied according to the degree of type of questions required spontaneous production and the infomant' 3 capacity to comprehend and 00mm:- icate. The informant was encouraged to give concrete examples of all state- ments. basic items included the presence and extent of each of the following features: 1) stress verbal symbols such as resolutions, homilies, cliches and The rationalization; 2) are prestige and security conscious, and do not enjoy the intrinsic benefits of health, work, leisure, money and property; 3) regard illness as an imperfection or disgrace, keeping neighbors, and are it a secret from the family and reluctant to seek medical care; troubles and are considered practical persons who )4) "shake off" their advise others; 5) have drive and compulsive energr, and are guilty or uneasy if own much not occupied; 6) are conscientious with a high sense of duty and responsibility; 7) are sensitive . �.3to criticism, regarding it as an attack on their integrity; 8) are proud and avoid help from others; 9) are reserved rather than openly affectionate or emotional; 10) emphasize being correct; 11) are not imaginative or creative; 12) are not seen as dependent by their relatives; 1h) do not have temper outbursts; 15) and are not After the interview, each item if score of 0 was given 1 2 was rated on a 13) do not discuss sex openly; ludic (25). scale of 0, 1 or 2. A the aSpect was noted to a minimal degree; a score of indicated that the characteristic was moderately present; while a score of indicated the definite and marked presence of the pattern. The scores for each item were added and the resultant score is termed the "denial personality score". 2. Clinical Evaluation: Each patient weekly intervals during and evaluation prior to and at following the course of treatment. The clinical was determined by was interviewed the patient's behavior in the few weeks following the end of the course of treatment and was based on the evaluation of the pat- ient's therapist, the therapist's supervising psychiatrist and the supervising psychiatrist in charge of the electroshock treatment unit. Patients were classed into three groups: much improved, moderately improved, or unimproved, criteria outlined previously (6). 3. Language gtggy: In addition to the clinical interviews, following the each patient standardized series of questions determining his attitude was examined with a toward his illness. trouble?" and "If you Two of the questions asked were, “What is youi'mein had one wish, what would you wish for?" The patients were tested before and during treatment and the verbatim responses were analyzed for changes in language according to the method previously described (7). RESULTS The relatives of scores ranged from O h? patients were interviewed. The<ienia1 personality to 25, with a median of 11. For statistical comparison �.14- the patients were divided into two groups. Patients with scores ranging from 11 0 to to 25 were 10 were frm considered the "high denial" group, while those with scores classed as low in denial tendencies. 1. Personality score and clinical response: Patients with high denial personality scores in these family interviews were most likely to be rated as much improved, and patients with low scores, however, the basis, with chance only one case was considered unimproved (Table 30% I). In clinical response rating occurred on a of the patients being regarded as mimproved. I TABLE Relation of Denial Personality Scores to Clinical Response to Electroshock Much Improved Moderately Improved Total Unimproved Personality Score 11 0 - 25 1h 9 1 2h 10 7 9 7 23 21 18 8 it? Total The proved difference in the denial scores between the patients, when compared sigzificant.* Although the much and moderately im- to the unimproved patients is statistically much improved patients have a higher mean score is not significant. 2. Qualitative observations: Although there is a relationship between high denial personality scores and the clinical rating, 30% of patients with than the moderately improved group, this difference low denial scores were also evaluated as showing a marked improvement. While trig/1:119 group of seven patients is a small one , certain common characteristics can be described. Although these subjects lack the competitive security needs of the high denial subjects, they or imaginative capacity or ability to think Si ~K- vb; { {ran-M at 1% level of confidence by show drive, prestige and a similar lack of creative critically of their Mann-Whitney U Test. own or other's �.5relate to the environment primarily by non-verbal forms of commmication. They are described by their families as laughing or crying feelings. They excessively; and as showing anger by muteness, ”go into a shell," ”walk out of the room in a huff,” or by violent tempers with table-pounding, throwing objects or direct physical assault. These patients are "ludic," by Weinstein and Kahn (12) to denote comic, language analysis described in a in clinical interviews term used tragic, or melodramatic behavior.* 1m: previous study (7), the 3. Personality score and Meg -a Applying the technic of i__n_ changes in language were compared with the denial personality scores. Nine patterns of language change, such as explicit denial of illness or symptoms, displacement, qualification, £33. have been described as characteristically occurring after electroshock. ified according to the plicit language As in the previous study, each patient was class- dichotomy of whether or not he showed three or more ex- changes. Patients with high denial personality scores showed a greater number of language changes, than those with low denial personality scores (Table II). The coefficient of correlation between the personality scores and the number of language changes the 1% is .71, significant + at better than level of confidence. TABLE II Relation of Denial Personality Scores to Clinical Language Changes During Treatment Number Langggge Changes 0 - 2 3 or more Personality Scores 11 .- 25 (20) 8 12 - (20) 17 3 25 15 o 10 Total This term was taken from Piaget who applied behavior of young children (8). *- it to the play and imitative �h. Illustrative Cases: Case 1. High Denial Personality Score: A 61-yearbold housewife was admitted to the hospital with a 15 history of insomnia, abdominal pain and fear of cancer. On admission she was depressed, retarded, and seclusive, evincing little interest in her month surroundings, and wandering aimlessly about the ward. The patient reaponsible person with and was unable home. her husband as a conscientious, dependable, integrity. She had no hobbies, outside interests, was described by much to relax. She was ”mortally As a consequence, she busied herself with chores at afraid" of doctors, minimized her illnesses and con- cealed ailments, even from her husband. Very restrained, she openly showed no affection or emotion, never discussed sex and rarely lost her temper. She had "a long memory for little things if she felt that she was wronged," a ”streak of stubborness," and would "just as soon hold another person responsible for her mistakes." She was proud and would ”rather go without food" than borrow or take money from others. According to the denial criteria, her score After 20 electroshock treatments, she was 20. became euphoric, took an interest in her personal appearance and participated in hospital activities. Her doc"model" ”while her who, a reluctant to discuss her personal patient toi/called feelings, asserted that she had no difficulties at hue-'had home, a wonderful band.uho was very good to her, considered herself lucky and eagerly anticipated her discharge.” Case She was discharged with a 2. A Low rating of "much improved." Denial Personality Score: hl-year-old housewife was admitted to the hospital with a two year history of depression following the birth of her fourth child. She cried frequently, lost interest in social activities, found it increasingly difficult to take care of her baby and had suicidal thoughts. On admission the patient �was' noted to pay little attention showed psychomotor The whom He it patient retardation and was was described by was not easy to her personal appearance, cried readily, circumstantial in speech. her husband as a "negative personality” with to get along because she was opinionated and argumentative. regarded her as "completely impractical, with no common sense." She was a poor housekeeper, constantly demanding help from other people, although not the kind of person who would put herself out for others. An excessively talkative person, she liked to engage in long, intellectual, pretentious conversations. When angry, however, she would become either completely mute, or "very nasty, just don't know any better.” Although considered a “cold" person, able to talk freely about sex. She frequently complained of physical implying you she was ailments and went to physicians readily. She was ”naive" and "unrealistic," believing, for example, that she had a flair for writing although others con- sidered her amateurish. Her personality score was rated as h. patient received eighteen electroshock treatments, which were terminated at her own insistence because she was too frightened to take any more. At the time of her discharge her doctor noted her as "quite depressed,” but The felt that hospital. it was doubtful that she could benefit from further treatment She was discharged with at the the recommendation for continued psychother- apy. DISCUSSION The structured family interview was designed to test the specific hypo- thesis derived from earlier observations that patients with the "explicit verbal denial” personality are most likely to Show both the language and behavioral changes to electroshock therapy which are rated as the examiner. The much improved by data supports this hypothesis and is also consistent with �the theory of the mode of action of electroshock therapy advanced by Weinstein, that “....the therapeutic efficacy of electroconvulsive therapy....derives from the production of a state of brain function in which the mechanism of denial is facilitated in characterologically Linn and Kahn in 1952 (9). They suggest diaposed individuals." The degree of explicit verbal denial is, however, only one personality aspect affecting the behavioral response to treatment. 0n the basis of the present data and methods of analysis a broader view of personality patterns in relation to improvement with as clinically EST is now possible. improved are characterized by such Those patients who are rated features as: l) non-empathic - unable to think critically or sensitively about the needs,feelings, or - commun- ications of others; 2) non-introspective - - unable to think critically about their own feelings or needs; unable to achieve insight even with the collaboration of others in a psychotherapeutic relationship; 3) rely heavily on nonverbal communication - - even tial when they are talkative there is little referenp communication, the words being cliched, stereotyped, or representative of feelings and emotions rather than transmitters of information and h) highly conventional - - without imaginative or creative capacity, and with few resources to deal with stressful or With re8pond new this pattern as the situations. common background, two classes of patients who to treatment can be defined: a) the driving, conscientious, independent, successful, emotionally-controlled person who can be characterized as the ”explicit verbal denial” personality type; b) the chronically inadequate, affectd::;;;&rfrom and ively labile ludic, dependent person, an impoverished socio- cultural background. While both types are rated as improved in their short tenm response to electroshock, preliminary folloWhup observations indicate that the "explicit verbal denial" personality type clinical response, while the Indie group is more likely to sustain the is likely to relapse quickly. �Consistent with our previous studies we have found that altered brain fun- ction is a necessary condition for behavioral change with electroshock therapy. The kinds of behavioral change shown with altered brain function, however, vary markedly in different patients. ment of symptoms and are states, become withdrawn, Some Show mood rated as improved. Others develop paranoid agitated or show additional somatic or are rated as unimproved. In this study in those cases we who were memory complaints, and here stressed the personality factors whose behavioral reSponse was considered the patients changes and denial or diSplace- rated as improved. we have not rated as only moderately improved or unimproved. If the basic hypothesis is correct, we should also find a relationship between personality and the behavioral response in patients who are rated as unimproved. Present information in this regard is minimal, as this problem has not'been approached with a specific hypothesis. raise questions concerning the relation of personality to type of mental illness and choice of therapy. Clinical observations support These observations the concept of a characteristic predepressed personality. Abraham (I) noted that states of depression occurred in obsessional persons. Arnot ‘2) describes depressions as being overly conscientious and perfectionistic. Hamilton and (5), reporting various aspects of the personality in involutional depression, include such features as "followed a rigid pattern of behavior....displayed a lack of imagination....narrow range of interests....thorough, cone Mann scientious, meticulous devotion to duty....lack of feeling for point of view of others....hard, uncompromising drivers....oversensitive....reserved.“ Cohen, et a1 (3) in an intensive study of manic-depressive psychosis, reported their patients as being highly prestige-conscious; little concerned with prdblems of interpersonal relatedness; stereotyped; conventional; having for communicative interchange; and unaware of little capacity other persons' feelings toward �.10himself or of his feelings toward others. They emphasized the patients' inability to communicate verbally and suggested that the therapeutic relationship should be in nandverbal terms rather than emphasizing the intellectual contents of the exchange. These studies of the personality background of depression show a that is pattern similar to those personality asPects which have been described as the "explicit verbal denial" personality. The factor of personality could thus most explain the fact that depression is the condition which responds best to electroshock treatment. The same personality factors which to a depressive reaction are those which forms of therapy. These factors enable make him him make a person susceptible responsive to noneverbal to respond, under the conditions of altered brain function, with those language and other behavioral changes which are evaluated as improved. Thus, the same stereotypy, conventionality, perfectionism, and prestige-consciousness, which produce a catastrophic response in the individual faced by the loss of a partner, job, business, or loved one permit the development of denial, minimization and displacement under the conditions of altered brain function and are deemed ”improved” by the family and the therapist. �SUMMARY AND CONCLUSIONS 1. Personality factors in 63 consecutive patients referred for electro- shock therapy were studied by means of a structured family interview. 2. The 3. The which results that aSpects of personality can be differentiated are significantly related to the response to treatment. show basic personality pattern of the patients who reSpond best can be characterized as a) non-empathic, b) non-introspective, c) communicate non- verbally, and d) highly conventional and stereotyped, with or creative capacity. h. 'Within the context of this of improved patients. One group is common little imaginative core, there are two main subdivisions comparable to the ”explicit verbal denial" personality, showingiﬁzch features as drive, conscientiousness, independence and emotional control. The other group consists of persons apt to be chron- ically inadequate and dependent, coming from deprived socio-cultural back- grounds, who are affectively 5. labile and ludic. relationship between these personality patterns and descriptions of the personality of depressed persons is noted. The same personality factors The which contribute to a depressive reaction, contribute to a behavioral change under the conditions of altered brain function following electroshock therapy which is evaluated as improvement. �~12REFEEENCES 1. Abraham, K.: Selected Papers Press Ltd., 1919. Amot, on Psychoanalysis. London: The Hogarth Predepressed Personality, A.M.A. Arch. Neural. Chiato, L6: 617-618, 1956. The 12.: & Psy- 3., Baker, G., Cohen, R. A., From—Reichmam, F. and Weigert, E. V.: In Intensive Study of Twelve Cases of Manic-Depressive Psychosis, Psychiat., 1.1: 103-137, 1951. Cohen, M. Pink, and Kahn, R. L.: Quantitative Studies of Slow Wave Activity Following Electroshock, EEG Clin. Neurophysiol., Q: 158, 1956. M. Hamilton, D. M. and Mann, W. A.: The Hospital Treatment of Involutional Psychoses, in Depression (Hock, P. and Zubin, J. , eds.) , New York: Grune & Stratton, 199-209, 1952. L., Fink, M. and Weinstein, E. A.: Relation of Amobarbital Test to Clinical Improvement in Electroshock, 11.14.11. Arch. Neurol. & Psydliato, 16-: 23-29, 1956. Kahn, R. 7. Kahn, R. L. and Fink, 14.: Changes in Language During Electroshock Therapy, in Psychopatholog of Commication (Hock, P. and Zubin, J. , Eds.) in press. ‘ 8. Piaget, J.: Play, Dreams and Imitation in Childhood. New York: W. W. 9. Weimtein, E. 1., Linn, L. and Kahn, R. L.: Psychosis During Electroshock Therapy: Its Relation to the Theory of Shock Therapy, Am. J. PSYChiato’ 3:99.: 22.26, 1952. 10. Weinstein, E. A., Kahn, R. L., Sugaman, L. A. and Linn, 1a.: Diagnostic Use of Amobarbital Sodium ("Anwtal Sodium") in Organic Brain Dis- ease, ll. Weinstein, Am. J. Psychiat., 113: 889-891;, 1953. E. A. and Kahn, R. L.: Personality Factors in Denial of & A.M.A. Arch. Neural. Psychiat., 92: 355-367, 1953. ness, Ill- Weinstein, E. A., Kahn, R. L. and Sugarman, L. A.: Ludic Behavior in Patients with Brain Disease, J. Hillside Hosp. , 2: 98-106, 1951;. 13. Weinstein, E. A. and Kahn, R. L.: Denial of Illness: Symbolic and Physiological Aspects. Springfield, 111.: Charles C. Thomas, 1955. �April 1, 1957. MEMORANDUM TO: Medical Affairs Committee FOR: Dr. Joseph S. A. Miller FROM: Department of Experimental Psychiatry SUBJECT: 1957. 1956 to April 1, September of Departmental Activities, Report Experimental of the Department of the of activities following report since the period covering of’Dr. Miller, the submitted request at Psychiatry is The September 1956. A. Progress in Ongoing Projects: the evaluate The signifito control study Evaluation: 1. Electroshock be com1956, will on April 1, instituted electroshock therapy, cant elements in been has been have studied. It 1957. Seventy patients pleted by the end of’May the electrointo insights have we and gained significant successful a most group, made 1955-56, in observation, the we original verified shock process. First, dethe is electroshock therapy behavior in in change that the prerequisite for function. brain in and sustained alteration degree velopment of a significant Under the conditions of altered brain function, however, patients respond in electroshock is follows that the improvement In some patients, various ways. the that was opinion our It disappears. rapidly while in others, it sustained, observations. these determinant in instrumental the was patient's personality in the of patients the personality studied have intensively we For this reason standard interview developed tests, this last group. By applying specially have we number of questionnaire tests, and a modifying psychological tests, and of type between personality the number of relationships determined a behavioral the we At predicting are time, the present behavioral response. and during our predictions electroshock to therapy, the of patients response As a result chance. than better been have months significantly the past few include to personality extend study our to we planning are of these observations, G). Section (see results psychotherapy in factors changes the been has perceptual of patients Our second interest in this group to deable have been we control of a By group, virtue induced by electroshock. and those treatment the to related which are changes termine those perceptual im— been have we In these observations, which are related to practice effects. and their the of the patients personality close interrelation.bf the pressed by two so behavior of is The these of aspects interrelation perceptual processes. in differences individual of undertake study a decided have to we close, that under the behavior eventual to such differences and to relate hope perception 0). Section (see function brain of altered special conditions Our which electroshock therapy of concept a to have led develop us studies Electrotreatment unit. of this management the in has been of significant help which function brain in induces changes treatment. It shock is a non-specific Under these two months. than less of usually time, persist for varying lengths depending environment different in ways to his the responds patient conditions, his he to better 'With relates certain a personality, upon his personality. �-2The and better that he relates to to other his patients. family, therapist, other people the less reason is there-for him to become tense, anxious or 6nce the feeling of well-being is set into motion, it is sustained depressed. by the patient's better ability to function with others. Electroshock therapy is not a specific treatment for a specific fbrm of mental illness. 2. Biochemical Changes in Electroshock: In the course of these studies of electroshock, we noted that other investigators had reported that there were and the one report fluid after in trauma, in Spinal changes enzymes specific noted similar changes after electroshock. Dr. Goldenberg and I undertook a study of these enzymes in order to verify the previous reports and to clarify our own picture of the electroshock process. To date, we have collected 30 spinal fluids. I anticipate that this phase of the work will continue until the end of 1957. 3. Communication Studies: Our interest in communication problems has led to two types of studies. In one, Dr. J. Jaffe has developed a technique for the analysis of recorded interviews which provides us with an objective index of change in behavior. Support for this phase of the work has been obtained from the Foundations' Fund for Research in Psychiatry. At present, he is analyzing the recordings of interviews with electroshock patients made earlier in the year, and his findings are correlating very well with the clinical results. we antiand the in of language changes to an technique analysis this applying cipate behavior that occur in ps;chotherapeutic interviews. analysis of the structured amytal test intero views according to changes in syntax and content. The original findings of this study were presented to the AmeriCan Psychopathological Association in June. Since then, all our amytal test interviews are being analyzed in like fashion and the original findings have been verified and amplified. ”e have come to understand that the language of our patients tells us readily whether or not changes have occurred in brain function and in behavior. Furthermore, correlations between the personality evaluations and the language changes have shown a direct relationship between high degree language changes and certain personwith other personality types. and changes minimal-to-no language types; ality Language is thus a recordable facet of behavior and we are ODtlmiStiC that a combination of the language analyses developed by Drs. Jaffe and Kahn would be a meaningful index of changes in behavior applicable to any form of psychiatric therapy, including psychotherapy. h. Egrebral Reactivity: As described in the previous report, our interest in the question of individual variability in cerebral reactivity has been stimulated by our electroshock studies. One part of this study is the A second is the study of the biochemical in changes fluid. of spinal study rate of development of electroencephalographic change induced by electroshock. Dr. Green has begun this phase of the work and since September has surveyed all EEG basic of their by records, and their an electroshock analysis our patients been has Mcgimide to the cerebral to Also, response hyperventilation. reSponse A second study is a language assessed and this phase of the work completed (see Section B). Beginning in May, the admissions new hOSpital the to that will screen is laboratory anticipated it and that various activation procedures will be tested, so that the definitive study can be undertaken in the Fall. Concurrently, Dr. Green has assessed the relationship between the electroshock seizure threshhold and cranial resistance as factors influencing the development of electroencephalographic abnormality. This study is in progress. �.3This study, under the direction of Dr. Sidney TaraNew York have and been before the the observations continued has presented chow, Neurological Society in January. The observations have been summarized in a reand A.M.A. Archives of which Neurology the in Psychiatry. will shortly appear port S. B. Ambivalence: Completed Projects: 1. Chlorpromazine-Insulin Coma: Control Study: An interim report on the results of this control study was submitted to the Research Committee of the Medical Board on January 31, 1957. In this study, 59 patients referred for insulin coma were divided into two groups - one-half receiving insulin coma and the other half receiving chlorpromazine therapy. It was our conclusion that chlorpromazine is as effective in modifying psychotic behavior patterns as insulin coma therapy. There was a tendency for the discharge ratings to be better for the chlorpromazine ,we to concluded insulin in comparison coma the than for insulin that, group. group coma therapy, chlorpromazine was safer, easier to administer, more controllable in had Tb evidence concluded had no also and that fewer side effects. apits effects, peared in the fifteen months of the study that either therapy had altered the basic schizophrenic process, nor did we feel that either form of therapy had a greater specificity for schizophrenic illnesses. At the conclusion of the study, the Medical Director placed chlorpromazine in the formulary and permitted its use by the Resident staff. Insulin Coma 2. Megimide Evaluation: During this period, Dr. Green has evaluated a new agent in electroencephalography, megimide, for its ability to bring out defects in brain function. The report of his findings Twere presented at the midwinter meeting of the Eastern Association of Electroencephalographers. 0. Projected Studies It is . 1957-58: in progress in the Department will The electroshock evaluation study will be completed this Spring and the next few months will be spent in correlating the information obtained and writing the reports. As indicated in the ongoing and have of studies these out number of developments grown it a progress notes, is anticipated that these will be incorporated in the_active research program. anticipated that the work continue for the remainder of the year. now A Behavioral Reapgggg: protocol has been 1. £ndividual_Differences in developed by Dr. Max Pollack, which incorporates the problem of personality affecting individual responsivity to electroshock. By determining the subject's patterns of perception in specially developed orientation and visual tasks, we hope to demonstrate a relationship between these patterns and the behavioral response, both under the special condition of altered brain function, and the general condition of hospitalization and psychotherapy. Such a study has bearing on the problems of the personality aspects of resistance to change in behavior under stressful conditions (as in forceful indoctrination, isolation, starvation); as well as the definition of suitable candidates for various psychiatric therapies. 2. Personality Factors in Doctor and Patient Affecting Choice of Thera : Our experiences with electroshock have led us to a unmber of hypotheses which relate personality factors in the patient and the therapist affecting the choice of treatment. We are in the process of developing our ideas into a workable hypothesis. We anticipate undertaking such a study by the end of the year. �D. Changes in rersonnelz- Since the last re\ort, this section has been redesignated as the Department the of time the at the to personnel In addition listed of Experimental Psychiatry. Max Research Dr. as Pollack, a have on we part-time basis, appointed, last report, New York from who University has his_Ph.D. Dr. Pollack, Assistant in Psychology. and mount the Sinai Hospital the at research been has psychologist a in 1955, He is experienced the six for Research Child past years. Ittleson Foundation for he that is anticipated research. in and It perceptual aspects in both personality A the indito study July on program basis a full-time be on lst. appointed will and the on perceptual personemphasis with behavior specific vidual differences in made various been has to and him been application by developed ality aspects has foundations for support. Technical a the be to Department, appointed will there Effective April let, FFRP (see Section Grant Under the of terms the analyses. Assistant for linguistic E) funds were made available for a technical assistant to carry out the language measurements devised by Dr. Jaffe. E. Funds: Foundations' Fund for Research in Psychiatry has granted Dr. Jaffe continuation overhead for h5,700 a26,000 of sum plus two the in years support for the been has developed during which past year. Dyad" the of "Languahe the of study FFRP The Kaufmann Foundation. grant will exthe This work had been supported by tend from April 1, 1957 to March 31, 1959. Health Mental fbr of National made Institute the been to have Applications subthe Green. Dr. protocol Also, work by undertaken of support for the program of Division and Development Research the to been has sent Pollack mitted by Dr. FoundaMalina and the to Army, States United the of the Surgeon-General's Office The tion. F. Publications and rresentations: In November, a summary of our studies on electroshock was presented at the Montreal a in Association in report American the Psychiatric of Meeting Divisional FollowChange Behavioral to Function Brain Altered entitled "Relation of Tests of "Electroencephalothe Green Dr. report December, presented Electroshock". In ing Electroenceh of Association Eastern the Negimide" at of Lffects and Clinical graphic studies during the of electroencephalographic In a summary February phalographers. Differences in "Individual entitled a two in was report presented the past years EEG Besponsivity" before the Metropolitan EEG Society. The Department has submitted a number of reports to various societies for the the at for been have presentation accepted Summer Papers and meetings. Spring the Psychiatry, of Biological Society the Research Association, Electroshock International Congress of Psychology and the International Congress for Psychiatry. American the Psysymposia at in to been have invited participate In addition, we These meetings. for Psychiatry International Congress and chiatric Association Department of this the experiences considerable detail summarize in reports will and to electroshock to with regard and two one-half specific the years, past over methods of the language anato have we present an opportunity also will drugs. to as some of our speculations well as presenting Dr. as devised by Jaffe, lysis the role and mode of action of the newer drug therapies in psychiatry. �G. Educationi_ Various members of this Department are continuing their education by formal courses. Dr. H. Korin has been enrolled in courses at the Graduate School of New York University with specific emphasis on statistics. Dr. J. Jaffe is completing the formal training requirements at the William Alanson White Institute of Psychoanalysis. Dr. Robert L. Kahn has been accepted for training in psychoanalysis at the William Alanson White Institute. H. Other Activities: 1. Israel Strauss November 1953. and Members Volume: The Israel Strauss Volume appeared in of this Department were active in the development fulfillment of that volume. 2. Resident Training: Since September 1956, two Residents have worked H. Esecover has been studying the problem of Dr. the in Department. actively psychotherapy with electroshock patients. In this study he has been supervised He made. has have been number conclusions and of a members the Deiartment of by demonstrated that patients differ considerably during the electroshock process and that no single type of psychotherapy is meaningful. Certain supportive and He is now in the process of have value. definite may approaches interpretive describing his observations. Dr. S. Friedman has contributed considerably to the ambivalence study. this work he was supervised by Dr. Tarachow. In During the period September to February, members of the Department participated in a weekly lecture series for the Resident staff on the subjects of research methodology and newer trends in psychiatry. Respectfully submitted, Max MFzgw Department of Experimental l’sychiatry _ ﬂillside Hospital Glen Oaks, New York Fink, M.D . �HILLSIDE HOSPITAL FOR PSYCHIATRIC TREATMENT. TRAINING AND RESEARCH JOSEPH S. A. MILLER, 75-59 263m: M. D. STREET. GLEN OAKS. NEw YORK FIELD STONE Medical Director LEON $7500 Lowwsrm Honorary Chairman Board of Directors SIMON KWALWASSER, M. D. ROY FOSTER Assoc. Medical Director Chairman Board Of Directors MAURICE BACHRACE Administrator E. COLEMAN President ALVIN Dear Sir : basis for the discussion of the research activities at the meeting of the Medical Affairs Committee on Monday, April 8th, I am herewith enclosing the following memoranda= As a 1. Report of Dr. Fink for the Department of Experimental Psychiatry. 2. Research activities in the Department of Biochemistry, by Dr. Harry Goldenberg. 3. Research in the Department of Medicine, by Dr. Arnold G. Blumberg Aside from the regular Medical Board members of the Medical Affairs Coxmnittee, there will also be present Dr. H. L. Rachlin, Chairman of the Research Comittee of the Medical Board and Dr. Max Fink, Director of the Department of Experimental t’sychia’cry. Yours sincerely, f4,WIM, Joseph S.A.Miller, M.D. JSJALI: 11b Medical Director encl. AN AFFILIATE OF FEDERATION OF JEWISH PHILANTHROPIES OF NEW YORK �April 1, 1957. MEMORANDUM TO: Medical Affairs Committee FOR: Dr. Joseph S. A. Miller FROM: Department of Experimental Psychiatry SUBJECT: Report of Departmental Activities, September 1956 to April 1, 1957. Experimental of the Department of the activities of following report since the period ofHDr. covering Miller, the request Psychiatry is submitted at The September 1956. A. Proggess in Ongoing Projects: the evaluate The signifito control study Evaluation: 1. Electroshock be com1956, will on April 1, instituted electroshock therapy, cant elements in been has studied. been have It pleted by the end ofTMay 1957. Seventy patients the electrointo insights have we and significant gained a most successful group, made 1955-56, in observation, the we original verified shock process. First, the deis electroshock therapy behavior in in change that the prerequisite for function. brain in and sustained alteration velopment of a significant degree Under the conditions of altered brain function, however, patients respond in electroshock is follows that improvement the In some patients, various ways. that the was opinion our It disappears. rapidly while in others, it sustained, observations. these in determinant instrumental the was patient's personality in the of patients the personality For this reason we have studied intensively standard interview developed tests, this last group. By applying specially have we number of questionnaire tests, a and modifying psychological tests, and of type between personality the number of relationships determined a behavioral the we predicting are At the present time, behavioral response. and during our predictions electroshock therapy, to reSponse of the patients As a result chance. than better been have significantly the past few months include to personality extend study our to we planning are of these Observations, G). Section (see results factors in psychotherapy changes the been perceptual has of patients Our second interest in this group deto able been have we control a group, induced by electroshock. By virtue of and those treatment the to which related are termine those perceptual changes imbeen have we In these observations, which are related to practice effects. and their the of patients the personality interrelation.of close the pressed by so behavior two is of The of these aspects interrelation perceptual processes. in differences individual of undertake study a decided to close, that we have under the behavior eventual to such differences and to relate hope perception G). Section (see function brain special conditions of altered which electroshock therapy of a concept to develop have led us Our studies Electrotreatment unit. this of management the in has been of significant help which function brain in changes induces shock is a non-specific treatment. It Under these two months. than less of usually time, persist for varying lengths depending environment different ways in his to responds the patient conditions, his to he better relates With certain a personality, upon his personality. �-2— family, his therapist, and to other patients. The better that he relates to other people, the less reason is there for him to become tense, anxious or depressed. Once the feeling of well-being is set into motion, it is sustained by the patient's better ability to function with others. Electroshock therapy is not a specific treatment for a specific form of mental illness. 2. Biochemical Changes in Electroshock: In the course of these studies of electroshock, we noted that other investigators had reported that there were Specific changes in enzymes in the spinal fluid after trauma, and one report noted similar changes after electroshock. Dr. Goldenberg and I undertook a study of these enzymes in order to verify the previous reports and to clarify our own picture of the electroshock process. To date, we have collected 30 spinal fluids. I anticipate that this phase of the work will continue until the end of 1957. Communication Studies: interest in communication problems has led to two types of studies. Tn one, Dr. J. Jaffe has developed a technique for the analysis of recorded interviews which provides us with an objective index of change in behavior. Support for this phase of the work has been obtained from the Foundations' Fund for Research in Psychiatry. At present, he is analyzing 3. Our the recordings of interviews with electroshock patients made earlier in the year, and his findings are correlating very well with the clinical results. we antiand the in of language changes to an technique analysis this applying cipate behavior that occur in pa chotherapeutic interviews. analysis of the structured amytal test interviews according to changes in syntax and content. The original findings of this study were presented to the American Psychopathological Association in June. Since then, all our amytal test interviews are being analyzed in like fashion and the original findings have been verified and amplified. We have come to understand that the language of our patients tells us readily whether or not changes have occurred in brain function and in behavior. Furthermore, correlations between the personality evaluations and the language changes have shown a direct relationship between high degree language changes and certain personality types; and minimalvto-no language changes with other personality types. Language is thus a recordable facet of behavior and we are optimistic that a combination of the language analyses developed by Drs. Jaffe and Iahn would be a meaningful index of changes in behavior applicable to any form of psychiatric therapy, including psychotherapy. h. Egrebral Reactivity: As described in the previous report, our interest in the question of individual variability in cerebral reactivity has been stimulated by our electroshock studies. One part of this study is the A second is the study of the biochemical in of changes spinal fluid. study rate of development of electroencephalographic change induced by electroshock. Dr. Green has begun this phase of the work and since September has surveyed all our electroshock patients by an analysis of their basic EEG records, and their reSponse to hyperventilation. Also, the cerebral response to Mcgimide has been assessed and this phase of the work completed (see Section B). Beginning in May, is anticipated that the laboratory will screen new admissions to the hospital it and that various activation procedures will be tested, so that the definitive study can be undertaken in the Fall. A second study is a language Concurrently, Dr. Green has assessed the relationship between the electroshock seizure threshhold and cranial resistance as factors influencing the development of electroencephalographic abnormality. This study is in progress. �.3’ 5. Ambivalence: This study, under the direction of Dr. Sidney TaraNew York have before been and the the observations presented chow, has continued Neurological Society in January. The observations have been summarized in a report which will appear shortly in the A.M.A. Archives of Neurology and Psychiatry. B. Completed Progects: 1. Chlorpromazine-Insulin Coma: Control Study: An interim report on the results of this control study was submitted to the Research Committee of the Medical Board on January 31, 1957. In this study, 59 patients referred for insulin coma were divided into two groups - one-half receiving insulin coma and the other half receiving chlorpromazine therapy. It was our conclusion that chlorpromazine is as effective in modifying psychotic behavior patterns as insulin coma therapy. There was a tendency for the discharge ratings to be better fer the chlorprcmazine we concluded that, in comparison to insulin coma the than for insulin group. group coma therapy, chlorpromazine was safer, easier to administer, more controllable in had evidence concluded had no ‘b that also fewer and side apeffects. its effects, peared in the fifteen months of the study that either therapy had altered the basic schizophrenic process, nor did we feel that either form of therapy had a greater specificity for schizophrenic illnesses. At the conclusion of the study, the Medical Director placed chlorpromazine in the formulary and permitted its use by the Resident staff. Insulin Coma 2. Megimide Evaluation: During this period, Dr. Green has evaluated a new agent in electroencephalography, megimide, for its ability to bring out demidTJere the The of his findinas at presented function. brain in report fects winter meeting of the Eastern.Association of Electroencephalographers. C. Projected Studies 7 l9§7~§8: the work now in the in Department will that progress anticipated is It continue for the remainder of the year. The electroshock evaluation study will be completed this Spring and the next few months will be spent in correlating the information obtained and writing the reports. As indicated in the ongoing and have of studies these out number of developments grown it a progress notes, is anticipated that these will be incorporated in the active research program. A i“Response: Behavioral protocol has been 1. lgdividual Differences in IVia}: Dr. Pollack, which incorporates the problem of personality affectdeveloped by ing individual responsivity to electroshock. By determining the subject's patterns of perception in specially developed orientation and visual tasks, we hOpe to demonstrate a relationship between these patterns and the behavioral response, both under the special condition of altered brain function, and the general condition of hospitalization and psychotherapy. Such a study has bearing on the problems of the personality aspects of resistance to change in behavior under stressful conditions (as in forceful indoctrination, isolation, starvation); as well as the definition of suitable candidates for various psychiatric therapies. 2. Personality Factors in Doctor and Patient Affecting Choice of Therapy: Our experiences with electroshock have led us to a number of hypotheses which relate personality factors in the patient and the therapist affecting the choice of treatment. We are in the process of developing our ideas into a workable hypothesis. We anticipate undertaking such a study by the end of the year. 17 , 914.4 f 3 f 1 b Va. 1,5 _. �D. Changes in Fersonnel: the Department been as has redesignated section this Since the last re ort, the time of the at listed the personnel to In addition of Experimental Psychiatry. Max Research as Dr. Pollack, a basis, last report, we have appointed, on part-time New York University from Ph.D. who has Dr. Pollack, his Assistant in Psychologr. and the mount Sinai Hospital the at in 1955, has been a research psychologist He is experienced six the Research for past years. Ittleson Foundation for Child he that anticipated is It in both personality and perceptual aspects in research. A program to study the indiJuly on basis lst. on the perceptual and personwill be appointed on a full-time vidual differences in behavior with Specific emphasis made various been to has and him by application been developed ality aspects has foundations for support. Technical a the Department, to be appointed will there Effective April lst, FFRP Section (see Grant of the Under terms the Assistant for linguistic analyses. the language out to assistant technical a carry made for available E) fUnds were measurements devised by Dr. Jaffe. 3- £211.42: Dr. Jaffe has granted Fund Research Psychiatry Foundations' in for The continuation overhead for $5,700 u26,000 of plus sum the two years in support for the been during past developed has which year. Dyad" the of "Languace the of study FFRP The will Fbundation. exKaufmann grant the by been had work supported This tend from April 1, 1957 to March 31, 1959. Health Mental for of National made Institute the to been Applications have subthe Green. protocol Dr. Also, by work undertaken support for the program of of Division and Development Research the to been sent mitted by Dr. Pollack has FoundaMalino and the to Army, States United the Surgeon-General's Office of the tion. F. Publications and Presentations: the at was presented electroshock on studies of our In November, a summary Montreal a in Association report in American Psychiatric the of Meeting Divisional FollowChange Behavioral to Function Brain entitled "Relation of Tests of Altered "Electroencephalothe Green report Dr. presented December, Electroshock". In ing Electroenceb of Association Eastern the Megimide" of at graphic and Clinical Lffects during studies electroencephalographic the of In a February summary phalographers. Differences in "Individual entitled a in report two was presented the past years EEG Besponsivity" before the Metropolitan EEG Society. the for societies various to number of submitted a reports The Department has the at for been have presentation accepted Summer meetings. Papers Spring and the Psychiatry, Biological of Society the Research Association, Electroshock for Congress Psychiatry. International and the Psychology of Congress International Psy— American the symposia at in In addition, we have been invited to participate These meetings. for Psychiatry International Congress and chiatric Association Department of this the experiences detail considerable summarize in reports will and to electroshock to regard with and one-half specific two years, over the past methods of anathe language to present have we an opportunity also will drugs. to as some of our speculations well as presenting lysis devised by Dr. Jaffe, as in psychiatry. therapies the newer drug of mode and of action the role �-5G. Education: Various members of this Department are continuing their education by formal courses. Dr. H. Korin has been enrolled in courses at the Graduate School of New York University with specific emphasis on statistics. Dr. J. Jaffe is completing the formal training requirements at the William Alanson White Institute of Psychoanalysis. Dr. Robert L. Kahn has been accepted for training in psychoanalysis at the William Alanson White Institute. H. Other Activities: 1. Israel Strauss Volume: November 1955. and Members The Israel Strauss Volume appeared in of this Department were active in the development fulfillment of that volume. 2. Resident Training: Since September 1956, two Residents have worked H. Dr. Esecover has been studying the problem of the in Departnent. actively psychotherapy with electroshock patients. In this study he has been supervised He has made. have been number and conclusions of a members of the Department by demonstrated that patients differ considerably during the electroshock process and that no single type of psychotherapy is meaningful. Certain supportive and He of the now have in value. is definite process may approaches interpretive describing his observations. Dr. S. Friedman has contributed considerably to the ambivalence study. this yprk he was supervised by Dr. Tarachow. In During the period September to February, members of the Department participated in a weekly lecture series for the Resident staff on the subjects of research methodology and newer trends in psychiatry. Respectfully submitted, Max MFzgw Department of Experimental i"sychiatry > hillside Hospital Glen Oaks, New York Fink, M.D. �April 1, 1957 Medical Affairs Cummittee TO: For: Dr. Joseph S.A.Miller From: Department of Biochemistry Subject: Report of Departmental Activities, July 1956 to March 31, 1957. Steroid Studies Studies were continued on the steroid hormones because of their importance in the physiological response to stress. Experiments with rats showed that the liver converts neutral and sex hormones to their sulfate conjugates which are subsequently voided in the urine. Female rat~ liver was far more active than male preparations in conjugating the steroids, particularly the male hormones. These findings indicate that the liver plays a major role in the maintaining hormonal balance, femalssbeing endowed with a regulatory device to dispose of excess male hormones produced in their bodies. Urinary steroid sulfate excretion studies on human subjects were carried out The and total chromatographic techniques. complexation with our newly developed sulfate output was found to be related to both sex and age. Interesting results were obtained with urine from schizophrenics, the level of one fraction (dehydronumber of cases. elevated sulfate) in a being epiandrosterone Drugs and Alkaloids New colorimetric, chromatographic electrophoretic techniques were establipsychothenpeutic drugs. These were recently and for both the psychotomimetic and presented at the American Chemical Society shed Meeting (Brooklyn, February 15, 1957). findings are now being applied to determining the role of trace urinary alkaloids in schizophrenia. our earlier chlorpromazine studies, which were dropped for lack of suitable instrumentation, are again under way with financial help from the National Institutes much throws because The of interest it light on Health. is ver great of subject from the be which cannot gained (microsome action gross liver function liver function tests in currentuse. we find the chlorpromazine molecule is in many ways The from information gleaned to some in isotopes. ways ideal superior an tracer, this study would also throw light on the Akerfeldt "six~minute blood test for from whether suffer a decide schizophrenics should to and us help schizophrenia" defect in oxidative metabolism leading to the in vivo production of hailucinogens. The Electroshock Lavels Therapy. in gholinesterase Earlier investi ations by Tower and others have indicated demonstrable changes in acetylcholine, acetylcholinesterase, and pseudocholinesterase in spinal fluid following electroshock therapy as well as other forms of head trauma. AccordingEEG of have to correlate undertaken Fink patients and Ur. patterns associates ly, EST values cholinesterase in concurrent and with alterations after during before, of spinal fluid. Simultaneous serum cholinesterase determinations on these patients blood red to extend these studies and cell we to carried plan also being out, are (true)cholinesterase. The specific enzyme methods in use were developed at Hillside Hospital and have recently been presented at the American Chemical Society Meeting in Brooklyn. Further reference is made to Dr. Fink's progress report for findings to date. Future plans: More of the same. Harry Goldenberg, Ph.D. �April 1, 1957. Medical Affairs Committee TO For: Dr. Joseph S.A.Miller From: Department of'Medicine subject: Report of Departmental Activities, July 1956 to March 31, 1957. to of An the patients of psychiatric Test: response l. Mecholylof mecholyl analysis between correlation a revealed has striking subcutaneously injections electroshock to and therapy. and diagnosis response age, response have machine blood recording automatic of an studies pressure 2. Preliminary machine for and of this the evaluate practicability to out accuracy been carried now seems As these of result a studies, the work mecholyl it test. on further of the evaluate to used be reproducibility machine usefully can likely that this the mecholyl test. 3. Drug evaluation studies on meprobamate are being carried out. h. Chemical studies with the laboratory department are being conducted on possible hepato-toxic effects of chlorpromazine in our patients. Proposed Research for the coming year: 1. Evaluation of meprobamate in psychiatric patients. three months). 2. (to be completed within Evaluation of reproducibility of mecholyl test employing a recording sphygmo- mamometer. by chromatographic with therapy chlorpromazine alterations of Evaluation 3. protein techniques. h. Evaluation of or Trilafon. a substitute fbr chlorpromazine. This will be either Spaﬁine Arnold Blumberg, M.D. �HILLSIDE HOSPITAL FOR PSYCHIATRIC TREATMENT. TRAINING AND RESEARCH JOSEPH S. A. MILLER, 75-59 263RD M. D. STREET. GLEN OAKS. NEw YORK FIELDSTONE Medical Director LEON LOWENSTEIN 3-7800 Honorary Chairman Board of Directors M. D. Assoc. Medical Director SIMON KWALWASSER, ROY FOSTER Chairman Board of Directors MAURICE BACHRACH E. COLEMAN President Administrator ALVIN A Proposed Study for the Behavioral Max From Assay of New Drugs Fink M.D. the Department of Experimental PBychiatny October 30, 1957. AN AFFILIATE OF FEDERATION OF JEWISH PHILANTHROPIES OF NEW YORK �AProposed Study for theBehavi9ralwg§§ay of New Dm mgs MaxFi‘nk M.D. * 1 . Problem: is little disagreement that the newer psychopharmamode of these drugs of action the behavior, alter cological agents and factors in the marked individual variability in response are unresolved problems. Difficulty in resolving these problems lies, While there in part, in the lack of a theoretic framework subject to operational the is assay perplexing and Particularly experimentation. analysis of new, i;g., clinically untested agents capable of altering behavior. Many the because reports are to assess studies difficult are present and classifications nosologic defined; the poorly population subjective; are unsatisfactory. Based on our previous studies, we have expressed the hypothesis that the efficacy of psychopharmacological agents in psychotic states measurable changes induce to persistent to their related ability is in cerebral function (1). Such alteration in cerebral function provides the milieu for changes in adaptation of the patient in his environmento In this view, alterations in cerebral function following drug administration are not "complications," or "untoward but the sing SEE 293 of the mode effects," of action of these therapies. Changes condition not sufficient but a a cerebral are physiology in necessary, for improvement. * Director, Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, N.Y. �,2This hypothesis is a direct outgrowth of four years of experimental investigations of electrcconvulsive, insulin coma and various drug therapies in use at Hillside Hospital. These studies are summarized in the appended report (1). we have used a wide t variety of measures of brain function (2, 3, h, 10, 12). Most successful have been changes in the frequency spectrum of the EEG, patterns of language and perceptual tasks. In our experiences with electroshock, slowing of most EEG frequencies has been helpful (2). In drug studies, however, this is less prominent, although fundamental; Language and perceptual tests, however, have given us clues as to ways of measuring brain changes, more subtle than present electroencephalographic techniques. It is this study to logic agents according to their effects the purpose of patterns and on perceptual tasks. to test the following: The compare various psychopharmacoon the study EEG, on language is specifically designed I (a) Can the extent of behavioral change in psychopharmacologic agents be related to the degree of (b) To EEG spectrum changes? what extent can visual discrimination measures of changes in language be tests, and refined to provide reliable, predictablezueasures of changes in clinical behavior? (c) To what extent can such measures predict the clinical usefulness of psychopharmacologic agents? �II. Method: 1. Subjects: All subjects are drawn from the adult impatient service of the Hillside Hospital. In general, these patients are erative, well educated good physical health. intelligent. All are and alert, coopT ambulatory and in 2. Procedure: Two methods of drug assay are in progress. (a) Acutg_Experiments: In the laboratory setting, with simultaneous EEG and language recording in process, single intravenous or oral doses of drugs are administered. the period of drug Patients are under constant observation for activity. (b) Clinical Experiments: Patients are referred by their therapist to the super- vising psychiatrist for treatment with psychopharmacologic agents. Prior to drug administration, EEG and language recording interviews are held. Perceptual tasks are completed. Drug administration then until toxicity is manifest, and drug reduced to a maintenance dose. Testing is repeated, and be- proceeds dosage at a rapid increment havioral observations made, at frequent, defined intervals. in previousstudies, subjects are randomly divided into As groups - an experimental and a control. The experimental group receives the medication, the control group placebo medication. two �3. measurements: (a) 33.29. is Recording with an 8 channel Medcraft instrument in progress. Records have been visually analyzed for changes in frequency, voltage, symmetry and rhythmicity (2). Activation by hyperventilation is routine. validity of other activating and photic hypoglycemia megimide (6), intravenous as procedures The stimulation is being assessed. (b) Perceptual. Within the past decade certain perceptual procedures have been shown to be (11, 12, 13). sensitive measures of cerebral dysfunction Such techniques as critical flicker fusion (OFF), and "embedded" of figures polychromatic the tachistoscopic recognition in a These visual background are being assessed (10, 12, 13). measures have the adVantage of giving a reliable quantitative complex measure of pretreatment functioning in terms of a continuous variable, rather than the qualitative dichotomy of "normal" versus "abnormal;" imposing no undue stress on the patient; and the apparatus and pro- relatively inexpensive. 1) Critical flicker fusion SCFFZ: As the rate of the that the illusion there develops of increased, flicker light is point this at of The the light flickering frequency steady. is light cedure are simple, convenient and is the CFF. The CFF threshold is measured using a Sylvania glow ratio is brightness is varied to robtain thresholds at different tube pulsed by an electronic power supply. The light—dark fixed, and �-5- levels. The psychophysical method of is descending steps limits using ascending and employed. 2) Tachistoscopic recognition of pseudoisochromatic gigures: The H—R-R pseudoisochromatic plates (American Optical Company) con~ sisting of a series of cards with numerous small circles of various sizesare used. The circles vary in color, and form outlines of various geometric patterns, as ring, cross and triangle. These patterns form a "figure" on a constant background. The "neutral" plates are recognized by all subjects - blind." These plates have been photographed and projection slides. initial normal and "color- mounted as 2" x 2" of exposure which permits accurate The speed identification of the figure is the index used. (0) Eggggggg. Interviews with patients are recorded. Both unstructare The records analyzed included. and ured structured periods are for diversity (7) of the dyadic speech. been found useful in analysis of changes in for changes in syntax (9), These methods have and behavior with other therapies. (d) Evaluation of clinical changes. Psychiatric evaluations are made at fixed intervals as to type and degree of changes in behavior, and a rating of "improvement" and is made. in "improvement" are The methods now of rating both change in behavior under study. Present ratings have been based on the Malamud-Sands Rating Scales and have been of limited usefulness. The present descriptive statements of the evaluator, �-6following an outline of specific areas of behavior combined with a review of the nurses' and resident therapist's notes is being continued. h. Pharmacologic Agents: Previous experience with amobarbital (8), megimide (6), reserpine (IA) and chlorpromazine (5) provides the background for the selection of new agents. At present, acute study of diethazine (SKF 1026-A) is in progress. Clinical studies of meprobamate, perphenazine and chlorpromazine are under investigation. have been formulated reaponse. to test other agents, with different spectral Available: The Department of Experimental Psychiatry was established at the Hillside Hospital in l95h. clinical duties. EEG . - III. Facilities Plans of the department have no Members They devote their full at the institution to time the research prognmns. Eight rooms of laboratories and offices in the principle medical building of the hospital are provided. These include: a) EEG Laboratory - equipped with Medcraft encephalograph and Grass photic-stimulator. on a A 8 channel Electro- technician is employed full-time research basis. b) Psychophysical Laboratory - Two Grass stimulators, Dumont oscilloscope and step-up transformer power supply in a rack-mounted assembly. This equipment has been used for the past three years to study threshold and after for simultaneous tactile stimuli of patients before induced states of altered cerebral function. �.37.- A tachistoscopic assembly consisting of two projectors, solenoidaactivated shutters, and opal glass screen is in use. c) Psxcholinggistic Laboratogz: A third laboratory has been established for the recording of interviews. a Magnecord tape recorder, two It is equipped with and mixer. microphones, Electrovoice auxilliary recorders for transcription are available. The available for study. All patients in the hospital are research programs have been well integrated into the hospital Two milieu so that manipulation of experimental variables are readily accomplished. �and Reggrts: Iv. Publications l. 2. of Physiodynamic Action of the Unified Theory Fink, Therapies, J. Hillside Hosp. (in press). M. : A and Kahn, R.L.:' Relation of EEG Delta Activity to Behavioral Response in Electroshock: Quantitative Serial Studies, A.M.A. Arch. Neurol. and Pachiat. (in press). 3. h. m: Diffuse of Effects and H.: Korin, , Altered Brain Function in Perception. Read at XV Int'l Congress of Paychology, Brussels, 1957. , : , Relation of Tests of Altered Brain Function to Behavioral Change Following mectroshock. Read at the A.P.A. Divisional Meeting, Montreal, November, 1956. 5. and Coleman, F.S.: Coma and Insulin of Chlorpromazine Comparative Study in the Therapy of Psychosis, J. Amer. Med. Assoc. , Shaw, R., Cross, 6., (in press). 6. Green, Fink, M.: Megimide, EEG. 7. Jaffe, J.: Clinical Effects of W M.A. and An EEG and Clin. Neuromvsiolu g: 180-181, 1957. Objective Study of Communication in Psychiatric Interviews, J. Hillside Hosp. (in press). 8. Kahn, R.L., Fink, M. and Weinstein, E.A.: Relation of Amobarbital Test to Clinical Improvement in Electro8c Psvchiat. 1956. 23-29, Meurol. A.M.A. Arch. lé: shock, 9. 10. ll. Durinf-j Ele ctroLanguage Changes in , of Cormnunication, shock Therapy, in P cho tholo Ein press). Crune and Stratton : Em‘oedded Figures After of Perception , Induced Altered Brain Function, Am. Psychol” 1.3: 361 (Abst.) 1957. : Effects of Visual, Vestibular and Somatosensorimotor Deficit on Autokinetic Perception, J. @332. §_2_: 398~LLlO, 1956 (with Battersby, 11.3., Pszchol., Pollack, Mr: Kahn, R.L. and Bender, 15.8.) �0-9- 12. Pollack, M.: Tachistoscopic Identification of Contour in Patients with Brain Damage, J, Cam . Ph 101. szchol., 50: 220-227, 1957, {with Battersby,‘W.S. and Bender, M.B.) 13. Visual Deficit After Brain Damage in Man as Measured with Rapidly Exposed Chematic Stimuli, Amer. Peyphol., 12: h68,(Abst.) (with Battersby,‘w.s. : and Bender, M.B{7: 1h. WachSpress, M., Blumberg, A.G., Fink, M. and Miller,J.S.A.: Evaluation of High Dose Reserpine Therapy for Relief of Anxiety, J. Hillside HOSE. 5: 67-77, 1956. �.10V. Financial Support: Support for the ongoing programsof the Department of Experimental ' Psychiatry is provided by U.S, Public Health M-927, (Altered Brain Function Following Electroshock), the Foundations' Fund for Research in Psychiatry grant 56-151 (Language of the Dyed), and the Board of Directors' Research Fund. The proper development of the specific aspects of this protocol require support for the following, for a two year period. 19 8 Dr. M. P01130k, PhoD. Senior Research Asst. Psychology EEG $ _ Technician - Hrs. Hannah Hosquera 12§9 8,250 $ ‘ 8,750 3,720 3,8u0 2,000 2,000 50 th 50 th 200 300 Equipment: (Over 2 year period). Analyzer (Edin) Flicker Fusion Apparatus EEG Projector, Slides Calculator (h,000) (800) (100) (880) hDO hOO Travel: ) (Amer. Psychol. Assoc. (Amer. Psychiatric ASSOC.) $ 15,060 Overhead (15%) TOTAL $ d 15,h80 2,26h 2,327 17,32h n 17,807 ' �\ KILLSIIE mSPITAL Glen Oaks, NOYO January 27, 1958. MORAN!!! '10: Medical Affairs Committee FOR: Joseph FRCM: Merimental Psychiatry 1958. January 1957 1, to 1, Report of Activities, April Miller, M.D. Deparhxent of SUBJECT: I. 30 A. -~.—-- INTROIIJCTION: achieved has professional work Department the of the nine months, In the past various of understanding We our reflecting have presented reports recognition. and these and international societies, national before physiodynamic therapies October the in work were presented of Five our aspects have been well received. psychiatric by been leading have accepted and other Journal reports the of issue Journals and will appear in 1958-59. convulmode of of action the of Our studies have given us a clear picture confidence to has us given information ibis coma and therapies. insulin sive to these in therapies which were fruitful and techniques extend the hypotheses behavioral concerning a ideas in protocols have expressed our drug therapy. We Psychothe both by received been well These having new ideas, of drugs. assay comand various pharmaceutical U.S.P.H.S. the of Center Research pharmacology 1958. for studies new the in been implemented have panies, . , . therapy, we were , . . number a. of ancillary led to electroshock In evaluating The value for psychiatry. have which basic significance broad, investigations found and assessed were change behavioral of indices of language measures as While a studied. "improvement" was The of defining problem satisfactory. been has approach operational an accomplished, not was satisfactory resolution which the criteria Also, studies. recent defined which was successful in our has an to led Hillside at various the therapies for determine patient referral of choice therapy. factors and affecting psychologic the sociologic evaluation of In addition, the ability of this department personnel to work together has been have the in hospital and Our relationships roles been amply demonstrated. hosthe from at staffs all cooperation excellent defined and we have received pital. II. PROGRESS IN (A) ONGOING PROJECTS: Therapy Evaluations: l. Flectroshock. We electroshock therapy. Our studies have defined the process of physiology; brain in induced changes the to behavioral the have related response behavioral of the type affect that and factors sociologic described personality and clinical behavioral between response the and defined relationship response; of various the types to relate us These studies permit ratings of improvement. PM 1090), electroshock and its varieties, (metrazol 3, convulsive therapy as drug "convulsive there. of concept (Indoklon) meaningful into a and lately, inhalant , pies '. �-2Based on these studies, reasonable criteria for the type of patient "do well" with convulsive therapy can be defined. Continuing studies will behavioral the in of role the personality amplify designed.to in this area are non-electroshock referbetween'out-patient differences the define to response; convulsive inhalant of and evaluation an (IIIc) rals and in~patient populations ' who therapy (111a). 2. . £235 Therapy. control coma-chlorpromazine insulin of conclusion our the Following 1958. and .A.M.A. in early will appear study, our report was accepted by he J the experimental program.for have developed a we months, six the During past which begun was (see IIIb), agents psychopharmacological new of evaluation 3. Selection of therapies: of the based on type generally is of therapy While the selection the Such as aspects decisions. such affect factors mental disorder, other and cultural education his communicate verbally, to facility of the patient have we and been have studied, "authoritarianism” background, and the degree of rebear significant a and aspects psychologic such historical reported that These services. for ancillary lationship to the choice of therapy or referral of the in factors these of results studies have led to an interest in the role socioof role the evaluate further to therapy, and we have designed a study (see IIIc). and therapy outpatient of inpatient psychologic factors in results (B) Language as measurable behavior: one. complex "in is a 'improvement psychiatry of definition and change behavioral of In evaluation of various therapies, the definition have sought we adequate, are While descriptions clinical improvement is crucial. Two methods of our behavior patients. the language in guides more objective for interviews of structured analysis of analyses have been developed - a syntactic and a dyadic of unstructured. The non-convulsive and convulsive induced by changes have described the do clinical reflect patterns these language therapy, and find that changes in to these techniques of the have application to led Our experiences evaluation. We the drug evaluation studies. effort in an in are of progress language other analyses In addition, methods. the of present the broaden applicability to (C) Neurophysiology of Behavior: the between relationship the noted we In the electroshock studies We concluded behavioral response. the and change neurophysiologic of degree and behavior in change to a essential was physiology cerebral in change that a coma therapy. insulin for conclusion We same the come had to to "improvement". chlorpromazine in treatment the response between Since we had observed a similarity was mode action of same the that seemed plausible therapy and insulin coma, it drugs. newer tranquilizing the for operative �-3review of the literature and some preliminary experiments supported the to potent are agents psychopharmacologic newer the that this hypothesis We have function. brain and affect predictably extent that they measurably and in of Psychiatry Congress International the at hypothesis this expressed new undertaken have we As a a Hillside the Hospital. result, the Journal of (see IIIb). various drugs therapies evaluating project .A Concomitantly, our interest has continued in the biochemistry of convulsive therapy. we have observed that diethazine, a potent anticholinergic demonstrated has a Further analysis electroshock effect. the drug, reverses These observadiethazine. LSDHZS to and mescaline between marked similarity as system cholinesterase-acetylcholine the of confirm the significance tions which behavior of psychotic the type a basic mechanism for psychotic behavior may be affected by convulsive therapy. Percgption: (D) have change behavioral of index an as studies of perceptual tests continued. We have defined the relationship between the degree of perceptual demonstrated Our have studies function. alteration and the degree of altered brain Our but the response, in perceptual only not type of personality the significance also in the physiologic response, to convulsive therapy. Our studies of tactile perception clarified the role of strength of stimulus and of the type of instructions (set) in the reported reponses. Individual Differences in Behavioral Responses: The program of study of the ways in which individual differences in various to of subjects and affect response physiology the perception, personality of neurophysiologic Green's Dr. studies under well way. is psychiatric therapies Dr. emphasis and Pollack's EEG electroshock, to the response differences affecting of the both phase in are drug to therapies on perceptual aspects as they relate collecting data in consecutive groups of subjects. (E) III. (A) New Pro ects - Pro am.l 8 Inhalant Convulsive Therapz: In the studies of electroshock, we have been puzzled by the significance of the electric current in the treatment response. In the convulsive-subconvulsive was aftreatment the for response seizure the of the control study, significance compound, inhalant an Recently, clear. not was current of the role but firmed, conﬂescribed simple was as a safe, of ether anesthesia, the to ethyl similar vulsant. We visited the laboratory at Spring Grove State Hospital, Maryland, We and observed the treatment. It was reliable, quick and easy for the patient. have obtained a supply of this compound and are undertaking a study on February of biochemical and effects psychologic of neurophysiologic, the clinical, lst, convulsive therapy using this compound. (B) Mbde of Action of Psychophammaoologic agents: experiences with other forms of therapy have led us to formulate a the In agents. essence, psychopharmacologic (see IIc) regarding hypothesis and kind of effect the degree to related behavior which is affect drugs to degree EEG. Fbr this the purpose,we by measurable in part, brain have on function, they and personnel equipment for special obtained and support have written a protocol from.the U.S.P.H.S. and various pharmaceutical concerns. Our �-l+- In these studies, patients referred for drug therapies, as chlorpromazine, promazine, reserpine, meprobamate, etc. , undergo special tests before and during treatment, which may predict and reflect the treatment response. (0) Psychologic and Sociologic Factors in Out Patient Therapy; result of our studies in inpatients defining certain psychologic sociologic factors as they affect treatment choice and treatment response, As a and we have made predictions regarding the outpatient population. to undertake a sociologic study of outpatients, and extend our studies this Spring. IV. (A) W318 We are planning inpatient AND. I’UBLICATIONS: Eigerimental Psychiatry Issue, Journal of Hillside Hospital: of this Department wrote five articles reflecting various aspects of our study program for the October 1957 issue of the Journal. This encompassed the whole issue. Such an effort is unique in the Journal‘s history. At Dr. Tarachow's (B) invitation, members Publications: In addition to these five articles, our report on the relation between EEG changes and treatment response in electroshock appeared in the Archives of Neurology and Psychiatry. Seven other reports have been accepted for publi cation and two others are in the hands of editors as of January let. (G) Presentations: Reports of our studies have been presented to psyc iatric, neurologic and psychologic societies. Twelve reports were made before National societies in the U.S. and three before International Congresses in Brussels and Zurich during the summer. These reports have been generally well received. V. PERSONNEL: changes in personnel have been made. We have requested, and the Research Committee and Medical Director have approved, a restatement of the titles for staff members from "Research Assistant" and "Senior Research Assistant" to "Research Associate". The present staff consists of nine members including: No Martin A. Green, M. D. Joseph Jaffe, M. D. Robert L. Kahn, Ph.D. Hyman Korin, Ph.D. Max Pollack, Ph.D. Associate (Neurophysiology) - Research " " (Psychiatry) -" " " (Experimental Psychology; " " (Experimental Psychology " " (Ehcperimental Psychology) - and four technical assistants: Mrs. Hannah Mosque'ra (EEG) , Mrs. Jean Kolodw and Mrs. Ann Horowitz(~?sycholinguistics) and Mrs. Janet Bowie (Secretary). �-5VI. (A) TENTﬁIIVE BUDGEE PROJECTION: 1228-52. Personnel: In addition to the personnel listed above, we will request the addition of a Research.Associate in Social Psychology; and a redesignation of the halftime neurophysiologist to a full-time status. These items will increase the budget by $9500 above authorized annual increments for ongoing personnel. (B) Supplies. Em ment and Travel: There will be an increase of $l000 in supplies and travel and a specific equipment expense of $5200 for an EEG Analyzer. This instrument will provide greater flexibility in EEG analysis. A supplementary request for this amount has been asked of the U.S.P.H.S. L Total Egpensesz (C) av" . total expenses for 1958-59 1957-58, an increase of $16,98h. The (D) will be $95,796. as against $78,812 k" "u. Income: In the past six months, this Department has been more successful than anticipated in attracting research funds from private and governmental sources. Fbr the current year, we anticipated $33,595 and so far have been advised that we can expect $h3,h31 for 1957-58, an increase of $9,836 over expectations. Fbr 1958-59; we have already been assured of $50,66h which is $7,233 more than 1957-58. It may be of interest that we already have funds for 1959-60 in the amount of $15,297. These grants totalling $115,235 have been made available to the Department for the period April 1, 1957 to December 1960. Max Mszb/b Fink, M. D. A}\ fork¢3”4 We Respectfully submitted, V‘ � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Progress and annual reports; research activities (folder title). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-005 Date A point or period of time associated with an event in the lifecycle of the resource 1957 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Letters; Personality factors in behavioral response to electroshock therapy (draft) by Robert L. Kahn and Max Fink; Progress reports of departmental activities; A proposed study for the behavioral assay of new drugs by Fink; Report of activities Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/e160cd659a1c0564650ed815c2ffda05.pdf 287e408e3d76bfef4519f4c1ea5b9ae6 PDF Text Text ( g , a n I E . ! r l , E i P me: plated the 70110113; Wt. it. own» 1957. tho ﬁrst wu- of of W mun-y oa- of tho clan-pu- of natal 1.1an“. WW with. W, mun-mm-m m mum of th- buio and We” pm dandy!” wmmuﬁow WW $81957. m: CW Mtnmwwmmtmunuhanmmmw has. at an a: 0. mm}. 6103111 ”My W; N's-pm“ m “ﬁrm" mmuhm-M muum m may. for in and tho «01015310 at! rum-Mu, mmmacnzwm mmtarmmmmmummmmm can control study. an. anon-mud in 6110me Wanna Maturation, nWtdﬁzomuuﬂmd Geno a» m In. 3mm mm, W nun mum. mm. m magma“, manur- m mum (Imp and 0! o. with the Ward am of nut 11.“.qu of we: Into applying an Into pitta-n- of cannula-ﬂan comma. obs-euro mined: at «unique! of and h mmmWWu-W-mmmwm when; mud. aunnmummmmpum. mn- We Wc wimp-MW" mm,mummwsnmmnud and m induced mum bu» for continua. mm which“! 1n mp”. �.g......__‘-_, <. . r._wr..v,... a.“ .. . an“... ~. My; ’1‘...” w V “rpm—c. v..-.~7.vv....v ”my—W..- m- 7 ~-‘ _ V- w..." ,___ w'J—ln'n .. ,_ —.-‘ \ ,u.,, .N nu . vvvwmr ,. » w..,.._.v..... d. mummdthonmm, unmask-Wt. that ad {in Was: manna. What“ umm Journal tho of thfor 'hponmnul um unk). we)... Why" m of tho é : mnm- Hospital. ﬂu sun and“: m “aA. m, W am. um lab-n 11.9. Edi. 11.». m, Ill: mm, m. “lemma. I» Bub. " - -.. _, “mt mu (Wong) W " " * .u " I (me) (Noun-um Why) _ “ - a wzutmpmmwmmayuM7 E i ‘ amurmwmmunnahrmummm,m hum). mum at rum mu. an Wanna cm» at munmmmanummmmumm. mm, mm . w m. E “n.— ﬁ__.__4w-~m_——__V O ”in. n ,. — �Richard Weiner FROM: FOR RELEASE FINN INCORPORATED 13u.East 59 Street RUDER & MAX York 22, New York PLaza 9-1800 New FOR: 7, 1958 HILLSIDE HOSPITAL A Island psychiatrist whose research points to the underlying Long changes necessary to reverse the depressive type of mental honored this Dr. week by Max be Fink, Director of the Department of Experimental Psychiatry at Hillside Hospital, A. E. illness will a major national psychiatric association. Glen Oaks (Queens), New York, will receive the first Bennett Neuropsychiatric Research Foundation Award. The Society of fé Biological Psychiatry will present the award at the group's 13th Annual Meeting in San Francisco, California, on May 11. The meeting is part of : '1‘ the American Psychiatric Association Annual Meeting. Dr. Fink will present a paper on his work Cholinergic Agent, Diethazine, on EEG titled, "Effect of Anti- and Behavior: Significance for Theory of Convulsive Therapy." The report describes experimental studies of the neurophysiologic for "shock" therapies. Dr. Fink and his associates at Hillside Hospital have observed that changes inla specific enzyme and biochemical bases system of the brain, acetylcholine-cholinesterase, are intimately to improvement in electroshock. However, changes related in the opposite direction are accompanied by hallucinations, delusions, and psychotic behavior. that decrease the activity of the acetylcholine normally present, in the brain excite psychotic activity. They also reverse the electroshock Drugs effect. Some of the newer hallucinogens, such as lysergic acid (LSD) and , �-2mescaline, are most potent in this regard. halts the hallucinogenic action of these shock effect. The On the other hand, chlorpromazine compounds and enhances Hillside research extends the understanding of the the electro- mode of action of convulsive therapies by defining the biochemical bases for the observed neurophysiologic effects. The studies have been supported by the National Institute of Mental Health and the Board of Directors' Research Fund of Hillside Hospital. Dr. Fink is Secretary of the Section of Convulsive Disorders and Brain Function of the American Psychiatric Association and President- Elect of the Nassau Neuropsychiatric Society. Hillside Hospital, an affiliate of the Federation of Jewish is a non—profit, non-sectarian hospital for psychiatric treatment, training and research. Philanthropies of New York, #### �_ »‘.>\7"» >v.— '— ~v- 16 Peace Missionary May ;’Have to Pacify “Family ' i i . ' i Mrs. Lola Stone, pretty young Long Island. housewife who’s on an interna— tional peace mission to ban nuclear tests, may have some pacifying to do when she gets home. The husband and two children of the globe-trotting proud of her campaign, but they miss her and Wish she’d 'peace missionary are hurry home to Kanes Lane, Huntington Bay. , .TA Reiecis 1 "‘We think she’s wonderful, we’re quite proud of her, but it urts some time,” her husband, Robert, said with a smile. ‘We’re counting the days.” Mrs. Stone is one of a group of five pacifists on a 4,000- Protest mile tour of European capitals ‘ By MBA ‘ They have been stalled in Helsinki for a week because of the reluctance cf the Soviet Union to grant them entry The Transit Authority today visas. brushed aside a Motorman’s “We are hoping the visas Benevolent Association protest will come through,” Mrs. Stone that it would be “dangerous” told her husband by phone for‘ motormen to leave their from Helsinki. “The most imcontrols on the EMT Myrtle, portant part of our mission Avenue line to help operate the lies ahead. We hope this is doors. just a routine delay.” “The MBA is making a DR. MAXIMILLIAN FINK The group flew from Idlemountain out of a molehill,” a wild April 14, and stopped at TA spokesman said. London, Paris, Bonn and West Theodore Loos of Jamaica, Berlin to interview national the association’s president, proleaders and “just plain people.” tested yesterday that a train’s Despite a brush-off "at 10 brakes might slip -— and the Downing St., official residence train start rolling—while the of British Brime Minister Harmotorman was out of his cab. old Macmillan, the overall re“Under our order,” the Tranaction was “favorable and opsit Authority spokesman said, timistic,” Mrs. Stone reported. “the motormen will have to l.The scheduled last lap of the leave his cab only under cerjourney was to be Russia, tain conditions . . . and those A Long Island psychiatrist where the group hoped to perconditions Only crop up once will receive the first A. E. Ben- suade Kremlin officials to in a blue moon. Even if the motorman leaves nett Neuropsychiatric Re- agree to an unconditional ban on nuclear testing as “a demhis controls, he’ll never be search Foundation Award. more than four feet from the He is Dr. Ma'ximillian Fink onstration of their sincerity.” Expenses of the trip are brake.” of 13- Bayview Ave., Great being borne by “Non Violent The TA said its order applied only to a few stations on Neck, director of experimental Action Against Nuclear Weapthe Myrtle Avenue line. At psychiatry at Hillside Hospital, ons,” the same group that sponsored the voyage of the those stations, there’s no Glen Oaks. “Golden Rule,” stopped change collector at night, so Dr. Fink ‘will receive the ketch, the conductor on the train col- award. Sunday from the Soci- by the Coast Guard off Hawaii. lects fares. The motorman will ety of Biological Psychiatry at be asked to help the conductor its annual convention in San Fishermen Angry out when a “big crowd” boards Francisco. the train. Over Empty Pond He is being honored for re“We only pick up an aver- search- into the effect of HARTFORD, Conn. (UP)— age of four persons per trip at “shock” Red-faced officials of the State all those stations put together,” “we’vetherapy. been able to discover Fish and Game Department the TA spokesman said. “We the mentally ill respond admitted somebody goofed . . almost never get a crowd how to shock therapy,” Dr. Fink when angry fishermen pomt') \ ' there." explained. “And, just as im- ed out in a department-proportant, we’ve learned why vided pamphlet that Day Pond some persons do not respond in Colchester was stocked with ”at trout and open for fishing. to such treatments.” j t'Dr.’ Fink has livedtin Long The anglers had risen before I Island since 1950, and was ap- daWn! ion:- opening day and made thetrip to the Mind, ' r 3 _ ' ‘ ' Psychiai‘risfs Will Honor L. Docfor _ _ giteconsider '11:, , Q . . ’ . U �1/15/59 Department of Egperimental Psychiatry and the of presentations a chronologic Following is list of members Experimental the of Department of the publications Psychiatry during 1958. M Publications: A. 1. Changes in Language During Electroshock Therapy, in of Communication, Hoch, P. and Zubin, Ps cho atholo 3. eds., Grune E Stratton, (Kaﬁn, R.L. and Fink, M.) 2. Lateral 3. h. 5. 6. Gaze Nystagmus as an Index of Sedation Threshold, Clin. Neurophysiol. l9: 162-163 (Fink, M.). Effect of Diethazine on EEG and Significance h for Theory 8101. 19: of Convulsive Therapy, EEG. Clin. Neuro 207-208 (abst.) (Fink, H.5. Experimental Studies of the E1ectroshock Process, Dis. Nerv. Syst. l2: 113-118 (Fink, M. and Kahn, R.L.). Comparative Study of Chlorpromazine and Insulin Coma 18h6-1850 166: J.A.M.A. of Psychosis, Therapy (Fink, M., Shaw, R., Gross, G. and Coleman, F.C.). Eleotroencephalographic Correlates of the ElectroshockM. 227 (Abst.) (Fink, Nerv. Dis. Syst. 12: Process, EEG. and Green, 7. 8. 9. 10. l1. R.,. Language of the Dyad, Psychiatry El: 2h9-258 (Jaffe, J.). Clinical and EEG. Effects of Megimide in Patients without M. 682-685 (Green, Cerebral Disease, Neurology g: and Pink, M.) Effect of Anticholinergic Agent, Diethazine, & on EEG and Psych. ﬁg: 380-388, Behavior, A.M.A. Arch. Neurol. (Fink, M.). Experimental Studies of Convulsive and Drug Therapies on A.M.A. Arch. Theoretical Implications, Psychiatry: Neurol. & Ps ch. 80: 733-73h (Abst.) (FinE, R., Kahn, R.E. and Green, M77. Brain Damage, Mental Retardation and Childhood Schizophrenia, 12. Oculomotor and Postural Patterns in Schizophrenic Children, A.M.A. Arch. Neurol. & Ps chiat.‘12: 720-726 (Pollack, M. and Krieger, H.P.5. 13. A.M.A. Arch. of Denial in Factors Illness, Interpersonal& Ps chiat. ﬁg: 653-656 (Jaffe, J. and Neurol. SiBtEj'W.H.). �1h. B. Predictions of Outcome, in Youthful Offenders at Hi hfields, Weeks, H. Ashley, e3. U. of Michigan P ress, Ann Arbor (N. Siegel). Presentations: EEG Correlates of the Electroshock Process, at the 1. Eastern Psychiatric Research Association, February, M. N.Y. (Fink, 3. and Green, M.A.). EEG Changes in of Individual Variability Significance During Electroshock Therapy, at Eastern Association of Electroencephalographers, March, Montreal, (Green, M.A.). and Drug Therapies Convulsive of Studies Experimental in Psychiatry: Theoretical Implications, at New York Society of and Society Neurological Clinical Psychiatry, March, N.Y. (Fink, M., Kahn, R.L. and Green, M.A.). Abnormal and Normal in and Attention Visual Perception ’Children, at American Orthopsychiatric Association, March, N.Y. (Pollack, M.). Patterns with Altered Brain Function, at Eastern Psychological Association, April, and M.). R.L. Fink, Kahn, (Jaffe, Philadelphia J., and F Behavioral Physiological Score to of Relation Response with Altered Brain Function, at Eastern Psychological Association, April, Philadelphia, Communication The (Kahn, R.L. and Fink, M.) 7. Intellectual Deficits in Patients with Space Occupying Lesions of the Cerebrum, at Eastern Psychological Association, April, Philadelphia (Pollack, M., Battersby, W.S., Kahn, R.L. and Bender, M.B.). Simultaneous of and of Perception Stimulation Intensity Stimuli in Cerebral Dysfunction, at Eastern Psychological Association, April, Philadelphia (Korin, H.). �-3- 10. Socio-Psychological Aspects of Diagnosis and Treatment: Theoretical Implications, Symposium - Eastern Psychological Association, April, Philadelphia, (Kahn, R.L. and Pollack, M.). Drug Induced Changes in Interview Patterns, at Conference on Psychodynamic, Psychoanalytic, and Sociologic Aspects of the Neuroleptic (tranquilizing) Drugs in Psychiatry, April, Montreal (Fink, M. and All. 12. 16. 17. 18. 19. Psychological Factors Affecting Individual Differences in Behavioral ResPonse to Convulsive Therapy, at American Psychiatric Association, May, San Francisco (Fink, M., Kahn, R.L. and Pollack, M.). Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy, at Electroshock Research Association, May, San Francisco (Kahn, R.L. and Fink, M.). Effects of Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy, at Society of Biological Psychiatry, May, San Francisco (Fink, M.). Social Factors in Selection of Therapy in a Voluntary Mental Hospital, at American Psychiatric Association, May, San Francisco (Kahn, R.L. and Pollack, M.) A Critique of "Pre-Conscious" Perception and the "Poetzl Phenomenon," at American Psychiatric Association, May, San Francisco (Pollack, M.). Role of EEG Frequency Shift in Behavioral Effects of Drugs, at Section on Neurol. & Psychiat. Queens. County Medical Society, June, N.Y. (Fink, M.). Effect of Anticholinergic Compounds on Post Convulsive EEG and Behavior, American EEG Society, June, Atlantic City (Fink, M.). EEG and Behavioral Effects of Psychopharmacologic Agents, at Collegium Internationale Neuro-Psycho Pharmacologicum, September, Rome, and Eastern Association of Electroencephalographers, December, N.Y. (Fink, M.). Prognostic Application of Psychological Techniques in Convulsive Therapy, at Eastern Psychiatric Research Association, October, N.Y. (Kahn, R.L. and Pollack, M.). 20. Jaffe, J.). ' Relationship between Seizure Threshold and Duration of Seizures to EEG Change During Electroshock, at IEastern Association of Electroencephalographers, December, New York (M.Green). �uuucav twain; by»: anuunsu .lmost as well as if he :ould see. Here he climbs the schdol steps with his ypewriter to attend ‘ a class. \\\\\\ &\\\\\\\\\\\\\\\\ \\\\\\\\\\\“ \\\\\\\ t J} \ MD Records Brain Waves Of Patients , A history written in brain waves is telling the story today 01' how successfully the mentally ill are responding to electro-shock and drug treatments. Dr. Max. Fink, a Great Neck psychiatrist who gave up a proﬁtable private practice to “prospect for Iacts”,»~ has developed a method of evaluating the brain waves of patients at Hillside Hospital, Glen Oaks,_ where he’s been leading an eight--man research team for four years. The brain wave "history”, recorded on graph paper and transmitted by an. electroencephalogram, enables the hospital's staff to “treat patients with more direction” Fink says. It works this way: The encephalogram picks up brain waves of a new patient and records a “base line” on the graph. As the patient is treatedand repeatedly tested the variations are recorded on the graph. Comparisions show whether a patient is . or isn’t . . . responding to a drug or shock treatment. , l f , 1 ; I 1 1 l K 1 ‘ . - - 3|! 1|: 1‘ “THE STUDY gives a new and keener sense of direction in treating the patients,” Fink said. For example: If a patient’s brain wave “history” shows that his response to is suddenly ' ' �“1191110 Jemeqm 01 31110 Buons KlaA 8 S1,, 1112833 301s Amman: amooaq 01 1113111 £11231 S1 911 -aonpu1 119011119110 9111 queued . 12 s1s1sax PWWI‘IXa 9H 'ppas 151111210st 1 ' ha] um 112112, 51901u19110 01121190 puno; aA'eq 9AA” 3511; 'BO‘BId mnsu! me 01111 111 11011 mm 1nd 219111 3111 lent 1elr SSJBABJ KHJBIOG 9113, g 3111 111911311 10 1110 [swam K1219 1; eu1uua1ap d19q 11mm (111 Fsoq am #4,!» '.1c'[ 5111110111 Emma 9111 3,5121 sanp seq wee], 91110:) unease; s‘xum ma; 1111111 19111311111 3,2111 ’Ielld sgqgepuno; [no panoddns A11u1o§ p112 ”3.190111 -‘Kq‘ s; 109(0ch 9111. was Hum ‘l‘summeu p003 KJIBA” paonp v; '-o.1d seq 21031on Jeeﬁ-e-ooo‘oow ép1s111H 112 pomém man ‘ 'sKes a: $11.11 1101129591 9111 $1110 9111 i “‘mou 919111“ pasn s1 as avg ii 13d 08 11190 AIa1'eu11x01dde”, o1 padumg ' .seq eBe1uaJJad 3111, 1911qu 3111 mm; paseapx aq 01 K11ua1o111ns pI—JJBAOOGJ smemman 110qu .10 8111p smeared 0111 10 “3,1130 13d 09 moqe” K1uo ‘1211dsoq 91.13, 12 pasn_ pue paldope sem pomaux aAem pa.11nb‘ax 011m ' KING. .‘mo ‘ ”0198 “'Janeq smamman 51311113. 'JCI sn smone 0), az1111n Apn1s emem 1112.1q PIPS RUM VICI «1-1qu 9111,, qu 01 mammal; man 11 'UOIS -SB.IBB.I 3111, 1199110 p118 An A13131d -1noa 'e 2193 52111 ‘wJo; [eu1 $1.10 511 o; xoeq ssa.1831 o1 su133q uo1z11puoo asoqm .10 ‘luauxaAmduu JO nonessao 'e uaaq $911 91311), sa;eo1pu1 uo111p1100 asoqm waned V 911'), -3AOJliﬁlt _ Kauanbaa; umoqs qde s1 3113111 mun aﬁesop 111 .10 peseaxou1 aq — ! B 33’ 000i u1ens pue’ ssans 10 p1.10m 9113, 01111 peseeﬁu uaqm 1121111 -soq b1 11:10 aAeq em ssa.1 spun 1111M -30.1d 4113; ho inmo- atn “‘1uaned XOGN e or 01 39.1391) 1101112» 9111’ 19111 ZS .r‘»_(’ ’ �February 25, 1959. Department of Experimental Paychiatry Annual Report - 1958 During 1958, the major emphasis of the staff of the Department of Experimental Paychiatry shifted from evaluation of convulsive therapy to systematic investigations of newer psychopharmacologic agents. These investigations, derived from the successful evaluations of the mode of action of convulsive therapy (l95h-l958), reserpine (1955), and chlorpromazine and insulin coma (1956-1957), are based on the neurophysiologic-adaptive hypothesis of physiodynamic therapies developed in the Department in 1957 ﬂggg. é? 197-206). the The many new compounds (J. Hillside interrelationship of the neurophysiologic effects of with the psychodynamic, perceptual, personality and sociologic aSpects of patients' behavior provide the framework for these investigations. In addition, linguistic indices developed in the Department during the past two years by Drs. Kahn and Jaffe are being studied as measures both of behavioral change and of neurophysiologic effect. During the year, the evaluation of convulsive therapies was continued effects of indoklon, an inhalant convulsant, with electroconvulsive therapy. 'This study was undertaken by two senior resident by comparing the psychiatrists, B. Alan and H. Lefkowits, and Drs. Green and Fink. While indoklon therapy was a successful treatment, technicallimitations made poor substitute for the established electrical methods. The it a study was of theoretic value in indicating that the significant element of convulsive therapy was the induction of the grand mal convulsion, with its attendant neurophysiologic effects, independent of the type of agent employed. �V , .2Investigations into the relations of sociologic factors to the selection of therapies at Hillside Hospital were extended by Drs. Kahn and Pollack. Not only were the factors of age, education, birthplace, and score on the California F Scale significantly related to the choice of therapy but these factors were also related to the results of therapy, the diagnosis and the duration of hOSpitalization. These observations were presented in the Sunday Conference of October 16, 1958. and On October 7 the study was repeated; similar studies of the population of other primarily psychotherapeutic hospitals, and the Hillside Hospital Out-Fatient Department were undertaken. To augment these studies, Dr. Nathaniel Siegel was appointed as Research Associate in Sociology, with the support of a grant from the Mental Health Board of Nassau County. In an extension of the communication studies, both the syntactic content analysis and dyadic diversification measures of formal aSpects of speech were applied to an evaluation of the changes in language patterns following the acute administration of various new psychotropic compounds. These measures demonstrated and the neurophysiologic The consistent changes both with the induced behavioral effects of the drugs. acute drug interviews were but one asPect of the continuing evaluation of the biochemistry of convulsive therapy. Previous studies had indicated that repeated induced convulsions resulted in an increased level of central nervous system acetylcholine activity. €g¥:;;;;:;;;;:§ of various anticholinergic stages of convulsive therapy we compounds By the acute administration to patients at various elucidated the synaptic chemical events which are the basis of the convulsive therapy process. �-3In addition, Mr. Karp and Drs. Kahn and Pbllack continued their perceptual studies in patients receiving psychodynamic therapies. The interrelation of psychotherapy with physiodynamic therapy was studied by Drs. Esecover, Jaffe and Kahn; and in the and H. Lefkowits began an latter part of the year, Drs. A. Kaplan investigation into the interpersonal factors in therapists, as well as patients, leading to the referral for physiodynannc therapies. During the year, Dr. H. Korin resigned, and was replaced by Mr. Eric Karp. TWO new staff appointments include Dr. Nathaniel Siegel, Assistant Professor of Sociology at Columbia University, as Research Associate in Sociology; and Dr. Donald Klein, research candidate at the New York Psychoanalytic scientist at Institute, as Creedmoor Institute Research Associate in Psychiatry. Support for this extensive program was provided by the Board of Directors, and continuing grants of the Foundations' Fund for Research in Psychiatry and the National Institute of Mental Health. At year end, this program received considerable Support from the Psychopharmacology Service Center of the National Institute of Mental Health, which augmented extensive commitment by a grant of $268,000. These its already further sums were increased during the year by support from the Mental Health Board of Nassau County which provided funds Smith, Kline & for sociologic studies; and from Bristol, Geigy, French, and wyeth Laboratories ~ who aided the drug evaluation program by grants as well as extensive supplies of the agents During the year, fourteen reports of the work of staff to be studied. members appeared; and twenty reports were presented to major professional societies. �-hIn addition to national societies, work of the Department was presented at the Conference on Psychodynamic, Psychoanalytic and Sociologic Aspects of Neuroleptic Drugs in Montreal, and the International Congress of Neuropsychopharmcology in Rome. Staff first members were awarded two prizes. Dr. M. Fink received the annual A.E. Bennett Peychiatric Essearch Award of the Society of Biologic Psychiatry for his report on the effects of anticholinergic agents on EEG and behavior. Dr. J. Jaffe received the Gralnick Foundation annual award for his report on the application of analysis of changes in fonnal aSpects of Speech in psychotherapy. �-5The staff of the Department of Experimental Psychiatry included, at year end: MEX Fink, M.D. Direeees Joseph Jeffe, M.D. Research Associate (Peychiatry) Donald F. Klein, Research Associate (Peychiatry) MQD. Robert L. Kahn, Fh.D. Max Pollack, Pth. Research Associate (Experimental Psychology) Research Associate (Experimental Paychology) Nathaniel Siegel, Ph.D. Research Associate (Sociology) Eric Karp, B.A. Research Assistant (Experimental Peychology) Martin A. Green, M.D. Associate in Research Abraham A. Kaplan, M.D. Associate in Research (Paychiatry) Barre Alan, M.D. Fellow (1957-58) Henry Lefkewits, M.D. Fellow (1958-59) The (Neurophysiology) technical staff included Mrs. Janet Bowie, Jean Kolodny, Mbsquera and Blanche Hannah Zaitz. addendum: In February Dr. George Krauthamer, Ph.D. was appointed as Research Assistant (Experimental Psychology). electroencephalography. He is a trainee in �nan-{u £55, 1959. lupurtuoat at ngcriunutal rayshxttvr ‘lunaal Icpcrt ~ 1955 ﬁtting 1953, it: 3.3.9 atyhnstg I! it. i‘l!‘ at tho ﬁapartunat it xxptriuaninl firth$¢%ry Ihlf‘ll tron utilisatog at convulsivt thurupr to tru‘unsttc tavnu‘acatinua a: utuar paynhnpitamnnoiauin attain. tunic tsvultxgntaill. inrtth Iron in. littl8if§1 evaluaiiOII or ﬁt. and: of 30‘s.: it nonralltvv thirty: (19$h~1956). IlllrpllO (1958). in: ohlcrv prunastnn uni 13.31%: can. 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M, ‘O ”#3; mm 0m. 30‘. . 3",; 3"“; AW 3.; It!!! ”all, I’D; lint: Luthuui‘s, lpﬂ. ltﬂiﬁrti Aasuoiuﬁn (firthtttry) Iliilfﬂh Atlliilii_ (lupotinuuttl rtvuhaztux) Intonrnh snln¢tutn (invtrilnttll P-vthnlacy) inaalvuh Asaaitnﬁc (80:103.:71 Icaiirdh Aaltcﬁaut .(lagnrlnnntul rurnlnlocy) £::o¢tnto in nasatvcl (lvuruphyntilugy) guspntsia in Ittoarol (rsywhaatry) villuu (19£?~$ﬁ) Ibllov (1955-59) ‘15:: Juan Janet tuulllod urn. tastu1¢i1 loioinr, Inuit. It. luntni aboqutti an: lxanaht 3a1$n. �1/15/59 Department of Experimental Psychiatrz list and the of presentations a chronologic Following is of Experimental members of the Department of the publications Psychiatry during 1958. A.“ Publications: 1. Changes in Language During Electroshock Therapy, in of Communication, Hoch, P. and Zubin, Ps cho atholo 3. e38., Urune E Stratton, (Kaﬁn, R.L. and Pink, M.) of Sedation Threshold, 2. Lateral Gaze Nystagmus as an Index162-163 (Fink, M.). EEG. Clin. Neurophysiol. lg: EEG and Significance for Theory on of Diethazine 3. Effect of Convulsive Therapy, EEG. Clin. Neurophzsiol. l9: 207‘208 (abate) (Fink, Process, his. h. Experimental Studies of the Electroshock M. and Kahn, R.L.). 113-118 (Fink, Nerv. l2: Coma and Insulin of Chlorpromazine 5. Comparative Study 18h6-1850 166: J.A.M.A. of Psychosis, Therapy G. and Coleman, F.C.). Shaw, Gross, M., R., (Fink, 6. Electroencephalographic Correlates of the ElectroshockM. S Nerv. Dis. st. $2: 227 (Abst.) (Fink, Process, o o stt. and Green, H.$. 7. 8. 9. 10. (Jaffe, J.). Pszchiatrz 3;: Effects of Megimide in Patients without M. Language of the Dyed, Clinical and EEG. 2h9-258 Cerebral Disease, Neurologz Q: 682-685 (Green, and Fink, M.) EEG and on Diethazine, Agent, of Anticholinergic Effect & Pszch. ﬁg: 380-388, Arch. Neurol. L.M.A. Behavior, (Fink, M.). on and Drug Therapies Convulsive of Studies Experimental Arch. A.M.A. Theoretical Implications, Psychiatry: Neurol. & Ps ch. 80: 733-73h (Abst.) (FInE, 3.. Kahn, F.I. and Green, M77. ll. Brain Damage, Mental Retardation and Childhood Schizophrenia, Am. J. Pszchiat. 115: h22-h28 (Pollack, M.). 12. Oculomotor and Postural Patterns in Schizophrenic Children, A.M.A. Arch. Neurol. & Ps chiat..12: 720-726 (Pollack, M. and Krieger, H.P.5. 13. Arch. A.M.A. of Denial in Factors Illness, Interpersonal& Ps chiat. ﬁg; 653-656 (Jaffe, . and Neurol. Slate, W.H.$. �1’40 B. Predictions of Outcome, in Youthful Offenders at Hi hfields, Weeks, H. Ashley, e3. U. of Michigan P ress, Ann Arbor (N. Siegel . Presentations: 1. EEG Correlates of the Electroshock Process, at the Eastern Psychiatric Research Association, February, N.Y. (Fink, M. and Green, M.A.). 2. EEG Changes in of Individual Variability Significance During Electroshock Therapy, at Eastern Association of Electroencephalographers, March, Montreal, (Green, M.A.). 3. and Drug Therapies Convulsive of Studies Experimental in Psychiatry: Theoretical Implications, at New York Society of and Society Neurological Clinical Psychiatry, March, N.Y. (Fink, M., Kahn, R.L. and Green, M.A.). Abnormal and Normal and in Attention Visual Perception Children, at American Orthopsychiatric Association, March, N.Y. (Pollack, M.). Patterns with Altered Brain Function, at Eastern Psychological Association, April, and M.). R.L. Fink, Kahn, Philadelphia (Jaffe, J., Relation of F Score to Behavioral and Physiological Response with Altered Brain Function, at Eastern Psychological Association, April, Philadelphia, Communication 6. The (Kahn, R.L. and Fink, M.) 7. Intellectual Deficits in Patients with Space Occupying Lesions of the Cerebrum, at Eastern Psychological Association, April, Philadelphia (Pollack, M., Battersby, W.S., Kahn, R.L. and Bender, M.B.). Simultaneous of and Stimulation Perception of Intensity Stimuli in Cerebral Dysfunction, at Eastern Psychological Association, April, Philadelphia (Korin, H.). �-3- 10; Socio-Psychological Aspects of Diagnosis and Treatment: Theoretical Implications, Symposium - Eastern Psychological Association, April, Philadelphia, (Kahn, R.L. and Pollack, M.). Drug Induced Changes in Interview Patterns, at Conference on Psychodynamic, Psychoanalytic, and Sociologic ASpects of the Neuroleptic (tranquilizing) M. Montreal (Fink, Drugs in Psychiatry, April, and 11. 12. 13. 16. 17. 18. 19. Jaffe, J.). Psychological Factors Affecting Individual Differences in Behavioral Reaponse to Convulsive Therapy, at American Psychiatric Association, May, San Francisco (Fink, M., Kahn, R.L. and Pollack, M.). Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy, at Electroshock Research Association, May, San Francisco (Kahn, R.L. and Fink, M.). EEG on Diethazine, of Agent, Anticholinergic Effects and Behavior: Significance for Theory of Convulsive Therapy, at Society of Biological Psychiatry, May, San Francisco (Fink, M.). Social Factors in Selection of Therapy in a Voluntary Mental Hospital, at American Psychiatric Association, May, San Francisco (Kahn, R.L. and Pollack, M.) A Critique of "Pre-Conscious" Perception and the "Poetzl Phenomenon," at American Psychiatric Association, May, San Francisco (Pollack, M.). Role of EEG Frequency Shift in Behavioral Effects of & Neurol. on Section Psychiat. Queens Drugs, at County Medical Society, June, N.Y. (Fink, M.). on Post Convulsive Effect of Anticholinergic Compounds EEG and Behavior, American EEG Society, June, Atlantic City (Fink, M.). EEG and Behavioral Effects of Psychopharmacologic Agents, at Collegium Internationale Neuro-Psycho Pharmacologicum, September, Rome, and Eastern Association of Electroencephalographers, December, N.Y. (Fink, M.). Prognostic Application of Psychological Techniques in Convulsive Therapy, at Eastern Psychiatric Research Association, October, N.Y. (Kahn, R.L. and Pollack, M.). 20. Relationship between Seizure Threshold and Duration of Seizures to EEG Change During Electroshock, at Eastern Association of Electroencephalographers, December, New York (M.Green). �law HILLSIDE HOSPITAL Glen Oaks, New York March 16, 1959 MEMO TO RESEARCH FROM: RE: ' COWITI'EE JOSEPH S.A. MILLER, M.D., MEDICAL DIRECTOR ATTACHED RESEARCH REPORT I herewith enclosing copy of Dr. sending it a few days in advance of the meeting, familiarize yourself with some of the main facts position to discuss this when it is presented at meeting on March 25th. am Fink's report, so that you might and be in a better the forthcoming �FebmaIy 25, 19590 Department of Experimental Peychiatry Annual Report - 1958 During 1958, the major emphasis of the staff of the Department of Experimental Paychiatry shifted from evaluation of convulsive therapy to systematic investigations of newer psychopharmacologic agents. These investigations, derived from the successful evaluations of the mode of action of convulsive therapy (l9Sh-l958), reserpine (1955), and chlorpromazine and insulin coma (1956-1957), are based on the neurophysiologic-adaptive hypothesis of physiodynamic therapies developed in the Department in 1957 Eggg. the ﬁg 197-206). The many new compounds (J. Hillside interrelationship of the neurophysiologic effects of with the psychodynamic, perceptual, personality and sociologic aspects of patients' behavior provide the framework for these investigations. In addition, linguistic indices developed in the Department during the past two years by Drs. Kahn and Jaffe are being studied as measures both of behavioral change and of neurophysiologic effect. During the year, the evaluation of convulsive therapies was continued by comparing the effects of indoklon, an inhalant convulsant, with electro- convulsive therapy. This study was undertaken by two senior resident psychiatrists, B. Alan and H. Lefkowits, and Dre. Green and Fink. 'While indoklon therapy was a successful treatment, technicallimitations made it a poor substitute for the established electrical methods. The study was of theoretic value in indicating that the significant element of convulsive therapy was the induction of the grand mal convulsion, with its attendant neurophysiologic effects, independent of the type of agent employed. �.2the to factors of the sociologic relations into Investigations Kahn and Drs. extended by were Hillside Hospital of at selection therapies Pollack. Not only were the factors of age, education, birthplace, and score on the California F Scale significantly related to the choice of therapy but and the of diagnosis the to results therapy, related also these factors were the duration of heapitalization. These observations were presented in the Sunday Conference of October 16, 1958. and On October 7 the study was repeated; similar studies of the population of other primarily psychotherapeutic undertaken. were Out-Patient Department and HOSpital Hillside the hoSpitals, To augment these studies, Dr. Nathaniel Siegel was appointed as Research Associate in Sociology, with the support of a grant from the mental Health Board of Nassau County. In an extension of the communication studies, both the syntactic content analysis and dyadic diversification measures of formal aspects of epeech were applied to an evaluation of the changes in language patterns following the acute administration of various new psychotropic compounds. These measures demonstrated consistent changes both with the induced behavioral and the neurophysiologic The effects of the drugs. acute drug interviews were but one aspect of the continuing evaluation of the biochemistry of convulsive therapy. Previous studies had indicated that repeated induced convulsions resulted in an increased level of central nervous system acetylcholine activity. By the acute administration of various tertiary-amine anticholinergic compounds to patients at various stages of convulsive therapy we elucidated the synaptic chemical events which are the basis of the convulsive therapy process. �-3In addition, Mr. Karp and Drs. Kahn and Pbllack continued their perceptual studies in patients receiving psychodynamic therapies. inter- The relation of psychotherapy with physiodynamic therapy was studied by Drs. Esecover, Jaffe and Kahn; and in the latter part of the year, Drs. A. Kaplan and H. Lefkowits began an investigation into the interpersonal factors in therapists, as well as patients, leading to the referral for physicdynamic therapies. During the year, Dr. H. Korin resigned, and was replaced by Mr. Eric Karp. TWO new staff appointments include Dr. Nathaniel Siegel, Assistant Professor of Sociology at Columbia University, as Research Associate in Sociology; and Dr. Donald Klein, research candidate at the New York Psychoanalytic scientist at Institute, as Creedmoor Institute Research Associate in Psychiatry. Support for this extensive program was provided by the Board of Directors, and continuing grants of the Foundations' Fund for Research in Psychiatry and the National Institute of Mental Health. At year end, this program received considerable support from the Psychopharmacclogy Service Center of the National Institute of Mental Health, which augmented extensive commitment by a grant of $268,000. These its already further sums were increased during the year by support from the Mental Health Board of Nassau County which provided funds Smith, Kline & for sociologic studies; French, and wyeth Laboratories - who and from Bristol, Geigy, aided the drug evaluation program by grants as well as extensive supplies of the agents During the year, fourteen reports of the work of staff to be studied. members appeared; and twenty reports were presented to major professional societies. �.1... In addition to national societies, work of the Department was presented at the Conference on Psychodynamic, Psychoanalytic and Sociologic Aspects of Neuroleptic Drugs in Montreal, and the International Congress of Neuropsyohophamacology in Rome. Staff first members were awarded two prizes. Dr. M. Fink received the annual A.E. Bennett Paychiatzic Research Award of the Society of Biologic Psychiatry for his report on the effects of anticholinergic agents on Em and behavior. Dr. J. Jaffe received the Gralnick Foundation annual award for his report on the application of analysis of changes in formal aspects of Speech in psychotherapy. �-5The staff of the Department of Experimental Psychiatry included, year end: Max Fink, M.D. M Joseph Jaffe, MlD. Research Associate (Peychiatry) Donald F. Klein, Research Associate (Psychiatry) MgD. Robert L. Kahn, Ph.D. Research Associate (Experimental Peychology) Pollack, Ph.D. Research Associate (Experimental Psychology) Max Nathaniel Siegel, Ph.D. Research Associate (Sociology) Eric Karp, B.A. Research Assistant (Experimental Psychology) Martin A. Green, M.D. Associate in Research Abraham.A. Kaplan, M.D. Associate in Research (Paychiatry) Barre Alan, M.D. Fellow (1957-58) Henry Lefkowits, M.D. Fellow (1958-59) The (Neurophysiology) technical staff included Mrs. Janet Bowie, Jean Kolodny, Mosquera and Blanche Addendum: Hannah Zaitz. In February Dr. George Krauthamer, Ph.D. was appointed as Research Assistant (Experimental Psychology). electroencephalography. at He is a trainee in �1/15/59 Department of Experimental Psychiatry and the of presentations a chronologic list Following is of members Experimental the of Department of the publications Psychiatry during 1958. Publications: A. 1. Changes in Language During Electroshock Therapy, in of Communication, Hoch, P. and Zubin, Ps chopatholo 3. eds., Grune & Stratton, (Kahn, R.L. and Fink, M.) 2. Lateral 3. h. 5. 6. Gaze Nystagmus as an Index of Sedation Threshold, Clin. Neurophysiol. 19: 162-163 (Fink, M.). EEG and Significance for Theory on of Diethazine Effect of Convulsive Therapy, EEG. Clin. Neurophysiol. 19: EEG. Experimental Studies of the Electroshock Process, Dis. M. and Kahn, R.L.). 113-118 (Fink, Nerv. Syst. 12: Coma and Insulin of Chlorpromazine Study Comparative Therapy of Psychosis, J.A.M.A. 166: 18h6-1850 G. and Coleman, F.C.). Shaw, Gross, R., (Fink, M., Electroencephalographic Correlates of the ElectroshockM. Process, Dis. Nerv. Syst. 12: 227 (Abst.) (Fink, and GreenTWMTfT—___-—*— (Jaffe, J.). 7. Language of the Dyad, Psychiatry 31: 2h9-258 8. without Patients in of Megimide Effects Clinical M. 682-685 (Green, Q: Cerebral Disease, Neurology and EEG. and Fink, M.) 9. 10. on EEG and Effect of Anticholinergic Agent, Diethazine, & Psych. g9: 380-388, Neurol. A.M.A. Arch. Behavior, (Fink, M.). on and Drug Therapies Convulsive of Studies Experimental A.M.A. Arch. Theoretical Implications, Psychiatry: Kahn, M., & (FinE, 80: 733-73h (Abst.) Neurol. Psych. R.E. and Green, M77. 11. Brain Damage, Mental Retardation and Childhood Schizophrenia, Am. J. Psychiat. 115: h22-h28 (Pollack, M.). 12. Oculomotor and Postural Patterns in Schizophrenic Children, A.M.A. Arch. Neurol. & Ps chiat. 12: 720-726 (Pollack, M. and Krieger, H.P.5. 13. A.M.A. Arch. of Denial in Factors Illness, Interpersonal& and 653-656 J. Ps (Jaffe, ﬁg: Neurol. chiat. Slote, W.H.§. �1h. B. Predictions of Outcome, in Youthful Offenders at H. Ashley, ed. 5. of Highfields, Weeks, Michigan Press, Ann Arbor (N. Siegel). Presentations: the EEG at Electroshock of the Process, Correlates l. Eastern Psychiatric Research Association, February, M. N.Y. (Fink, and Green, M.A.). EEG Changes in of Individual Variability Significance During Electroshock Therapy, at Eastern Association of Electroencephalographers, March, Montreal, (Green, M.A.). Experimental Studies of Convulsive and Drug Therapies in Psychiatry: Theoretical Implications, at New York Society of and Society Neurological Clinical Psychiatry, March, N.Y. (Fink, M., Kahn, R.L. and Green, M.A.). Visual Perception and Attention in Normal and Abnormal Children, at American Orthopsychiatric Association, March, N.Y. (Pollack, M.). Communication Patterns with Altered Brain Function, at Eastern Psychological Association, April, and M.). R.L. Fink, Kahn, (Jaffe, Philadelphia J., Relation of F Score to Behavioral and Physiological Response with Altered Brain Function, at Eastern Psychological Association, April, Philadelphia, (Kahn, R.L. and Fink, M.) Intellectual Deficits in Patients with Space Occupying Lesions of the Cerebrum, at Eastern Psychological Association, April, Philadelphia (Pollack, M., Battersby, W.S., Kahn, R.L. and Bender, M.B.). Simultaneous of and of Stimulation Perception Intensity Stimuli in Cerebral Dysfunction, at Eastern Psychol~ ogical Association, April, Philadelphia (Korin, H.). The �-3- 10. Socio-Psychological Aspects of Diagnosis and Treatment: Theoretical Implications, Symposium - Eastern Psychological Association, April, Philadelphia, (Kahn, R.L. and Pollack, M.). Drug Induced Changes in Interview Patterns, at Conference on Psychodynamic, Psychoanalytic, and Sociologic Aspects of the Neuroleptic (tranquilizing) M. Montreal (Fink, Drugs in Psychiatry, April, _ and 11. 12. 13. 16. 17. 18. 19. Jaffe, J.). Psychological Factors Affecting Individual Differences in Behavioral Response to Convulsive Therapy, at American Psychiatric Association, May, San Francisco (Fink, M., Kahn, R.L. and Pollack, M.). Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy, at Electroshock Research Association, May, San Francisco (Kahn, R.L. and Fink, M.). EEG on of Agent, Diethazine, Effects Anticholinergic and Behavior: Significance for Theory of Convulsive Therapy, at Society of Biological Psychiatry, May, San Francisco (Fink, M.). Social Factors in Selection of Therapy in a Voluntary Mental Hospital, at American Psychiatric Association, May, San Francisco (Kahn, R.L. and Pollack, M.) A Critique of "Pre-Conscious" Perception and the "Poetzl Phenomenon," at American Psychiatric Association, May, San Francisco (Pollack, M.). Role of EEG Frequency Shift in Behavioral Effects of & Neurol. on Section Psychiat. Queens Drugs, at County Medical Society, June, N.Y. (Fink, M.). on Post Convulsive Effect of Anticholinergic Compounds EEG and Behavior, American EEG Society, June, Atlantic City (Fink, M.). EEG and Behavioral Effects of Psychopharmacologic Agents, at Collegium Internationale Neuro-Psycho Pharmacologicum, September, Rome, and Eastern Association of Electroencephalographers, December, N.Y. (Fink, M.). Prognostic Application of Psychological Techniques in Convulsive Therapy, at Eastern Psychiatric Research Association, October, N.Y. (Kahn, R.L. and Pollack, M.). 20. Relationship between Seizure Threshold and Duration of Seizures to EEG Change During Electroshock, at Eastern Association of Electroencephalographers, December, New York (M.Green). �1/15/59 Department of Experimental Psychiatry and the of presentations Following is a chronologic list of Experimental the members Department of the of publications Psychiatry during 1958. A. Publications: in Therapy, Electroshock During Language Changes in 1. and Zubin, P. Hoch, Communication, of cho Ps atholo 3. eds., Grune & Stratton, (Kaﬁn, R.L. and Fink, M.) of Sedation Threshold, 2. Lateral Gaze Nystagmus as an Index162-163 (Fink, M.). EEG. Clin. Neurophysiol. 19: EEG and Significance for Theory on of Diethazine 3. Effect of Convulsive Therapy, EEG. Clin. Neurophysiol. 19: h. 5. 6. 7. 8. 9. 10. 11. 12. 13. Process, Dis. Experimental Studies of the Electroshock M. and Kahn, R.L.). 113-118 (Fink, Nerv. Syst. 12: Coma and Insulin Comparative Study of Chlorpromazine 18h6-1850 166: J.A.M.A. of Psychosis, Therapy and G. Coleman, F.C.). Shaw, Gross, R., (Fink, M., Electroencephalographic Correlates of the ElectroshockM. 227 (Fink, (Abst.) Nerv. Dis. Syst. 12: Process, and Green, M.,. 2h9~258 21: (Jaffe, J.). the Dyad, Psychiatry Language of without in Patients of EEG. Megimide and Effects Clinical M. 682-685 (Green, Cerebral Disease, Neurology g: and Fink, M.) EEG and on Diethazine, Agent, Effect of Anticholinergic & Psych. ﬁg: 380-388, Neurol. Arch. A.M.A. Behavior, (Fink, M.). on and Drug Therapies Convulsive of Studies Experimental Arch. A.M.A. Implications, Theoretical Psychiatry: (FEEET'MTT’Kahn, 733—73h & 80: (Abst.) Ps ch. Neurol. ﬁ.f. and Green, M77. Brain Damage, Mental Retardation and Childhood Schizophrenia, Am. J. Psychiat. 115: h22—h28 (Pollack, M.). W..— Oculomotor and Postural Patterns in Schizophrenic Children, A.M.A. Arch. Neurol. & Ps chiat..12: 720-726 ,fPollack, M. and Krieger, H.P.5. Arch. A.M.A. of Denial in Illness, Interpersonal& Factors Ps chiat. ﬁg: 653-656 (Jaffe, J. and Neurol. Slote, W.H.$. �1h. B. Predictions of Outcome, in Youthful Offenders at Hi hfields, Weeks, H. Ashley, ed. U. of Michigan Press, Ann Arbor (N. Siegel). Presentations: EEG Correlates of the Electroshock Process, at the 1. Eastern Psychiatric Research Association, February, M. N.Y. (Fink, and Green, M.A.). EEG Changes in of Individual Variability Significance During Electroshock Therapy, at Eastern Association of Electroencephalographers, March, Montreal, (Green, M.A.). and Drug Therapies of Convulsive Studies Experimental in Psychiatry: Theoretical Implications, at New York Society of and Society Neurological Clinical Psychiatry, March, N.Y. (Fink, M., Kahn, R.L. and Green, M.A.). Abnormal and Normal and in Attention Visual Perception Children, at American Orthopsychiatric Association, March, N.Y. (Pollack, M.). Patterns with Altered Brain Function, at Eastern Psychological Association, April, and M.). R.L. Fink, Kahn, (Jaffe, Philadelphia J., Relation of F Score to Behavioral and Physiological Response with Altered Brain Function, at Eastern Psychological Association, April, Philadelphia, Communication The (Kahn, R.L. and Fink, M.) Intellectual Deficits in Patients with Space Occupying Lesions of the Cerebrum, at Eastern Psychological Association, April, Philadelphia (Pollack, M., Battersby, W.S., Kahn, R.L. and Bender, M.B.). Simultaneous of and of Stimulation Perception Intensity Stimuli in Cerebral Dysfunction, at Eastern Psychological Association, April, Philadelphia (Korin, H.). �-3Socio—Psychological ASpects of Diagnosis and Treatment: 10. Drug Theoretical Implications, Symposium - Eastern Psychological Association, April, Philadelphia, (Kahn, R.L. and Pollack, M.). Induced Changes in Interview Patterns, at Conference on Psychodynamic, Psychoanalytic, and Sociologic ASpects of the Neuroleptic (tranquilizing) M. Montreal (Fink, Drugs in Psychiatry, April, ‘ and 11. 12. 16. 17. 18. 19. Jaffe, J.). Psychological Factors Affecting Individual Differences in Behavioral Reaponse to Convulsive Therapy, at American Psychiatric Association, May, San Francisco (Fink, M., Kahn, R.L. and Pollack, M.). Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy, at Electroshock Research Association, May, San Francisco (Kahn, R.L. and Fink, M.). EEG on of Agent, Diethazine, Effects Anticholinergic and Behavior: Significance for Theory of Convulsive Therapy, at Society of Biological Psychiatry, May, San Francisco (Fink, M.). Social Factors in Selection of Therapy in a Voluntary Mental Hospital, at American Psychiatric Association, May, San Francisco (Kahn, R.L. and Pollack, M.) A Critique of "Pre-Conscious" Perception and the "Poetzl Phenomenon," at American Psychiatric Association, May, San Francisco (Pollack, M.). Role of EEG Frequency Shift in Behavioral Effects of & Neurol. on Section Psychiat. Queens Drugs, at County Medical Society, June, N.Y. (Fink, M.). Effect of Anticholinergic Compounds on Post Convulsive EEG and Behavior, American EEG Society, June, Atlantic City (Fink, M.). EEG and Behavioral Effects of Psychopharmacologic Agents, at Collegium Internationale Neuro-Psycho Pharmacologicum, September, Rome, and Eastern Association of Electroencephalographers, December, N.Y. (Fink, M.). Prognostic Application of Psychological Techniques in Convulsive Therapy, at Eastern Psychiatric Research Association, October, N.Y. (Kahn, R.L. and Pollack, M.). 20. Relationship between Seizure Threshold and Duration of Seizures to ERG Change During Electroshock, at Eastern Association of Electroencephalographers, December, New York (M.Green). �1/15/59 Department of Experimental Psychiatry and the of presentations Following is a chronologic list of EXperimental members the of Department of the publications Psychiatry during 1958. Publications: A. 1. Changes in Language During Electroshock Therapy, in of Communication, Hoch, P. and Zubin, Ps cho atholo M.) and E R.L. (Kahn, Fink, Grune Stratton, J. eds., 2. Gaze Nystagmus as an Index of Sedation Threshold, 3. h. 5. 6. 7. 8. 9. 10. 11. 12. 13. Lateral M.). 162-163 (Fink, Clin. Neurophysiol. 19: EEG Theory for and on Significance of Diethazine Effect of Convulsive Therapy, EEG. Clin. Neurophysiol. lg: EEG. Process, Dis. Experimental Studies of the Electroshock Nerv. Syst. 12: 113-118 (Fink, M. and Kahn, R.L.). Coma and Insulin of Chlorpromazine Comparative Study 18b6-1850 166: J.A.M.A. of Psychosis, Therapy and G. Coleman, F.C.). Shaw, R., Gross, (Fink, M., Electroencephalographic Correlates of the ElectroshockM. 227 (Fink, (Abst.) Nerv. Dis. Syst. 12: Process, and Green, ﬁ.$. 2h9-258 (Jaffe, J.). the of g1: Dyed, Psychiatry Language without in Patients EEG. Megimide of and Effects Clinical M. 682~685 (Green, Cerebral Disease, Neurology g: and Fink, M.) EEG and on Diethazine, Effect of Anticholinergic Agent, & 380-388, Q9: Neurol. Arch. A.M.A. Psych. Behavior, (Fink, M.). on and Drug Therapies Convulsive of Studies Experimental Arch. A.M.A. Implications, Theoretical Psychiatry: Kahn, (Fink, & ﬁ., 80: 733-73h (Abst.) Ps ch. Neurol. R.I. and Green, M77. Childhood and Schizophrenia, Mental Retardation Damage, Brain Am. J. Psychiat. 115: h22-h28 (Pollack, M.). Oculomotor and Postural Patterns in Schizophrenic Children, & Ps chiat._12: 720-726 Neurol. Arch. A.M.A. (Pollack, M. and Krieger, H.P.5. Arch. A.M.A. of Denial in Illness, Factors Interpersonal& and 653-656 J. Ps (Jaffe, chiat. g9: Neurol. Slote, W.H.$. �1h. B. at Predictions of Outcome, in Youthful Offenders U. H. of Ashley, ed. Weeks, Highfields, ichigan Press, Ann Arbor (N. Siegel). Presentations: the at EEG Electroshock of Process, the Correlates 1. Eastern Psychiatric Research Association, February, M. N.Y. 2. (Fink, and Green, M.A.). EEG Changes in Significance of Individual Variability During Electroshock Therapy, at Eastern Association of Electroencephalographers, March, Montreal, (Green, M.A.). and Drug Therapies Convulsive of Studies Experimental in Psychiatry: TheoreticalNewImplications, at York Society of Neurological Society and Clinical Psychiatry, March, N.Y. (Fink, M., Kahn, R.L. and Green, M.A.). Abnormal and Normal and in Attention Visual Perception Children, at American OrthOpsychiatric Association, March, N.Y. (Pollack, M.). Patterns with Altered Brain Function, at Eastern Psychological Association, April, and M.). R.L. Fink, Kahn, Philadelphia (Jaffe, J., and F Behavioral Physiological to Score of Relation Response with Altered Brain Function, at Eastern Psychological Association, April, Philadelphia, Communication The (Kahn, R.L. and Fink, M.) 7. with Space Occupying Intellectual Deficits in Patients Eastern Psychological Lesions of the Cerebrum, at Association, April, Philadelphia (Pollack, M., Battersby, W.S., Kahn, R.L. and Bender, M.B.). Simultaneous of and of Stimulation Perception Intensity Stimuli in Cerebral Dysfunction, at Eastern Psychol— ogical Association, April, Philadelphia (Korin, H.). �-3- 10. Socio-Psychological ASpects of Diagnosis and Treatment: Theoretical Implications, Symposium - Eastern Psychological Association, April, Philadelphia, (Kahn, R.L. and Pollack, M.). Drug Induced Changes in Interview Patterns, at Conference on Psychodynamic, Psychoanalytic, and Sociologic Aspects of the Neuroleptic (tranquilizing) Drugs in Psychiatry, April, Montreal (Fink, M. _ and 11. 12. 16. 17. 18. 19. Jaffe, J.). Psychological Factors Affecting Individual Differences in Behavioral Response to Convulsive Therapy, at American Psychiatric Association, May, San Francisco (Fink, M., Kahn, R.L. and Pollack, M.). Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy, at Electroshock Research Association, May, San Francisco (Kahn, R.L. and Fink, M.). EEG on of Agent, Diethazine, Effects Anticholinergic and Behavior: Significance for Theory of Convulsive Therapy, at Society of Biological Psychiatry, May, San Francisco (Fink, M.). Social Factors in Selection of Therapy in a Voluntary Mental Hospital, at American Psychiatric Association, May, San Francisco (Kahn, R.L. and Pollack, M.) A Critique of "Pre-Conscious" Perception and the "Poetzl Phenomenon," at American Psychiatric Association, May, San Francisco (Pollack, M.). Role of EEG Frequency Shift in Behavioral Effects of & on Neural. Section Psychiat. Queens Drugs, at County Medical Society, June, N.Y. (Fink, M.). Effect of Anticholinergic Compounds on Post Convulsive EEG and Behavior, American EEG Society, June, Atlantic City (Fink, M.). EEG and Behavioral Effects of Psychopharmacologic Agents, at Collegium Internationale Neuro-Psycho Pharmacologicum, September, Rome, and Eastern Association of Electroencephalographers, December, N.Y. (Fink, M.). Prognostic Application of Psychological Techniques in Convulsive Therapy, at Eastern Psychiatric Research Association, October, N.Y. (Kahn, R.L. and Pollack, MI). 20. Relationship between Seizure Threshold and Duration of Seizures to EEG Change During Electroshock, at Eastern Association of Electroencephalographers, December, New York (M.Green). �\\.\" ‘\ Soptubor 1, 1959 rm m2 mm H.927 Dumb-at of mparimntal Psychiatry HWPM WEE Glen H. L. m, 1. thmm 3. 3mm 8mm, h. Publications, 1951: - 1959 5. Presentations, 1951; 6. Smnmry #1, September 1. - 1959 1951:: - 7. Sunny #2, Mary 1. 8. Smmry #3, April 1, 1957 2. #1:, February 1, 1959 Five Years, 199; - - Sophombor 1956 ~ January 1, 1956 Am; 1, - February March Asaoomboa EEG 1957 1, 1958 Ha: (kparmanul 1, 1959 1959 Principal Investigator Research Associates I. I.) Psychology) (Neurophysiology) Technician Secretuy m,n.n. Robert L. Kahn.Ph.Do Hymn Karin, £11.13. Eda M,M¢A. Martin A. momma. mummﬁub. 19%4953 1958 ’ 1956 .1951; 1959 ‘- 1957 1956 Joseph Jaffe,M.D. Donald F. K1o1n,24..n. 1959 Nathaniel 319301,Ph.D. 1958 «- Georgo Hanna Mosquera Janet Baltic Associates, supported throng: other grants: Research Associate Mouth Associate amorob Associate Research Associate (kperimntal Paydnol.) ( Psychiatry) (Psychiatry) (Sociolm) Max Pollackﬁhon. . «- - �he mm: Amwhmr reporwd here would nab have has: possible without the interact and support of the Ecuador of Hillside 808mm, Dr. 18ml Sinus, ﬂu Hard of Directors and the Hr. Maurice when faith sustain“! an. pmm aux-mg its only uwnmau. W, mutter, Wemﬂsoindcbtodtothexmmnnandmm Ina-k, the Pomdntiona' Fund for Board of Nassau County and the um and Rosearoh I Waumdﬂu in Psychiatry, the 1mm Health mm sum. My Wane-la, tonamg pharmoouticll and Ranch Laboratories, Wyeth Laboratories, Bristol Laboratories, thou support in amt-fully achnﬂadgod. �3m. m Dam“ me labor-mm- of on of Exparimntsl Psychiatry oatsblishad so musics Homul in Smtmber, 1951:. During this fivc your period mumpbyuoloéio, psychologc (personality and pamptm), linguistic, and sociolcgio upsets of 'soutic" psychiatric have been tho pmipu [£001. mums 1. WC The Thong: =, visit or the convulsive mnpy process as the induction of a nonnspeciftc state of altered brain function, similar to omnioosrsbnl trams was supportcd and upliﬂed (10, 11. 21). Within this altered osrobn}. milieu, subjects were seen to respond in variom ways (26) , ”lino: m9}: post "successful" no explicit verbal dsnial (7. 31). This lotto)? adsptation was most prominent in chamooerclogioﬂly disposed indvidmls (36). J? in altshﬂon bran function was pro-requisite to boluvionl orange Grand m1 scams were column]. to this 26). 11, 8, (7* The alterations but (26) induction was (34:2). not electrical pm: in mmfunction were measured in various ways including doom(6.n,12,2h,39), language patterns (h.7.3h.31.h3; Mb). pen-mm mu (2,16,17,37,h63 magma) and tests of real]. (8). 1n Wham "v I". 316mb numbers tho appsndix. on to publications or pneumatic” (B- ) listed in �variety of beluvieml changes lure eeen during convulsive therapy (26; 8-17). Such patterns were viewed as edepteticne to altered brain A Motion, and were believed dependant upon chencterologic end environ- mental tactore (7, 25, 26, 36, ho). Clinical retina: of improvement cbeemr or the behavioral change. in the subject (26). Adaptations chmcterieed by denied www.mm 1n behavim' (13.17) and in language (7. WM— Such adaptations! were related to habitual node. were new as value Judgments by the W or conduct (character, The ML (inability per-MW) BMW (36; 3-11, 32). of the altered behavioral nodes wee noted ee dependant upon the degree and duration of mm alterec breln function. the expectatlone, an! the type and degree of family and medical support. Different behavioral patterns were beet supported by WIt m eke typee or psychothonpy (19).. that the ’nemphwelolcglcel beele of lie in on duration in central emptic suggeeted M? commune therepy any cholinerglc - cannot-31c relationship, with a predominant to incremd cholinergic activity as the operationally significant wt :3th. illumination: were based on the nutimdllp of man voltage EEG Olav wave activity to behavioral change (6, 11, 26) and the blocking at Such poet-mun ; electmgrephic and behavioral changee by central entichonnergic agents (21; 3h: 35; bl. 1&2) and by centre]. unpethwmtic agents (ha). ”664%? ;;;m u— 00'“ ? 4, @3. M‘,£~§. W m 4/: “3/93,”?1 will, ’?.L<»Jv%ué~éiy.i �-3.‘ Become of linguistic behavior in structured (7, 31) and unstructured (1h, 29 ; 13-21.) creaeed denial, interviews shoved characteristic alterations towards in- minutiae, displacement, stereotypy and repetitivemes, related to the degree of altered brain function (8.214). These changes were blocked or reversed by enticholinsrgic mlucinogm (21. ha) . Various perceptual tasks provided indices of behavioral, change and were related to the degree of altered brain function. These included the perception of cinulteneoue tactile figures (37; 3-16), color tigorcs (1:1). and stimli (17), embedded (Gottschsbdt) techistoaoopioelly exposed words (37) and embedded upsets or age, years of education, nativity and degree of stereotypy and conventionslity (measured by Column F Scale) were related to selection of therapy, duration or hospitalisation, e diegmeie and treetsent response in hospitalised patients (15, 36,. to, 1:5). Sooiopsyohologic 2. Nsmmmlogio—Adspuve mom-1e of Sonauc' Theron. Based on these studies, a hypothesis of the node of action of other psydxistx'ic therapies such as insulin coho, leucotoav and psychotropic drugs, was expressed (10, 33, 38). This View holds that the efficacy of these therapies depends upon the indiction of states of altered brain The become which prominent. in adoptive varying mttems my much, adaptive pettem is releted to the type, degree end duration of altered brain function, the personality of the subject, and tolersnoes end expectaﬂons of the environmnt. Elicitation of this Wthesis as applied to drug therapies is our in progmss, supported by uspm greats 111.2092 and 111-2715. ' ' �3. Eula Gena Thong. in iniﬂal case yettem e'mdy showed the significance both or denial and peraieten’e in insulin coma altered brain function for the behavioral change (3)} thenpy In an insulin chlorpruesim control stuck, no differences in hospital. immanent ratings were observed in the eve treatmnt gronpl (27). Chlorpruuine was eater, easier to administer, pernitted continued coma «- administration and allowed for greater degrees or concurrent relatimehip therapy then insulin insulin In. eon-a. These observations cm by psychotropic drugs led to a mlaoenent d in thin institution. Phameabherapz. in evelmting various peyohophamoeutieele is derived from then methane and linguistic analyses of intmenone of effects acute azhinietretien and chronic clinical emu-tration of variom nu compound: are in progress. EEG patterns, along such The ongoing program Mamie continue as eynehmiaatien-deeynahroniuﬂun and tmqnency units are being related to behavioral (21, 3h, The neuromyeiologic 141, 1:2) and linguistic changes (21, 1:3). basis of experimentally induced hallucinogenic etetee have also been interpreted as an alteration in synaptic chemical relations, such that the effective levels of cholinergic activity is decreased (ha). Initial work on this hypotheail (21. ha) in now being �WERE 195, 'mmWnumucm-mmw Mann WIWQWMWW. mwnmmmmmmmum mmuaummmmamrm; Mahatma! W mmummmmmmmm,m W, wmmmuarmmmm. mama“: “Wt. Mad. W3; and Mummmuwmeuvﬂ. awning” mmmuammwmwmmmmu WMoututmdm. �“Wm mmuwdmdmw. ammawmm mmnmummummmmmw wmmbﬂtwmm.ndatm,$m mmmummmm mmummumamm mwam-uwummmrw,ummm m.m,mmmmwmammsm WQMWQIWWWMSwtu-umw wwmmwammpammmmvs? “1959; nmumwwmmummm ammwmmmm,mmawmm ”www.mwmnuumm Wumnmwm.mmmuw mammwmaasgmmm nmnm,mmmtnmmmnm mamamwmtmmmmwmu:m -muramn.t.mnummungnrmmmww vmwmmmmmmma am QWWM.WWMW”M¢:M,10§ wmumu. mammmuamsmaumu Wuwmumdthynm. WWWuﬁMWq anti-Hum mmmmuumxmnmnmmmumm �Wﬁmmum, unlimpmmting Watfmofiu tho It»?! also participated in tho Intomtiml New W. Allied sum held in Mansion in m mm. and on cm: in out: during the your mama tin £111:an or George Knuth-gr,- am. :and Dmld P. mm, 11.1). "as to the Bowman Dr. mutt L. m. “hr the ﬂares-Mao, htttommammumd'ma‘ mmucnof WW, waist of Dr. Hospital. mum POM, 11me Jam MW wanna. manning ammuummummpmh «ma tho patina: of Faculty Huber and Wu Director of the White Hanson at mums. mun mm conﬁrming mmttorthommm obhinndfmamﬁoudot of mm Hum: of Dix-om, mm m the mm ham). mum at prom the mud sum mus mu: serum, and mu supper: from the Health Board of 13mm county. �Why Wm M aunt-m « .. 199 In I‘m. 11.». Ian-u 1. Dan. 11.8. mran-u. 3.3. L. in: am m. M. I. m1, W(up.W. I'd. M. m m. m 15.3. 3.9. mum”. unh- Mn. A. 3.». um. mun-emu, Maul am m (Wily) mu m (ham m) m m Mb (Win W) m m (mm) m um um (W) Wh‘ 'W) (W m Ann-cw. W ma:unm(W) Must. a um :- mm (mm) m(m~ml an. ' * ' (may) M M. m mm Jun mum �Hillside Hospital Department of Experimental Psychiatry Following is a chronologic list of the presentations and publications of the members of the Department of Emperimental Psychiatry during 1959. A. Publications: 1. Effect of an Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy. Biological & Grune N. Y. pp. 18h-19h ed. Masserman, chiat P, Stratton, J., , (Fink; Egg. 2. Alteration of Brain Fpnction in Therapy. Psychopharmacology Frontiers, 6d. Kline, No, Little, Brown & COO, Boston, pp. 3 Fink, Mo .3. Significance of EEG Pattern Changes in Psychopharmacology. g(Fink, ) M. ). 2 : 398 (abst. Neurophysiol._ EEG Clin. h. Effect of Electroconvulsive Therapy on Intractabie Pain. A.M.A. Arch. Neurol. and Ps chiat. ﬁl: 37-b2 (weinstein, E. A., Kahn, R. L., and Eargman, P.5. 5. Electroencephalographic and Behavioral Effects of Tofranil. Psych. Assoc. J. g; 1665-1718 (Fink, M.). 6. Canad. Psychological Factors Affecting Individual Differences in Behavioral Response to Convulsive Therapy, J. N.M. D. 128: 2h3-2h8 (Fink, M., Kahn, R. L., and Pollack, M.). 7. Effects of Diffuse Altered Brain Function on Perception, Phat Int. Con . Ps chol., Publ. North-Holland, Amsterdam, pp. 23 8- 239 (Fink, M., Kahn, R. L., and Korin, H. ). 8. Complex Visual Perception in Patients with Brain Tumor. Proc. XV Int. Con . Ps chol., Pub1.North-Holland, Amsterdam, pp. 2 33-237 (gander, M. B., Battersby, w. 3., and Pollack, M. ). 1/5/60 �9. Therapy of Schizophrenia: Role of Alteration of Brain Function on h92Behavior, Con ess Re orts II Int. Con . Ps chiat II: h93 (Abst. nk, M., Kahn, R. L., and Karin, H.5. 10. EEG of Seizures of and Duration to Degree Threshold Relationship of Delta Activity Induced During Electroshock, EEG. Clin. Neurophysiol. g: 399 (Abst.) (Green, M.). ll. Prognostic Application of Psychological Techniques in Convulsive Therapy, Dis. Nerv. Sys. g9: 180-184 (Kahn, R. L. and Pollack, M.). 12. Communication Networks in Freud's Interview Technique, Psych. Quat. 33: h56-h73 (Jeffe, J.). 13. Sociopsychologic ASpects of Psychiatric Treatment in a Voluntary Mental Hospital: Duration of Hospitalization, Discha e Ratings and Diagnosis, A.M.A. Arch. Gen. Ps chiat. l5 565-S7h Kahn, R. L., Pollack, M., and Fink, M.5. Set in the Perception of Simultaneous Tactile Stimuli, Jour. Psychol. 12.: 38h-392 (Korin, H. and Fink, M.). The Role of Am. Perception Across Sensory Modalities, (Abst.) (Krauthamer, G.). Form Am. Psychol. lg; 396 16. Relation of Tests of Altered Brain Function to Behavioral Change Following Induced Convulsions, The First International Congress of Neurolo ical Sciences (III: §EG Clinical Neurosﬁgsiology and Epilepsy5, PBrgamon, London, pp. 513—519 (Fink, M., Kahn, R.L., and Karin, H.). 17. Personality Factors in Behavioral Response to Electroshcnk Therapy, J. Neuropsychiatgy l; h5-h9 (Kahn, R. L. and fink, M=). 18. Symbolic Reorganization in Brain Injuries, in Handbook of Paychiatgy, ed. Arieti, 3., Basic BOOkS, No Yo, V01. I, pp. 9 "9 l (Weinstein, E. A. and Kahn, R. L.). �B. Presentations: l. EEG and Ebhavioral Effects of Tofranil, International Conference on Depression and Allied States, Montreal (Fink, M.). 2. Sociopsychologic Factors Affecting Therapist-Patient Relationships, American Academy of Psychoanalysis, Philadelphia (Kahn, R.L.). 3. Effect of Induced Cerebral Dysfunction in Man on Tachistoscopic Perception of Embedded Color Figures, Eastern Psychologic Association, Atlantic City (Pollack, M.). h. Behavioral Changes with Different Methods of Induced Cerebral Dysfunction, Eastern Psychological Association, Atlantic City (Karp, E.). 5. Sociopsychologic Aspects of Peychiatric Treatment, Eastern R. (Kahn, L.). City Atlantic Association, Psychological 6. Language Patterns as Measures of Behavioral and Neurophysiologic Change, American Psychiatric Association, Philadelphia (Fink, M.). 7. Personality Correlates of (Krauthamer, G.). EEG, Metropolitan EEG Society, 8. Relation of Social Attitude to Psychiatric Treatment, Meeting, A.P.A., New York (Kahn, R.L.). 9. Comparison of New York N. Y. Divisional Intellectual Functioning in Childhood, Adolescent and Adult Schizophrenics, N. Y. Divisional Meeting, A.P A., (Pollack, M.). New York 10. Symposium on "Paycholinguistic Analysis of the Psychiai‘ic Interview", N. Y. Divisional Meeting, A.P.A., New York (Jaffe, :.). 11. Social Background and the Doctor-Patient Relationship, Acad. Psychoanalysis, New York (Jaffe, J.). �Hillside Hospital Department of Experimental Psychiatry Following is a chronologic list of the presentations and publications of the members of the Department of Experimental Psychiatry during 1959. A. Publications: 1. Effect of an Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy. Biological Ps chiat , ed. Masserman, J., Grune & Stratton, N. Y. pp. 18h-19h (F%:E, M.;. Alteration of Brain Function in Therapy. Psychopharmacology Frontiers, ed. Kline, N., Little, Brown & 00., Boston, pp. -3 , . . 3. Significance of EEG Pattern Changes in FBychopharmacology. g(Fink, ) M. ). 398 (abet. Neurophysiol._2: EEG Clin. . Effect of Electroconvulsive Theraﬁg on Intr:1ctabm Pai A.M.A. Arch. Neurol. and ngchiat. Ql: 37- (weinstein, E. A., hahn, R. L., and rgman, P. . Electroencephalographic and Behavioral Effects of Tofrénil. Canad. 14.3 1663“].715 (Fink, Mo). ASSOC. J. szch. Psychological Factors Affecting Individual Differences in Behavioral Reaponse to Convulsive Therapy, J.N.M.D. lag; 2h3-2h8 (Fink, M., Kahn, R. L., and Pollack, M.). 7. Effects of Diffuse Altered Brain Function on PercWptio Prsc. XV Int. Con . P chol., Publ. North-Holland, Amsterdam, pp. 53 3- 239 (335E, M., Kahn, R. L., and Korin, H. ). Complex Visual Perception in Patients with Brain Tumor. Proc. XV Cong. Psychol., Publ. North-Holland, Amsterdam, pp. 2 33-?37 n er, M. B., Battersby, w. 3., and Pollack, M. ). 1/5/60 Int. �“beam, 9. Therapy of Schizophrenia: Behavior, h93 C as Re 14., Alteration of Brain Function on 1:92Con . Ps chia rts II Int. II: , H321 '£.""‘EER"', orinL", ‘. an hn, Role of 10. Relationship of Threshold and Duration of Seizures to Degree of EEG Delta Activity Induced During Electroshoclc, EEG. Olin. Neurophzsiol. _2_: 399 (Abst.) (Green, M.). 11. Progncs tic Application of Psychological Techniques in Convulsive Therapy, Dis. Nerv. Sys. g9: 180-184 (Kahn, R. L. and Pollack, M.). 12. Communication Networks in Freud’s Interview Technique, Psych. Bust. 23: 156-1473 (Jaﬁ‘e, J.). 13. Sociopsychologic Aspects of Psychiatric Treatment in a Voluntary Mental Hospital: Duration of Hospitalization, Discha e Ratings and Diag10818, AeMeAe Arch. Gene P3 Chiate ;: 565-571; Kahn, Re Lo, Pollack, M. '. 14., and—Tink"—‘T, 1h. The Role of Set in the Perception of Simultaneous Tactile Stimuli, Am. Jour. Psychol. 1g: 38h-392 (Korin, H. and Fink, M.). tion Across Sensory Modalities, Psychol. 3;: 396 15. Form Perce 16. Relation of Tests of Altered Brain Function to Behavioral Change Following Induced Convulsions, The First Internatior; 3.1 Congress of Neurolo ica3_Sciences (LII: EEG, Clinical Neurop._,jsiolog and Epilepsy), ﬁrgamon, London, pp. 13- 19 ink, M. , v-iahn, R.L., and Karin, H.) . (Abst. (Krauthamer, G.). Am. 1?. Personality Factors in Behavioral Response to Electroshntrk Therapy, J. Neuropgychiatg l: h5-h9 (Kahn, R. L. and :nk, ). 18. Symbolic Reorganization in Brain Injuries, in Handbook of Pa hia ed. Arieti, 3., Basic Books, N. Y., Vol. I, pp. '935-931 (Weinstein, E. A. and Kahn, Re Le). ; �B. Presentations: 1. EEG and Behavioral Effects of Tofranil, International Conference on Depression and Allied States, Montreal (Fink, M.). 2. Sociopsychologic Factors Affecting Therapist-Patient Relationships, American Academy of Psychoanalysis, Fhiladelphia (Kahn, R.L.). Man on Tachistoscopic Cerebral Induced in Dysfunction of 3. Effect Perception of Embedded Color Figures, Eastern Paychologic Association, Atlantic City (Pollack, M.). h. Behavioral Changes with Different Methods of Induced Cerebral Dysfunction, Eastern Psychological Association, Atlantic City (Karp, E0). 5. Sociopsychologic Aspects of Paychiatric Treatment, Eastern R. (Kahn, L.). City Atlantic Association, Psycholqgical 6. Language Patterns as Measures of Behavioral and Neurophysiologic M.). (Fink, American Fhiladelphia Association, Paychiatric Change, 7. Personality Correlates of (Krauthamer, G.). EEG, Metropolitan LEG Society, 8. Relation of Social Attitude to Psychiatric Treatment, Meeting, A.P.A., New York (Kahn, R.L.). 9. Comparison of New York N. Y. Divisional Intellectual Functioning in Childhood, Adolescent and Adult Schizophrenics, N. Y. Divisional Meeting, A.P,A., (Pollack, M.). New York 10. Symposium on "Pbycholinguistic Analysis of the Piychiai-ic Interview", N. Y. Divisional Meeting, A.P.A., New York (Jaffe, q.). 11. Social Background and the Doctor-Patient Relationship, Acad. Psychoanalysis, New York (Jaffe, J.). � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Progress and annual reports; research activities (folder title). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-006 Date A point or period of time associated with an event in the lifecycle of the resource 1958-1959 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Department of experimental psychiatry annual reports; Letter acknowledging that Fink will receive the first A. E. Bennett Neuropsychiatric Research Foundation award; Newspaper clipping, Long Island Daily Press, Psychiatrists will honor L.I. Doctor; Lists of publications of the members of the department of experimental psychiatry; Newspaper clipping, MD Records Brain Waves of Patients; Summary 1954-1959; Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/c8ad48ee340bb2be9a377798690b07da.pdf 3394a0c397923bbc0e9ed1a479ee352e PDF Text Text K . K. K K K .K y » K K . , a . K . K r KK . K K K K . K K . K. K KKK K K K K . . KI . _ KK K K K K . K K K K K K K K K K K . K K A K K K K K K K K K . K .K K K K _ K K K K K K S . K K . KK K K . K K K K. _ K K K K K . _ K K K K K KK K K K K K _ K. K _ K K K ‘ K .K K K K K _ K K .K K K K K K K K . KK K .\ K K KKK.KK I. K. K .K K K e? .p . K. K Jr K. . K K. K K K K KK . . w . K _ .K K K. K . K K. K K K . . _ K K K K K . . K K K K. KK K K K K . K K K _ K K K K K K K .K K _ K K . K K K K K K K K K K K K _ K K K . . K K K K K K K K K K K K K K K K K K K . K K K KK .K . K �2 9th Annual Report JANUARY 1, 1956—DECEMBER 31, 1956 Glen Oaks, Queens FOUNDED 1927 Joseph S. A. Miller, M. D., Medical Director AN AFFILIATE OF THE FEDERATION OF NEW YORK 0F JEWISH PHILANTHROPIES �Hillside Hospital is a non-profit, non-sectarian mental hospital for the treatment of voluntary patients suffering from early and curable mental symptoms. Patients are admitted regardless of their ability to pay. Hillside provides training for physicians in post-graduate psychiatry and psychotherapy and puts major emphasis on research in all phases of treatment. The hospital considers itself a pilot institution, pioneering in the human and efficacious application of psychiatry to the mentally ill. The hospital is licensed in the New York State Department of Mental Hygiene. It is approved for a two-year residency in psychiatry by the Council on Medical Education of the American Medical Association, the American Board of Psychiatry and Neurology and the American College of Surgeons. The Dental Department is certified by the American Dental Association as an approved hospital department. Hillside Hospital is an affiliate of the Federation of Jewish Philanthropies and a participant of the United Hospital Fund and the Greater New York Fund. HIGHLIGHTS Page 3 Hillside gets Ford grants Israel Strauss Adolescent Pavilion in its second year . . . . Page 6 . . . . Page 10 Hillside affiliating institution for student nurses at Queens college . Page 11 Social Service strengthens rehabilitation program . Page 14 . Chlorpromazine added to regular hospital drug formulary Research program strengthened . . . . . Page 18 �1956 has been a year of “Shakedown" for Hillside during which its Board and Executive Officers have experienced the first full year of operation without the supporting advice of its founder, Dr. Israel Strauss, who died during 1955. In view of the change throughout the organization of the hospital, it has been a year of consolidation and improvement. We are indebted to Dr. Dudley D. Shoenfeld, our Vice President, for his invaluable counsel in helping to reorganize the staff planning in the hospital. He was greatly assisted in this work by Dr. Joseph S. A. Miller, Dr. Simon Kwalwasser REPORT OF THE PRESIDENT OF THE BOARD OF DIRECTORS and Maurice Bachrach. has frequently been necessary for the Governing Board to ask advice and guidance from the Medical Board. We have had splendid cooperation from them. The two presidents of the Medical Board serving through the calendar year, Dr. Samuel Atkin and Dr. David Epstein, have been particularly helpful. It During 1956, the hospital has been able to expand its services in the OutPatient Department through the use of funds made available by the State Mental Health Authority through the N. Y. State Department of Mental Hygiene, and funds from the City of New York through the New York City Community Mental Health Board. Further funds from the City of New York for indigent mentally ill persons have enabled the hospital to maintain its services at a high level and to serve that segment of the community which most needs the services of a philan- thropic hospital. The research program, conducted at Hillside under the guidance of Dr. Maximilian Fink, has made excellent progress. The directors continue their deep interest in all areas of psychiatric research and anticipate further broadening of these activities. Psychiatry as a science still is in a rather fluid state and many new avenues of exploration offer hope and ideas. The compelling need is to look intensely for new information. At long last, throughout the United States, substantial organizations have become cognizant of these needs. Among these, the great Ford Foundation has allocated many millions specifically for research in psychiatry. In addition, large sums have been allocated to the country’s hospitals. In 1956, Hillside received a grant of $104,000. At Hillside we bring a sympathetic attitude to our patients, solace and encouragement to their families and decided improvement to a large proportion of the persons we treat. We make judicious use of all modern therapies available in the field and our record of improvement is excellent. We can be proud of it. But we aspire to find new and better techniques that will send more patients out of the hospital completely “recovered” rather than “improved”; new methods that will permit release of patients in a far shorter time than is now required. to these goals that we at Hillside are dedicated and we firmly believe that, as elsewhere in medicine, these aims can only be achieved by means of widespread and continued research. It is Alvin E. Coleman �REPORT OF THE MEDICAL DIRECTOR During 1956, Hillside Hospital completed almost thirty years of continuous operation, rendering high-level psychiatric services to the community. During these three decades, the Hospital increased its bed capacity for inpatients fivefold, established a ranking place as a therapeutic center for both inpatients and outpatients, became a notable hospital for resident training in the field of psychiatry and, in the past few years, developed an important research department. For over eight years, it has been a proud member of the family of the Federation of Jewish Philanthropies and, in conjunction with other agencies in Federation, it has developed and rendered meaningful aftercare and rehabilitative services. During the past year, there was an improvement in the coordination of professional services rendered in both the adult and adolescent inpatient departments. There was considerable expansion in our outpatient service with improvement of procedures and treatment in the aftercare clinic. Our practical experience with the Adolescent Pavilion and our attempts to augment our research programs have pointed up the need for expansion, both in personnel and in space. Every few years the advent of some special form of physical treatment—shock, surgery, and now new drugs—has reopened the debate concerning so-called specific versus non-specific treatments, short-term versus long-term hospitalization and therapy, treatment of many patients or clients rather than a few. All of these can really be related to the general question of the importance of quality versus quantity. One of the distinguishing features of American medicine is its goal and also, think, its practice of rendering qualitatively better medical services, as opposed to mere quantification. I Hillside Hospital has developed a distinctive philosophy which has led to the creation of a unique structure to implement its philosophy. Since the field of psychiatry is still in its developmental stages, it is characterized by frequent and rapid changes in all phases of its thinking and practice. Each change is a challenge to the Hospital’s established structures and points of view and we must continually decide whether a psychotherapy-centered, multi-disciplined treatment program such as ours delivers the best service that can be devised for the relatively long-term curable patient. How is a mental patient best served by a psychiatric hospital? This, of course, will depend on the type of mental patient. Some patients are easily treated by a consultation or two, by a course of shock treatment, or with tranquilizing drugs, or with a rest or vacation. Some need only a course of physical treatment with return within a month or two to their homes, to continue whatever treatment they may need in a clinic or with a private psychiatrist. Others, and these are the ones that Hillside has more experience with, require hospitalization of at least six to twelve months. These are patients who cannot or should not remain at home or in the community, and cannot therefore benefit from either a single psychiatrist's or clinic’s ministrations but rather need the hospital milieu or therapeutic environment of a team of professionals working with the patient, with �a psychiatrist at the center to emotionally re-educate the patient. Such emotional re-education through the process of properly understood and related inliving experiences lead to a patient becoming aware of emotional aspects that he did not suspect he had before and to recognize that there are more people who care rather than so many who are hostile to him. If at the same time, as at Hillside, important relatives, especially the nearest of kin are worked with by a professional trained in that field, the psychiatric social worker, the family's attitudes concerning the patient and his illness are changed for the better; and if this happens, the patient now has not only regained much of his lest esteem and self-confidence, but the very family environment has been improved and guarantees that the patient may continue and even enlarge upon gains initially made in the hospital. Thus, not only a single patient has been treated, but there has been complete reorientation of an entire family. Authorities in dynamic psychiatry, in child welfare and development, in community welfare, in the field of geriatrics, all agree that the most important ingredient in the total treatment of emotional problems at any age, is the psychological understanding and the meaning of the symptoms, even the physical ones, as various ways of attempting to meet the problems of anxiety and emotional crises. Of the various psychological and dynamic approaches to the problems of behavior, none have contributed as much as psychoanalysis. Hence the practice of hospital psychoanalytic psychiatry at Hillside. This is by no means to lessen the importance of the adjunctive services and especially of the medical and physical agents. The physical symptoms are often parallel or concomitant expressions of 'certain types of emotional distress and emotional disorder; and physical agents like drugs, are often very effective in shortening periods of acute panic or distress and thus allowing for earlier or more meaningful participation in psychotherapy. Since the problems of emotional disorder are mainly interpersonal ones, problems of getting along properly or happily with other people, psychotherapy whether in or out of a hospital is in our opinion the basis of all therapy of persons with severe emotional disturbances. The past year has been characterized by a rapid growth of psychiatric services in general hospitals. These, by their very nature, deal with more acute physical and mental disorders, while special psychiatric hospitals treat those psychiatric problems which specifically require more extensive hospitalization, removal from home and community for a long enough period to afford an opportunity for reeducation and resocialization of the patient. It is therefore clear that the two types of hospitals deal with different problems and have different basic principles, precisely because they deal with different types of patients. The growth of the general hospital practice of psychiatry is therefore not a factor toward the displacement of the special hospital but rather for the widening and enrichment of the total constellation of treatment services available to psychiatry, so that the general and special hospitals enhance and reinforce each other for the benefit of all patients. Joseph S. A. Miller, MD. �ADOLESCENT PAVILION Age range of patients The Israel Strauss Adolescent Pavilion is now in its second year. It is a dramatic example of the kind of pioneering Hillside Hospital does. The Pavilion provides a treatment program for emotionally disturbed girls between the ages of 12 and 16. It is an unusual experiment in tackling a major problem of our society . . . the rehabilitation of girls who are unable to live and function successfully in the community. Practical aspects of treatment Grave concern with the number of severely disturbed young people in our country has not resulted in enough practical work. The Adolescent Pavilion is a brave in all and facilities with the deal this experience to problem, using attempt psychiatric therapy of the Hillside Hospital in a treatment program oriented to the special needs of these patients. The number of girls who can be treated is very small compared to the need. But the knowledge to be gained from experience with them should prove immensely valuable. Flexibility of program The Adolescent Pavilion has its own, specially-designed living quarters and treatment facilities, and a separate staff. Its program is necessarily fluid and flexible enough to allow the constant adjustments necessary in a new and untried field. Some changes from original plans became necessary as work progressed this year. Twenty patients were admitted in 1956 and 25 discharged. Capacity of the Pavilion was reduced to 16 since it proved impossible to work successfully with the 20 originally planned. Basic treatment philosophy The basic treatment philosophy remains the same. The aim is to provide a wholesome living experience within the Pavilion with as intensive psychotherapy as seems advisable for the individual patient. But the concept of such a wholesome experience has gradually, step by step, taken in more areas, personnel and facilities beyond the Pavilion’s confines. As soon as girls are able, they are encouraged to use recreational and planned activities at the main hospital, to make contacts with the other staff there and to socialize with adult patients. As they are able, the girls are permitted to go to the nearby public high school and out into the community. A basic concern is to try to help with those aspects of the personality that are ill while never forgetting to encourage arid develop those that remain healthy. Family or family-type Work with parents or parent substitutes is intensive and a very important part of the treatment. When they are able, the girls are permitted and encouraged to spend time with family or friends. Some girls, unfortunately, have no family to go to. The use of volunteer help to fill this vacuum is being further explored. After-care and follow-up Another important need is the provision of after-care and follow-up. Unlike the mature patient, the Pavilion deals with personalities not yet fully formed. Their potential is unknown. It takes time to find out how fruitful the work will be. It had been hoped that close follow-up would be possible by providing after-care relationships �for all the girls in the Hillside Out-Patient Clinic. This proved impractical because it interfered too much with the ordinary pursuits of young people who, in most cases, lived at great distances from the hospital. For those girls who cannot conveniently use the Clinic, a variety of good treatment facilities elsewhere are recommended. encouraging to report that referrals to the Pavilion have come this year from more widespread sources, including a variety of family and social agencies, schools, treatment centers, private physicians and girls' residence clubs. It is also encouraging to report that, while it is too soon to reach any conclusions from the work in progress, the hospital does feel the work of the Adolescent Pavilion is becoming increasingly helpful. It is Prognosis for the future �I 7‘" . «F ‘ HillSIde In 1956 treated 561 ts, of ”709189 hospital days. The e-‘ﬁ Q‘ﬁt‘rhte were patients. Of theﬁital treated», 365 ﬁne Evaluatipnﬁg discharged :- . ’ ' I I; eme '. I Is . 5 ', I I 2 __ way f. ou come In a ~ I. ’ gcomparison. - f ‘quOﬁ rials». " ndon nt ' ‘ to denote mental condition at the time of Idischarg ient’ 5 condition gmbebaviqr he en left This is g 'uII a}; I: ‘ 1"7.” : ' o’ I ‘ _ I I . I I no chan-e I "”3 '_ .' .- or ’ f I : I I ﬁle-5V; "j ' m“ iable Rent; m that symptoms have disapﬁbare nd the patient conseemeﬁn good ‘e'ans Ion at the hospital, but there is no certainty of how he will function when he Eats back into I own an ial and working community; recovered means that, in “i has bee ef‘mucharrlﬁrmd reas c ad . tioma‘t ' I. atient will be or better" I; he did befor ‘ 1 -I r 3“ .92 *I f _ "1"" . _ I ’ . mandfuw;¥ tmhﬁ tateat I Mu ,, . lmpr. 4O 36 39 . �m O S PIT �PSYCHOTHERAPY AND MEDICAL SERVICES Major process of Psychotherapy continues to be the major emphasis and the core of treatment at Hillside Hospital. Other forms of therapy, each in its own way very important to the patient’s progress, are all part of the treatment program and are prescribed according to the patient’s particular needs. However, one of the main criteria for accepting patients at the hospital is their ability to participate profitably in psychotherapy. Analysis of hospital Patients are seen individually by well-qualified psychiatrists for psychoanalytically oriented treatment three or four times a week. Each patient is assigned to a specific psychiatrist who remains ”his doctor” for the length of his stay. The psychiatrist is the leader of the hospital “team” that plans and supervises the patient’s day-to-day treatment. The other members of the team are a psychiatric social worker, a psychologist, professional representatives of the adjunctive services — Occupational Therapy, Group Activities and Creative Therapy — and the Nursing Department. Types of therapy in use, including new drug therapies . . . facilities for treating the “whole" patient: physically and psychotherapeutically Group therapy continues to be used for selected patients. The hospital continues the use of electroshock therapy for about one-third of patients, especially those suffering from more severe emotional disorders. The extent to which it is used has, in many cases, been modified in accordance with the results of research conducted by the Department of Experimental Psychiatry. During 1956, as a result of a controlled research study, Chlorpromazine was substituted for insulin coma in certain patients. It had been found safer, easier to administer, and to have fewer side effects. For certain other patients at the hospital, insulin coma is still the treatment of choice. Chlorpromazine has now been added to the drug formulary of the hospital and made part of the regular therapeutic procedures. There is continuing work and interest at Hillside in Reserpine and the other newly developed drug therapies. Growth of non-psychiatric The Intra-mural Clinic and allied medical services of the hospital are concerned with the non-psychiatric, physical problems of the patient. Close cooperation between the medical staff and the psychiatric staff has brought the hospital nearer its goal of “treating the whole patient.” hospital treatment treatment “team" medical services The lntra-mural Clinic The continued cooperation of a large visiting staff in all the various branches of medicine, made it possible for the clinic to see 411 patients for a total of 11,844 visits this year. The Dental Department 10 The Dental Department, newly certified by the American Dental Association as a qualified hospital dental department, anticipates adding a dental intern to the staff. New equipment and a newly decorated interior have done much to facilitate and improve treatment. The dental clinic treated 736 patients this year, an increase of almost 25% over 1955. �f . The Psychology Department, in response to increased demand for psychological examinations, added one full-time psychologist this year and provided for the addition of two more early in 1957. Almost twice as many tests were admin- The Psychology Department istered this year as last. The department has been accepted and used as an integral member of the hospital team. Its services have been called for in pre-testing hospital personnel, and in connection with vocational counselling and rehabilitation plans worked out by the Social Service Department. The Nursing Department continues to pioneer in training nurses and aides in the special skills required for proper care of the mentally ill. The nurse fulfills a unique position in being in direct contact with the patient for long period of time. And yet the only training she generally receives in psychiatry is a brief threemonth period during student training. This department has organized two special training programs, one for psychiatric aides and one for nurses, which enable them to perform more effectively and with more understanding as working members of the hospital team. addition, members of the professional nurse staff participated in trips to various private and state psychiatric hospitals to observe new methods and techniques. In During the past year, students from Central lslip continued visits to Hillside as part of their psychiatric training. This year, Hillside became the affiliating institution for basic psychiatric experience for student nurses at Queens College. The hospital was fortunate in acquiring for its own staff 10% of the college’s first graduating class. The Nursing Department �Three departments of the hospital, make an essential contribution to each patient’s therapy. Each has a specific function and each is prescribed as a regular part of treatment planned in cooperation with the psychiatric staff. Group Activities Department The Group Activities Department organizes meaningful social, educational and work activities that draw patients into groups where they will have opportunities to form relationships with other patients and deal with situations that mirror community life. Each member of the department’s staff of professional social group workers is assigned as a member of a psychiatric team which plans a program designed to meet a patient’s specific problems. The group worker reports on the patient’s performance and reactions to group ‘and social situations. .Under the guidance of the staff, patients participate in self-government groups, special interest classes, a choral group, athletic activities, and current events discussions; they publish a newspaper, operate a patients’ library and engage in club activities suited to various age levels. In addition, they plan and take part in social functions, attend religious services and enjoy a varied program of evening entertainments which frequently include appearances by outstanding celebrities who generously give their time and talent. This year has seen the development of an adult education program, in conjunction with Adelphi College, which, in a ten-week course, offers popular subjects similar to those offered by the extension programs of universities and the New York City Board of Higher Education. Occupational Therapy Department Occupational Therapy the patient works in various crafts such as ceramics, wood, metal, leather, jewelry making, weaving and needlework. They offer him a creative outlet that increases his self-confidence, helps him to discover new skills and has therapeutic value in relieving tensions. By observing the way a patient reacts to tools and materials, how he copes with success or failure and how he carries out instructions and responds to authority, the staff is able to gauge his problems and his progress. In 1956 two registered therapists were added to the staff, bringing the total to six. Each therapist is part of the hospital team that plans the occupational program for each patient according to the patient's needs. In This year, for the first time, craft classes were scheduled which offer patients interested in particular crafts an opportunity for more intensive and specialized instruction. Another innovation was that the Commissary, a patient-run store, was brought under the direction of this department and patients were assigned there by doctor's prescription as a form of vocational training. 12 �distinguished visitor this year was Miss Ruth Shamah, Israeli delegate to the World Federation of Occupational Therapists, who spent three months at Hillside working and observing the methods used in the department. A Creative Therapy is a very special psychodiagnostic and therapeutic tool de~ vised by Dr. Ernest Zierer and his associate, Mrs. Edith Zierer. It consists of a series of controlled painting tests designed to reveal the patient's unconscious conflicts. The results are tabulated and interpreted in diagrams which present a “personality profile” considered to be a reflection of the patient’s ability to solve his life problems. Creative Therapy Department The department administered 1,423 tests during the year. In addition to regular consultations with the hospital team, progress reports were discussed at special conferences with treating psychiatrists and the supervisors. I3 �THE PATIENT Work of the Social Service Department The Social Service Department is the patient’s most direct and constant link with his family and the community outside the hospital. Its activities before admission, during the patient’s stay at the hospital and after he leaves, make easier both for the patient and for his family the many adjustments necessary to meet the economic and emotional problems that complicate successful treatment. 14 Number of yearly interviews and contacts the course of its work this year, the Social Service Department conducted 5,137 interviews with patients, 5,095 interviews with relatives, 7,555 telephone contacts with social agencies and 6,701 telephone contacts with relatives of patients. The department processes all admissions, functions actively throughout the patient’s stay and is intimately concerned with the patient’s welfare on discharge and for several months thereafter. Rehabilitation aspects of the social service program the past year the department has made a concentrated effort to strengthen the rehabilitation aspects of the social service program of the hospital. Experience has shown that the best results are achieved when maximum support is extended immediately on discharge and continued through the first six months to a year. Future plans are particularly concerned with opening up new avenues of cooperation with community agencies whose services can do so much to help the patient again become a useful and happy member of his community. In 1956 the following agencies have made marked and increased contributions in this connection. Contributing agencies to rehabilitation programs The Foster Home Program, which exists jointly with the Jewish Community Service of Long Island, was used to place newly discharged patients in a supervised family environment. This year the program also was used for patients awaiting admission to the hospital, with the result that hospitalization was averted in at least one case. In In ' �AND THE COMMUNITY The Altro Workshop which provides discharged patients with transitional gainful employment was used by thirteen patients during 1956. Through a grant by Mrs. Israel Strauss and the Federation of Jewish Philanthropies, a joint program with the Jewish Family Service of New York was initiated. This service permits discharged patients who need further counseling to get immediate help. Expansion of this service is expected to show the value of continued and prompt counseling in averting rehospitalization. Together with the Jewish Family Service of Long Island, the department developed a special program that helps keep the home intact when a mother has to be hospitalized. Homemakers are assigned to fill the gap during the mother’s absence and sometimes even after the mother returns, if this seems necessary. The program with the Division of Vocational Rehabilitation has been expanded. A vocational counselor is available to patients one day a week. Vocational guidance begins while the patient is still in the hospital and may continue after discharge. Training facilities are provided for those whose adjustment to the community might be made easier by learning new skills. The department is especially appreciative of the cooperation of the New York City Department of Education. The Home Instruction Program provides two teachers who come to the hospital several days a week to give instruction to patients under 21 who have not completed high school. The results have been very successful; 40 patients received instruction this year and six were graduated. During the coming year the program will be expanded to include patients over 21, who, on completing the work, will be able to take High School Equivalency examinations. Follow-up reports indicate that many patients develop an interest in carrying their education further after leaving the hospital. The Casework Program started last year in the After-Care Clinic, for the purpose of coordinating rehabilitative planning, has proven its effectiveness and is now an established service offered to patients and their families. The Social Service Department has continued to work very closely with the Federation Employment and Guidance Service. Their excellent facilities make it possible for many patients to receive job placement and vocational guidance soon after leaving the hospital. 15 �HILLSIDE LEAGUE The Hillside League and the work of “The Bridge" The Hillside League is an organization of former patients of Hillside Hospital. After facing almost certain extinction in 1954 and having an encouraging revival in 1955, it has made astonishing strides in the past year. That many of its planned goals have been achieved is due, in large measure, to the untiring and selfless efforts of “The Bridge, Inc.", a group of women and their husbands who conducted a successful fund raising drive and who continue in their wholehearted devotion to the League. Activities at Bridge headquarters 1956, the Hillside League moved to new quarters (supplied by “The Bridge”) at 231 West 83rd Street, in Manhattan. Here, in an area many times the size of its original rooms, members enjoy a comfortable, newly furnished lounge, equipped with a phonograph, television, table games and cards. The area is flexible enough to provide for large groups as well as intimate gatherings. The League is open every evening from Monday through Friday and one week-end a month for large social functions. Help with personal Hillside psychiatric social worker has been assigned as a full-time director of the League and is available for individual consultation and for referral service with regard to housing, employment, further treatment and other personal welfare problems. Thanks again to the efforts of “The Bridge,” the volunteer staff of the League has grown to meet the needs of a much larger membership. Membership From a low of 38 in 1954, the active membership has grown to almost 200, and in addition the League draws upon an active mailing list of almost 500. A club program, with membership arranged according to age group and interest has been an important development made possible by the increased membership welfare problems In A and staff. The Hillside League looks forward to the next year as one in which it will be well equipped to fulfill a vital function in helping patients continue the progress made at the hospital. QUEENS OUT-PATIENT CLINIC Hillside Hospital believes that in the Queens Out-Patient Clinic it has developed a pilot unit that demonstrates the highest level of clinical functioning and serves as a center for stimulating interest and training in psychiatry. Work of the clinic 16 The Clinic offers psychotherapy on a twice-a-week basis, up to a year’s duration, to residents of Queens, Nassau and Suffolk Counties, who require treatment but �are unable to pay for private care. For a family with an average income psychiatric service can become a severe economic burden. The Clinic meets an urgent need in a community rapidly growing in population but relatively lacking in out-patient psychiatric facilities. The Clinic setting, in addition, offers the advantage of psychiatric social work consultation for members of the patient’s family. ’ Intensive screening, by means of psychological tests and pre-admission consultation, make it easier for the treating psychiatrist to make early plans for the patient's treatment program. In contrast to the usual lengthy course of psychiatric treatment, the Clinic has developed a philosophy of attempting to accomplish limited goals. Often, by relieving his symptoms, the Clinic frees a patient to continue on with his life, with the strengths he utilized before he became ill. The Clinic treated 271 patients in 1956, the average length of treatment being eight months. Thirty psychiatrists, accepted after very careful selection, work on a part-time basis to make this extensive program possible. Permanent staff Goal of the clinic's treatment program Number of patients and staff members members of the Hospital are always available for consultation. 1956, the Clinic initiated a separate service for administering electroshock therapy on an out-patient basis. Recovery, on the whole, was dramatic, rapid and tremendously appreciated by the patient and family since it meant avoiding hospitalization. In MANHATI‘AN AFTER-CARE CLINIC The Manhattan After-Care Clinic serves Hillside patients as a link between their hospital stay and the resumption of community life. This is often a very trying time because the patient may suddenly be subjected again to old family stresses, job strains and social difficulties. The Clinic, conveniently located at Mt. Sinai Hospital, is open five nights a week and the average course of treatment is twice-a-week for a period of three months. Function of the clinic Successful accomplishment of the Clinic’s goals depends in good measure on cooperation between Clinical Assistants and Social Service Caseworkers. The Clinic takes this opportunity to acknowledge the extent to which that cooperation exists and functions. Accomplishment of goals l7 �THE HOSPITAL treatment of the mentally ill depends on intensive research . . . on a better understanding of why people become mentally ill and a surer knowledge of how treatment effects improvement. Hope for this rests with a wide variety of professional research workers in the many disciplines concerned with human behavior. As in any other field of medicine, progress in the Research and progress Research in mental illness is spurred on by the grave and immediate need for new insights and is complicated by the fact that the field of exploration is limited, almost entirely, to human beings, rather than lower animals. Hillside's hope is to include every possible approach. Work continues along those lines that seem to offer the most promise. Areas of basic study Psychotherapy remains the area of basic study and treatment. But because past experience has amply demonstrated that electroshock therapy is, for certain conditions, the most valuable of the known physical therapies, the hospital has devoted a major effort this year to study and further elaboration of its use and effects. Three other studies whose purpose was to devise more clearly objective methods of evaluating progress in therapy were developed, and a control study of Chlorpromazine-insulin coma was completed. Department of Experimental Psychiatry This year, the Research Service Was redesignated as the Department of Experimental Psychiatry, indicating its continued growth and anticipating the addition of a Department of Clinical (Psychodynamic) Research. Two new members were added to the staff in 1956. Support for the program came from contributions of the Board of Directors, from the renewal, for three years, of the Electroshock Study Program of the National Institute of Mental Health of the U. 8. Department of Health, Education and Welfare, and from the Kaufman Foundation of New York. Departmental research in Medicine and Biochemistry Research in the Department of Medicine concentrated chiefly on a study of new drug therapies. The Department of Biochemistry continued work on studies of hormonal balance and undertook a study of the relationship between certain physiological defects and schizophrenia. Funds for the latter were provided by the National Institutes of Health. �AND THE COMMUNITY During the year, increased recognition of the staff and work of the hospital came from a large number of lay and professional publications. The hospital is keenly aware of the value of this public interest because greater attention by the general public to the field of mental health will lead to greater support by govern- Publications and Presentations ment and private agencies, foundations and institutions. Berkowitz, Anne: A Study of the Caseworker’s Function at Hillside Hospital, J. Hillside Hospital, 5: 56-60, 1956. Fink, M: Denial of Blindness Following Cerebral Angiography, J. Hillside Hospital, 5: 238-245, 1956. Fink, M., Kahn, R. L. and Korin, H.: Relation of Tests of Altered Brain Function to Behavioral Change Following Electroshock; Presented at the Divisional Meeting, American Psychiatric Association, Montreal, November 8, 1956. Fink, M. and Kahn, R. L.: Quantitative Studies of Slow Wave Activity Following Electroshock, EEG Clin. Neurophysiol., 8: 158, 1956. Goldenberg, H., and Goldenberg, V.: Inhibition of Serum Cholinesterase by Lysergic Acid Derivatives. Sumicro Detection of LSD, J. Hillside Hospital, 5: 246-257, 1956. Goldenberg, H.: Decantation as a Precision Step in Colorimetric Analysis, Anal. Chem., 28: 1003, 1956. Goldenberg, H.: Recent Advances in Enzyme Methodology; Presented at a Symposium sponsored by the American Association of Clinical Chemists at the 123rd Meeting of the American Association for the Advancement of Science, New York, December 1956. Goldenberg, H.: Concerning the Inhibition of Pseudocholinesterase by Hallucinogens; Presented at the New York Academy of Sciences, April 1956. Green, M. A. and Fink, M.: Electroencephalographic and Clinical Effects of Megimide; Presented at the Eastern Association of Electroencephalographers, New York, December 5, 1956. Green, M. A.: The Use of Electroencephalography in Differentiating Psychogenic Disorders and Organic Brain Diseases, Amer. J. Psychiat., 113: 27-31, 1956, (with P. Bergman). Green, M. A.: Neurological Manifestations of Conversion Hysteria, Trans. A.N.A., 80: 196-198, 1956. Jaffe, J.: Experimental Alteration of Communication in Doctor-Patient Relationship; Presented at the Nassau Neuropsychiatric Society, April 15, 1956. Kahn, R. L. and Fink, M.: Changes in Language During Electroshock Therapy; Presented at the American Psychopathological Association, New York, June 1, 1956. Kahn, R. L., Fink, M. and Weinstein, E. A.: Relation of Amobarbital Test to Clinical Improvement in Electroshock, Arch. Neurol. & Psychiat., 76: 23-29, 1956. Kahn, R. L., Fink, M. and Korin, H.: Studies of Mode of Action of Electroshock; Presented at the Nassau Neuropsychiatric Society, April 15, 1956. Kahn, R. L., Linn, L. and Weinstein, E. A.: Personality Factors Influencing the Rorschach Responses in Organic Brain Disease; Presented at the New York 19 �Neurological Society, February 14, 1956. Also, Arch. Neurol. & Psychiat., 76: 226-267, 1956. Kahn, R. L., and Pollack, M.: Effects of visual, vestibular and somatosensorimotor deficit on autokinetic perception, J. Exp. Psychol., 52: 398-410, 1956, (with Battersby, W. S. and Bender, M. B.). Kahn, R. L.: Patterns of Social Interaction in Brain Disease, Amer. J. Psychiat., 113: 138-142, 1956, (with E. A. Weinstein). Kahn, R. L.: Confabulation as a Social Process, Psychiatry, 19: 383-396, 1956, (with Weinstein, E. A. and Malitz, S.). Kahn, R. L.: Delusions About Children Following Brain Injury, J. Hillside Hosp., 5: 290-301, 1956, (with Weinstein, E. A. and Morris, G. 0.). Korin, H., Fink, M. and Kwalwasser, 8.: Relation of Changes in Memory and Learning to Improvement in Electroshock, Conf. Neurol. 16: 88-96, 1956. Lurie, Abraham, Miller, Joseph S. A., Bellak, L., Black, B. F.: Rehabilitation of the Mentally Ill Through Controlled Transitional Employment, Amer. Orthopsychiatric Assoc., 1955 Annual Meeting. Also, Digest of Neurology and Psychiatry, July 1956, Institute of Living. Lurie, Abraham: Book review—Delinquent Boys by Dr. Albert K. Cohen, J. Jewish Communal Services, Summer 1956. Lurie, Abraham: Integrating Services for Improved Patient Care; Discussant at 50th Anniversary of Social Service Dept. of Mt. Sinai Hospital, October 18, 1956. Lurie, Abraham: Identifying Casework Responsibility in a Multi-Discipline Health Setting; Workshop Chairman, National Conference of Jewish Communal Service, 1956. Pinsky, Louise: The Impact of Mental Illness on a Patient’s Family, Jewish Communal Service, Spring 1956. Pollack, M. and Kahn, R. L.: Unilateral “Spatial Agnosia” (“lnattention”), Brain, 79: 68-93, 1956, (with Battersby, W. S. and Bender, M. B.). Wachspress, M., Blumberg, A. G., Fink, M. and Miller, Joseph S. A.: Evaluation of High-Dose Reserpine Therapy for the Relief of Anxiety, J. Hillside Hospital, 5: 67-77, 1956. Zierer, Ernest and Zierer, Edith: Dynamics of Creative Therapy; Presented at the University Clinic in Tubingen, Neckar, Germany. Zierer, Ernest and Zierer, Edith: Structure and Utilization of Creative Therapy; Presented at the Institute of Psychotherapy and Depth Psychology in Stuttgart, Germany. Zierer, Ernest and Zierer, Edith: Non Artistic Creative Activity; Presented at the Art Academy of Stuttgart, Germany. Zierer, Ernest and Zierer, Edith: Seminar on Creative Therapy as applied at Hillside Hospital and Extramurally; Presented at the meetings of the Zierer Study Group in Stuttgart, Germany. Zierer, Ernest and Zierer, Edith: What is Creative Therapw Presented at the broadcast over the Suddeutscher Rundflunk “Millelwelle.” Zierer, Ernest: Dynamics of Creative Therapy; Presented at the National Psychological Institute for Psychoanalysis, New York. Zierer, Ernest and Zierer, Edith: Structure and Therapeutic Utilization of Creative Activity, Amer. J. Psychotherapy, 10: 481-520, July 1956. ' ‘ 20 �TEACHING AND TRAINING The Resident Training Program at Hillside continues to emphasize the interrelation between the training program and the treatment program. Each resident carries a case load of about 15 patients under the supervision of staff and visiting instructors, and attends lecture conferences conducted by the medical directors. Lecture seminars in the fields of psychopathology and psychotherapy, and reading seminars, are conducted by special instructors chosen from the hospital staff. Qualified residents are assigned to the department of Experimental Psychiatry for clinical and other psychiatrical research projects. During the year there were 18 residents in training. The Resident Training Program The hospital training program extends also to Clinical Assistants in the Outpatient and After-care clinics and on-the-job training of personnel. Regular lec- Training for other staff members The Sunday Clinical Conferences, open to and attended by psychiatrists and other professional personnel and by outstanding visiting physicians, are part of the resident training program and are based on cases prepared by the residents. They continue to make a significant contribution to the training picture on the New York Psychiatric scene. Sunday Clinical Conferences The Annual Israel Strauss Lecture, established in 1955 in honor of Hillside’s founder and late president, was delivered this year on April 8th. The speaker was William Malamud, MD, Professor and Chairman of the Department of Psychiatry and Neurology of the Boston University of School of Medicine. His Israel Strauss Lecture Hillside's Committee on Community Education continues active and its program of lectures to the laity promote interest and understanding of mental hygiene problems in the community. Community Education The Medical Library, considerably enlarged by the acquisition of the entire medical library of the late Dr. Israel Strauss, was able this year to increase its services and usefulness to the staff by the employment of a full-time librarian. Medical Library The Journal of the Hillside Hospital again showed an increase in the number of its subscribers, an indication of the prestige and general acceptance it enjoys. A 504 page Israel Strauss Memorial Volume containing articles by psychiatrists and other friends of Dr. Strauss, was published in 1956. Journal of the tures and conferences are scheduled for nurses and attendants, social workers, members of the various adjunctive services and for affiliating students from other educational institutions. subject was “Current trends in basic psychiatric research.” Hillside Hospital 21 �REPORT OF THE ADMINISTRATOR Deficits While the cost of running the Hospital increased again, from $1,175,635 to $1,326,454, the deficit this year has been substantially reduced because the City of New York increased its contribution toward the care of the indigent mentally ill from $14 to $16 a day. The average number of patients per day. 192, remained the same as last year —97% of capacity. However the length of stay increased somewhat and the total number of patients treated was 561 this year compared to 575 in 1955. Comparison of costs: 1955-1956 . . . Salaries Food . . . . Maintenance and Grounds Administrative EXpenses Medical Supplies . Repairs and Replacements Clinics . . . . . Total Total No. Patients Total Patient Days . . . . Average income per patient day Average cost per patient day Average loss per patient per day . . . . . . 1955 1956 $732,977 106,397 50,551 67,017 28,130 25,279 165,284 $797,805 113,428 59,436 82,608 23,950 35,105 214,122 $1,175,635 $1,326,454 575 69,903 561 70,189 $14.45 $15.34 $15.44 $15.84 $ .89 $ .40 Costs of expanded out-patient services should be noted that the largest portion of the $150,819 increase was used for expansion of the Out-patient service. This increase was entirely offset by grants from the New York City Community Mental Health Board, the State Mental Health Authority, and increased subvensions from the Federation of Jewish Philanthropies. Increases in salaries reflect a rise in salaries and salary rates rather than an increase in personnel. Other increases reflect the general pattern of rising costs for goods and services. Costs of the Israel Strauss Adolescent Pavilion 1956 it was decided to compute the costs of running the Israel Strauss Adolescent Pavilion separately from those of the main hospital. While the pavilion operates as an integral part of the hospital, it is a new and costly experiment, which, if included, somewhat distorts the general operating picture. It In The operation of the Adolescent Pavilion showed a deficitof $37,752, an increase of 13% over 1955. The difference is entirely accounted for by salaries for additional personnel found necessary for successful operation. Maurice Bachrach 22 �SOCIETY OF THE HILLSIDE HOSPITAL ‘President . . . Alvin E. Coleman *Chairman of the Board Roy Foster *Honorary Chairman of the Board Leon Lowenstein *Vice-President Dudley D. Shoenfeld, M.D. *Vice-President D. Herbert Beskind ‘Vice-President George W. Galinger Manuel Lee Robbins +Treasurer Alfred Levinger ‘Ass’t Treasurer Arnold S. Askin Ass’t Secretary Hilda Strauss Assistant Secretary Alfred Appel 'Secretary Board of Directors A. Leon Lowenstein“ Roy Foster" Jacob Abrams George W. Galinger‘ Arthur Garson Maurice Glinertt Mrs. Henry Goldman, Jr. Meyer Goldstein Louis A. Green M. Victor Leventritt Alfred Levinger? Morris L. Levinsonrl: Milton B. Loeb Sandor Lorand, M.D. Alfred Appel Arnold S. Askin“ John M. Bendheim D. Herbert Beskind‘ Saul Blickman Alvin E. Coleman Morris David Edwin Elson1~ Thomas Epstein Arthur C. Fatt‘ David Finkle David Finn: Charles H. Meyer“ Arthur Murray Manuel Lee Robbins” lrving Rosenbaum S. H. Scheuer“ Walter Scheuer Dudley D. Shoenfeld, M.D.‘ Harry Silverson Hilda Strauss Nathan Wigod Morton 8. Wolf Walter D. Yankauer Chairmen of Standing Committees Medical Affairs Committee D. Herbert Beskind Executive Committee Roy Foster House and Grounds Committee George W. Galinger Co-Chairmen Nathan Wigod Jewish Hospital Coleman Liaison Committee—L. Alvin E. I. Legal Committee Charles H. Meyer Publicity Committee Arthur C. Fatt Finance Committee Arnold S. Askin Social Service Committee Hilda Strauss Personnel Committee Meyer Goldstein ‘Executive Committee Members tDeceased in 1956 *Elected in 1956 23 �PROFESSIONAL AND ADMINISTRATIVE STAFF Medical Director Joseph S. A. Miller, MD. Associate Medical Director Simon Kwalwasser, M.D. Administrator, Maurice Bachrach, B.S. George Yessin, M.D. Jack H. Tabor, M.D. Supervising Psychiatrists Gerhard Schauer, M.D. Martin A. Green, M.D. Robert Navarre, M.D. Eugene Glynn, M.D. Supervising Psychiatrist Israel Strauss Adolescent Pavilion Alice Slater Stahl, MD. Director of Out-Patient Services Robert R. Luttrell, MD. Director of Research in Experimental Psychiatry Maximilian Fink, M.D. Internist, Arnold Blumberg, MD. Director of Laboratories, Harry Goldenberg, Ph.D. Resident Staff Ruth Adams, M.D.* Stanley Brodsky, M.D. Frederick Coleman, M.D. Warren Cox, M.D. Ilhan Ermutlu, M.D. Harold Esecover, M.D. Stefano Fajrajzen, M.D. Marie Friedman, MD. Stanley M. Friedman, MD. Ruth Fuchs, M.D. Harold Galef, MD. Robert S. Gilbert, M.D. Eugene D. Glynn, M.D.“ Victor Goldin, MD. Michael Gould, MD. David N. Graubert, M.D.* George E. Gross, M.D.* Peter Guggenheim, M.D.+ A. Russell Lee, MD. Joel Markowitz, M.D.* Robert Nodine, MD. Paul Pressman, M.D. Arthur Root, M.D. Jack R. Royce, M.D.* Robert Shaw, M.D.* Charles G. Silverman, M.D.* Myron Stein, M.D. Morton Wachspress, M.D. Leon Lefer, M.D. Other Professional St aff Heads Nathalie Burbach, R.N., M.A. Director of Nursing Abraham Lurie, M.S.S.W. Director of Social Service Abraham Levine, Ph.D. Director of Psychology Ernest Zierer, Ph.D. Director of Creative Therapy Eileen P. Fisher, B.S. Director of Occupational Therapy Zetta Putter, M.S. Director of Group Activities Angelina Canavan, B.A. Dietician Department Heads Dorothy Croghan Accounting Supervisor Lillian Dailey Office Manager Thomas R. Lumley Superintendent of Buildings & Grounds Sarah Travers Executive Housekeeper ‘Completed residency in 1956 fin military service 24 �MEDICAL BOARD *President *Vice-President ‘Secretary . . . M. David Sidney Tarachow, M.D. Sidney L. Green, M.D. Epstein, M.D. *Treasurer * Ex-President David Warshaw, M.D. Samuel Atkin, M.D. Psychiatrists Samuel Atkin, M.D.‘ Arnold Eisendorfer, MD. M. David Epstein, M.D.“ Margaret E. Fries, M.D.* I. Peter Glauber, M.D. George S. Goldman, M.D. Sidney L. Green, M.D.‘ William Karliner, M.D. Sylvan Keiser, M.D. Sarah R. Kelman, MD. Emanuel Klein, M.D. Sidney Klein, M.D.“ Samuel 2. Orgel, M.D. H. L. Rachlin, M.D.“ Lawrence J. Roose, M.D. Irving J. Sands, MD. Robert A. Savitt, M.D.* Martin Schreiber, M.D. l’sidor Silbermann, M.D.* Otto Sperling, M.D. Sidney Tarachow, M.D.‘ Non-Psychiatrists Director of Department of Medicine Lester Cohen, MD. 'Director of Department of Surgery Director of Department of Neurology Morris B. Bender, M.D. Director of Department of Gynecology Julius Jarcho, MD. ‘Department of Dentistry David Warshaw, MD. Paul Scheman, D.D.S. Chairmen of Standing Committees Adolescent Pavilion Sidney L. Green, M.D. Education of Resident Staff Arnold Eisendorfer, M.D. Community Education and Public Relations Robert A. Savitt, M.D. Group Psychotherapy Samuel 2. Orgel, M.D. Credentials Committee for Psychiatric Staff and Promotions Martin Schreiber, M.D. Manhattan After-Care Clinic Sarah R. Kelman, M.D. Credentials Committee for Non-Psychiatric Staff and Promotions David Warshaw, M.D. Credentials Committee for Resident Staff Sidney Klein, M.D. Queens Out-Patient Clinic William Karliner, M.D. Research Committee Hyman L. Rachlin, M.D. Publications Committee I. Peter Glauber, M.D. Journal Sub-Committee Sidney Tarachow, MD. 'Ex-officio 25 �CONSULTING, ATTENDING AND VISITING STAFFS: AND CLINICAL ASSISTANTS Consultants Psychiatry Leonard Blumgart, M.D. Sandor Lorand, M.D. Nathaniel S. Selby, M.D. Dudley D. Shoenfeld, M.D. A. M. Rabiner, M.D. Medicine Alfred Angrist, M.D. Morris S. Bender, M.D. Oscar Levin, MD. I. Jesse Levy, MD. Neurology Hans Strauss, M.D. I. S. Wechsler, M.D. Dentistry Morris Fierstein, D.D.S. Attending Psychiatrists Samuel Atkin, M.D. Arnold Eisendorfer, MD. M. David Epstein, M.D. Margaret E. Fries, MD. I. Peter Glauber, M.D. George S. Goldman, M.D. Sidney L. Green, MD. William Karliner, M.D. Sylvan Keiser, M.D. Sarah R. Kelman, M.D. Emanuel Klein, M.D. Sidney Klein, M.D. Samuel 2. Orgel, M.D. Hyman L. Rachlin, M.D. Lawrence J. Roose, MD. Robert A. Savitt, M.D. Martin Schreiber, M.D. lsidor Silbermann, M.D. Otto Sperling, M.D. Sidney Tarachow, M.D. Associate Attending Psychiatrists Frank Berchenko, M.D. Cornelius Beukenkamp, M.D. Mark L. Gerstle, Jr.+ Soll Goodman, M.D. Attilio Laguardia, M.D. Samuel R. Lehrman, M.D. Abraham S. Lenzner, M.D. Martin H. Orens, M.D. Abraham Kaplan, M.D. Louis Kaywin, M.D. Bruce Kendall, M.D. George P. Krupp, M.D. Peter Laderman, M.D. Nathaniel S. Lehrman, M.D. Harold S. Leopold, MD. William W. Pike, M.D. Adjunct Attending Psychiatrists Edward R. Adelson, M.D. Renato J. Almansi, M.D. Herman S. Alpert, M.D. Irving L. Bauer, M.D. Milton M. Berger, M.D. Lionel H. Blackman, M.D. Isadore H. Cohn, M.D. Alexander J. Friedman, MD. Albert E. Goldbert, M.D. Albert Harrison, MD. Thomas Hora, M.D. tResigned in 1956 26 David Milrod, M.D. Hugh Mullan, M.D. Helene Papanek, MD. Benjamin B. Rubenstein, M.D.+ Irvin Salan, M.D. Frederick F. Shevin, M.D. Jay Stanton, M.D. Aaron Stein, M.D. Samuel Tabbat, M.D. Fred U. Tate, M.D. Leonard Weinroth, M.D. Herbert Wieder, M.D. Arthur Zitrin, M.D.1- �Visiting Director Lester Cohen, MD. Visiting Physician George Sabrin, M.D. Visiting Physician L. Rosenblum, M.D. Visiting Physician A. Blumberg, MD. Associate Physician M. Kalkstein, M.D. Associate Physician J. Weinstein, M.D. Visiting Neurologist Medicine Adjunct Physician A. L. Berger, M.D. Adjunct Physician W. B. Brett, M.D. Visiting Dermatologist C. Stritzler, M.D. Associate Dermatologist Joel Schweig, MD. Adjunct Dermatologist N. Goldfarb, MD. Neurology Morris B. Bender, MD. Associate Neurologist Adjunct Neurologist Harry Harter, M.D. Director David Warshaw, MD. Visiting Surgeon Sidney Hirsch, M.D. Visiting Neurosurgeon Joseph Siris, M.D. Visiting Urologist L. G. Goldberg, MD. Adjunct Urologist Albert Sutton, M.D. Visiting Orthopedist A. H. Lewert, M.D. Director Julius Jarcho, MD. Visiting Gynecologist M. Warner, MD. Visiting Gynecologist H. Dubrow, M.D. Surgery Kurt Adler, M.D. Associate Orthopedist J. Schneiderman, M.D. Visiting Proctologist B. Warner, M.D. Visiting Ophthalmologist E. Seretan, M.D. Associate Ophthalmologist A. Minsky, M.D. Visiting Otolaryngologist S. Clayton, M.D. Visiting Anesthesiologist Georges Bean, M.D. Gynecology Associate Gynecologist Jack Cohen, MD. Associate Gynecologist B. Greenblat, M.D. Adjunct Gynecologist Eugene Streim, M.D. Radiology Visiting Radiologist Bernard Epstein, M.D. Director Paul Scheman, D.D.S. Associate Director J. G. Rubin, D.D.S. Associate Stanley Spiro, D.D.S. Associate Dentist B. Schwaid, D.D.S. Adjunct Dentist B. Lebow, D.D.S. Adjunct Dentist H. Lewis, D.D.S. Dentistry Adjunct Adjunct Adjunct Adjunct Adjunct Adjunct Dentist Dentist Dentist Dentist Dentist Dentist H. Adler, D.D.S. J. Goldberg, D.D.S. S. Platt, D.D.S. S. Plotnick, D.D.S. E. Friedman, D.D.S. M. Protell, D.D.S. Optometry Staff Optometrist Edward L. Steinberg, O'.D. Podiatry Staff Podiatrist Sam Sokolov, Pod. D. 27 �Clinical Assistants in Manhattan and Queens Clinics _ Lester I. Abend, ‘M.D. Ruth Adams, M.D. Romano Antonelli, M.D. Howard Boskey, MD. Paul Bradlow, M.D. Arline Caldwell, M.D. Mischa Caplan, M.D. Dominick J. Carlisi, M.D. Lionel Chertoff, M.D. Rita M. Chalef, M.D. Gloria Chung, MD. Julius Colantuond, M.D. Fred Dalton, M.D. Edward Einhorn, M.D.1- Joseph Feldman, M.D.+ Philip Friedland, M.D.t Hans Freymuth, M.D.1Arthur Gillman, M.D.t Harry Gonda, MD. David Graubert, M.D. Martin Hurvitz, M.D. Howard Hess, M.D. Gunthar Jacob, M.D. Wilbur Jarvis, M.D. Buck Luria, M.D. Meyer Monchek, M.D. Mathias Nachumi, M.D.1- Beatrice Nachtigal, M.D. Iris Orens, M.D. Edward Pinney, Jr., MD. Joshua Ramot, M.D. Willem W. Roosen, M.D. Henry Rosberger, M.D. Joseph D. Rosen, M.D. Gabriel Rubin, MD. Herman Tannor, M.D. Leon Tec, M.D. Clara Torda, M.D. Morton Wachspress, M.D. Irving Waitzel, M.D.l‘ tResigned 1956 STSANDL . are necessary to a v TO THE HOSPITAL he Society. The following form, however, se of the Hillside Hospital, the sum of - rty, such as bonds, stocks, etcetera, is serted instead of the words “the sum of 28 �l .,v . I ' I ., ‘ ,- . . �Glen Oaks, Queens, New York, �Hillside Hospital is a non-proﬁt, non-sectarian mental hospital for the treatment of from Patients mental curable and are early symptoms. voluntary patients suffering admitted regardless of their ability to pay. I Hillside provides training for physi- cians in post-graduate psychiatry and psychotherapy and puts major emphasis on research in all phases of treatment. The hospital considers itself a pilot institution, ill. the to the and human mentally in efﬁcacious application of psychiatry pioneering I The hospital is licensed in the New York State Department It is approved of Mental Hygiene. Medical Council the in on by psychiatry for a two-year residency Education of the American Medical Association, The American Board of Psychiatry and Neurology and the American College of Surgeons. The Dental Department is Association Dental American the as an approved hospital department. by certiﬁed I Hillside Hospital is an afﬁliate of the Federation of Jewish Philanthropies and a York Fund. New Greater the and Fund United the Hospital participant of M. DAVID EPSTEIN, M.D. �I The responsibilities and functions of the Medical Board fall roughly into two broad categories: 1. It is a consultative and advisory body to the Medical Director and the Board of Directors in all matters pertaining to medical functioning of the Hospital. In this capacity, it assists materially in the formulation of basic policy, and in the establishment of both short-range and long2. In addition, it range plans, directions and goals performs duties relative to the implementation of these plans and policies and plays an active role in the practical day-to-day operations and needs of the hospital, whether this be in terms of active supervision of the junior members of the staff, supervision of the Out Patient Clinic or the After-Care Clinic, careful and methodical screening of all candidates for positions on the professional staff, either House or Visiting, or working with other departments within the hospital, such as Psychology or Social Work It is not possible to report on all the activities of the Medical Board since the last report was rendered. However, some of the more important areas of Board activity are worthy of individual mention During the past year, the Liaison Committee of the Medical Board, working with the Medical Director and Lay Board, has been able, after long and delicate negotiations, to bring to a successful culmination the question of the establishment of a Psychiatric Service at our neighbor institution, the Long Island Jewish Hospital. One of Hillside’s Attending Psychiatrists will organize a staff at Long Island Jewish Hospital and will maintain liaison with Hillside Hospital. We will be glad to continue to render whatever assistance we can, and we look forward to a productive, progressive collaboration between the two institutions The Journal of the Hillside Hospital, under its able editor, has continued to grow and is achieving ever wider recognition in the professional world. The caliber and standards of the publication have remained consistently high. In the ﬁeld of publication a new project has been recommended and will shortly be carried out, viz. a series of monographs I I I I on important psychiatric subjects to be issued under the The Adolescent imprimatur of Hillside Hospital I Pavilion, a pilot project established several years ago, and a rather unique undertaking, has taken a great deal of time and work. It has gone through a variety of growing pains in its early exploratory and experimental period, but it is now an established and important aspect of the Board’s interest and efforts. Although it continues to present problems, or better, because it does, much is being learned about problems of adolescent psychopathology and their treatment and a sizable body of knowledge is being accumulated which will no doubt lead to advances in understanding and to important research results. In addition, the Pavilion continues to After much serve as an important training facility careful study and planning, the Medical Board has set the machinery in motion to establish a new project. This is to be a Child Therapy Unit, for the intensive treatment of a selected group of children and their parents where necessary, to be operated as part of the Out Patient Department. Such a unit would be a most valuable adjunct to our training program and will also help in ﬁlling an urgent need in the community. The basic set-up is ready to start functioning as soon as one or two remaining obstacles are overcome, and it is ardently hoped that this plan will be brought to fruition in the very near future Possibly two of the most important functions of the Medical Board are the organization and supervision of the Educational and Research Divisions of the Hospital. Under the guiding hand of the Educational Committee, our Resident Training Program continues to operate most successfully and the program of formal and didactic training and supervision is more than adequate. The Committee is constantly studying and re-evaluating the educational program, always seeking ways and means of reﬁning and improving teaching methods at the Resident level, a universal problem with which every training hospital has to cope. Currently, the Committee is exploring ways of expanding and rounding out the train- I I ing program, with a View to having Hillside accredited for a three-year residency, possibly with the aid of affiliations with other institutions. Such a development would be eminently desirable In the area of Research, much has been accomplished and the Committee or the Board charged with this responsibility has functioned most actively. In collaboration with the Directors of the various research divisions, a large number of projects have been studied and evaluated. In addition, several members of the Board and Attending staff are engaged in individual research projects of great interest and promise. The Board is still seeking ways of expanding the Research Program, broadening it to make it more inclusive and comprehensive by adding a Research Division devoted to the more purely psychological aspects of mental disorders. Unfortunately, our efforts thus far have not been successful, but the search for a suitable and available person to head such a program goes on actively. It is with profound regret that we are compelled to note the loss through retirement of two of our oldest and most respected Board members— Doctors Julius Jarcho and David Warshaw, both of whom have become Consultant Physicians, from which lofty eminence we trust their invaluable advice and experience will continue to be available to us A closing word now about our view of the future. We have no doubt that Hillside Hospital now stands at a critical point in its historical development and evolution.Great and important changes can be expected and far-reaching decisions will have to be made. These changes are made necessary by the need to expand and to be prepared to meet the exigencies of a rapidly expanding science of Psychiatry and even more rapidly growing community needs for service and for trained personnel. We must gear ourselves and plan with foresight for these changes. Hillside can and should become a vital element in the psychiatric world and an important training and research center. To make it such will require Vision, courage, perhaps even daring, and cooperation on the part of all who are associated with it. I I �//2 I TQM/r/M' e/0 poéra/ In 1957, Hillside saw many changes, some obvious, some not yet evaluated, in attitude and treatment, in ﬁnancial status, in acceptance in the eyes of the comI of am constructive these For signs progress, munity happy to commend our staff, the professional and nonprofesslonal personnel, the Medical Board and the everready help and unselﬁsh interests of the Board of DirecAs a non-proﬁt, non-sectarian hospital for the tors treatment of voluntary patients suffering from early and curable mental symptoms, the function of Hillside as a teaching and research center has enabled it to pioneer in many forms of therapy. To help in this area, an unusual number of grants were awarded to Hillside in 1957. Some $256,400 were allocated for research and nonthe contributions Of the making up operating purposes. grants, the largest was $104,800 from The Ford Foundation. Other sums were: Max Einhorn Estate, $50,000, Hillside Hospital Board of Directors, $50,000, and the US. Public Health, Institute of Mental Health, $35,000 Increasing attention from the nation’s press is being focused on the research, training and therapy programs of leading mental hospitals. We believe this is of great help to everyone in the ﬁeld of mental health. No small share of this publicity was directed at Hillside Hospital during 1957 However successful this side of Hillside’s remained still the in on 1957, emphasis was program the patient. At Hillside, the ﬁrst person a patient sees I I I I is his doctor. The large medical staff is concerned with various aspects of his recovery, but the doctor assigned to each patient is the most important person to look to for treatment, consultation, advice and help. The social worker assigned to help with the problems of the patient outside the hospital, as well as within its walls, stays with him as long as needed. The nurses and attendants offer to the patient the understanding of A new special training and constant association booklet dealing with these aspects of a patient’s relationship with the staff, and endeavoring to answer his questions and allay his doubts, has been written and made available to patients and their doctors, as well In 1957, as consultants and interested researchers the three alternate ways of dealing with Hillside’s patients and their varied needs evolved more strongly. A patient is helped to rejoin his family and the community not only by Hillside but by the various private and state employment groups, interested voluntary organizations, as well as the family which ideally gained new insight and understanding under the guidance of the social service worker He may need the continued attention of a social service worker, sometimes for as long as eight months. A continuous relationship such as this gives anchorage and stability to the patient. Should further psychotherapy be needed, he is referred to the After-Care Clinic, the Jewish Family Service, or other I I I I When the discharged patient cannot be sent back home, because the original environment is not suitable to maintaining recovery he is placed in private residence care through our liaison with the Jewish COmmunity Services of Long Island. Happily settled in newer, more sympathetic surrounding, the patient then can be seen in therapy for six to eight months. This time limit is arbitrarily set in the belief that the patient can be moved to a dynamic effort to With the entire emphasis of recover more quickly Hillside on an “open hospital,” the tendency more and more is to treat and hold the patient so far as possible in his normal environment. Carrying this a step further, Hillside now believes that its future lies not in enlarging the hospital’s facilities, but in expanding the pré-hospital The main orienguidance, and Out Patient Service tation, therefore, of the patients and staff at Hillside is to the inevitable return to the community and useful citizenship. The goal of the hospital’s treatment services. organizations I I both at the in patient and out patient levels, is to provide the best qualitative treatment for our patients, so that the result, ideally, is not merely an improved or recovered individual, but an improved or reclaimed family unit or small segment of the present and future community. Joseph S. A. Miller, M.D. �I 1957 was a good year for Hillside Hospital, and no apparent recession set in, with regard to the work of the hospital, or the demands made upon it were concerned. During the year, new ideas were presented and developed, such as the training of registered nurses in psychiatry at Hillside, in collaboration with the Queens Medical College. This plan inured to the beneﬁt of the hospital in that some of the nurses remained to practice with us. Additional funds secured from the New York City Community Mental Health Board and the Nassau County Mental Health Board permitted the further expansion of services in the Out Patient Clinic where, at the end of 1957, we were treating 205 patients each week We suffered a great loss through the death of our long time Treasurer, Alfred Levinger, who had been one of the original founders of the institution. During 1957, the Board of Directors created the new position of Honorary Director, and the first Director so honored was Mrs. Israel Strauss, the wife of the founder of our institution. Saul Blickman, one of our directors ‘of long One of the most standing, was similarly honored important events of the year was the appointment of Dr. Lewis L. Robbins as Director of Professional Siervices. Dr. Robbins, a nationally known psychiatrist, who has been with the Menninger Foundation for 18 years, will join the Hillside staff in July 1958 Our research work has continued and expanded through the ﬁnancial aid of several government organizations and private I I I ﬂﬂﬂﬂﬂ/ﬂ ' foundations, as well as donations of the Hillside Board of Directors. During 1957, the staff of the Department of Experimental Psychiatry extended our knowledge of the way various treatments affect our patients and have clariﬁed our understanding of electroshock, insulin coma, and the newer tranquilizers. Their studies have been presented before national and local psychiatric and psychologic societies, and eight reports have been published during the year. Three reports were presented at the International Congress of Psychiatry in Zurich and of Psychology in Brussels during the summer The need for greater research efforts is apparent to all who are even casually interested in this ﬁeld of health, and it does seem incumbent upon the governments of the United States and of each state, as well as private funds, to offer more generous support for these efforts. But surely, within the foreseeable future, progress will be made and we, at Hillside, are not alone in believing this. At the 1957 convention of the American Hospital Association, Dr. Julian P. Price, Chairman of the Joint Commission on Accreditation of Hospitals of the American Medical Association said: “The chemical nature of certain mental diseases will be discovered and their control brought about through the giving of drugs.” RecognizingIthe tremendous human values this will have, not to mention the enormous dollar savings, let us try our best to hasten this day with our own efforts and money. I ALVIN E. COLEMAN �of 545 total treated patients. Hillside a 1957, Admissions and Discharges—1n with an average daily census of 192. New admissions totalled 81 and readmissions after been an had discharged 351 of the end patients the 32. totalled By year, of summaries statistical the is similar to data This average stay of 182 days. recent years. %/tm/ / MARRIED F No. of patients treated Males Sex Females Admission (13-19 (20-29 Age (30-39 (40-49 (50-59 (60 plus No. of patients admitted Average no. days hospitalized (adults) WIDOWED M F DIVORCED & SEPARATED M F �I In any evaluation of discharges, it is important to realize that the terms used to denote mental condition at the time of discharge only signify a comparison between the patient’s condition and behavior when he came to the hospital and when he left, a relatively short period The following comparisons use terms which are deﬁned as follows. Unimproved means there has been I no change; improved means that symptoms or problems have been somewhat helped but still persist to an appre- ciable extent; much improved means that symptoms have disappeared and the patient seemed in good condition at the hospital, but there is no certainty Of how he will function when he gets back into his own social and working community; recovered means that in addition to what has been said for much improved, there is reasonable expectation that the patient will be able to return tO his community and function as well, or better than he did before he became ill. %/ , DIAGNOSIS ADULTS ADOLESCENTS /lﬂﬂ// a) a TOTAL NO. OF PATIENTS WHOLE SHOCK THERAPY 5'2 0F INSULIN COMA THERAPY % % RECOVERED MUCH IMPROVED IMPROVED UNIMPROVED Psychoneurosis 63 3 66 19% 12% 10% 46% 40% 4% Manic depressive psychosis 84 1 85 24‘} 34% 27% 43% 27% 3% Involutional psychosis 63 63 18% 39% 22% 49% 20% 9% 1 8% 26% 50% 16% 40% 20% 40% 39% 36% 12% 118 9 127 36‘)? Others 8 2 10 3% Totals 336 15 351 100% Schizophrenia % 76% 14% 18% 13% �%y¢%/%¢Q/% m/ giwzéw %%éa/ I One of the main criteria for accepting. patients at Hillside is their ability to participate proﬁtably in psychotherapy. Patients are seen individually three times a week for psychoanalytically oriented treatment by their assigned psychiatrists. The psychiatrist is the leader of the hospital “team” that plans and supervises the patient’s day-to-day treatment. The other members of the team are a psychiatric social worker, a psychologist, professional representatives of the adjunctive services—Occupational Therapy, Group Activities and At Hillside, the staff is Creative Therapy—and the Nursing Department much larger in proportion to the number of patients than in other mental hospitals. Thus, Hillside’s emphasis is entirely on the patient as an individual. Although all the latest physical and pharmaceutical techniques are used as needed, such as electroshock, insulin, Serpasil, treatment does not revolve the to since these supplementary around only they techniques are primarily psychotherapeutic approach. All departments bring into play the tools of treatment, prescribed according to the patient’s particular needs, and all aimed not only at relieving him of symptoms, but getting at the causes as well, so that he may be returned to full usefulness as a human being. The Psychology Department. under the direction of Dr. Abraham Levine, continued to expand both in staff and services. In addition to six new staff Uma Dr. for Hillside training a diagnostic year’s provided appointments, The Vocational CounselChowdhury, a cultural anthropologist from India ling Program was expanded through the addition of staff members. The Department conducted 222 new adult patient examinations, 21 examinations for the adolescent patients and 248 Out Patient examinations. 117 psychological I I discharge examinations were administered for In Patient adults, 8 for adolescents, and 19 for Out Patients. The Nursing Department. under the direction of Mrs. Nathalie Burbach, participated in all initial presentations, discharge conferences and team meetings, enabling them to offer more understanding and knowledgeable nursing care. 36 Psychiatric Aides were trained, and 57 student nurses from Queens College received psychiatric nursing experience. Central Islip School of Nursing continued to send student nurses for semi-weekly visits to compare opera‘ tion of state and private hospitals, and student nurses and nursing personnel from St. Vincent’s Psychiatric Unit in Manhattan Visited to obtain information generally helpful in the preparation of patients transferring from St. Vincent’s The Intramural Clinic has continued to handle all major to Hillside An of hospitalization. patients’ the during course arising physical problems overall supervision of the effect of the drugs used in psychotherapy was conducted with special emphasis on Chlorpromazine and Meprobamate. 1756 examinations were conducted for treatment in such specialized ﬁelds as Dermatology, Gynecology, Medicine, Neurology, Ophthalmology, Orthopedics, Otolaryngology, Podiatry, Proctology, Radiology, Surgery and The Dental Department made Urology 1123 examinations including restorations, I I �extractions, prosthetic treatments, and X-rays. Under the direction of Dr. Paul Scheman, a staff of 12 Visiting dentists continued to adapt consultation and treatment procedures to the special needs of the mental patient. The department, certiﬁed by the American Dental Association, presented a series of lectures for dentists who treat “problem patients”. tMa/QMM/féze gar/12w The Occupational Therapy Department. under the direction of Eileen P. Fisher, in order to give more intense individual treatment, registered no more than 45 patients at a session. No therapist has more than twelve patients to work with at a time. Though the Department treated fewer patients per month, the average daily attendance remained the same, since there was closer followa up on all patients and a closer relationship with individual doctors. The Department works closely with all members of the psychiatric team, particularly the social workers. A special class program was organized on a selective basis, offering individual instruction in ceramics, jewelry and sewing. A student training program is being planned as a result of approval as an alﬁliating center for students from New York University Lectures on the principles and uses of Occupational Therapy in a psychiatric hospital were given to student nurses, new personnel and visitors. I The Creative Therapy Department. under the direction of Dr. Ernest Zierer and his associate, Mrs. Edith Zierer, continued experiments with con- trolled painting tests, designed as a psychodiagnostic tool to stimulate the patient into projecting his unconscious conﬂicts by painting. An average of 42 patients were treated daily. A total of 4,509 paintings were analyzed and a total of 1,593 tests administered A new questionnaire form of tests was added to help the patient gain insight into his actions and reactions. The patients are encouraged in regularly scheduled individual sessions to give verbal interpretations of their paintings within the framework of the situation, also tied in with the test results Lectures were given to visiting psychiatrists, social workers and students. I I �@ﬁéﬂ/ [lﬂﬂ/ ﬂ @ammmw/ / �I Hillside Hospital believes in treating the mental patient within the community, rather than in isolation, away from family and familiar surroundings. Directly responsible for improving communications between the patient, his family and his community is Hillside’s Department of Social Services. Under the direction of Abraham Lurie, the Department works to help the patient keep his place in society, and return to it In 1957, the Dea better, more useful citizen partment was reorganized to include the Group Work Division. The Department, therefore, now consists of two divisions: The Casework Division, directed by Louise Pinsky, an assistant director of the Department, and the Group Work Division, directed by Arnold Eisen, also an assistant director of the Department As a result of this merger of staffs, there have been several improvements and developments in the program offered patients, and it is believed that the goal of integrating the patient with his family and the community is closer through these changes. The Casework Division. with the knowing cooperation of the patients and their families, works to maintain and strengthen family ties, and to I I solve, with the patients, their individual problems of rehabilitation. Through the Division, the hospi- tal reaches out from the patient to the family to the community. This link is established and maintained before the patient enters Hillside and continues for as long after the patient has left the hospital as seems necessary. In dealing with the realities of the home and the community situations that have contributed to the problems of the patient, the Division is concerned with such speciﬁcs as working opportunities, living arrangements, care of children, care of aged and interim ﬁnancial support Last year, a total of 1,566 applications for admission to the hospital were received. The majority of referrals (89%) came from the New York City area, but applications were received from every geographic section in this country and also as far away as Brazil As in previous years, twice as many female applicants as male applicants sought admission. Patients were referred by psychiatrists, social agencies, hospitals, churches, synagogues, courts, schools, trade unions, as well as by communities, expatients, and through publicity. Of particular signiﬁcance was the fact that the percentage of I I patients not found suitable for admittance was 19.2%, as compared with 25% the previous year and 26% in 1955. Thus, the trend, started two years ago, after the establishment of an Intake Service, continues to demonstrate the effectiveThe activity ness of pre-screening applications of the casework division is reﬂected in the following statistics: I Interviews with patients, including Out Patient Dept. and Adolescent Unit .................... 5,110 Interviews with relatives, including Out Patient Dept. and Adolescent Unit .................... 5,860 Collateral Interviews ............................ 186 Interviews with discharged patients ............ 253 Interviews with relatives of discharged patients ...................... 256 Telephone contacts with social agencies ...................................... 5,425 Telephone contacts with relatives of patients .................................... 10,077 The Group Work Division is concerned with �providing a milieu in which patients can form social relationships, assume responsibilities, develop new interests and learn new skills and so begin to ﬁnd places, ﬁrst in the hospital community, and then in the outside community Among important developments this year was an orientation and intake program designed so that the new patient, helped by the social group worker, quickly learns the social structure of the hospital, and examines some of the groups available to him. With help, he makes preliminary choices based on previous experience as well as current social interest and need As part of the trip program, another new development, patients go to bowling alleys, ice and roller skating rinks, and restaurants. Some patients undertake longer trips to museums, the United Nations, or other places. Since this requires planning, it is a measure of the group’s ability to unite in a common goal and These new to sustain interest in the activity developments supplement the program which is the patient’s most direct link with the community I I I he has voluntarily left behind. With a group worker assigned as advisor, all patients meet regularly in democratic self-government. They work to solve their problems in living together, assume some responsibility for group discipline, and plan their social life. Many activities are carried out by delegated members who serve on planning committees to choose books and records, plan parties and dances, and other social activities An important aspect of life at Hillside is the chronological grouping based on age and similarity of interest. There are currently clubs serving all ages and giving each patient a chance to be a member of a social unit of his choice. The Library Group, for example, selects new books and magazines for patients from a practically unlimited list. The Newspaper Group is responsible for the writing and production of a monthly literary magazine, “Inside Hillside” and other publications In addition to these self-chosen activities, all patients participate in a series of current events discussion groups, in order to keep informed about daily events in the community they hope to rejoin. Patients are encouraged to assume leadership in all matters—and share their skills with each other. As a result, at varying intervals during the year, there have been patient-conducted groups in such varied activities as tennis, I I �bridge, play reading, and theatrical production The Group Work Division operates with a director, supervisor, four social group workers, two graduate social work trainees, eleven undergraduate ﬁeld work students, two part-time musical teachers, and 25 part-time volunteer workers Last year, ten graduate social workers were placed at Hillside for specialized training. The Division works closely with two outside organizations, The Bridge, a group of women who help recently discharged patients to re-establish themselves socially, to find jobs, and to maintain themselves ﬁnancially while doing so, and The Hillside League, a club for ex-patients of Hillside. Located in quarters maintained by The Bridge, at 231 West 83 Street in Manhattan, the League offers social club privileges to members, including games, TV and meeting space, and, in addition, provides special help in ﬁnding housing, employment, further treatment, and solving other personal problems in readjustment The QueEns OII‘I‘ Paﬁen‘l‘ Clinic. located at the Hospital, provides psychotherapy for residents of Queens, Nassau and Suffolk Counties who are unable to afford a private psychiatrist. Directed by Dr. Robert R. I I I Luttrell, the Out Patient Clinic insures the availability of qualiﬁed specialists who focus on early treatment and prevention of emotional illness. The geographical location of the hospital’s clinic, in a corner of Queens, bordering on Nassau County, makes a resource for psychiatric care available to one of the country’s fastest growing population In 1957, the clinic treated 316 patients areas in individual psychotherapy. Of these, 134 cases were carried over from 1956 and 182 were started in treatment. 163 were discharged during the year from individual psychotherapy. Group therapy, a new development in 1957, has resulted in six discharged of the 23 patients in the group. Eight patients received electroshock therapy and 67 patients were seen in continuous casework. 267 psychological tests were performed and 285 patients were evaluated by the “intake” team. I Diagnoses of discharged patients were: Psychoneurosis ..............................................53 Schizophrenia and manic depressive ............ 46 Involutional melancholia .............................. 9 Character disorder ........................................55 Conditions at discharge were: Improved ...................................................... 1 14 Much improved ............................................ 20 Not improved .............................................. 29 I Average length of treatment at the clinic was about nine months. Because the clinic is an out patient facility, families remained intact and there was little or no loss of jobs. As with in patient care, fees are based on ability to pay, with the average fee about $6 per week. (The cost to provide this service is approximately $30 per week.) Another out patient service provided by the Hospital is the After Care Clinic which operates ﬁve evenings a week at Mt. Sinai Hospital, a convenient location for most patients. The Clinic assists the discharged Hillside patient to resume his community status, and deals with the immediate problems of job replacement, living and resumption of old environmental contacts that may have originally contributed to the patient’s illness Group psychotherapy was instituted on a trial basis in this clinic during 1957 in an effort to meet some of the continuing needs of these patients. I I �17% mm/ %ﬁ”2ﬂ7ﬂﬂlgy Research. When one out of ten adults is hospitalized for mental illness every year, it is obvious that much is still to be learned about why people become mentally ill. As much as has been learned about the care of the mentally ill in the past 20 years, there are still new areas to be studied, such as blood chemistry and the delayed effects of the electroshock treatment Hillside believes that in addition to treating mental patients, it is obligated to undertake research. So advanced is the hospital’s outlook that it is one of the few mental hospitals with a biochemistry laboratory. Although the amount of current research on the subject of mental illness is inﬁnitesimally small, Hillside employs a staﬂ of scientists and trained researchers seeking the answer to why people become mentally ill and a surer knowledge of how treatment effects the improvement of mental patients The Department- of Experimental Psychiatry. during 1957, under the direction of Dr. Max Fink, completed the ﬁrst phase of its studies on the mechanism and effects of therapeutic techniques presently employed. Following the elucidation of the neurophysiologic and psychologic bases of the process of convulsive therapy, a control convulsive-subconvulsive study was undertaken in 1956 and completed in 1957. This study clearly demonstrated the changes in brain function which are the necessary prerequisites for change in behavior; and the psychologic, sociologic and language aspects which are fundamental In concurrent to “improvement” after convulsive therapy studies, the equivalence of chlorpromazine therapy for insulin coma, and the advantages of newer drug therapies were demonstrated in a chlorpromazine-insulin coma control study. Consequent upon these observations, an hypothesis of the mode of action of tranquilizers was described and a program of be- I I I I havioral assay of new drugs undertaken Basic studies into patterns of communication continued. By applying new techniques of psycholinguistics, objective methods of evaluating behavioral change and “improvement” were described and are now being tested. Studies in tactile and visual perception, neurophysiologic and psychologic bases for individual differences in response to drugs and convulsive therapy, and biochemical changes in spinal fluid after induced convusions continued Support for this program increased through grants from the Foundation’s Fund for Research in Psychiatry, the National I �Institute of Mental Health, and the Psychopharmacology Center of the National Institute of Health. A research grant of $31,700 was awarded to Hillside by the Foundation’s Fund for Research in Psychiatry. The grant was given to Dr. Joseph Jaffe of the hospital’s Department of Experimental Psychiatry for research in the nature of the psychiatric interview. The Biochemistry Department was concerned principally with blood enzyme levels in the hospital patients and with their urinary alkaloid excretion patterns. Results of a third study ﬂatly contradicted European reports of a blood test for schizophrenia. Under the direction of Dr. Harry Goldenberg, laboratory co-workers determined that serum cholinesterase levels in patients receiving electroshock therapy vary according to sex, with female patients generally higher. Work with rats suggests that these ﬁndings may be related to an abnormal adrenal metabolism Preliminary studies on the more acutely ill mental patients revealed an excessive excretion of aromatic metabolites in the urine, in agreement with the reports of other workers. It is not yet known whether this phenomenon has a causal relationship to schizophrenia European claims of a blood test for schizophrenia which is based on serum oxidase (ceruloplasmin) assay were unsubstantiated. Positive tests were obtained in various conditions other than mental disease (pregnancy, upper respiratory infections, cancer), while many well-fed patients gave negative tests. It was concluded that the I I European patients who were studied probably were suﬂering from a Vitamin C deﬁciency. M ~”‘waﬁrm/WNWwWa/WM‘ WM l/lMWn/WWVWVWW vv 4 MUM/WWWW4“:WM WW “WA/WWW Mil/wk} WWW «WWW-mekmrmwwvymmm AWWx W'WWVWWWWWMrMWW/VW MANN“ �I During 1957, members of Hillside’s staff were much in demand as guest lecturers and convention speakers. As the hospital continues to prove its value as a pioneer in the “open hospital” philosophy, more and more demands are made on the staff for intensive training courses, lectures and publications. Staff members spoke at meetings of national organizations including the American Psychiatric Association, and the National Conference of Jewish Communal Service, state groups including the New York State Society for Mental Health, and local groups including the North Queens Mental Hygiene Association and the Queens County Mental Health Society I Staff members reported on therapy and research and other results in a large number of professional publications, The Journal of the Hillside Hospital, edited by Dr. Sidney Tarachow, included articles by staff members and also outside contributors. �Publications 1957: R. L. I Esecover. H.. Juffe. J. and Kuhn. R. L.: Psychotherapeutic Techniques with Electroshock Patients, J. Hillside Hosp. (in press) and Green. M. A.: Experimental studies of the Electroshock Process Dis. Nerv. Syst. ( in press) I I I Fink. M.. Kuhn. Fink. M.. Shuw. R.. Gross. G. and Colemun. F. 5.: Comparative Study of Chlorpromazine and Insulin Coma in the Therapy of Psychosis, J. Amer. Med. Assoc. (in press) Threshold, EEG Clin. Neurophysiol. (in press) I I Fink. M.: Lateral Gaze Nystagmus as an Index of the Sedation Fink. M.: Individual Differences in EEG Responsivity. Read at Metropolitan EEG Society, New York, February 1957 Fink. M.: Criteria in Evaluation of Clinical Behavioral Change: Neurophysiologic Aspects. Presented at A.P.A., Round Table, Chicago, May 1957 I and Green. M. A.: Experimental Studies of the Electroshock Process. Read at the Society of Biological Psychiatry, Atlantic City, June 1957 Therapy of Schizophrenia: Role of Alteration in Brain Function in Behavior. Presented at Int. Congress of Psychiatry, Zurich, Sept. 1957 Korin. H.: Effects of Diffuse Altered Brain Function on Perception. Presented at the XV Int. Congress of Psychology, Brussels, August 1957 Behavioral Patterns in Induced States of Altered Brain Function. Read at the New York Divisional Meeting, A.P.A., Nov. 1957 Shift for Psychiatry. Read at Metropolitan EEG Society, N. Y., Nov. 1957 81 I Fink. M.. Kuhn. R. L. Fink. M. and Kuhn. R. I..: Fink. M.. Kuhn. R. L. and Fink. M. and Kuhn. R. L.: Fink. M.: Signiﬁcance of EEG Frequency I Fink. M.: Effects of Diethazine on EEG and Signiﬁcance for Theory of Process of Convulsive Therapy. Read at Eastern Association of Electroencephalographers, New York, Dec. 1957 Electroshock: Quantitative Serial Studies, A.M.A. Arch. Neurol. I I I I Fink. M. and Kuhn. R. L.: Relation of EEG Delta Activity to Behavioral Response in Psychiat. 78: 516-525, 1957 I Fink. M.: A Unified Theory of the Action of Physiodynamic Therapies, �J. Hillside Hosp. 6: 197-206, 1957 I Goldenberg. H.. and White. D. L.: Chromatographic, Electrophoretic and Colorimetric Procedures for the Psychotomimetic and Psycho- therapeutic Drugs; Presented at the Meeting-in-Miniature of the Metropolitan-Long Island Sub-section, New York Section, American Chemical Society, Brooklyn, New York, February 15, 1957 I Goldenberg. H.. and Goldenberg. V.: Speciﬁc Colorimetric Determination of Cholinesterase Activity in Blood and Spinal Fluid; Presented at the Meeting-in-Miniature of the Metropolitan-Long Island Sub-section, New York Section, American Chemical Society, Brooklyn, New York, February 15, 1957 Inhibition of Serum Cholinesterase by Mental Drugs, Ann. N. Y. Acad. Sci., 66: 466-467, 1957 Electroshock, J. Hillside Hosp. 6: 229-240, 1957 Juffe. J.: Criteria in Evaluation I Juffe. J.: I Green. M. A.: Signiﬁcance of Individual Variability Study of Communication in Psychiatric Interviews. Read at the New York Divisional Meeting, A.P.A. Nov. 1957 Response to Electroshock Therapy. Presented at Electroshock Research Association, Chicago, May 1957 Induced Altered Brain Function. Read at Amer. Psychol. Assoc., New York, August 1957 Hosp. 6: 216-228, 1957 I I I I in EEG Response to Juffe. J.: I An Objective Kuhn. R. L. and Fink. M.: Personality Factors in Behavorial Kuhn. R. L. and Fink. M.: Perception of Embedded F igurm After Kuhn. R. L. and Fink. M.: Perception of Embedded Figures After Induced Altered Kuhn. R. L.. Pollack. M. and Fink. M.: Social Factors in Selection of Therapy in 3 Voluntary Mental Hospital, J. Hillside Tarachaw. S. and Friedman. S.): Perception Experiments in 241-250, 1957 I I I I I Kuhn. R. L. and Fink. M.: Personality Factors in Behavioral Response to Electroshock Therapy, Conf. Neurol. (in press) N. Y. Neurol. Society, N. U., Jan. 1957 Goldenberg. H.: An Objective Study of Communication in Psychiatric Interviews, J. Hillside Hosp. 6: 207-215, 1957 of Clinical Behavorial Change: Psycholinguistic Aspects. Presented at A.P.A., Round Table, Chicago, May 1957 Brain Function, Amer. Psychol. 12: 361, 1957 I a Study of Ambivalence. Read at Section on Neurology & Korin. H. (with Psychiatry of N. Y. Academy of Medicine and Karin. H. and Fink. M.: Role of Stimulus Intensity in Perception of Simultaneous Cutaneous Electrical Stimuli, J. Hillside Hosp. 6: Korin. H. (with Tarachow. S. and Friedman. S.): Perception Experiments in a Study of Ambivalence, Arch. Neurol. & Psychiat. 78: 167-176, 1957 I Karin. H. (with Tarachow. S. and Friedman. S.): The Relation of Ambivalence to Aggression and Authority in Psychoneurotic Patients. Read at Amer. Psychol. Assoc., New York, Sept. 1957 I Karin. H. (with Tarachow. S. and Friendman. 5.): Studies in Ambivalence. Presented before Schilder Society, New York, Oct. 1957 I Pollack. M. (with Goldfurb. W. and Dorsen. M.): Pain Reactions in Schizophrenic Children. Presented at Amer. Orthopsychiatric Assoc., Chicago, March 1957 I Polluck. M. (with Krieger. H. P.): Oculmotor and Postural Patterns in Schizophrenic Children. Presented at Amer. Academy of Neurology, Boston, April 1957 I Pollack. M. (with Buttersby. W. S. and Bender. M. 3.): Figure-ground Perception in Patients with Cerebral Tumor. Read at Eastern Psychol. Assoc., N. Y., April 1957 I Pollack. M. (with �Battersby. W. S. and Bender. M. B.): Defects in Visual Perception in Brain Tumor Patients. Presented before Int. Congress of Psychol., Brussels, July 1957 M. I Pollack (with Battersby. W. S. and Bender. M. B.): Visual Deﬁcit After Brain Damage in Man as Measured with Rapidly-Exposed Chromatic Stimuli. Presented at Amer. Psycho]. Assoc., New York, Sept. 1957 l Pollack. M. (with Goldfurb. A.): Cultural and En- Vironmental Factors Affecting Complex Perception in the Institutionalized Aged. Presented at the Gerontological Society, Cleveland, Oct. 1957 l Pollack. M.: Brain Damage, Mental Retardation and Childhood Schizophrenia. Presented at New York Divisional Meeting, A.P.A. Nov. 1957 and“; a. I Pollack. M. (with Goldfarb. W.): Face-Hand Test in Schizophrenic Chil- dren, AMA. Arch. Neurol. & Psychiat. 77: 635-642, 1957 farb. W.): Patterns of Orientation I Pollack. M. (with Gold- in Children in Residential Treatment for Severe Behavior Disorders, Amer. J. Orthopsychiat. 27: 3, 538-552, 1957 Battersby. W. S. and Bender. M. I Pollack. M. (with BJ: Tachistoscopic Identiﬁcation of Contour in Patients with Brain Damage, J. Comp. Physiol. Psychei. 50: 3, 220-227, 1957 (with Battersby. W. S. I Pollack. M. and Bender. M. 3.): Visual Deﬁcit After Brain Damage in Man as Measured with Rapidly-Exposed Chromatic Stimuli, Amer. Psychol. 12: 7, 468, 1957 I Pollack. M. (with Goldfarb. W.): Cultural and Environmental Factors Affecting Complex Perception in the Institutionalized Aged, J. Gerontol., 12: 4, 437-438, 1957 I Zierer. E. (with Zierer. Edith): Leonardo Da Vinci’s Artistic Proclivity and Creative Sterility, The American Imago, Vol. 14, No. 4«, 1957. Each publication is a tribute to the vision of the hospital’s founder, the late Dr. Israel Strauss. �gar ZM/ *w U 473/ c Jywwﬂky The Residenf Training Program at Hillside continues to emphasize the interrelation between the training program and the treatment program. Each Resident carries a case load of about 15 patients under the supervision of staff and visiting instructors. and attends lecture conferences conducted by the medical director. Lecture seminars in the ﬁelds of psychopathology and psychotherapy, and reading seminars, are conducted by special instructors chosen from the hospital staff. Qualiﬁed Residents are assigned to the Department of Experimental Psychiatry for clinical and other psychiatric research projects. During the year there were 18 Residents in training, 15 in the adult in patient service and three in the Israel Strauss Adolescent Pavilion The hospital training program extends also to Clinical Assistants in the Out Patient and After-Care Clinics and on-the-job training of personnel. Regular lectures and conferences are scheduled for nurses and attendants, social workers, members of the various adjunctive services and for afﬁliating students from other educational institutions. Included in the latter was the establishment of a very important afﬁliated training program for student The Sunday Clinical Connurses from Queens College ferences. open to and attended by psychiatrists and other professional personnel and by outstanding visiting physicians, are part of the Resident training program and are based on cases prepared by the Residents. They continue to make a signiﬁcant contribution to the training picture on the New York The third annual Israel Strauss Lecture, psychiatric scene established in 1955 in honor of Hillside’s founder and late president, was delivered this year on May 5th. The speaker was Norman Reider, M.D., Chairman, Education Committee of the San Francisco Psychoanalytic Institute. The topic of his lecture As anticipated, the Medical was “Transference Psychosis" Library has become a very important feature of the teaching and research activities of the hospital The Journal of the Hillside Hospi‘l‘al again showed an increase in the number of its subscribers and an indication of its greater inﬂuence and wider acceptance in the ﬁeld. Thus the Journal has met the expectations with which it was launched in 1952. I I I I I ��The Israel Strauss Adolescen'l' Pavilion. in its third year, continues as a resident treatment center for a selected group of emotionally ill girls between the ages of 13 and 17. Due to the experimental nature of work with adolescents, only a limited number of applicants are accepted. Because of the intensiveness of the program, adolescent girls are kept at the Pavilion under treatment for a much longer period of time than the adult patients. In 1957, the average period of hospitalization for the adolescents was 300 days, as compared to 192 days for the adults I Although there have been recurring problems with shortages of trained personnel, the pilot program of the Adolescent Pavilion has proceeded as planned, and many new discoveries have been made The seventeen girls who Were admitted in 1957 were afforded the opportunity for intensive psychotherapy and a well- I structured living experience. In an atmosphere reminiscent of a girls’ boarding school, a professional team has worked to make this unique program succeed. The team, under the direction of Dr. Alice Slater Stahl, includes three psychiatrists, a psychologist, nurses, teachers, an occupational therapist, a group activity worker, plus the non-professional help of nurses’ aides, members of the housekeeping and kitchen departments and volunteers. A two story building includes all therapy facilities as well as dining and lounging areas. The semi-private rooms are furnished to allow for the fact that disturbed adolescents are often more destructive than adult patients I It is �believed that if Hillside can work out techniques for treating emotionally ill adolescent girls, much can be learned about the problems of child guidance and juvenile delinquency. Certainly much of what has been learned in the past year can be applied to adult treatment. During the year, it was discovered that the original plan for isolating the girls did not work out as Well as integrating certain aspects of the program with adult activities. It has also been found that certain adolescents made more rapid recovery when transferred to adult cottages. The plan to let the girls attend school in the outside community was abandoned in favor of school inside the Hospital, though sep- arate from the Pavilion since the experience of “going to school” is important to the youngsters The girls became in- I terested in sewing and put on two fashion shows of their handiwork. One of these fashion shows was the highlight of the 10th Annual Hillside Hospital Field Day. They also made the drapes for the dining and recreation rooms in the Pavilion. In addition, unusual work has been done in ceramics, painting and metals I Of the 120 applications received during the year, 26 patients were screened and 17 were admitted. An attempt was made to evaluate each applicant to determine suitability of $52,400 from The Ford Foundation was used to expand the research, training and patient facilities, including extensions and improvements of the Adolescent Girls Pavilion During the year, the Out Patient Clinic of the Adolescent Unit provided I treatment for 22 girls. Four doctors worked to provide a total of almost 450 psychotherapeutic sessions. Two social workers continued their casework and counselling services with the families, and helped with vocational planning, schooling, job hunting and social problems The After Care program has I provided short term aid in the transition period between the hospital and community life, as well as longer term psychotherapy. Work With Other Organizations. No organization dealing with patients can operate in a completely isolated manner. Hillside’s emphasis on treatment of the patient as a whole, with particular regard to the family, pre-admission care, and post discharge care and follow-up, has resulted in working relationship with the following agencies whose invaluable cooperation has made these programs possible: ALTRO WORKSHOP FEDERATION EMPLOYMENT AND GUIDANCE SERVICE based not only on the criteria of illness, but upon the patient’s ability to beneﬁt from the hospital’s facilities, as well as the DEPARTMENT OF PSYCHOLOGY OF COLUMBIA UNIVERSITY existing group composition at the time. There was an average waiting period of three months after acceptance A grant JEWISH FAMILY SERVICE OF NEW YORK I JEWISH COMMUNITY SERVICES OF LONG ISLAND NEW YORK ASSOCIATION FOR NEW AMERICANS �/% ﬁﬁwl/ 7/ [Ma/whzm'éW/Mt This Annual Report has given a great deal of data regarding service to patients, treatment facilities and research. It has summed up a large complex organization’s work on behalf of the mentally ill, their families and the community which surrounds them. A most signiﬁcant aspect of our work is the extent to which we have been able to mobilize ﬁnancial support from many sources. Perhaps the most concrete and rigorous index of the adequacy of a philanthropic organization’s performance can be gleaned from the way in which it is supported in the realistic world of ﬁnance. It is therefore signiﬁcant that we passed this rigorous test quite successfully during 1957. Our work received excellent support from the City of New York, through its contributions toward the care of the medically-indigent, mentally-ill patient. The Federation of Jewish Philanthropies of New York gave substantial help in deﬁcit ﬁnancing. Without Federation’s tremendous interest, its constant readiness to give advice and assistance, and its careful and generous consideration of our ﬁnancial requirements, Hillside could not have developed the excellent and challenging programs described in this report. Our research programs, started only a few years ago, have begun to command increasing attention in the psychiatric world and signiﬁcant attention—support-wise—in the community at large. More than ﬁfty percent of our research expenditures were met by outside sources, such as the United States Public Health Service and various foundations. The total research deﬁcit was met by contributions from our Board of Directors and their friends Our chief items of expense are for treatment and training programs. The table below gives the comparative total cost of these programs for 1956 and 1957. I The In Patient Service continued to operate at 97% of capacity, while— at the same time—the average income per patient day followed the trend established several years ago of rising each year, in this case by 130 per day. The average cost per patient day, however, rose by $1.53. Therefore, the average loss per patient day in the In Patient Service rose from 40c to $1.80. These changes rise out of the whole complex of increasing cost of operation. In 1956, total expenses of $1,326,454. represented a rise of 12.82% over the previous year; in 1957, with expenditures rising by $169,238, the percentage increase was virtually the same—13%. It is interesting to note the extent to which this year’s increase is related to inﬂationary forces in the community, or to actual improvement or changes in services rendered. It is therefore signiﬁcant that those aspects of expense which are most stable and most clearly related to the price index—Salaries, Food, and Maintenance and Grounds—rose by 7%, 5% and 5% respectively, while the following items more clearly related to quality and quantity of service rendered rose as follows: Administrative Expense 20% Medical Supplies Repairs and Replacements Clinics (Out Patient Service) 24% 39% 30% Again, as in the past several years, the Out Patient Clinic Services accounted for the largest item of increase, reflecting the continued expansion of our preventative programs. This expansion was made possible entirely by grants from the New York City Community Mental Health Board, the State Mental Health Authority, the Federation of Jewish Philanthropies of New York and, during 1957 — for the ﬁrst time — by the participation of the Nassau County Mental Health Board. Included in the increased cost of Out Patient Services was the expansion of the Foster Home Care Program for discharged patients, carried jointly with the Jewish Community Services of Long Island and made possible by the Federation ofJewish Philanthropies. MAURICE BACHRACH COMPARISON OF COSTS 1956-1957 1956 Salaries ................................................................ $ Food .................................................................... Maintenance and Grounds ................................ Administrative Expenses .................................... Medical Supplies .................................................. Repairs and Replacements .................................. Clinics .................................................................. 1957 797,805. 113,428. 59,436. 82,608. 23,950. 35,105. 214,122. 3 855,848. Tofal ............ 1.326.454. 1.495.692. Total No. Patients ................................................ Total Patient Days ................................................ Average Income per patient day ........................ $ Average cost per patient day .............................. Average loss per patient per day ........................ $5 119,350. 62,654. 98,952. 29,811. 49,021. 280,056. 561 545 70,189 15.44 15.84 $ .40 $ 69,987 15.57 17.37 1.80 �PRESIDENT—Alvin E. Coleman* CHAIRMAN OF THE BOARD—Roy Foster* HONoRARY CHAIRMAN OF THE BOARD—Leon Lowenstein‘ VICE-PRESIDENT—Dudley D. Shoenfeld, M.D.* Herbert Beskind” VICE-PRESIDENT—George W. Galinger* SECRETARY—Manuel Lee Robbins* TREASURER—~Arn01d S. Askin“ VICE-PRESIDENT—D. ASSISTANT SECRETARY—Alfred ASSISTANT SECRETARY—~M. Appel Victor Leventritt ASSISTANT TREASURER—Arthur Carson ASSISTANT TREASURER—Harry Silverson HONORARY DIRECTORS—Hilda Strauss and Saul Blickman Board of Directors A. Jacob Abrams Alfred Appel Arnold S. Askin“ John M. Bendheim D. Herbert Beskind“ Saul Blickman Alvin E. Coleman" Morris David Thomas Epstein Arthur C. Fatt" David Finkle David Finn Roy Foster“ George W. Galinger“ Arthur Carson Maurice Glinert Meyer Goldstein Jacob Epstein KatzT M. Victor Leventritt Budd LevinsonT Morris L. Levinson Milton B. Loeb Sandor Lorand, M.D. Leon Lowenstein* Charles H. Meyer* ' Walter Scheuer Dudley D. Shoenfeld, M.D.* Harry Silverson Hilda Strauss Irving Weissglassi Nathan Wigod Morton S. Wolf * Walter D. Yankauer“ Arthur Murray Manuel Lee Robbins* Irving Rosenbaum S. H. Seheuer‘ Chairmen of Standing Committees Foster MEDICAL AFFAIRS COMMITTEE—D. Herbert Beskind FINANCE COMMITTEE—Arnold S. Askin EXECUTIVE COMMITTEE—Roy HOUSE AND GROUNDS COMMITTEE— George W. Galinger, Nathan Wigod—Co-Chairmen LEGAL COMMITTEE—Charles H. Meyer SOCIAL SERVICE coMMITTEE—Hilda Strauss LIAISON coMMITTEE—L. 1. Jewish Hospital—Alvin E. Coleman PUBLICITY COMMITTEE—Arthur C. F att PERSONNEL COMMITTEE—Meyer Goldstein PLANNING coMMITTEE—Meyer Goldstein GIFTS AND LEGACIES COMMITTEE—Walter D. * Executive Committee Members T Elected in I957 Yankauer �Miller, M.D. ASSOCIATE MEDICAL DIRECTOR—~Simon Kwalwasser, M.D. ADMINISTRATOR—Maurice Bachrach, B.S. SUPERVISING PSYCHIATRISTS—George Yessin, M.D. Gerhard Schauer, M.D. Robert Navarre, M.D. Zenos M. Linnell, M.D. Harold Esecover, M.D.* MEDICAL DIRECTOR—Joseph S. A. DIRECTOR, ISRAEL STRAUSS ADOLESCENT PAVILION— Alice Slater Stahl, M.D. SUPERVISING PSYCHIATRIST, ISRAEL STRAUSS ADOLESCENT PAVILION, OUT PATIENT DEP’T.—Eugene Glynn, DIRECTOR OF OUT PATIENT SERVICES—Robert M.D. R. Luttrell, M.D. DIRECTOR OF RESEARCH IN EXPERIMENTAL PSYCHIATRY— Maxirriilian Fink, M.D. INTERNIST—Arnold Blumberg, M.D. DIRECTOR OF LABORATORIES—Harry Resident Staff Norman Ackerman, M.D. Barre Alan, M.D. Stanley Brodsky, M.D.* Bernard Cohen, M.D. Frederick Coleman, M.D.* Warren Cox, M.D. Alan Dobrow, M.D. Necdet Ecder, M.D. Ilhan Ermutlu, M.D. Stefano Faj rajzen, M.D. Marie Friedman, M.D. Stanley M. Friedman, M.D.* Ruth Fuchs, M.D.” Harold Galef, M.D.* Robert S. Gilbert, M.D.T Victor Coldin, M.D.* Michael Gould, M.D. Sherwin Harris, M.D. Edwin Kleinman, M.D. A. Russell Lee, M.D.” Leon .Lefer, M.D.* Henry Lefkowits, M.D. Sidney Lytton, M.D. Robert Nodine, M.D. Goldenberg, Ph.D. Paul Pressman, M.D. Arthur Root, M.D.* Alvaro Rozo, MD. Herbert Schulman, M.D. Myron Stein, M.D.* Carl Towbin, M.D. Margery Wile, M.D. Other Professional Staff Heads Goldie Krupa, R.N.—DIRECTOR OF NURSING Abraham Lurie, M.S.S.W.—DIRECTOR OF SOCIAL SERVICES Abraham Levine, Ph.D.—DIRECTOR 0F PSYCHOLOGY Ernest Zierer, Ph.D.—DIRECTOR 0F CREATIVE THERAPY Eileen P. Fisher, B.S.—DIRECTOR OF OCCUPATIONAL THERAPY Arnold Eisen, M.S.S.W.——DIRECTOR OF GROUP WORK DIVISION Angelina Canavan, B.A.——DIETITIAN n Department Heads * Completed residency in 1957 1’ Deceased 1957 Dorothy Croghan—ACCOUNTING SUPERVISOR Lillian Bailey—OFFICE MANAGER Thomas R. Lumley—SUPERINTENDENT 0F BUILDINGS & GROUNDS Sarah Travers—EXECUTIVE HOUSEKEEPER snag—hr, g .. f �PRESIDENT—M. David Epstein, M.D.* VICE-PRESIDENT—Robert A. Savitt, M.D.* SECRETARY—Sidney L. Green, M.D.* TREASURER—Paul Scheman, D.D.S.* Ex-PRESIDENT—Samuel Atkin, M.D.* Samuel Atkin, M.D.* Arnold Eisendorfer, M.D.* M. David Epstein, M.D.* Margaret E. Fries, M.D. I. Peter Glauber, M.D.* Emanuel Klein, M.D. Sidney Klein, M.D. Samuel Z. Orgel, M.D. H. L. Rachlin, M.D.* Lawrence J. Roose, M.D. George S. Goldman, M.D. Sidney L. Green, M.D.* William Karliner, M.D. Sylvan Keiser, M.D. Sarah R. Kelman, M.D. Robert A. Savitt, M.D.* Martin Schreiber, M_D_ Isidor Silbermann, M.D.* Otto Sperling, M.D Sidney Tarachow, M.D.* Cohen, M.D.* DEPARTMENT OF NEUROLOGY—Morris B. Bender, M.D. DEPARTMENT OF DENTISTRY—Paul Scheman, D.D.S. DIRECTOR OF DEPARTMENT OF MEDICINE—Lester DIRECTOR OF DIRECTOR OF ADOLESCENT PAVILION—Sidney L. Green, M.D. COMMUNITY EDUCATION AND PUBLIC RELATIONS—Robert A, Savitt, M.D. C‘REDENTIALS; COMMITTEE FOR PSYCHIATRIC STAFF & PROMOTIONS—— Martin Schreiber, M.D. CREDENTIALS COMMITTEE FOR NON-PSYCHIATRIC STAFF & PROMOTIONS:— Paul Scheman, D.D.S. STAFF—Arnold Eisendorfer, M.D. GROUP PSYCHOTHERAPY—Samuel Z. Orgel, M.D. MANHATTAN AFTER-CARE- CLINIC—Sarah R. Kelman, M.D. EDUCATION OF RESIDENT PATIENTCLINIC—William,Karliner, M.D. RESEARCH COMMITTEE—Hyman L. Rachlin, M.D. QUEENS OUT Peter Glauber,M.D. JOURNAL .SUB-COMMITTEE—Sidney Tarachow, M.D. ‘iTDQM;MIT-'I‘EE‘FOR ADIUNCTIVE‘ SERVICES—4'1. 'Peter Glauber, M.D. PUBLICATIONS COMMITTEE—e41. :CREDENTIALSCOMMI‘TTEE TORSUPERVISING- PSYCHIATRIC AND RESIDENT STAFF—— Sidney Klein, M.D.. COMMITTEE FOR LIAISON WITH LONG ,ISLANDRJEWYSH HOSPITAL..— Arnold/Eisendorfe‘r, M.D. , ‘*E’ixéé tsive :Coimmitte'e» M ember; \ i" 'V I ' > v , ‘ ' : " �%[7ZMW% WWM/ W Consultants Psychiatry up OZ Medicine Neurology Leonard Blumgart, M.D. Sandor Lorand, M.D. Irving J. Sands, M.D. Nathaniel E. Selby, M.D. Dudley D. Shoenfeld, M.D. Alfred Angrist, M.D. Morris S. Bender, M.D. Oscar Levin, M.D. .1. Jesse Levy, M.D. A. M. Rabiner, M.D. Surgery Gynecology Dentistry Hans Strauss, M.D. I. S. Wechsler, M.D. David Warshaw, M.D. Julius Jarcho, M.D. Morris Fierstein, D.D.S. George S. Goldman, M.D. Sidney L. Green, M.D. William Karliner, M.D. Sylvan Keiser, M.D. Sarah R. Kelman, M.D. Emanuel Klein, M.D. Sidney Klein, M.D. Attilio Laguardia, M.D. Samuel Z. Orgel, M.D. Hyman L. Rachlin, M.D. Lawrence J. Roose, M.D. Robert A. Savitt, M.D. Martin Schreiber, M.D. 5011 Goodman, M.D. Samuel R. Lehrman, M.D. Abraham S. Lenzner, M.D. Martin H. Orens, M.D. William W. Pike, M.D. Aaron Stein, M.D. Isadore H. Cohn, M.D. Irving J. Crain, M.D. Albert E. Goldberg, M.D. Albert Harrison, M.D. Thomas Hora, M.D. Abraham Kaplan, M.D. Louis Kaywin, M.D. Bruce Kendall, M.D. George P. Krupp, M.D. Peter Laderman, M.D. Harold S. Leopold, M.D. David Milrod, M.D. Irving Salan, M.D. Frederick F. Shevin, M.D. Jay Stanton, M.D. Samuel Tabbat, M.D. Fred U. Tate, M.D. Leonard Weinroth, M.D. Herbert Wieder, M.D. Attending Psychiatrists ' Samuel Atkin, M.D. Frank Berchenko, M.D. Arnold Eisendorfer, M.D. M. David Epstein, M.D. Margaret E. Fries, M.D. I. Peter Glauber, M.D. Isidor Silbermann, M.D. Otto Sperling, M.D. Sidney Tarachow, M.D. Associate Attending Psychiatrists Cornelius Beukenkamp, M.D. Alexander J. Friedman, M.D. Mark L. Gerstle, J r., M.D. Adiunct Attending Phychiatrists Edward R. Adelson, M.D. Renato J. Almansi, M.D. Herman S. Alpert, M.D. Irving L. Bauer, M.D. Benjamin J. Becker, M.D. Julius Belinkoﬁ, M.D. Milton M. Berger, M.D. Lionel H. Blackman, M.D. Hugh Mullan, M.D. Helene Papanek, M.D. �MD. VISITING PHYSICIAN—George Sabrin, M.D. DIRECTOR—Lester Cohen, Rosenblum, M.D. VISITING PHYSICIAN—A. Blumberg, M.D. ASSOCIATE PHYSICIAN—M. Kalkstein, M.D. ASSOCIATE PHYSICIAN—J. Weinstein, M.D. ADJUNCT PHYSICIAN—A. L. Berger, M.D. ADJUNCT PHYSICIAN—W. B. Brett, M.D. VISITING DERMATOLOGIST—C. Stritzler, M.D. ASSOCIATE DERMATOLOGIST—Joel Schweig, M.D. ADJUNCT DERMATOLOGIST—N. Goldfarb, M.D. VISITING PHYSICIAN—L. VISITING NEUROLOGIST—Morris B. Bender, M.D.T ASSOCIATE NEUROLOGIST—Kurt Adler, M.D. ADJUNCT NEUROLOGIST—Harry Harter, M.D.I Hirsch, M.D. VISITING NEUROSURGEON—Joseph Siris, M.D. VISITING UROLOGIST—L. G. Goldberg, M.D.’r VISITING UROLOGIST—Daniel Kaufman, M.D. ADJUNCT UROLOGIST—Albert Sutton, M.D. VISITING SURGEON—~Sidney VISITING ORTHOPEDIST—A. H. Lewert, M.D. Schneiderman, M.D. VISITING PROCLTOLOGIST—B. Warner, M.D. VISITING-OPHTHALMOLOGIST——E. Seretan, M.D. VISITING GYNECOLOGIST—M. VISITING GYNECOLOGIST—H. Warner, M.D. Dubrow, M.D. Cohen, MD. ASSOCIATE GYNECOLOGIST—Bernard Greenblat, M.D. ADJUNCT GYNECOLOGIST—Eugene Streim, M.D. ASSOCIATE GYNECOLOGIST—Jack VISITING RADIOLOGIST—Bernard Epstein, M.D. DIRECTOR—Paul Scheman, D.D.S. ASSOCIATE DIRECTOR—J. G. Rubin, D.D.S. ASSOCIATE DENTIST—B. Schwaid, D.D.S. ASSOCIATE DENTIST—B. Lebow, D.D.S. ADJUNCT DENTIST—H. Lewis, D.D.S. ADJUNCT DENTIST—H. Adler, D.D.S.’r ADJUNCT DENTIST—S. Plotnick, D.D.S. ADJ-UNCT DENTIST—E. Friedman, D.D.S. ADJUNCT DENTIST—M. Protell, D.D.S. ADJUNCT DENTIST—L. Basson, D.D.S. STAFF OPTOMETRIST—-Edward L. STA-FF Steinberg, O.D_. OPTOMETRIST—Bernard Attinson, O.D. ASSOCIATE ORTHOPEDIST—J. Minsky, M.D. OTOLARYNGOLOGIST—S. Clayton, M."D. ANE-S'THESIOLOGIST—Ceorges Bean, M.D. ASSOCIATE OPHiTHALMOLOGIST——A. VISITING VISITING STAFF 'PODIATRIST—Sam Resigned 195;? I Deceased 1795-7 T Sokolov, Pod.0. �Lester I. Abend, M.D. Ruth Adams, M.D.* Romano Antonelli, M.D. Howard Boskey, M.D. Paul Bradlow, M.D. Stanley Brodsky, M.D. Arline Caldwell, M.D. Mischa Caplan, M.D. Daniel Chansky, M.D. Lionel Chertoﬁ, M.D. Rita M. Chalef, M.D. Gloria Chung, M.D.“ * Resigned I 957 Ralph W. Clemments, M.D. Julius Colantuono, M.D.* Frances Colonna, M.D. Fred Dalton, M.D.* Irving J. Farber, M.D. Robert D. Ferrell, M.D. Philip Friedland, M.D. Harvey Coldey, M.D. Victor Goldin, M.D. Sumner I. Goldstein, M.D. Clara Gonda, M.D. Harry Gonda, M.D. David Graubert, M.D. Howard Hess, M.D.* Martin Hurvitz, M. D. Gunthar Jacob, M.D. Wilbur Jarvis, M.D. Peritz Levinson, M.D. Buck Luria, M.D. Daniel Miller, M.D. Meyer Monchek, M.D. Beatrice Nachtigal, M.D. Iris Orens, M.D.* Edward Pinney, J r., M.D. Joshua Ramot, M.D.* William Roosen, M.D. Phoebe Rosen, M.D. Joseph D. Rosen, M.D. Henry Rosberger, M.D. J ehuda Rozanski, M.D. Gabriel Rubin, M.D. Charles Silberman, M.D. Herman Tannor, M.D.“ Leon Tec, M.D. David M. Tillim, M.D. Clara Torda, M.D. Aimee Wiggers, M.D. �Hillside Hospital is a member of: AMERICAN HOSPITAL ASSOCIATION AMERICAN PSYCHIATRIC ASSOCIATION FEDERATION OF JEWISH PHILANTHROPIES GREATER NEW YORK HOSPITAL ASSOCIATION HOSPITAL ASSOCIATION OF NEW YORK STATE NATIONAL CONFERENCE OF JEWISH COMMUNAL SERVICE NEW YORK STATE DEPARTMENT OF MENTAL HYGIENE NEW YORK STATE DEPARTMENT OF SOCIAL WELFARE NEW YORK STATE WELFARE CONFERENCE QUEENSBORO COUNCIL FOR SOCIAL WELFARE UNITED HOSPITAL FUND WELFARE AND HEALTH COUNCIL OF NEW YORK CITY We are fully accredited by: JOINT COMMISSION ON ACCREDITATION OF HOSPITALS 1%gzlled/ZJ ”42/ QWMJ . OF THE UNITED STATES AND CANADA (NO p recise words are necessar y to a valid le g ac y to the We are approved for re51dent tralnlng by: . . é % WM . . Society. The following form, however, may be suggested.) AMERICAN MEDICAL ASSOCIATION AMERICAN DENTAL ASSOCIATION ' We .C arr y Jom t progr am S i n which 5 p eciﬁc s e rvice~b to p atients are ad, , , mlnlstered by the hospltal and pald for by tax-supported publlc agenCIes: I give to the Society of the Hillside Hospital, for the use 0/ the Hillside ' _ _ Hospital, the sum of _ $_—__—_(if land or any speciﬁc property, NASSAU COUNTY MENTAL HEALTH BOARD such as bonds ’ stocks ’ ece t ‘e r a, iS g i”e n ’ a b r'“3f NEW YORK CITY COMMUNITY MENTAL HEALTH BOARD should be inserted instead of the words “the sum of NEW YORK STATE MENTAL HEALTH AUTHORITY NEW YORK CITY DEPARTMENT OF HOSPITALS DIVISION OF VOCATIONAL REHABILITATION, NEW YORK STATE DEPARTMENT OF EDUCATION NEW YORK CITY, BOARD OF EDUCATION UNITED STATES PUBLIC HEALTH SERVICE, INSTITUTES OF MENTAL HEALTH We have established programs of community education and community mental hygiene with: QUEENS COUNTY MENTAL HEALTH SOCIETY NASSAU COUNTY MENTAL HEALTH SOCIETY ' descnp tio " 0/5 h 5 P r 0P3 r‘9’ $_____”). �An aﬂiliate 0f the Federation of Jewish P/zilant/Lropies of New York �31:! ANNUAL REPORT V~ A FOR THE YEAR 1958 HILLSIDE HOSPITAL GLEN OAKS, QUEENS, N. Y. ��Federatwn f 0 a partzczpant 0f- the Fund and the Créat‘erg ��TABLE OF CONTENTS report of the director of professional services report of the medical director report of the President of the Medical Board report of the President of the Board of Trustees treatment psychotherapy and medical services psychology department intramural clinic nursing department department of dentistry occupational and creative therapy adolescent pavilion organization chart insert social service department casework division group work division Manhattan after-care clinic Israel and Hilda Strauss League Queens out-patient service Training programs Sunday clinical conferences Israel Strauss lectures medical library research experimental psychiatry department of biochemistry medical department Hillside publications Hillside journal grants and awards received 1958 report of the administrator society of the Hillside Hospital 3 4 6 7 10-13 ‘10 10 11 11 11 12 12 16-17 14-19 14 15 18 18 18 19 19 19 19 22-23 22 22 23 24- 25 25 27 30-32 �report of the director of professional services LEWIS L. ROBBINS, M.D. As a very new member of the staff of Hillside Hospital, I should like to look ahead rather than participate in a review of the past year. A forward-looking plan for the future development of Hillside Hospital is essential if it is to serve best the needs of the community today and tomorrow. The three main areas of activity at Hillside today are clinical service, education and research. We will never lose sight of our primary day-to-day service, which is the treatment of the mentally ill. Yet to consider enlarging the capacity of Hillside—to help more of the people who are psychiatrically ill—is not the answer for the future. Experience of larger institutions indicates the weakness of this approach. When the capacity of a psychiatric hospital is expanded beyond a certain point, individualized treatment of patients gives way to regimentation. The result is that the quality of clinical service falls. It is more probable that Hillside can best serve the community by striving to advance our knowledge of psychiatry for the greater good of everyone, whether or not he is ever a patient at Hillside Hospital; and by training professional personnel who will later make use of what they have learned here in other institutions throughout the country. The main shortage in psychiatry today is knowledge. Although there have been tremendous advances in the past 50 years, much remains to be learned. And while much has been spent in the development of all types of psychiatric facilities, relatively little ﬁnancial support has been given to psychiatric research. It is therefore recommended that the excellent facilities of Hillside Hospital and its present and potential relationships with other institutions in the area be utilized primarily for the advancement of psychiatric knowledge. A unique and productive approach would be the long-range goal of an Institute for Advanced Psychiatric Studies established at Hillside. Although there exists today an excellent research program at Hillside, it represents but a small fraction of the many types of AHEAD research that could be successfully conducted here. The clinical program of the hospital provides a great variety of clinical problems, as well as opportunity for thorough observation. The forward-looking philosophy of Hillside Hospital, along with its utilization of personnel from many different disciplines, constitute an excellent foundation for the development of a broad research program. Such a research program would develop spontaneously if personnel were adequate—both qualitatively and quantitatively—to take care of our clinical responsibilities. A staff must be developed who are not only good clinicians but who also possess an interest in and capacity for both teaching and research. The need for trained personnel in psychiatry is urgent. Hillside already has accepted education as one of its principal functions; and this function could very well be expanded without detracting from the research objectives which may be established. Hillside Hospital thus will continue to be a pilot institution providing the best psychiatric treatment currently available, constantly striving to develop newer and better methods, and sharing its experience with others for the welfare of the general community. Its future is limited only by the imagination of its staff, the leadership of its Board, and the support of its community. 3 �the of report medical director JOSEPH S. A. MILLER, MD. This will be my last Annual Report as Medical Director of Hillside Hospital. When I came to Hillside in 1947, there was a one-half time Assistant Medical Director, six Residents, one and a half social workers, no psychologists, and only a fair complement of nurses and attendants. There were eighty-eight patients. There was no out-patient department, and only the beginnings of an after-care program. There was no organized research. The teaching was carried on by the Medical Director and by members of the Medical Board. From about 1948 on, the services and facilities of the hospital began to grow. The new Lowenstein Pavilion was opened in 1949 and practically doubled the bed capacity. The number of Residents was increased to twelve and, in addition to a full-time Associate Medical Director, Staff or Supervising Psychiatrists were added. More attention was now paid to the discharge and rehabilitation plans and, with the interest and support of the Federation of Jewish Philanthropies, with whom we had just become affiliated, we enlarged our Social Service Department. In 1951, we began a small out-patient clinic and also improved the services of our aftercare clinic. With the construction of the Elizabeth Sloman Lowenstein Building in 1954, the small out-patient clinic was developed into a service able to treat some two hundred patients twice weekly. That year, also, the Israel Strauss Pavilion for Adolescent Girls was established. Supervised clinical training and teaching of the Residents was enhanced; teaching in basic clinical psychiatry, clinical diagnosis and psychotherapy was extended; regular stated clinical, diagnostic and discharge conferences were instituted; and we appointed special instructors to give didactic instruction in psychopathology and psychotherapy. 1951 saw the beginning of organized research at Hillside with a biochemistry research laboratory set up under Dr. Werbin. He was succeeded in 1954 by Dr. Harry Goldenberg, who now heads our Bio-chemical Research Department and who has made some original contributions which have been recognized and supported by grants from the United States Public Health Service and by funds from our own Board of Trustees. The largest contributions in the ﬁeld of organized research were made in the area of experimental psychiatry, especially electroshock therapy and tranquilizers, headed since 1954 by Dr. Maximilian Fink. There have been other signiﬁcant changes and trends. First of all there has been a change in the type of mental patient coming to the hospital. Our patients now are of the borderline-psychotic type, although they still fall generally within the qualiﬁcations for voluntary admission. There has been a deﬁnite drop in the average age of the patients from the mid-thirties to the midtwenties. Signiﬁcant, this year was the replacement of the insulin coma treat- ment by the tranquilizer, chlorpromazine. We also improved and enlarged our occupational therapy and group activity services, and, under the able direction of Dr. Aaron Stein, our group psychotherapy programs. Our out-patient services, ably directed by Dr. Robert Luttrell, and our community mental health clinics, with support from the New York City and Nassau County Mental Health Boards, have been regarded as models of clinic operation. Our attending psychiatrists, notably Drs. Martin Orens and Abraham Lenzner, have contributed greatly to the teaching and clinic conferences. At the close of the year a well-deﬁned program for the out-patient treatment of school age children was completed. The Israel Strauss Adolescent Pavilion completed 4 years of operation. The experiences gained there will mean not only an improved teaching and treatment program, but also, in the not too distant future, a worth-while research program. Our Resident Training Program has maintained its high standards, but has pointed up the need for more in-hospital or on-the-premises teaching and clinical supervision. This in turn has called for a larger number of better qualiﬁed supervising or staff psychiatrists, a call we have begun to meet. We have been aided to a generous extent by National Institutes of Mental Health in receiving a number of training grants for our Residents and teaching grants for our special instructors. There is a need for a more comprehensive research program involving projects which will deal, in a more integrated fashion, with the physical, mental and ecological factors in development and treatment of emotional disorders. The Journal of Hillside Hospital has, under the able direction of its editor-inchief, Dr. Sidney Tarachow, achieved a national reputation in scientiﬁc circles. �In the decade since Hillside joined the family of Federation, we have beneﬁted not only from their planning and other special committees, but even more from the association with Federation’s hospitals and agencies in common purposes. Mt. Sinai Hospital provided us with space for processing and interviewing patients in our after-care clinic for discharged patients. Since 1950, we have had a rich and fruitful liaison with the Jewish Community Services of Long Island, through which we have been able to establish supervised psychiatric services as well as a very worth-while family care or foster home program for our discharged mental patients. This program resulted in our winning the Milton Weil Award from Federation in 1955. As soon as the Long Island Jewish Hospital had begun its operations, we helped establish their psychiatric service. We are indebted to them for their outstanding help. Mention ought to be made here too of our help from the Federation Employment Service, and our dual participation in a vocational rehabilitation program with the Altro workshops. I want to mention also, our ever-friendly relations with the Jewish Family Service, who have not only provided ofﬁce space for our Social Services Department in Manhattan, but have also been cooperating with us in a long-range case work guidance program for our discharged patients. In these days of the “open hospital” and the establishment of psychiatric services and out-patient clinics in general hospitals, the question arises about the future of the separate or special mental hospital. The answer is that there will always be patients who will require in-resident therapy in a controlled therapeutic environment. The small psychiatric hospital need not be separated— indeed it should work in close relationship with the community and its hospitals, institutions and agencies. Hillside will become more and more of an open hospital in the modern sense, depending largely upon the education of, and acceptance by, the community. However, within the framework of its special treatment, teaching, and research services, it ought to remain as far as possible, autonomous. The mental hospital provides the essentials for the emotional re-educative process in which the patient is able to re-live and review his earlier and unsuccessful relationships. He learns to become a better functioning part of the new and smaller society of the hospital, and this in turn ﬁts him for better or improved adjustment in the larger society outside. The small mental hospital employs facilities for more individualized treatment—where he may be observed in his behavior toward others and taught how to live with them, and how to exploit his own personality assets. Fortunately for Hillside, my successor, Dr. Lewis L. Robbins, has a rich background of professional experience in teaching, treatment, research and administrative ability. His views and attitudes in regard to the special mental hospital—the types of psychiatric and other professional personnel needed, the hospital environment and the various adjunctive needs of the patients— are salutory and knowing. I close my ﬁnal report on Hillside with the utmost conﬁdence in the future that awaits this great institution. I am proud of the many achievements made during my stewardship. It is needless to state that this could not have been done except with the help of a marvelous staff as well as the cooperation of the Medical Board and the Board of Trustees. My thanks to all the professional staffs and employees of the hospital, and especially the heads of departments. And I want especially to thank my two “Chief Lieutenants” who worked with me for the good of the hospital and contributed so much to its success during the past decade: Dr. Simon Kwalwasser, Associate Medical Director and Mr. Maurice Bachrach, able and talented Administrator. I greet Dr. Lewis L. Robbins, with whom it is a pleasure to have been thus brieﬂy associated in the common venture at Hillside, and who, I am sure, will raise the hospital standards and services to even greater heights. Although this is my last Report on the Hospital as Medical Director it is not really a “bill of divorcement”. I am happy and proud to have been asked to continue as a general consultant to the Hospital, and as a special instructor to the Residents. I cannot close on a better note than by greeting the more than a hundred Residents who trained under me during these past'12 years. Hillside can well be proud of them, scattered as they are over the United States, and contributing, wherever they are, to the treatment, teaching and research aspects in the ﬁeld of psychiatry based on their early training and treatment experiences of their Alma Mater—Hillside. �the of report President of the Medical Board ROBERT A. SAVITT, M.D. 6 During the past year the Medical Board has continued to function actively in its role as an advisory and consultative the and Director Medical the to group Board of Directors. Through its standof which comprised committees are ing the various echelons of the attending staff, the Board is directly involved in all of the medical activities of the hospital. The Credentials Committee for the Supervising and Resident Staif under the chairmanship of Dr. Roose, has spent countless hours interviewing and processing applicants for psychiatric residency training. Over a period of collected is on information being years the method of choosing residents. It is expected that when this is collated and correlated, it will yield valuable guide the for criteria in determining posts choice of psychiatric personnel. As in previous years the residency training program continues to be a major interest of the Medical Board. In this connection Dr. Arnold Eisendorfer’s committee has held periodic conferences with Dr. Miller, the Medical Director, in order to further advance the means whereby Hillside will become accredited for a three year residency. One of the important recent advances in resident education and training has come by way of the revised group psychotherapy program. This is expertly directed by Dr. Aaron Stein and coordi- nated by Dr. Samuel Orgel.’s committee. Better liaison has been established between the psychiatric attending staff and the hospital’s adjunctive services. Dr. I. Peter Glauber and his colleagues are formulating a series of conferences and lectures which will increase the mutual exchange of educational and scientiﬁc information with the Psychology and Social Service Departments. Under the superb guidance of its editor, Dr. Sidney Tarachow, the Journal of the Hillside Hospital has expanded its circulation and widened its scientiﬁc achievement in this country and abroad. Currently, several manuscripts are being carefully considered by the Publications Committee for selection in the projected Hillside Hospital Monograph Series. On the basis of liaison agreements entered into during the past year with our neighbor, Long Island Jewish Hospital, a Psychiatric Service has been established at that hospital. It is being administered by Dr. Samuel Lehrman of our Board in collaboration with a number of additional psychiatrists from our attending staff. The Adolescent Pavilion has raised many provocative questions and problems which are gradually approaching resolution. It is expected that our experiences will serve as points of orientation and enlightenment for other psychiatric facilities dealing with the treatment of adolescents. Dr. Margaret Fries and her co-workers are elaborating a method of organizing clinical data which will be of great value in the study of adolescents, is expected to ﬁnd a place in the total resident educational program throughout the hospital. The Medical Board activities also reach out into the community of which Hillside is an integral part. Many of its attending psychiatrists render valuable service to the Queens Out-Patient Clinic and the Manhattan After-Care Clinic in terms of training and supervision of the in and colleagues, presenyounger tation of periodic clinical conferences. The Israel Strauss Memorial Lecture has become a notable yearly medical event which attracts a large audience from the psychiatric and related scientiﬁc professions. The annual Hilda Strauss Mental Health Lecture has also reached deeply into the local community’s stream of mental hygiene activities. It is with deep regret that the Board reports the loss of its beloved member, Dr. Sidney Klein. He died in August 1958, and left behind a legacy which exempliﬁed his love and loyalty to Hillside. Under the terms of his will this is to be devoted to special studies in child and adolescent psychiatry. A suitable memorial in his honor is being planned. I wish to express my deepest appreciation to my many colleagues on the attending staff, to the Medical Director, the Director of Professional Services, to the Board of Directors and those too numerous to mention, for their cooperation and devotion to Hillside Hospital. �report of the President of the Board of Trustees ALVIN E. COLEMAN A milestone in the 31 year history of Hillside Hospital was the appointment of the internationally known psychiatrist, Dr. Lewis L. Robbins, as Director of Professional Services. At the same time that Dr. Robbins is helping us to look ahead, he has helped to put the current program of the hospital in a signiﬁcant perspective. Our prime object is the continued improvement of the quality of the treatment available to our patients, and the scope and value of the knowledge that we are able to impart under our teaching and research programs. Each year it seems more evident that the future of the treatment of mental disease rests in the ability to conduct extensive research in order to learn entirely new methods. We are fortunate to have on our staff capable and farseeing men who are leading us along challenging pathways to the future. During 1958, a Department of Medicine, headed by Dr. Arnold Blumberg, was added to the research program. The Department of Experimental Psychiatry, headed by Dr. Maximilian Fink, did some outstanding work in the ﬁeld of electroshock and tranquilizer drug effects upon the patients’ personality and behavior. The U. S. Public Health Service allocated a 5 year grant of $268,000 for this department and appointed Dr. Fink to serve as a consultant to the Council of the National Institute of Mental Health, which itself passes upon applications for grants from those working in this ﬁeld. Four pharmaceutical houses, Bristol Laboratories, Wyeth Laboratories, Smith, Kline 81 French, and Geigy Chemical Company, provide ﬁnancial grants for further detailed study of how the new psychotropic drugs affect human behavior. The general use of insulin as a mode of treatment was discontinued because it has proven to be too hazardous for results obtained and that the same or similar results are now apparently available through the use of new drugs. The Department of Biochemistry, headed by Dr. Harry Goldenberg, made substantial progress in further studies based upon the premise that mental illness is accompanied by metabolic and other biochemical defects which can be detected. Dr. Goldenberg’s work, too, has received considerable recognition by the U. S. Public Health Service in the form of substantial public grants. Further plans for the modiﬁcation of the building and the treatment program are now being studied. Six new ofﬁces were added to the pavilion for adolescent girls at a cost of $35,000. A joint psychiatric service with Long Island Jewish Hospital, our neighbor, was established through the appointment as Chief of this service of Dr. Samuel Lehrman, Attending Psychiatrist of Hillside and a member of our Medical Board. Through the aid and encouragement of the Nassau County Mental Health Board, it was decided to open a Child Therapy Unit in April, 1959. This will be 50% supported by funds from Nassau County. During 1958, Hillside received a number of important bequests including the balance of the funds left to it under the will of the late Edwin Elson, our former Trustee; the total of this bequest was $52,000. We also received $20,000 from the estate of Dr. S. Klein, who had for many years been a valued member of our Medical Board; and $37,950 from the estate of Wilhelm Levinger, brother of our beloved former Trustee, Alfred Levinger, who had been one of the founders of this hospital. We were awarded a grant by the U. S. Public Health Service of $150,000 toward the minimum required sum of $300,000 for the construction of a building to be used solely for research in mental health. One of our ever-loyal and generous trustees, Mr. Si Scheuer, made it possible for us to promptly qualify and accept this muniﬁcent grant by himself giving us $50,000 towards the construction of this building, which will be knOWn as the Scheuer Building for Research. A 75th birthday was celebrated by one of our most distinguished trustees who has done so much for the Hospital by making possible the magniﬁcent facilities it now enjoys, namely our Honorary Chairman, Leon Lowenstein. We all wish him many more happy birthday anniversaries. 7 ��N 1958, there 342 patients who had this Hillside themselves treatment. admitted to numHospital Of for voluntarily ber, 211 were new admissions, and 131 were readmitted patients of whom 27 I were had previously received treatment at Hillside. the Included in males, 236 106 the 342 female females. were patients, 0f total are the 23 girls admitted to and treated in the Adolescent Pavilion. The average daily census of patients was 195; and the average stay of each ‘ i .‘ ‘ 9.. ’v;'r‘{1 'v: .2» ‘ . - “Amway-713w v ,, . patient was for 196 days. Upon discharge front the hospital, a patient’s condition is evaluated on a he when behavior mental his and basis: enthe status in diﬂerence comparative tered the hospital, and when he left. The ﬁve categories are listed below, (ﬁgures in parentheses indicate the number of patients who left Hillside in 1958) Unimproved (41): no change in condition. have still but been alleviated persist problems or Improved (137): symptoms to an appreciable extent. Much improved (134): symptoms have disappeared and the patient seemed in good condition while hospitalized; however there is no certainty as to his behavior when he returns to his normal environment at home and at work outside of the hospital. Recovered (24). the prognosis is that the patient will be able to return to his social and working community and function as well, or better than he did before he became ill. Without Mental disorder (5) Qied (1 ) OSPITAL ‘ �STAFF EXECUTIVES Abraham Levine, Ph.D. Sylvia Markham, M.A. Leonette Vanderhost, M.A. Director, Psychology Dept. Associate Psychologist Senior Psychologist treatment psychotherapy and medical services The center and core of the treatment program at Hillside is psychotherapy. The ability of the patient to beneﬁt considerably from psychotherapeutic treatment in this area is one of the main criteria for admission. The patient must voluntarily admit himself and be in an early and incipient stage of mental illness. (The long-term, chronic case, requiring custodial care, is referred to other institutions.) The Hillside patient has thus been selectively admitted, receives psychotherapy a minimum of three times a week. In addition, patients participate in group therapy, and all of the other accepted modern therapies, activity therapy, occupational, creative and recreational, drug therapy, and milieu therapy. é 10 _ / s .. .4 . Each team of psychiatric, nursing, social service and other professional personnel of Hillside Hospital meets regularly to pool its knowledge to help its patient along the road to mental health. psychology department The department continued to make its contribution to the understanding of a In the concept of milieu therapy, the whole life of the patient in the hospital, including associations and activities are designed to facilitate his treatment. The therapeutic program thus changes as the patient changes. To conduct this extensive program, Hillside utilizes a “team” approach integrating the skills of the specialists on its staff, under the general supervision of the medical director. Leader of the team is the psychiatrist who is assigned to a patient upon admission, and who remains in charge of the patient for the duration of his stay. Working closely with the psychiatrist, and coordinating the efforts toward the mental health and welfare of the patient are consulting psychiatrists, psychologists, psychiatric nurses, occupational and creative therapists, psychiatric social workers and psychiatric attendants. The team concept is a broad one, and under it conferences are held at which are presented initial diagnosis of newly admitted patient; periodic reports on status of patient and his response to treatment; pre-discharge consultation and rehabilitation, or after-care plans. patient’s strengths, weaknesses, and highly complex psychic states by means of psycho-diagnostic examinations. Objective results obtained through these tests have been helpful to the hospital staff in delineating a history of conﬂicts, defenses, personality. The tests help to reconstruct and chart the patient’s life to show what forces were at work to bring him to the hospital. They provide much informative material needed to plan treatment. Psychological tests are administered upon admission and before separation from the hospital. Last year 541 tests were administered to hospitalized patients and out-patients. Expansion of the department has made possible the inclusion of a vocational counseling program. This program has been especially helpful in developing a placement program within the hospital where a patient may acquire work experience that helps prepare him for the future when he leaves the hospital and returns to his community. In 1958, a doctoral candidate from the Department of Psychological Foundations and Services at Teachers College, Columbia University participated in the psychological counseling program. �STAFF EXECUTIVES Mrs. Goldie Krupa Miss Nancy Jeffries Miss Jean Hendry Miss Helen Schippincase Miss Eleanor MacPhillips Miss Flora McCartney Mrs. Alice McDonough Mrs. Edna Telesca Director of Nurses Assistant Director 0 f Nurses Nursing Instructress Day Supervisor Afternoon Supervisor Night Supervisor I ntra-M and Clinic Nurse Departmental Secretary nursing department intramural clinic This department maintains the patient’s physical health and cares for his non- psychiatric medical needs. Frequent consultations are held between Hillside’s staff and the Intramural Clinic’s specialists to integrate the mental and physical treatment programs. Under the direction of Hillside internist, Dr. Arnold C. Blumberg, the Intramural Clinic handled 2184 patient visits in 1958. The greatest number of patient referrals to Clinic specialists, were in the ﬁelds of Internal Medicine, closely followed by Opthamology, Dermatology and Gynecology. Important services also were rendered in Orthopedics, Otolaryngology, Proctology, Surgery, Urology, Neurology, Podiatry and Radiology. Plans have been made for the Intramural Clinic specialists to take an active part in a psychiatric training program for non-psychiatric physicians. Last year an In-Service Training Program for registered nurses was instituted. The program, which consists of lectures by psychiatric supervisors and doctors, has been of tremendous value to the nursing staff. Knowledge gained and shared has enabled the nurses to perform more effectively to the beneﬁt of the patients and the hospital. The policy of conducting ﬁeld trips through the hospital for students from Central Islip and St. Vincent’s Schools of Nursing was continued. In addition, during 1958, for the third consecutive year student nurses from Queens College received their psychiatric nursing experience at Hillside. F orty-four students participated in the teaching-working program. The training program for psychiatric aides was recognized by the Queens County Mental Health Society, which presented awards and certiﬁcates of honorable mention to four aides trained by the Nursing Department. The awards were made to focus public attention on the important role played by the indispensable psychiatric aides, who contribute so much to the patient through their interest, kindness, attention and skill. department of dentistry Approved by the American Dental Association, it is the oldest intramural department in the hospital. Its staff of 10 dentists, directed by Dr. Paul Scheman, last year received 1112 visits and rendered professional services in orthodontia, periodontia, restorative dentistry and oral surgery and X-ray. New dental equipment acquired in 1958 made it possible to vastly improve the dental care to patients. Members of the department frequently appeared before dental organizations to read papers and give lectures on methods of treating dental patients with emotional problems. ‘ ; I 11 �O. T. STAFF EXECUTIVES Director Eileen P. Fisher Joseph C. Chase Senior Occupational Therapist Adult-Section Esther Burack Senior Occupational Therapist Adolescent Pavilion occupational and creative therapy 12 Two adjunctive services at Hillside, which make an important contribution to the patient and staff are the Occupational and the Creative Therapy departments. Each of these departments has a speciﬁc function, and each is prescribed as a regular part of treatment in cooperation with the psychiatric staff. The OCCUPATIONAL THERAPY department, which is a member of the treatment team, performs a dual function. It provides a program under which a patient can work in various handicrafts, which offer a creative outlet that increases his self-conﬁdence. It also helps the psychiatric staff by reporting on the patient’s attitudes and reactions while he is so engaged. From these reports, which detail responses to success or failure with a project such as weaving, jewelry making, ceramics, the psychotherapist gains further insight to his patient not only at work, but also in his relationship with others in the group. In 1958, the department had maintained a close association with the hospital team. Occupational therapists attended meetings three times a week to contribute their knowledge of a patient, and also submitted regular progress reports to the psychiatric staff. The addition of one therapist to the staff during the year made possible the initiation of an occupational therapy program right in the patient’s room. This enables the therapist to reach a more disturbed patient more quickly and to give him more individual attention. At year’s end, a new prescription form was devised to effect an even closer working relationship between the C. T. STAFF EXECUTIVES Director Dr. Ernest Zierer Creative Therapy Associate Edith Zierer Director doctor and the occupational therapist. The form contains pertinent information which provides a direct guidance line and a higher degree of integration between the psychiatrist and the occupational therapist, indicating areas of concentration that will be most helpful to the patient. CREATIVE THERAPY at Hillside is a specialized form of art therapy devised and developed by Dr. Ernest Zierer. Department Director and his associate, Mrs. Edith Zierer. This therapeutic and psychodiagnostic tool involves the administration of a series of painting tests that reveal a visual expression of the patient’s attitudes toward recurrent life situations. This unique program furnishes a “personality profile” of the patient. This proﬁle supplies the psychiatric staff with documented ﬁndings delineating the patient’s stress and frustration tolerances, strength of motiﬁcation, actual and potential functional capacity and his ability to “integrate” into the societal structure. During the year, an average of 49 patients took part in the program daily and a total of 1640 tests were administered. adolescent pavilion STAFF EXECUTIVES Dr. Alice Stahl, Director Dr. Zenos M. Linnell, Supervisor Dr. Eugene Glynn, Director of After-Care Clinic Dr. Sidney L. Green, Consultant Mrs. Kathleen Cliggett, Head of Nursing Mrs. Sylvia Riback, Senior Social Worker The Israel Strauss Adolescent Pavilion, now in its ﬁfth year, was a pioneering venture of Hillside Hospital. It was 1. 2; �set up to treat and rehabilitate adolescent girls who need hospitalization for emotional problems during a most crucial transistory period of their lives. Hillside Hospital, in venturing into this hitherto neglected ﬁeld, recognized that adolescence is an ideal time to employ the knowledge and skill of modern psychiatric care to help young people when help can be decisive. The Pavilion provides individual psychotherapy, milieu therapy, a school program, a group activities program and nursing care for girls between the ages of .13 and 17. It also conducts an intensive social work program with the families of all patients to create a healthier climate and better understanding at home, of the girls’ problems. The 23 patients admitted to the Pavilion in 1958 remained in the hospital for an average of 315 days, as compared to the 182 days for adults. The conditions range from transient behavior problems to the major psychoses. The staff includes a supervisor, three resident physicians, three registered nurses, two social workers, two school teachers, a group activity worker, an occupational therapist and 16 psychiatric aides. The patients live in a two-story building that includes all therapy facilities, studio-type bedrooms for two girls, dining rooms, lounge and recreation areas. The girls, however, attend school classes in another building to simulate as much as possible the atmosphere of “going to school”. As soon as they are able to, girls are encouraged to join in recreational activities outside their own group in the Pavilion. There have been two notable advances during the year. The ﬁrst is a more structured and individualized program. Under this program the group work department offers a . variety of activities and each patient is required to sign up for two of those activities. The structured program helps the patient to do what she cannot do for herself. The second advance has been to use the concept of individual and group responsibility to foster growth. Housekeeping duties have been assigned to girls and the relationship between various privileges and the patients’ readiness to exercise self control has been stressed. As the Pavilion gains wider recognition among members of the 4" psychiatric profession, greater numbers of referrals continue to come in from distant parts of the country. However, to maintain its high standard of individual attention,the Pavilion restricts its patients to 16 at any given time. The operation of the Adolescent Pavilion is in conformance with the basic thesis of Hillside Hospital; early treatment for those mentally ill patients who can beneﬁt in a relatively short period of time. Even though the adolescent years are directly related to the Hillside orientation, it was obvious at the time the Pavilion was set up, that the adolescent years are the “difﬁcult years.” This period of greatest individual change also is the period about which relatively little is known to the psychiatrist. Five years of treatment of adolescent girls have resulted not only in the improvement of the patients involved but also have led to insights and approaches to modiﬁed and new treatment concepts. These results already have been applied to adolescents, as well as young adults. Follow-up studies of discharged adolescent patients presently are being conducted. In summary, the operation of the Adolescent Pavilion has provided an exciting area for a combined treatment and research project. i 13 �CASEWORK DIVISION EXECUTIVES Abraham Lurie Director, Dept. of Louise Pinsky Sylvia Solovey Sylvia Riback Seymour Silverberg Social Service Department casework division 14 The Social Service Department is the hospital’s most direct link between the patient and his family. The department’s function is to help the patient and his family cope with the personal, social and economic problems caused by the illness. It helps a patient come into the hospital, to stay in the hospital by working with the family members in an effort to relieve pressures on the patient, and ﬁnally, to leave the hospital, and return to a good home climate. This is accomplished by participating directly and actively in the planning that concerns the patient. To accomplish this, in the course of 1958, the Casework Division of the Social Service Department conducted 11,593 interviews with patients, (including those in the Adolescent Pavilion and the Out-Patient Department) and their families. There were, in addition, 10,517 telephone contacts with relatives of patients. This represents an increase over last year’s ﬁgures because a drop in median age of patients, to include many more teenagers, made it necessary for social workers to spend more time with patients and their families. About 35% of the adult patients admitted in 1958 to the hospital are between the ages of 17 and 25. This is due to two principal factors: the policy of selecting patients in the early stages of mental illness, and also the fact that young people are more Social Services Assistant Director, in charge of Casework Supervisor Supervisor Executive Director of the “Bridge” likely to seek hospital help when they are mentally ill. (Older people frequently reﬂect social taboos concerning this type of hospitalization.) The preponderance of young people has changed the social structure of the hospital in many ways including such things as the types of group activities. In 1958, a more intensive effort was also made to screen the 790 male and 1220 female applicants to determine those who could best beneﬁt from the treatment of the hospital, prior to their screening at the clinic. Collaborative relationships with social agencies were continued. One of the most active joint programs was with the Jewish Family Service, which permits discharged patients who need further counseling to get immediate help. At the close of the year, 18 patients (and their families) were receiving aid. Though still a pilot project, this two year old program offers considerable promise for further expansion. Nineteen patients were placed during the year through the F oster Home Program, conducted jointly with the Jewish Community Services of Long Island. This extremely active and important program beneﬁts those patients who, which home have to discharge no upon to return, or who should not, for their well-being return to the same environment in which they lived before admission to the hospital. An invaluable service, which, on occasion, makes possible the hospitalization of a mother, is the Homemaker Service, conducted with the cooperation of the two aforementioned Jewish agencies. This service, supplied to temporarily motherless children, enables the mother-patient to derive maximum beneﬁt from therapy by freeing her from worry about the care of her children. In 1958, 10 families were helped over this particularly difﬁcult time through this program. The Altro Workshop, in the East Bronx provides transitional employment to discharged patients and was used by 13 patients during 1958. The work gainful providing by program, in a protective shop where each employee works at a rate of speed that does not tax him, makes it easier for the �ex-patient to eventually resume normal employement in the community. The Federation Employment and Guidance Service, the New York State Employment Service and the Division of Vocational Rehabilitation have continued to cooperate to the fullest in helping patients secure job placement soon after leaving the hospital. The school program provided by the New York City Board of Education was particularly signiﬁcant in 1958 because of the large number of young patients. Sixty-two patients under the age of 21, who had not yet completed their high school educations were enrolled; 17 were graduated, and six patients passed their high school equivalency examina- tions. The mental patient, unlike the general hospital patient, usually requires longer care and long-time follow-up after discharge. These social service programs indicate Hillside’s recognition of this fact, and the hospital’s community responsibility to provide leadership and coordination of other agencies who could help in the continued care of mental patients during, and after hospitalization. Thus, dozens of private agencies (particularly those afﬁliated with the Federation of Jewish Philanthropies) and public agencies are able to pool their resources. work division group The Group Work Division, under the direction of Arnold Eisen, focuses on the re-socialization of the patient, re-orienting him to group living. The patient is helped to function in an improved manner with his family, friends, employer, fellow-employees and the community in general. A major change in 1958 has been the increased development of community links and a closer coordination with the Casework Division. During the year this division developed a number of new services, programs, ideas and approaches: The New Patients Orientation Group, formed to soften the impact of hospitalization on a new arrival and to supply factual, comforting information to help alleviate fears. Development of Community Program Resources, under which community agencies open their doors to patients on speciﬁed occasions. Trips have been made to YMHA, YWHA, YWCA and YMCA branches in Manhattan, Jamaica and North Hills. Special Cooperative Services with Community Agencies: In cooperation with the Federation Employment and Guidance Service, Group Vocational Guidance sessions were held to discuss the job market, stimulating patient interest in the post-discharge period. Under the Discharge Plan expatients returned to the hospital to tell patients of their experiences at the postdischarge social rehabilitation center, the Hillside League. This has been most effective in relieving separation anxiety. Joint Patient-Family Programming is an outgrowth of Field Days, at which both visitors and patients participate in recreational activities. As an experiment, patients were permitted to invite members of their families to a dance at the hospital. The success of this social event has resulted in planning of other joint events in the future. Internal Programming in 1958 was responsible for establishing several additional lounges, dance therapy, English lessons for foreign-language speaking patients, and other similar programs. A weekly newspaper, edited and published by the patients is now available in addition to their quarterly literary magazine. 15 ��., ~ g _ f TAk 7., . a u, 1 .«f ~ . . I ‘ 1.. . . e. . at. 5,. w ., , >11. .K .,, . . m 7 . ,i . .m.«:, ¢ , . .. L . .w . . . m k . v . . ¢iyu§$ta$ﬂw€u1qﬁm . . \ _.. sub A w ~ m . . v- 4% .. . A. f, . . is» n , N . , ‘ g . ‘ ‘ . / , _ «JD, . . . m a a h ., . . 1: , .. 2 I 1:“ K, ﬂ - w a _ ,. x . . . V . . \ g _ . ., . . _ . . W I K I . . u ‘ . . < l V m . q v I . . _ . ~ v. .. o . . . :8 , ; ‘ V . ‘ . .P A ‘ v �L , Bid-"“1 ' . Gﬁ'emiggry R5e'sea-rqh: Fé‘llby’ﬁ Adjupptjve" ' ’ I , ', Therapies v V ' "' VCI'mlc'al ' ‘ V SoCi’al swipes �‘ ” BOARD ' ;‘ COMMITIEES: Medical Advisory Board . 7, Outside/Affiliations f ‘ Dietary AVDM-IvNiS-TR'ATI'VE‘ SERV‘IQE ' As'sT. ADMINISTRATOR ‘ ADMINISTRATOR Buildings Grounds _ Department . Auditing Secreta rial 0“. Pool» Finance Budgets Diets Menus Dayshift Night Shift ., rchasing Inventory Cleaning 1 P_u 1? Linen Decorating Sto res .- 7 ChefsStaff " . Water Gas Heat Buildings ~ Kitchen Dining Rooms ”Po rters Storekeeping ’ Payrblls Reports Construction .Ma'i nte n anee Craftsmen Porters Attendants ’La'bo‘re'rs Gardeners. Linen Room Engineers Laundry ‘ ' ‘ . Typing. Personnel Supplies Purchases ~' '7 . Medical Budgetary Control ‘ Reports 0 _ ' . Mail Room _ Communications -' , '1 . Medical" _ Statistics 'Grougnds Maids .. gitceou»nts._ : ' i=Bookkee‘pers‘iv~ . ‘ ,Audito rs 'QI e rks Secre'ta ries ' Q, .' Typists - Receptionist Telephone Operators ‘ Typing Pom Trucks“ Cars Gatem’en security A. .4..._. n a em. Hillside Hospital a nd. its Patients . _ ' ��STAFF EXECUTIVES Director of Out-Patient Services Robert R. Luttrell. MD. Assistant Director of Robert Navarre, M.D. Out-Patient Services Miss Sylvia Solovey Mrs. Joan Weisman Mrs. Anne Wexler Mrs. Ida Baumstein Mrs. Estelle Pitts Manhattan after-care clinic The Manhattan After-Care Clinic, located is at week, ﬁve a nights open Mt. Sinai Hospital, a convenient location for most discharged patients. It assists the Hillside discharged patient to resume his role in the community and to deal with the immediate problems of job adjustment and resumption of old environmental contacts. Approximately 30 patients are seen twice Weekly in an effort to bridge their adjustment from the hospital setting to the community setting. The treatment is intense but brief. The importance of this Clinic cannot be underestimated because this helps people who come to the clinic to avoid readmission to the hospital. If they can be helped during the ﬁrst few months, their chances of adjustment in the community are greatly improved. Group or individual therapy is provided, depending on the needs of the patient. Israel and Hilda Strauss League The Israel and Hilda Strauss League is an organization maintained for the social rehabilitation of former patients of Hillside Hospital. Situated in quarters at 231 West 83rd Street, Manhattan, the League furnishes a meeting place for social and recreational purposes. A lounge is equipped Supervising Social Worker Sta]? Psychologist Caseworker Caseworker Caseworker Queens out-patient service with a record player, radio, television, magazines and table games. Its existence is made possible through the devotion and unﬂagging efforts of a group of women volunteers from the community who sponsor the League by raising funds and by offering personal services. The group name “The Bridge”, is symbolic of the purpose of this volunteer organization; $30,000 was raised last year by “The Bridge” for the League. A former Hillside psychiatric social worker, Seymour Silverberg, is assigned as a full-time director of the League. He is available for individual consultation and referral service relating to housing, employment, further treatment and other personal welfare problems. Active membership in the League is now 366, an impressive growth compared to its start in 1954 with 38 members. Devoted volunteer participation has kept pace with the membership. The Queens Out-Patient Service was established to help the emotionally disturbed person before his mental health problems grow and require hospitalization. Psychotherapy is offered to residents of Queens, Nassau and Suffolk Counties who require treatment but cannot assume the economic burden of private care. Selection is made on the same basis as that for in-patients: patients suffering from acute emotional illness are selected after careful screening to determine their likelihood of responding to intensive treatment of a year or less, based on twice-a-week visits. In 1958, 33 psychotherapists worked on a part-time basis to treat 306 patients in individual psychotherapy and 30 patients in group therapy sessions. Usual length of treatment consisted of eleven months. Of the 306 patients treated, 156 were patients admitted to the Clinic in the previous year, and 150 were new patients. To select the 150, 222 patients were fully screened by social workers, through psychological tests and interviews with psychiatrists. Statistics, however, do little to reveal the amount of anguish and tension successfully resolved. They must be translated into the numbers of families kept together, the jobs saved, the fears allayed. �Training programs Hillside’s Resident Training Program continues to emphasize the interrelation between the training program and the treatment program. In 1958, there were 20 Residents in training. Each Resident carried a case load of about 15 patients under the supervision of staff and visiting instructors. In addition, he atttended lecture conferences conducted by the medical director. Instructors from the Medical Board conducted lecture and reading seminars in the ﬁelds of psychopathology and psychotherapy. Qualiﬁed Residents were assigned to the Department of Experimental Psychiatry for clinical and other psychiatric research projects. Seven student case workers from three schools of Social Work were assigned to the Casework Division of the Social Services Department; and six graduate students received training in the Group Work Division of the Department. The training programs extend to Clinical Assistants in the Out-Patient and After-Care Clinics and on-the-job training of personnel. Regular lectures and conferences are scheduled for psychologists, nurses and attendants, social workers and members of the variOUS adj unctive services. Israel Strauss lecture The Annual Israel Strauss Lecture, established in 1955 in honor of the founder and late President of Hillside, was delivered in 1958 on April 20. The speaker was Dr. Paul H. Hoch, Commissioner of New York State Department of Mental Hygiene. His subject was The Open Hospital. Sunday clinical conferences The Sunday Clinical Conferences, open to and attended by psychiatrists and other professional personnel and by outstanding visiting physicians are part of the Resident Training Program and are based on cases prepared by the Residents. They make a signiﬁcant contribution to the training programs in the ﬁeld of psychiatry in the metropolitan area. Medical library The Arany Lorand Memorial Library with Miss Rosalind Lazarus as Librarian continued its rapid expansion program. During the year, 470 books and monographs were added, and 110 periodicals subscribed to. The personal library of the late Dr. Sidney Klein was incorporated. A generous bequest of Joseph Meyer was applied to the psychiatric collection. A gift in the name of Dr. Attlio Laguardia was used to augment the teaching collection. l 19‘ ��- ‘ , ». V , ESEAR CH at Hillside Hospital is a multi-disczplined combined approach of biochemists, chemists, physicists, psychologists, psychiatrists, sociologists and statisticians. Even though the treatment program at Hillside is psychoanalytically oriented, the hospital recognizes that every approach must be explored and utilized in order to increase knowledge and improve the therapy of mental patients. Serious mental illness, with all its disruptive influences, today touches one family in three, since one person in 10 requires hospital treatment for a psychiatric disorder at some time during his life. Hillside believes that the mental health problem requires a total approach, and that progress in the treatment of the mentally ill depends vitally on a program of intensive, never-ending research. A staﬁr of scientists and trained researchers is constantly engaged in the laboratories, in a program of test-tube probing into the mental health program. Research goes on at Hillside on three fronts: in the Department of Experimental Psychiatry, in the Department of Biochemistry and in the Department of Medicine. ESEAR0 �STAFF EXECUTIVES Director Max Fink, M.D. Research Associate (Psychiatry) Joseph .laf’fe, M.D. Research Associate (Psychiatry) Donald F. Klein, MD. Sr. Research Associate (Experimental Psychology) Robert L. Kahn, Ph.D. Research Associate (Experimental Psychology) Max Pollack, Ph.D. Research Associate (Sociology) Nathaniel Siegel, Ph.D. Research Assistant (Experimental Psychology) Eric Karp, B.A. Associate in Research (Neurophysiology) Martin A. Green, MD. Associate in Research (Psychiatry) Abraham A. Kaplan, MD. Barre Alan, M.D. Henry Lefkowitz, M.D. TECHNICAL STAFF Fellow (1 957-58) Fellow (1958-59) Mrs. Janet Bowie .lean Kolodny Hannah Mosquera Blanche Zaitz experimental psychiatry 22 During 1958, the major emphasis of the staff of the Department of Experimental Psychiatry shifted from the evaluation of convulsive therapy to systematic investigations of newer drug therapies. These investigations were based on the theories developed in the Department in 1957, which derived from the successful evaluation of the mode of action of convulsive therapy. Studies were conducted on measures of speech behavior developed in the Department during 1956 and 1957. In an extension of the communication studies, the language indices were applied to drug therapy. The evaluation of convulsive therapies was continued in 1958, by comparing the effects of indoklon, an inhalant convulsant, with electroconvulsive therapy. Results indicated that while the indoklon worked, it was a poor substitute for ECT. The study was important because it illustrated graphically that the convulsion was the important factor, not the electrical stimulus. Investigations into the relations of sociologic factors to the selection of therapies at the hospital showed that not only were the factors of age, education and birthplace signiﬁcantly related to the choice of therapy, but these factors were also related to the results of therapy, the diagnosis and the duration of hospitalization. Similar studies of the population of other primarily psychotherapeutic hos- pitals, and the Hillside Out-Patient Clinic were also undertaken. A grant from the Mental Health Board of Nas- sau County helped support and augment these studies. The acute drug interviews were but One aspect of the continuing evaluation of the biochemistry of convulsive therapy. Other research projects during the year consisted of perceptual studies in patients receiving psychodynamic therapies; the inter-relation of psychotherapy with physiodynamic therapy; and the inter-personal factors in therapists, as well as patients, leading to the referral for physiodynamic therapies. Three members were added to the staff during the year, and the department received support through continuing grants of the Foundations’ Fund for Research in Psychiatry, the National Institute of Mental Health, the Psychopharmacology Service Center of the National Institutes of Mental Health, the Mental Health Board of Nassau County; and from Bristol; Geigy; Smith, Kline 81 French; and Wyeth Laboratories. Staff members were honored with two awards: Dr. Maximilian Fink received the ﬁrst annual A. E. Bennett Psychiatric Research Award of the Society of Biologic Psychiatry for his report on the effects of anticholinergic agents on EEG and behavior; Dr. Joseph Jaffe received the Cralnick annual award for his report on the application of analysis of changes in formal aspects of speech in psychotherapy. department of biochemistry The Department of Biochemistry, headed by Dr. Harry Goldenberg as Director and Dr. Vivian Fishman as Senior Biochemist showed a major growth during 1958, with the assistance of three research grant awards from the National Institutes of Mental Health. The laboratory staff was increased to seven members to make possible more intensive fundamental biochemical studies as well as the initiation of several collaborative clinical projects. The change in the hospital treatment program from shock therapy to chemotherapy introduced new problems which required laboratory assistance. As an aid to the drug therapy program, toxicological tests were set up to detect various pharmaceutical preparations in body ﬂuids. The laboratory was called upon periodically during the year to conﬁrm suspected drug intoxication. A chemical study was carried out with Dr. Arnold Blumberg, of the Department of Medicine to assess the prognostic signiﬁcance of the physiological response to mecholyl. While this study was in progress, it was noted that mecholyl triggers the release of adrenaline in the urine, as well as smaller amounts of related substances. In connection with adrenaline studies it was observed that preferential excretion of adrenaline occurred in normal subjects in the laboratory following the induction of a stress reaction with the drug LSD. Maj or emphasis in the laboratory continued on the premise that mental disease is accompanied by detectable chemical changes in the body. Blood and urine studies were undertaken to determine whether there is any correlation between body chemistry and the various psychiatric disorders. Studies were also continued on enzyme systems concerned with the elimination of toxic substances from the body. �Intensive studies were also made to demonstrate metabolic defect in the liver whereby toxic substances are formed but not eliminated at a sufﬁcient rate to maintain sanity. At Hillside, it is felt that a balanced biochemical program, involving both chemical and other fundamental studies will best serve the present and future welfare of the hospital. Inter-departmental clinical studies help to bind the various hospital activities into one fabric; and the theoretical studies provide more lasting insight into the physical aspects of mental disease, whose corrective treatment offers a more lasting support to psychotherapy. medical department As new drugs are introduced into the treatment of emotional disorders, studies of the basic physiology open new vistas in the understanding of the pathology of mental disease. During 1958, the Medical Department under the direction of Dr. Arnold C. Blumberg collaborated with the Department of Biochemistry on studies of the inter-relation of the adrenaline system and emotional disease. All patients on drug therapies were screened and medically controlled by the Medical Department. Toxic reactions to the drugs were carefully scrutinized and a report on the hypotensive response to toxic doses of meprobamate were submitted for publication. Alterations in liver function with the phenothiazine derivatives were also observed in cooperative studies with the Department of Biochemistry. �Hillside publications During 1958, the Hillside Hospital Staff made numerous appearances as guest lecturers and speakers at conventions in this country and abroad. They appeared before major national professional societies, as well as before lay groups. In addition to national and local societies, reports on hospital programs were presented at conferences in Rome and Montreal. Staff members reported on therapy and research in a large number of professional publications, and in the Journal of the Hillside Hospital. FINK, M.: Lateral Gaze Nystagmus as an Index of Sedation Threshold, EEG. Clin. Neurophysiol. 10: 162-163. FINK, M.: Effect of Diethazine on EEG and Signiﬁcance for Theory of Convulsive Therapy, EEG. Clin. Neurophysiol. 10: 207-208 (Abst.). FINK, M.: Effect of Anticholinergic Agent, Diethazine, on EEG and Behavior, A.M.A. Arch. Neurol. & Psych. 80: 380-388. FINK, M.: Effects of Anticholinergic Agent, Diethazine, on EEG and Behavior: Signiﬁ- cance for Theory of Convulsive Therapy. Presented at the Society of Biological Psychiatry, May, 1958 in San Francisco. 24 FINK, M.: Role of EEG Frequency Shift in Behavioral Effects of Drugs. Presented at Section on Neurol. & Psychiat., Queens County Medical Society, June, 1958 in New York. FINK, M.: Effect of Anticholinergic Compounds on Post Convulsive EEG and Behavior. Presented at the American EEG Society, June, 1958 in Atlantic City. FINK, M., SHAW, R., GROSS, G., COLEMAN, F.C.: FINK, M.: EEG and Behavioral Effects of Collegium Internationale Neuro-Psycho M.: Clinical and EEG. Effects of Megimide in Patients without Cerebral Disease, Neurology 8: 682-685. FINK, M., GREEN, M. A.: EEG Correlates of Signiﬁcance of Individual Variability in EEG Changes During Electroshock Therapy. Presented at the Eastern Association of Electroencephalographers, March, 1958 in Montreal. Psychopharmacologic Agents. Presented at Pharmacologicum, September, 1958 in Rome; and also at the Eastern Association of Electroencephalographers, December, 1958 in New York. the Electroshock Process. Presented at the Eastern Psychiatric Research Association, February, 1958 in New York. FINK, M., GREEN, M. A.: Electroencephalo- graphic Correlates of the Electroshock Process, Dis. Nerv. Syst. 19: 227 (Abst.). FINK, M., JAFFE, J.: Drug Induced Changes in Interview Patterns. Presented at the Conference on Psychodynamic, Psychoanalytic, and Sociologic Aspects of the Neuroleptic (tranquilizing) Drugs in Psychiatry, April, 1958 in Montreal. Comparative Study of Chlorpromazine and Insulin Coma Therapy of Psychosis, J .A.M.A. 166: 1846-1850. GREEN, M., FINK, GREEN, M. A.: A.: Relationship between Seizure Threshold and Duration of Seizures to EEG Change During Electroshock. Presented at the Eastern Association of Electroencephalographers, December, 1958 in New York. GREEN, M. H.: Chairman of Symposium on Catechol Amines. Held at the New York Academy of Sciences, October, 1958. GOLDENBERG, H.: Biochemical Aspects of Mental Disease. Presented at the Jewish GOLDENBERG, Chronic Diseases Hospital, Brooklyn, New York in February, 1958. FINK, M., KAHN, R. L., GREEN, M. A.: Experi- GOLDENBERG, FINK, M., KAHN, R. L., POLLACK, M.: Psychological Factors Affecting Individual Differences in Behavioral Response to Convulsive H., BLUMBERG, A. G., GOLDENBERG, V.: Inﬂuence of LSD and Vasotonic Drugs on Urinary Excretion Patterns. Presented at the 125th Meeting of the American Association for the Advancement of Science, Washington, D.C., December, 1958. FINK, M., KAHN, R. L.: Experimental Studies of the Electroshock Process, Dis. Nerv. Syst. 19: 113-118. H., GOLDENBERc, V.: Urinary Excretion of Aromatic Metabolites in Mental Disease. Presented at the 125th Meeting of the American Association for the Advancement of Science, Washington, D.C., Decem- mental Studies of Convulsive and Drug Therapies in Psychiatry: Theoretical Implications. Presented at the Neurological Society and New York Society of Clinical Psychiatry, March, 1958 in New York. Therapy. Presented at the American Psychiatric Association, May, 1958 in San Francisco. FINK, M., KAHN, R. L., GREEN, M.: Experi- mental Studies of Convulsive and Drug Therapies on Psychiatry: Theoretical Implications, A.M.A. Arch. Neurol. & Psych. 80: 733-734 (Abst.) H.: New Analytical Procedures Based on Dye Partition Analysis. Presented at the Long Island Jewish Hospital, New Hyde Park, New York in March, 1958. GOLDENBERG, GOLDENBERG, ber, 1958. H., WHITE, D. L.: Standardized Method for the Assay of Serum Oxidase Activity (Ceruloplasmin) , Clin. Chem. 4: 551, 1958. GOLDENBERG, �Presented at the 10th Annual Meeting of the American Association of Clinical Chemists, Iowa City, September 1958. V.: Colorimetric Determination of Carboxylic Acid Derivatives as Hydroxamic Acids, Anal. Chem., 30: 1327, 1958. GOLDENBERG, GOLDENBERG, V., GOLDENBERG, H.: An Im- proved Method for the Estimation of Serum Copper, Clin. Chem. 4: 551, 1958. Presented at the 10th Annual Meeting of the American Association of Clinical Chemists, Iowa City, September 1958. J., KAHN, R. L., FINK, M.: Communication Patterns with Altered Brain Function. Presented at the Eastern Psychological Association, April, 1958 in Philadelphia. JAEEE, J., SLorE, W. H.: Interpersonal F actors in Denial of Illness, A.M.A. Arch. Neurol. 81 Psychiat. 80: 653-656. JAFFE, .IAFFE, J.: Language of the Dyad, Psychiatry 21: 249-258. F INK, M.: Changes in Language During Electroshock Therapy, in Psychopathology of Communication, Hoch, P. and Zubin, J., Eds., Grune 81 Stratton. KAHN, R. L., M.: The Relation of F Score to Behavioral and Physiological Response with Altered Brain Function. Pre-' sented at the Eastern Psychological Association, April, 1958 in Philadelphia. KAHN, R. L. FINK, KAHN, R. L., FINK, M.: Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy. Presented at the Electroshock Research Association, May, 1958 in San Francisco. KAHN, R. L., POLLACK, M.: Socio-Psycholog— ical Aspects of Diagnosis and Treatment: Theoretical Implications. Presented at the Symposium—Eastern Psychological Association, April, 1958 in Philadelphia. KAHN, R. L., POLLACK, M.: Social Factors in Selection of Therapy in a Voluntary Mental Hospital. Presented at the American Psychiatric Association, May, 1958 in San Francisco. KAHN, R. L., POLLACK, M.: Prognostic Application of Psychological Techniques in Convulsive Therapy. Presented at the Eastern Psychiatric Research Association, October, 1958 in New York. H.: Intensity of Stimulation and Perception of Simultaneous Stimuli in Cerebral Dysfunction. Presented at the Eastern Psychological Association, April, Philadelphia. KORIN, LEVINE, A.: A Comparative Evalution of Latent Schizophrenic and Overt Schizophrenic Patients with Respect to Certain Personality Variables, J. Hillside Hosp. 7: 131-152. P.: Oculomotor and Postural Patterns in Schizophrenic Children, A.M.A. Arch. Neurol. 81 Psychiat. 79: POLLACK, M., KRIEGER, H. 720-726. Predictions of Outcome, in Youthful Offenders at Highﬁelds, Weeks, H. Ashley, Ed. U. of Michigan Press, Ann Arbor. SIECEL, N.: L.: Juvenile Delinquency. Presented to the Sociology Department at Hofstra College on November 26th, 1958. VANDERHOST, Hillside Journal POLLACK, The Journal of the Hillside Hospital showed once again an increase in the number of its subscribers as an indication of its greater inﬂuence and wider acceptance in the psy— chiatric and related ﬁelds. In this country and throughout the world about 1200 copies are subscribed for by medical schools, training hospitals, social service agencies and many institutions in other countries, particularly Israel. In 1958, 15 major articles by members of the Hillside staff and by other professional contributors, were published in four issues. Contributions come from various parts of the US. and especially the West Coast. The Journal offers an unusual feature by reporting clinical conferences in full including the entire discussions. Now in its 7th year the Journal is still under the able leadership of Dr. Sidney Tarachow. The Editorial Advisory Board consists of Morris B. Bender, M.D., Dudley D. Schoenfeld, M.D., and Sandor Lorand, MD. The Associate Editors are Renato Almansi, M.D., Abraham S. Lenzner, M.D., Samuel R. Lehrman, M.D., Joseph S. A. Miller, M.D., Aaron Stein, M.D. POLLACK, M., BATTERSBY, W. S., KAI-IN, R. L., BENDER, M. B.: Intellectual Deficits in Pa- Grants and Awards Received 1958 LEVINE, A., HARRIS, J., CAMINSKY, I., LURIE, A., BACHRACH, M., MILLER, J.: An Explora- tory Vocational Counseling Program in a Mental Hospital, J. Hillside Hosp. 7: 153-161. 5.: Pathological Reactions in Women After Parturition. Presented to the Department of Obstetrics at St. Albans Naval MARKHAM, Hospital on December 13th, 1958 in New York. S.: The Dynamics of Post-Partum Pathological Reactions as Revealed in Psychological Tests, J. Hillside Hosp. 7: 178-189. MARKHAM, POLLACK, M.: Visual Perception and Attention in Normal and Abnormal Children. Presented at American Orthopsychiatric Association, March, 1958 in New York. M.: A Critique of “Pre-Conscious” Perception and the “Poetzl Phenomenon”. Presented at the American Psychiatric Association, May, 1958 in San Francisco. POLLACK, M.: Brain Damage, Mental Retardation and Childhood Schizophrenia, Am. J. Psychiat. 115: 442-428. tients with Space Occupying Lesions of the Cerebrum. Presented at the Eastern Psychological Association, April, 1958 in Philadelphia. ........ Foundations Fund for Research U. 5. Public Health Service in Psychiatry .................. $74,460 16,250 25 �«saw». �report of the administrator “Kim. MAURHIIBACHRACH The 1958 Annual Report strikes a new note which reﬂects the tremendous strides that are being made in the ﬁeld of mental health. The hospital’s operations during 1958 were effected by the profound changes which came with the introduction of the psychotropic drugs. Chemotherapy has enabled us to entirely discontinue Insulin Shock Therapy and is reducing the use of Electro Shock Treatment to a point where it may soon be eliminated. These changes produced certain changes in our expense picture, in that the cost of giving the physical therapies, which are being abandoned, is reduced. But, there are attendant increases in costs for drugs and, more importantly, a need for expansion of personnel in the adjunctive and activities therapies. Another profound inﬂuence is introduced by the Professional Department program which our Director of Professional Services, Dr. Lewis L. Robbins, had recommended at the end of 1958. It is almost certain that the implementation of these recommendations including, as they do, a considerable increase in the number of full time Staff Psychiatrists, as well as expansion of the Social Service, Occupational Therapy, Psychological and Group Activities Staffs, will change our expense picture considerably, although they may have no impact on the 1958 experience as such. Comparison of Costs 1957-1958 1957 Salaries .......................................... $855,848 Food .............................................. 119,350 Maintenance and Grounds ............ 62,654 Administrative Expenses .............. 98,952 Medical Supplies .......................... 29,811 Repairs and Replacements .......... 49,021 Clinics ............................................ 280,056 Total ................ $1,495,692 1958 $936,330 127,142 72,049 108,693 31,997 48,101 337,712 $1,662,024 The above table shows that the total cost for the entire Hillside Hospital complex increased by 11% during 1958. One-half of this total increase occurred in salaries which increased by 9%. This is in keeping with our experience for the past ten years, where salaries have been increasing steadily at the rate of seven to ten percent per annum due largely to the need of the Hospital to keep pace with the increasing cost of living. Very little, if any, of this increase during 1958 can be ascribed to additional staff. The largest percentage increase, 21%, was in the cost of Out-Patient Services. This reﬂected a combination of increased costs and continued expansion of clinical work from Out-Patient Services, but this should be contrasted with the 307(increase in the cost of Out-Patient Services during 1957. This indicates that although our Out-Patient Services are still expanding, the rate of expansion is slowing down. The other items, food, maintenance and grounds, administrative, medical supplies and repairs and replacements, increased by varying amounts, but they are all in keeping with the general picture of roughly 1071 increase for all expenses. Service Statistics 1957 Total Number of Patients ........................ 545 Total Patient Days .................................. 69,987 Average Income per Patient Day ............ $15.57 Average cost per Patient Day .................. $17.37 Average loss per Patient Day .................. $ 1.80 1958 536 70,691 $16.58 $18.73 $ 2.15 The data given in the above table refer to ln-Patients only. The total number of patients treated and the number of patient days show no signiﬁcant change over 1957. The average income per patient day as well as average cost per patient day increased with costs rising faster than income, so that the average loss per patient day rose from $1.80 to $2.15, an increase of 16%. The reason for this increase in the average loss per patient was that, although there was a slight increase in average income per patient day, all of this increase coming from fees paid by patients or the patient’s family, the per diem rate paid by the City of New York remained the same during 1958, in spite of increased costs. Our research programs continued to expand with a concurrent increase in cost; but these increases were almost entirely absorbed by increased support by the National Institutes of Mental Health, so that deficits arising out of research operations were held to a relatively modest ﬁgure, $35,000, which was made up by the Board of Trustees of Hillside Hospital. 27 �Financial Support Picture Hillside Hospital has been fortunate over the years in the support it has received from the Federation of Jewish Philanthropies. Year after year, since 1948, the Federation has carefully reviewed the Hospital’s fees and supplied a grant which was always consonant with the Hospital’s deﬁcit requirements. Our gratitude to the Federation of Jewish Philanthropies is profound and we hope that we will continue to deserve the support of the Jewish Community, as it is expressed through the Federation. We have received legacies from time to time, and as our reputation and tradition grows, these are becoming .increasingly more. The following is a list of legacies received by the Society of the Hillside Hospital from 1948 to 1958. It is interesting to see that each year the number and amounts of these legacies is growing. We hope that a larger and larger number of persons who desire to beneﬁt humanity and especially to bring about some amelioration of the suffering of the mentally ill, will ﬁnd it possible to name Hillside Hospital as a beneﬁciary in their Wills. Amount Simon Lefcort ................................ $ 2,000 Leonora Solinger Baum ................ 23,317 (A) Florence Tim .................................. 1,000 Rose Simon .................................... 456 Max Richter .................................... 5,000 Solomon Rothfeld .......................... 10,000 Harry T. Epstein ............................ 8,835 250 Year 1948 1949-1958 1949 1949 1950 1950 1952 1953 Beatrice S. Bowman ...................... 1953 Aaron C. Horn ................................ 3,000 Flora Haas ...................................... 60,000 (B) 1954 250 Dora Monness Shapiro .................. 1955 Robert L. Leeds .............................. 2,500 Charles Benoff ................................ 1956 380 28 Max Einhorn .................................. 77,155 897 Julius Grossman ............................ 1956 Hermenia Goodman ...................... 2,000 Christine King ................................ 1,058 Wilhelm Levinger .......................... 37,950 Joseph Meyers ................................ 2,500 (C) 1957 Notes: (A) Approximately $2,300 per year in perpetuity (B) Restricted for care of Adolescent Girls (C) Restricted for Medical Library 1957 1958 1958 1958 During 1958, the following persons other than Trustees made gifts to the Hospital as noted below: Amount Bernard M. Baruch, Jr ......................................... 3 500.00 Bristol Laboratories .............................................. 2,500.00 Grand Street Boys Foundation ............................ 675.00 Jack Bleibtreu ........................................................ 185.00 Wyeth Laboratories .............................................. 1,500.00 Lightolier .............................................................. 1,000.00 Susan Greenwall Foundation ................................ 200.00 Smith, Kline 81 French Laboratories .................... 2,500.00 Gustave Levy .......................................................... Edward Goldberger ................................................ Alfred Hazan .......................................................... J. A. Samuels .......................................................... Gaisman Foundation .............................................. Laurence Alexander .............................................. 100.00 500.00 100.00 100.00 100.00 150.00 William J. Hammerslaugh .................................... 500.00 Henry Homes ........................................................ 1,000.00 l.M.M. Charities .................................................... 500.00 Carol B. Loeb Foundation ...................................... 1,000.00 Blanche Ittleson .................................................... Blanche Freeman .................................................. 100.00 Sylvia 100.00 Krohn ............................. 100.00 Arabel Foundation ................................................ 1,000.00 Eugene Blum .......................................................... 4,000.00 Edward L. Fabian .................................................. 5,000.00 Geigy Chemical Corp ............................................. 5,000.00 Lawrence Mark ...................................................... 100.00 Louis Neiweg .......................................................... 1,049.00 Samuel Silverman .................................................. 200.00 Our gratitude to these benefactors is of course profound. It is our hope that as our work becomes known to a larger and larger circle of interested individuals, they will send us gifts for the support of our work. ��Director, Israel Strauss Adolescent Pavilion Alice Slater Stahl, M.D. Supervising Psychiatrist, Israel Strauss Adolescent Pavilion Zenos M. Linnell, MD. Director, half—time, Adolescent After Care Clinic Eugene Glynn, MD. Society of the Hillside Hospital Officers President Alvin E. Coleman * Chairman of the Board Roy Foster* Honorary Chairman of the Board Leon Lowenstein* Vice-President Dudley D. Shoenfeld, M.D.* Vice-President D. Herbert Beskind * Vice-President George W. Galinger* Secretary Manuel Lee Robbins* Treasurer Arnold S. Askin * Assistant Secretary A. Jacob Abrams Assistant Secretary M. Victor Leventritt Assistant Treasurer Arthur Garson Assistant Treasurer Harry Silverson Honorary Directors Hilda Strauss and Saul Blickman Board of Trustees A. Jacob Abrams Jonas AdlerT Alfred Appel Arnold S. Askin* John M. Bendheim D. Herbert Beskind* Saul Blickman 30 David BunimT Alvin E. Coleman* Martin ColemanT Morris David Thomas Epstein Arthur C. Fatt* David Finkle David Finn Director of Out-Patient Services Robert R. Luttrell, MD. Assistant Director of Out-Patient Services Robert Navarre, MD. Director of Research in Experimental Psychiatry Maximilian Fink, M.D. Roy Foster* George W. Galinger* Arthur Garson Maurice Glinert Meyer Goldstein Jacob Epstein Katz Carl L. Kempner‘l' Harold P. KurzmanT M. Victor Leventritt Budd Levinson Morris L. Levinson Milton B. Loeb Sandor Lorand, M.D. Leon Lowenstein* Charles H. Meyer* Arthur Murray Manuel Lee Robbins* Irving Rosenbaum S. H. Scheuer* Walter Scheuer Dudley D. Shoenfeld, M.D.* Harry Silverson Hilda Strauss Irving Weisglass Nathan Wigod Morton 5. Wolf* Walter D. Yankauer* Chairman of Standing Committees Executive Committee Roy Foster Medical Affairs Committee D. Herbert Beskind Finance Committee Arnold S. Askin House and Grounds Committee George W. Galinger Nathan Wigod, Co-Chairman Legal Committee Charles H. Meyer Social Service Committee Hilda Strauss, Honorary Chairman M. Victor Leventritt, Chairman Personnel Committee Meyer Goldstein Internist Arnold G. Blumberg, MD. Director of Laboratories Harry Goldenberg, Ph.D. Resident Staff Nominating Committee Walter Yankauer Gifts and Legacies Committee Walter Yankauer Committee on Administrative Savings Arnold S. Askin Building Committee D. Herbert Beskind 81 George W. Galinger, Co-Chairmen *—-Executive Committee Members f—Elected in I958 Professional and Administrative Staﬁ' Medical Director Joseph S. A. Miller, MD. Director of Professional Services Lewis L. Robbins, MD. Associate Medical Director Simon Kwalwassr, M.D. Administrator Maurice Bachrach, B.S. Supervising Psychiatrists George Yessin, M.D. Gerhard Schauer, M.D. Harold Esecover, M.D.* William Benjamin, M.D. Morton Wachspress, MD. Norman Ackerman, M.D.** Barre Alan, M.D. Reva Berstock, M.D. Bernard Cohen, M.D.** Warren Cox, M.D.** Alan Dobrow, M.D. Necdet Ecder, M.D. Elhan Ermutlu, M.D.** Marie Friedman, M.D.** Michael Gould, M.D.** Sherwin Harris, M.D. Raymond Hollander, M.D. Doris Kells, M.D. Edwin Kleinman, M.D. Henry Lefkowits, M.D. Sidney Lytton, M.D. Stanley Machlin, M.D. Harvey Mandel, MD. Robert Nodine, M.D.** Paul Pressman, M.D.** Henry Rosett, M.D. Alvaro Rozo, M.D. Mollie Schildkrout, M.D. Jack Schnee, M.D. Herbert Schulman, MD. David Steinman, M.D. Carl Towbin, M.D. Margery Wile, M.D. Other Prof esional Staff Heads Director of Nursing Goldie Krupa, R.N. Director of Social Services Abraham Lurie, M.S.S.W. Director of Psychology Abraham Levine, Ph.D. �. .W. <| ', Psychiatrists afﬁx] .4; Director of Creative Therapy Ernest Zierer, Ph.D. Director of Occupational Therapy Eileen P. Fisher, B.S. Director of Group Work Division Arnold Eisen, M.S.S.W. Dietitian Angelina Canavan, B.A. Supervisor Clinical Laboratory and X-Ray John Croghan, R.T., M.T. Department Heads Accounting Supervisor Dorothy Croghan Manager Lillian Dailey Superintendent of Buildings & Grounds Thomas R. Lumley Executive Housekeeper Sarah Travers Oﬂ‘ice *—Resigned in 1958 **—Completed residency in 1958 Medical Board President Robert A. Savitt, M.D.* Vice President Sidney Tarachow, M.D.* Secretary Sidney L. Green, M.D.* Treasurer Paul Scheman, D.D.S.* Est-President M. David Epstein, M.D.* Manhattan After-Care Clinic Sarah R. Kelman, M.D. Samuel Atkin, M.D. Arnold Eisendorfer, M.D.* M. David Epstein, M.D.* Margaret E. Fries, MD. I. Peter Glauber, M.D.* George S. Goldman, M.D. Sidney L. Green, M.D.* William Karliner, M.D.* Sylvan Keiser, M.D. Sarah R. Kelman, M.D. Emanuel Klein, M.D. Sidney Klein, M.D.iL Samuel R. Lehrman, M.D. Samuel Z. Orgel, M.D. Hyman L. Rachlin, M.D.* Lawrence J. Roose, MD. Robert A. Savitt, M.D.* Martin Schreiber, M.D.* Isidor Silbermann, M.D. Otto Sperling, M.D. Sidney Tarachow, M.D.* Consulting, Attending and Visiting Staffs Non-Psychiatrists Psychiatry Director of Department of Medicine Lester Cohen, M.D.* Leonard Blumgart, M.D. Sandor Lorand, M.D. Irving J. Sands, M.D.l~ Nathaniel E. Selby, M.D. Dudley D. Shoenfeld, M.D. Director of Department of Surgery Sidney Hirsch, M.D.* Director of Department of Dentistry Paul Scheman, D.D.S.* Chairman of Standing Committees Adolescent Pavilion Sidney L. Green, M.D. Credentials Committee for Psychiatric Attending Staﬂ & Promotions Martin Schreiber, M.D. Credentials Committee for Non-Psychiatric Visiting Staff & Promotions Paul Scheman, D.D.S. Education of Resident Staﬂ Arnold Eisendorfer, M.D. Group Psychotherapy Samuel Z. Orgel, M.D. Queens Out-Patient Clinic Martin H. Orens, M.D. Sub-Committee for Child Guidance Clinic Isidor Bernstein, MD. Research Committee Sidney Tarachow, M.D. Publications Committee I. Peter Glauber, M.D. Committee for Adjunctive Services I. Peter Glauber, M.D. Credentials Committee for Supervising Psychiatric and Resident Staﬂ Lawrence J. Roose, M.D. *—Executiue Committee Members i—Deceased in 1958 Medicine Alfred Angrist, M.D. Morris S. Bender, M.D. Oscar Levin, MD. I. Jesse Levy, MD. Neurology A. M. Rabiner, M.D. Hans Strauss, MD. I. S. Wechsler, M.D. Surgery David Warshaw, M.D. Gynecology Julius Jarcho, M.D. Dentistry Morris Fierstein, D.D.S. Attending Psychiatrists Samuel Atkin, M.D. Frank Berchenko, M.D. Isidor Bernstein, MD. Arnold Eisendorfer, MD. M. David Epstein, M.D. Margaret E. Fries, MD. I. Peter Glauber, M.D. George S. Goldman, MD. Paul Goolker, M.D. Sidney L. Green, M.D. William Karliner, M.D. Sylvan Keiser, M.D. Sarah R. Kelman, M.D. Emanuel Klein, M.D. Sidney Klein, M.D.T Attilio LaGuardia, M.D.TT Samuel R. Lehrman, M.D. Samuel Z. Orgel, M.D. Hyman L. Rachlin, M.D. Lawrence J. Roose, MD. Robert A. Savitt, M.D. Martin Schreiber, M.D. Isidor Silbermann, M.D. Otto Sperling, M.D. Aaron Stein, M.D. Sidney Tarachow, MD. Associate Attending Psychiatrists Renato J. Almansi, M.D. Alexander J. Friedman, MD. 5011 Goodman, M.D. Louis Kaywin, M.D. Bruce Kendall, M.D. Abraham S. Lenzner, M. D. Martin H. Orens, M.D. William W. Pike, M.D. Geraldine Pederson-Krag, M.D. i—Deceased in 1958 H—deceased I959 31 �Visitings Optometry Medicine Staff Optometrist Edward L. Steinberg, OD. Director Lester Cohen, M.D. Staff Optometrist Bernard Attinson, OD. Visiting Physician George Sabrin, M.D. Visiting Physician Louis Rosenblum, M.D. Podiatry Staff Podiatrist Sam Sokolov. Pod.O. Visiting Physician Arnold G. Blumberg, M.D. *—Resigned in 1958 Associate Physician Jerome Weinstein, M.D. Clinical Assistants in Manhattan and Queens Clinics Adjunct Physician Arnold L. Berger, M.D. Adjunct Physician Wilbur B. Brett, M.D. Visiting Dermatologists Conrad Stritzler, M.D.* Associate Dermatologist .loel Schweig, M.D. Adjunct Dermatologist Norman Goldfarb, M.D. Neurology Adjunct Attending Psychiatrists 32 Edward R. Adelson, M.D. Herman S. Alpert, M.D. Alvin B. Balaban, M.D. Irving L. Bauer, M.D. Benjamin J. Becker, M.D. Julius Belinkofi, M.D. Milton M. Berger, M.D. Lionel H. Blackman, M.D. Isadore H. Cohn, M.D. Irving J. Crain, M.D. Joseph H. Feldman, M.D. Jules Glenn, M.D. Albert E. Goldberg, M.D. Albert Harrison, M.D. Thomas Hora, M.D. Abraham Kaplan, M.D. Eugene Kaplan, M.D. George P. Krupp, M.D. Peter Laderman, M.D. Harold S. Leopold, M.D. (on leave) David Milrod, M.D. Helene Papanek, M.D. Irving Salan, M.D. Frederick F. Shevin, M.D. Jay Stanton, M.D. Samuel Tabbat, M.D. Fred U. Tate, M.D. Leonard Weinroth, M.D. Herbert Wieder, M.D. Associate Neuroligist Kurt Adler, M.D. Surgery Director Sidney Hirsch, M.D. Visiting Neurosurgeon Joseph Siris, M.D. Visiting Urologist Daniel Kaufman, M.D. Adjunct Urologist Albert Sutton, M.D. Visiting Orthopedist A. H. Lewert, M.D. Associate Orthopedist Julius Schneiderman, M.D. Visiting Proctologist Benjamin Warner, M.D. Visiting Ophthalmologist Edward Seretan, M.D. Associate Ophthalmologist Arthur Minsky, M.D. Visiting 0tolaryngologist Sam Clayton, M.D. Visiting Anesthesiologist Georges Bean, M.D. *—Resigned in 1958 Gynecology Visiting Gynecologist Marie P. Warner, M.D. Visiting Gynecologist Hilliard Dubrow, M.D. (on leave) Associate Gynecologist Jack Cohen, M.D. Associate Gynecologist Bernard Greenblat, M.D. Adjunct Gynecologist Eugene Streim, M.D.* Radiology Visiting Radiologist Bernard Epstein, M.D. Associate Radiologist Paul Steinhorn, M.D. Dentistry Director Paul Scheman, D.D.S. Associate Director J. Gordon Rubin, D.D.S. Associate Dentist Benjamin Schwaid, D.D.S. Associate Dentist Bernard Lebow, D.D.S. Adjunct Dentist Henry Lewis, D.D.S. Adjunct Dentist Samuel Plotnick, D.D.S. Adjunct Dentist Elsa Friedman, D.D.S. Adjunct Dentist Martin Protell, D.D.S. Adjunct Dentist Leon Basson, D.D.S. Lester I. Abend, M.D. Edward R. Adelson, M.D. Romano Antonelli, M.D. Howard Boskey, M.D. Paul Bradlow, M.D.* Stanley Brodsky, M.D. Arline Caldwell, M.D.* Daniel Chansky, M.D. Lionel Chertoﬂ, M.D. Ralph W. Clemments, M.D. Frances Colonna, M.D. Stefano Fajrajzen, M.D. Irving J. Farber, M.D. Philip Friedland, M.D. Ruth Fuchs, M.D. Harvey Goldey, M.D. Sumner I. Goldstein, M.D. Clara Gonda, M.D. Harry Gonda, M.D. Martin Hurvitz, M.D. Gunthar Jacob, M.D. Wilbur Jarvis, M.D. Norman Levy, M.D. Peritz Levinson, M.D.* Zenos Linnell, M.D. Buck Luria, M.D. Howard Mele, M.D. Daniel Miller, M.D. Meyer Monchek, M.D. Beatrice Nachtigal, M.D. Iris Orens, M.D. Edward Pinney, Jr., M.D.* Phoebe Rosen, M.D.* Joseph D. Rosen, M.D.* Jehuda Rozanski, M.D. Gabriel Rubin, M.D.* Leon Tec, M.D. David M. Tillim, M.D. Clara Torda, M.D. Aimee Wiggers, M.D.* *—Resigned in 1958 ��HIL LSIDE HOSPITAL ‘3 ��JANUARY 1, 1960—JUNE 30, 1961 Society of the Hillside Hospital Board of Trustees GLEN OAKS, NEW YORK OFFICERS PresidentD. Herbert Beskind Vice Presidents George W. Galinger Charles H. Meyer ' S. H. Chairman, of the Board Alvin [3. Coleman Scheuer Walter Honorary Chairmen of the Board Roy Ecstie'r Leon towenste‘in Dudley‘D.-Shoenfeld, MD. D. Yankauer Treasurer Arnold .s. Askin Assistant Treasurers Arthur Garson MauriCe Glinert Secretary Jacob Epstein Katz Assistant Secretaries A. Jacob Abrams M. Victor Leventritt M EM B EIR‘S' A. Jaco‘b‘Abram's; George W. G'alinger Arthur Garson Maurice Glinert Meyer Goldstein" Jacob Epstein Katz’r Carl L. Kempner Harold P. Kurzman Robert L. Leeds, Jr. M. Victor Leventritt Budd Levinson Milton B. Loeb Sandor Lorand, M.D. Jonas Adler Alfred Ap'per Arnold S. Askin* John M. Bendheirn D. Herbert Beskind" ' David Bunim Alvin E. C'Ol'eman' Martin Coleman Thomas Epstein Arthur C. Fatt Roy Foster“ Leon Lowenstein* Charles H. Meyer Charles Revrson Manue‘lLee Robbins S. H. Seheuer Dudley D. Schoenfeld, John W. Straus Irving Weisglass Nathan Wigod M-.D.* Morton 8,. Wolf Adolph Woolner Walter D. Yankauer CHAIRME-N of STANDING COMMITTEES of THE BOARD of TRUSTEES Executive committee Alvin E; Coleman Finance. Committees Maurice Glin'ert Sub-Committee on Investments Adolph Woolner Gifts & Legacies Committee Jacob E-.; Katz - *Executiv.e Cémmittge‘ ' ”Deceased House & Grounds Committee George W. Galinger Nathan Wigod Legal Committee Charles H. Meyer Medical Affairs Committee M. Victor Leventritt New Building Committee David Bunim Nominating Committee Walter D. Yankauer Personnel Committee Harold P. Kurzman Public Relations Committee Arthur C. Fatt Social SerVice- Committee Maurice fGIin‘ert �ever—changing approach to the treat- President’s Report Hillside Hospital was founded in 1927 by Dr. Israel Strauss and his colleagues of the Committee of Jews for Mental Health, whose objective was to provide good psychiatric care to those who could not afford to pay for the service. Today’s Hillside Hos— pital is one of the few voluntary, nonprofit psychiatric hospitals in the United States. In 1958, the Board of Trustees determined to establish new goals for their hospital. Our physical size and personnel resources anticipated recent recom— mendations of the Joint Commission on Mental Illness. We endorse these recommendations and wish to participate in the solution of this major health problem by continuing our treatment program, by seeking an improved quality of patient care, and by providing outstanding professional training for doctors, nurses, social workers and other professionals. To accomplish these goals and to broaden the treatment program as a basis for fundamental research in mental illness, Dr. Lewis L. Robbins assumed the responsibilities of Medical Director. Dedicated lay members of the Board of Trustees together with the staff and the distinguished physicians who served on the Medical Board, have been continually reviewing the ment of mental illness and evaluating new concepts of care. The character of Hillside Hospital as a pilot institution seeking to broaden the frontiers of understanding mental illness is now well integrated. The years 1960 and 1961 saw the planning of a new building program designed to provide the physical facilities for current concepts of treatment, professional development and research. An activities therapy build— ing is needed to house the manifold creative, occupational, athletic and social activities which we know are so vital in the treatment of our patients. Equally important, offices, conference rooms and working areas must be created for the broader research program which will include, in addition to biochemical research and experimental psychiatry, a comprehensive effort in dynamic psychiatry. Adequate residence facilities are necessary to house our staff members. Funds toward the cost of these physical improvements are substantially in prospect and it is entirely possible to contemplate that construction can begin during 1962. In this progress report of today’s Hillside, I take great pleasure in the accomplishment of the ﬁrst and major phase of progress toward the long range goals we have set. The efforts, wisdom and material support of the trustees of the Society and the Federation of Jewish Philanthropies, and the informed and dynamic leadership which Dr. Robbins provides, instills great conﬁdence that the image of tomorrow’s Hillside will shine even brighter than today’s. D. HERBERT BESKIND President, Society of the Hillside Hospital �Professional and Administrative Staff Samuel Davis Assistant Administrator ADMINISTRATION Lewis L. Robbins, M.D. Medical Director STAFF PSYCHIATRISTS William Benjamin, M.D. Muriel Benton, M.D. Max Fink, M.D. Maurice Bachrach Administrator David Graubert, M.D. Irwin Greenberg, M.D. B. Bernie Herron, M.D. Elsa Katz, M.D. Donald Klein, M.D. John c. Kramer, M.D. Henry Lefkowits. M.D. Robert R. Luttrell, M.D. Robert Navarre, M.D. Paul Salkin, M.D. Alice S. Stahl, M.D. Barbara Ure, M.D. Morton Wachspress, M.D. George Yessin, M.D. PROFESSIONAL DEPARTMENT HEADS ACTIVITIES THERAPIES Morton Wachspress, M.D. NURSING EXPERIMENTAL Jean Axten, R.N. Director Frances Anderson, R.N. Associate Director PSYCHIATRY Director Max Fink, M.D. Eli Levy Director Assistant Director Joseph Chase Director, Occupational Therapy PSYCHOLOGY LABORATORY HarryrGoldenberg, Ph.D. Director Phyllis Hurteau, R.N. Associate Director lnservice Education John Croghan OUT-PATIENT DEPARTMENT Supervisor ADOLESCENT PAVILION Alice S. Stahl, M.D. MEDICAL LIBRARY Director James Montgomery MEDICAL SERVICES BIOCHEMISTRY Arnold Harry Goldenberg, Ph.D. G. Blumberg, M.D. Director Director RODSrt R. Luttrell, M.D. DII'CCTDI' Harvey Goldey, M.D. Assistant Director Hershey Marcus, M.D. Director Child Therapy Unlt Abraham Levine, Ph.D. Director CREATIVE THERAPY Mrs. Edith Zierer Director SOCIAL SERVICES Abraham Lurie Director Louise Pinsky Assistant Director, Casework Sidney Pinsky Supervisor, Group Work SOCIOLOGY Nathaniel Siegel, Ph.D. ADMINISTRATIVE DEPARTMENT HEADS FOOD ACCOUNTING SERVICE SERVICES Sol Fuchs Dorothy Croghan HOUSEKEEPING OFFICE BUILDINGS and SERVICES GROUNDS Robert Jones May K. Bottomley Thomas Lumley CLINICAL ASSISTANTS ADULT UNIT Nobel Endicott, M.D.. Sumner Goldstein, M.D. Curtis. Kendrick, M.D. Lionel Chertoff, M.D. Ralph Colp, Jr., M.D. Alan Dobrow, M.D. Raymond Edelman, M.D. Dahiel Miller, M.D. iris Orens, M,D. Esther Robbins, M.D. Jack Schnee, M.D. Maurice Shilling, M.D. JamesWatson, M.D. CHILDREN’S UNIT Sidney Finkel, M.D. John Price, Jr., M.D. Esther Robbins, M.D. Mollie Schildkrout, M.D. PSYCHIATRIC RESIDENTS Lucie Arato, M.D. Paul Ar'onow, M.D. Peter Ferber, M.D. Edward Gelardin, M.D. Seymour Gers, M.D. WarrenH. Goodman, M.D. Joseph Gross,'M.D. ' ‘ Edward‘s. Hartmann, M.D. Jerome L, Jacobs, M.D; Abraham Jankowitz, M.D. Henry K‘aminer, M.D. Herbert J. Levo’witz; M.D. Arnold Lieber, M.D. Julia Mehlman, M.D. Herman Oliver, M.D. Raymond W. Rakow, M.D. Rita S. Reuben, M.D. Ger-aid D. Roberts, M.D. Judy M. Roheim, M.D. Bertram H. Rosen, M.D. Ronald'Sa‘german, M.D. DECEMBER George Satran, M.D. Martin Shepard, M.D. Herbert J. Steinberg, M.D. Dan'ield Weitzner, M.D. Charlotte M. Zitrin. M.D. 31,1960-JUNE 30,1961 �Medical Director’s Report When one considers that there are hundreds of thousands of patients in public and private hospitals in the United States, one is forced to the conclusion that this represents a tremendous waste of human lives and community resources. The majority of these patients are in large public hospitals which have been viewed by the Joint Commission on Mental Illness as too large to provide the necessary individualiza— tion of treatment and the therapeutic relationships which are so important. Hillside Hospital with its 375 admissions and discharges per year does provide the type of treatment needed, but the service we can give is but a mere drop of water in the vast ocean of human misery. It would take us forty—ﬁve years to treat as many patients as are currently in just one of the nearby public institutions. The solution to the problem of mental ill— ness does not lie in the expanding of treatment facilities as much as it does in ﬁnding better answers to the causes and treatment of emotional dis— orders, and in passing on our knowledge to all those who are needed to treat the mentally ill. In accordance with these principles, Hillside Hospital has chosen to make research and training its primary goals. As always, it continues to be a pilot institution providing the best psychiatric treatment that is currently available, and is constantly trying to develop new knowledge and to share what we learn with others. The development of research and education are never any better than the clinical programs on which they are based. Conversely clinical pro— grams which do not include educational and research activities become sterile. During these past three years, our emphasis has been on further im— proving our clinical services and concomitantly expanding the psychiatric residency training program. Although there has been much progress in the several on—going research programs, the improvements in our clinical and educational activities should provide opportunities for considerable new effort in this important area. This report treats of our progress in connection with the restated goals of our hospital. The problems in ﬁnding solutions to the questions of mental illness are enormous, but we are taking steps towards assisting in the ﬁnding of needed answers. The work, the effort, support and dedication of our trustees and staff augur well for the future. LEWIS L. ROBBINS, M.D. Medical Director �Progress Toward Our Stated Goals move from closed to open units as was previously the practice. An open hospital has been estab— lished. Doors are rarely locked. I The therapeutic activities now I constitute the major of the part I Goals are quoted from the survey and report made by Dr. Robbins in late 1958. TREATMENT and TRAINING “The psychiatric hospital should be thought of primarily in terms of its staff and of the facilities for occupational therapy, recreational therapy, educational therapy, group living experiences and the like; as a total community in which the bed is used only to sleep in at night. A psychiatric hospital should be a thera— peutic community in which every aspect of the patient’s stay is designed to meet his therapeutic needs. To insure the best possible results includes not only the prescription of the speciﬁc treatment procedures mentioned . . .and the type of therapy best suited to meet the needs . . . but also the ‘emotional atmosphere’ in which they are to be carried out.” Patient care has been much more I individualized. staff has been reor— I Our treatment and treatment teams esganized tablished. Led by a full time senior staff psychiatrist the team is composed of staff psychiatrists, psychiatric residents, social caseworkers, I group workers, psychologists, nurses, and activities therapists. In order to stabilize patients in re— lation to stall, patients now remain on the same living unit, rather than I patients’ program. The treatment program has been approved by the Joint Commission on Hospital Accreditation. A children’s outpatient clinic has been opened. “The patients admitted to Hillside Hospital fall into the groups of those patients with severe psychoneuroses, early or incipient psychoses, and rather severe character disorders. Such patients require the optimum of psychiatric talent for help and one should be able to bring to bear in their treatment the best skills that are available. Even the most experienced psychiatrists need to have the participating skill of an adequate staff both qualitatively and quantitatively in all the areas of psychology, psychiatric social work, psychiatric nursing and the adjunctive therapies.” An Activities Therapy department has been established. The Occupational Therapy staff has been increased. I I Recreational Therapy staff I The has been increased. has been A work patient program I initiated. activities therapy Occupational are I related to work and to treatment I I rather than just to arts and crafts training. A pilot vocational rehabilitation program has been established with Altro Workshops. A program in which volunteers plan and lead patient activities has been established. �“One fact which seems to work against the success of the admission policy is the accumulation of a waiting list for admission.” The patient waiting list has been eliminated. The admission screening process has been improved. I I “The main shortage in psychiatry today is knowledge. . . One of the major responsibilities of every psychiatric facility is not only to provide the best possible service to patients, but also to train personnel. Psychiatry like all other branches of medicine, is best learned by intimate contact with patients and with one’s teachers, rather than in the classroom. Thus, the clinical staﬁ is simultaneously a faculty working in close day to day personal contact with the students The resident. . .can only meet the clinical needs of the patients in his care if he is given adequate supervision by more experienced teachers. The resident psychiatrist is a very busy person having on an average twelve patients at a time and admitting a new patient approximately every ten days. It is not possible to add some very necessary experiences (such as outpatient psychotherapy) to the residency program because of their already very heavy schedules. It would be desirable to increase the number of residents, not only to provide training for more doctors, but also to decrease the case— load for each resident. There has long been a desire to develop a full three year residency training program at Hillside Hospital. Experi- ence again has demonstrated that it is better for residents to obtain all of their psychiatric training in one place rather than to move from place to �place. This provides them with a more integrated three year educational experience. Specialized experience in certain areas, such as psycho- somatic medicine, geriatrics and neurology can be developed through liaison with other nearby institutions. It is, therefore, recommended that the excellent facilites of Hillside Hospital and its actual as well as potential relationships with other institutions be used primarily for the advancement of psychiatric knowledge. I I I I I The full time psychiatric staff has been greatly enlarged. The number of psychiatric resi— dents has been increased. The number of patients per doctor, and the number of residents per supervisor has been reduced. The quality of supervision has improved. Residency training in psychiatry has been approved by the American, Medical Association for three years. I dency training has increased qualiApplicants for psychiatric resi- I I tatively and quantitatively. The number of grants from the United States Public Health Service for training has been increased. Clinical training has been extend— ed into the Adult and Children’s Out-Patient clinics. I been improved and increased. of function Educational voluntary I non-paid attending staff increased. afﬁliations for psychiatTraining I ric residents established with Formal classroom training has I Creedmoor, Long Island Jewish Hospital, Monteﬁore Hospital and Meadowbrook Hospital. Graduate and undergraduate training in psychiatric nursing in I I afﬁliation with Queens College and Adelphi College. Inservice training program for nursing personnel established. Graduate training in Psychiatric Social Work and Group Work in afﬁliation with Adelphi College, Columbia University, Yeshiva and New York University. RESEARCH “A lthough millions and millions of dollars have been spent in development of all kinds of psychiatric facilities, only a small amount of money has been spent in the important area of psychiatric research . . . Far greater sums of money are being spent for research and other illnesses which have a much smaller incidence than do psychiatric disorders . . . Re— search is developed in most hopitals, as a derivative of the clinical and educational activities in the institution . . . investigations which must go forward on many fronts simultaneously; physiological, psychological and social. Because man is a biological, psychological and social being, the ultimate.answers in respect to psychiatric illness will not be found in any one area alone even though from time to time one may seem more promising than the others. Therefore, it is also encumbent upon every psychiatric institution not only to treat patients as well as our present knowledge permits and to educate psychiatric personnel, but also to continue to investigate the nature of psychiatric illnesses in order to eliminate many gaps in our knowledge.” I The research programs in experimental psychiatry, biochemistry and medicine have been in existence for many years under the re- �spective leadership of Dr. Max Fink, Dr. Harry Goldenberg and Dr. Arnold Blumberg. These programs have continued to produce valuable achievements, some of which are reported below. It is’ hoped that the next few years will see even greater emphasis on the research aspects of the goals for Hillside Hospital. I I Eight percent of the total Hillside Hospital budget is currently devoted to research. National recognition of the research work done at Hillside Hospital. Dr. Donald Klein was appointed as a United States Public Health Service career investigator. Dr. Max Fink was appointed to the committee on Clinical Psychopharmacology of the National Institutes of Mental Health, who sponsor a national program for the screening of new drugs in the treatment of mental illness, joining Dr. Lewis L. Robbins, who has continued as Consultant to the Review Committee in Mental Health Research; and the sponsorship of the ﬁrst International Conference on the EEG and Human Psychopharmocology, at the World Congress of Psychiatry, Montreal, June 1961 by the Department of Experimental Psychiatry. Dr. Harry Goldenberg, was hon— ored by appointment as Chairman of the Van Slyke Awards Committee, Chairman of the divisional meeting of the American Association for the Advancement of Science, and panel member of the Eastern Analytical Symposium. Dr. Vivian Fishman’s drug research studies were recognized by the National Institutes of Health with an invitation to present her ﬁndings before the Psychopharmacology Round Table in Atlantic City. EXPERIMENTAL PSYCHIATRY Dr. Fink and his staff completed their survey of forty psychotropic compounds and showed the electroencephalogram (EEG) to be the best available measure of psychotropic drug activity. Typologies of patient response to I I two major psychotropic com— pounds—chlorpromazine and imipramine were deﬁned. This work enables psychiatrists to determine the best drug for each patient. BIOCHEMISTRY Dr. Goldenberg and his staff investigated the chemical changes which occur in chlorpromazine due to glandular activity. Animal trials led to the discovery that two products (“metabolites”) derived from chlorpromazine may be equivalent or superior to the parent drug. Other animal studies were carried out in the laboratory dealing with the stress phenomenon; these experiments have led to observations that may be signiﬁcant to the solution of the problems of senile psychosis and atherosclerosis. I I MEDICAL RESEARCH Dr. Blumberg in his program of medical research has developed a ﬁrm basis for the mecholyl test. He has demonstrated the stability and the reliability of this test in chemical use. It is now used as an effective medical screening device to determine the patients receptivity to somatic psychiatric treatment. I �Publications A FINK, 'M_.: .EEG Techniques in Study of Psychotropic Drugs. Discussion.Actaiof Int.'I Meeting‘oh Techniques for Study of Psychotropic Drugs, Modena, Soc. Tip'o'grafic‘a Mo'de'nse, 1961. FINK, M. and KAHN, R. L.: Behavioral Reproducibility of the Mecholyi Test, Psychosomatic Med. 22: 1,1960. Convulsive Therapy. A.M.A. Arch. Gen. Psychiat. 5: 30-36, BLUMBERG A. 'G., LADERMAN- P. and FINK, M. Efficacy of Divided and FINK, M., KAHN, R. L. KARP, E.. POLLACK, M., GREEN, M., ALAN, B. and LEFKOWITS, H. 1.: Inhalant Induced Convulsions: Significance of the Theory. of theConvulsive Therapy Precess. A.M.A‘. Arch. Gen. Psychiat. BLUMB_,ER,G G.: 'Single Dose Schedules in Insulin' Coma Therapy, Am. 1. Psychiatry 116: 839-40, March, 1960.; and KLEIN, D F.: Severe PapiIIedema Associated With BLUMBERG, A. G. Drug Therapy, Am. J. Psychiat. 116:: 168- 170, 1961. BLUMBERG, A, G. and GOLDENBERG. H. Relation of the Mec‘hoiyl Test to Catechoiamine Excretion, Proc. Soc. Exp. Biol. 6: Med 106: 867-869, 1961. H. Union and Management Trainees: A Comparative Study of BOGARD, Personality and Occupational Choice, 1. of Applied Psychology 44: 56-63, 1-960. Nursing Staff Functions in a Treatment Setting, 1. Hillside Hosp. 9: 88-93,1960-. CLIGGETT, K.: Occupational Therapy at the Adolescent PaVIIion, 1. Hillside Hosp. 9: 80-87, 1960. ENGEL, R.: a Case of Depersonalization, 1. Hillside Hosp. 9: 106-127 1960. FAJRAJZEN, 8.: _On Effect of Anticholinergic Compounds on Post-Convulsive EEG and Behavior of Psychiatric Patients, EEG Clin. Neurophysiol. 12: 359-369, FINK, M.: 1960.- FINK, M.: EEG and BehaviOraI Effects of Psychopharmacologic Agents. In. Neuro-PsychopharmacoiQE-Yy ed. P, Bradley. Amsterdam, Elsevier, pp. 441-446, 1960. FINK, M., 1AFFE, 1. and KAHN, R. |:.: Drug IndUCed Changes in Interview Patterns: Linguistic an‘d Neurophysiologic lndices. In Dynamics of Psychiatric Drug Therapy. red. G. J. Sarwer-Foner, Springfield, "L, C. C. Thomas, 1960, pp. 29-44. FINK, M.: EEG and Behavioral fects of Tofranii, Ef- EEG C-IiII. Neuro- physiol. 12: 243-44 (abst.) 1960. FINK, M.: Differential Treatment and Prognosis in schizophrenia, by R. D. Wirt and W. Simon. Book Review, A..M.A Arch. Gen. Psychiat. 2: 121- 122,1960. Problems of Antagonists to Psychotropic Drugs. Discussion. Neuro—Psychophar‘macology 2: 30-32, ed. E. Rothlin. Amsterdam, Eisevier, 1961. FINK, M.:- Patterns In 11961. 4: 259-266, 1961. V. and‘GOLDENBERG, FISHMAN, H.: MetaboIi-sm of Chiorpromazine: 0rganIc-Extractable Fraction from Human Urine. Proc. Soc. Exp. Biol. 6: Med.104: 99,1960. 3.: Helping the Disturbed Adolescent Acéept Hospitalizatibn. Social Work 6.69 75.1951 FREEMAN, M.‘E. and FRIEDMAN, M. R.: .AfMethod-of Organizing Clinical Data: A Teaching Aid for Training ResiFRIES." dents apy. Psychoanalytic PsychotherHillside Hosp. ‘9: 25-47, 1960. in 1. GALE, M. .and SHATZKY, B.: P.S. 611 y—Queens Annex: ASchool in .a Psychiatric Hospital. 1. Hillside Hosp. 9: 94-99, 1960. Aftercare Program for Adolescents. 1. Hillside Hosp. 9,: 61'65, 1960. GOLDENBER-G, H., FISHMAN, V., WH'ITTIER, 1. and BRINITZER, W.: Urinary Aromatic Excretion Patterns schizophrenia, A.M.A. Arch. Gen. Psychiat. 2: 221.1960. in GOLDENBERG, H. and FISHMA-N, V.: Species Dependence of Chiorpromazine Metabolism, Proc. Soc. Exp. Biol. 8: Med. 106. #26884 1961. GREEN, S. L., KWALWASSER, S., and STAHL,.A. S.: The Role of the Psychiatrist in a Residential Treatment Unit. for AdoleSCen'ts. PSychi‘at. Quart. 34: 662-691, 1960. Relation Between Threshold and Duration of Seizures a'nd Electrbgraphic Change During Convulsive Therapy. 1. Nerv. Ment. Dis. 130: 235-239, 1960. M. A.: Approaches to Psychiatric Consultation in a Research Hospital Setting. A.M.A. Arch. Gen. Psychiat. 3: 691-697, 1960. GREENBERG, I.: I.: Acute lnterc-urrent Psychosis During the Course -of Familial Periodic Paralysis. Am. 1. GREENBERG, Psychiat. 116: 260-263, 1961. I.: Comparison; of the Cross-Cultural Adaptive. Process with Adolescence. compr. Psychiat. 2: GREENBERG, 44-50, 1961. 1.: ESECQVER, H., KAHN, R: L. and FINK, M.: Modification of 1AFFE, 1.. Psychotherapeutic Transactions by Altered Brain Function. Am. 1. Psychother. 15: 46-55, 1961. 1AFFE,1., FINK, M., and KAHN, R. L: Changes in Verbal Transactions with Induced Altered Brain Function. J. Nerv. Ment. Dis. 130: 235-239, 1960: Language Patterns as Character Defenses: Implications for Psychoanalytic Technique. Psychological' and, Psychiatric Aspect of Speech and Hearing, Disorders, ed. D. A. Barbara. Springfield, III., C. C. Thomas, 1960. pp. 138-151. 1AFFE, Formal 1.: and FINK, M;: Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy. J. Neuropsychiat. 1: 242245, 1960. KAHN, R. L. and FINK, M.: Figure-Ground Discrimination after Induced Altered Brain Function. A.M.A. Arch. Neurol. 2: 547-551, 1960. KAHN, R. L., POLLACK, M. and FINK, M.: Social Attitude (California F Scale) and Convulsive Therapy. J. Nerv. Ment. Dis. 130: 187-192, 1960. KAHN, R. L., POLLACK, M. LGLYNN, E.: An GREEN, Social Factors in the Doctor-Patient Relationship. In PsyChoanaly'sis and Social Process, ed. 1. Masserman. New York, Grune 8: Stratton, 1961, pp‘. 81-88. 1AFFE, and POLLACK, M.: Sociopsychological Factbrs Affecting Therapist-Patient Relationships. Psychoanalysis and Human Va'lues, ed. 1. Masserman, New York, Grune 8: Stratton, 1960. pp. 155-168. KAHN, R. L. and POLLACK, M.: The Relationship of Mental and Physical states in Institutionalized Aged Persons. Am. 1. Psychiat. 117: 120-124, 1960 (with Goldfarb, A. I. and Gerber, l. E.). KAHN, R.» L. and POLLACK, M.: Brief Objective Measures for the Determination of Mental Status in the Aged. Am. 1. Psychiat. 117:, 326-328, 1960 (with Goldfarb, A. I. and Peck, A.). KAHN, R. L. Staff Attitudes Toward Psychiatric Treatment in .a Voluntary Mental Hospital. 1. Hillside Hosp. KAHN, R. L.: 10: 97-106, 1961. KAHN, R. L., POLLACK, M. and GOLDFARB, A. I.: Factors Related to In- dividual Differences in Mental Status of Institutional Aged. In Psychopathology of Aging, New York, Grune & Stratton, 1961, pp. 104-113. and LEFKOWITS, H. 1.: Influence of Staff Attitudes and Environmental Factors on Treatment Selection. 1. Hillside Hosp. 10: 8496, 1961. KAPLAN, A. I. �Alterations of Visual Excitability in Patients with Lesions of the Cerebral Optic Pathways. KARP, E.: Trans. A.N.A. 156-159, 1959 (with Battersby, W. S. and Wagman, I. H.). Neural Limitations of Visual Excitability: Alterations Produced by Cerebral Lesions. Arch. Rural. 3: 24-42, 1960 (with Battersby, W. 5., Wagman, I. H. and Bender, M. D.). KARP, E.: ROSEN, B. H.: Case Report of Auricu- lar Fibrillation Following the Use of Imipramine (Tofranil). J. Mount Sinai Hosp. 27: 6, Nov.-Dec., 1960. Effect of Interpersonal Relationships Upon Verbal Conditioning. J. Abnormal I. Social Psychology 60: 241-6, 1960. SAPOLSKY, A.: KAVAZANJIAN, T.: The Role of the Clinical Psychologist in the Adoles- and STAHL, A. 3.: The Treatment Of “Provocative” Behavior in the Disturbed Adolescent. J. Hillside Hosp. 10: 67-81, 1961. 1960. STAHL, A. 8.: The cent Pavilion of the Hillside Hospital. J. Hillside Hosp. 9: 65-71, F.: Mepazine (Pacatal): Clinical Trial with Placebo Control KLEIN, D. and Psychological Study. Psychopharm. 1: 280-287, 1960 (with J. R. Whittier, G. Levine and D. Weiss). and GREEN, 3. L.: Treatment Program at the Israel Strauss Pavilion for Adolescent Girls. J. Hillside Hosp. 9: 14-24, 1960. KWALWASSER, S. LEVINE, A.: Appraising Ego Strength from the Projective Test Battery. J. Hillside Hosp. 9: 228-240, 1960. LINNELL, Z. M.: Authority as 3 Treatment Modality with Adolescents in a Psychiatric Hospital. J. Hillside Hosp. 9: 48-60, 1960. LURIE, A. and PINSKY, L.: Collabora- tion between Psychiatric Hospital and Community Agencies in the Rehabilitation of Mental Patients. Mental Patients in Transition, ed. Milton Greenblatt, Springfield, ”L, C. C. Thomas, 1951. Effect of Brain Tumor on Perception of Hidden Figures Sorting Behavior and Problem Solving Performance. Dissertation Abstracts. 20: 8, 1960. POLLACK, M.: POLLACK, M.: Comparison of Childhood, Adolescent and Adult Schizophrenias. A.M.A. Arch. Gen. Psychiat. 2: 652-660, 1960. POLLACK, M.: The Face-Hand Test in Retarded and Non-retarded Emotionally Disturbed Children. Am. J. Ment. Def. 64: 758-761, 1960 (with E. Gordon). and FINK, M.: Socio~ psychological Characteristics of Patients who Refuse Convulsive Therapy. J. Nerv. & Ment. Dis. 132: 153157, 1961. POLLACK, M. POLLACK, M., KARP, E., KRAUTHAMER, 6., KLEIN, D. F. and FINK, M.: Neuropsychologic Response Pat- terns of Some Psychotropic Drugs. Neuro-Psychopharmacology 2: 381384, ed. E. Rothlin. Amsterdam, Elsevier, 1961. ROBBINS, L. L. and WALLERSTEIN, R. 8.: Operational Problems of Psychotherapy Research: 1. Initial Stud- ies. Bull. Menninger Clin. 24: 164189, 19690. SCHILDKROUT, M. S. First Five Years of the Israel Straus Adolescent Pavilion Program. J. Hillside Hosp. 9: 5-13, 1960. WALLACH, S. S., WALLACH, M. B. and 6.: Observation of Involuntary Eye Movements in Certain Schizophrenics. J. Hillside Hosp. 9: 224-227, 1961. YESSlN, ZIE‘RER, E. and ZIERER, E.: The Integration Quotient in Creative Ther— apy. J. Hillside Hosp. 9: 156-170, 1960. �Administration and Finance 5‘ The extent of future development of Hillside Hospital will depend upon the readiness of the community to support its program. At this point it is not possible to project our budget for five or ten years in the future, but it is possible to choose a course of development and to have some general awareness of the fact that expansion of Hillside’s program . could easily double . . . the current budget. In addition to the staff augmentation, there will, of course, have to be a concomitant increase in housekeeping, administrative personnel and it is evident already that additional facilities, not only for staﬂ but also for patients, are required. The current dining facilities are already overtaxed and the areas for occupational, educational and rec— reational activities are much too limited and inadequate. Consideration must be given, therefore, to con— struction not only of a research building, but also more adequate facilities for patient activities, staﬁ meeting rooms, library and dining rooms.” The charts graphically illustrate the ﬁnancial operation of our hospital during the ﬁscal year ended June 30, 1961. Sizable deﬁcits were incurred in our in-patient and outpatient services because of the increase in the quality of patient care. As we continue to make progress and as we continue to improve wages and salaries, we believe that these deﬁcits will increase if we are to continue to meet our stated objectives. Without the ﬁnancial assistance of the Federation of Jewish Philanthropies and our Board of Trustees, the progress of which this report treats, would have been impossible. The professional development program has required corresponding expansion and improvement of administrative services. Housekeeping and Maintenance services have been enhanced through the application of industrial management techniques. HILLSIDE Hospiut GLEN OAKS KIFF. COLEAN, VOSS 3 SOUDER THE OFFlcE 0F YORK a SAWYER N, Y. ARCHITECTS �Work measurement, preventative maintenance, a planned painting program and modern equipment have been emphasized. These programs have resulted in signiﬁcant improvements in hospital appearance and services so important to the “therapeutic community.” To provide the base for effective organization to achieve stated goals of our hospital, an intensive personnel management program has been planned and implemented. Personnel policies have been developed, consolidated, and published, job analyses have been performed, a job grading program has been established, a merit evaluation program has been implemented, and salary scales were increased for professional and service staff. The results of these efforts have been an increas— ingly stable and efﬁcient employee group of high morale. Our most immediate need is for the space which will express the professional development program in physical terms. Psychiatrists’ oﬂice space is inadequate, teaching facilities including our Medical Library are limited, Activities Therapies areas are widely dispersed and insufﬁcient, and Research space does not meet current needs. To meet our space needs, we have developed a master plan for future construction. Our plans provide for construction of an Activities Therapies building, addi— tional research facilities, and a staff housing project. Following construction of these buildings, we will reconstruct presently existing facilities so that they too, may meet present and future space needs. SERVICE COSTS ln-Patient Service‘ COST $26.65 L088 $1 .56 INCOME *Average per patient-day SERVICE STATISTICS ........................ Number of in-patients treated ........... Number of out-patients treated .......... Number of out visits ................... ln-Patient days 69,941 539 659 14,614 INCREASE IN EXPENDITURES TREATMENT and TRAINING 1958-1959 $924,703 1960-1961 UP 42% $1,310,908 RESEARCH 1956-1959 1960-1961 $ 152,638 $ 198,275 UP 30% ADMINISTRATIVE SERVICES‘ 1956-1959 $ 729,595 $904,863 1960-1961 UP 24% MAURICE BACHRACH Administrator TOTALS 1958-1959 $1,806,936 1960-1961 $2,414,046 *lncludes Administration. Accounting, Food Service, Housekeeping, Maintenance, Office Services and Medical Records. �JANUARY 1, 1960—JUNE,30, Jeena' Attending Psychiatric Staff ATTENDING PSYCHIATRISTS Hyman L. Rachlin, M.D.‘ Lawrence J. Roose, M.D.* Samuel Atkin, M.D.* Frank Berchenko, M.D. Robert Savitt, M.D.' Martin Schreiber, M.D.* Isid'or Silbermann, M.D." Otto Sperling, M.D.t Aaron Stein, M.D.* Sidney Tarachow, M.D.* A. lsidor Bernstein, M.D. Arnold Eisendorfer, M.D.' M. David Epstein, M.D.I' Margaret E. Fries, M.D.‘t I. Peter Glauber, M.D.t George S. Goldman, M.D.‘T Paul Goolker, M.D.* Sidney L. Green, M.D.* William Karliner, M.D.‘ Sylvan Keiser, M.D. Sarah R. Kelman, M.D.‘ Emanuel Klein, M.D. Simon Kwalwasser, M.D. Samuel R. Lehrman, M.D.‘ Abraham S. Lenzner, M.D. Joseph s. A. Miller, MD! Martin H. Orens, M.D.: Samuel Z. Orgel, M.D.* ASSOCIATE ATTENDING PSYCHIATRISTS Renato J. Almansi, M.D. Alexander J. Friedman, M.D. SoIl Goodman, M.D. Abraham I. Kaplan, M.D. Louis Kaywin, M.D. Bruce Kendall, M.D. Geraldine Pederson-Krag, M.D. William W. Pike, M.D. Jay Stanton, M.D. ADJUNCT ATTENDING PNYCNIATRISTS ’lebur Jarvis; M D_. ‘ Edward R. Adelson, M.D. Herman S. Alpert, M.D. Alvin B. Balaban, M.D. Irving L. Bauer, M.D. Benjamin J. Becker, M.D. Julius Beli’nkoff, M.D.. Milton M. Berger, M.D. Lionel H. Blackman, M.D. Rita M. Chalef, M.D. Isadore H. Cohn, M.D. Irving J. Crain, M.D. Joseph H. Feldman, M.D. Jules Glenn, M.D. Albert E. Goldberg, M.D. Michael Gould, M.D. Lebert Harris, M.D. AIbErt Harrison, M.D. Thomas Hora, M.D. Martin Hurvitz, M.D. Eugene H.Kaplan,.M.D. .Paul Kay, M.D. George R. Krupp, M. D. Peter Laderma'n, M. D.. Myer D. Mendelson, M.Dd" David Milrod, M. D. Helene Pap‘anek, M.D Henry Rasner, M. Irving Salan, M. D. Frjéd' U. Tate; M. D. B. Frank Vogel, MDi. Leonard Weinroth, M D ‘ . D Herbert Wie’de'r, M.D. Consulting Physicians and Surgeons MEDICINE Lester Cohen, M.D.* George Sabrin, M.D. Louis Rosenblum, M.D. Jerome Weinstein, M.D. Wilbur 8. Brett, M.D. Arnold L. Berger, M.D. DERMATOLOGY Joel Schweig, M.D. Norman Goldfa’rb, M.D. Eugene L. Bodian, M.D. GENERAL SURGERY Sidney Hirsch, M.D.* Stephen Deckoff, M.D. UROLOGY Daniel Kaufman, M.D. Albert Sutton, M.D. ORTHOPEDICS A. H. Lewert, M.D. Julius Schneiderr‘n‘an, M.D. PROCTOLOGY Benjamin Warner, M.D. NEUROLOGY Kurt Adler, M.D. Joseph Siris, M.D. Martin Green, M.D. OPHTHALMOLOGY Edward Seretan, M.D. Robert Jampel, M.D. OTOLARYNOLOGY DENTAL sen VICLE Director Palil Schemari, .:D D. S.- ‘ Associate Director J. GordonRuDin, D'.‘D._S.. Associate Dentists Benjamin S'c'hwai‘d} '73-'Bernard: Lebow, D. D.S. Adjunct Dentists Lepn Bas'son, D. D. S‘Carl Blacharsh D Herbert Eormani‘ EISa Friedman, Henry Lewis, D. Martin Protéll, D S; ' Sam Clayton, M.D. Samuel Henken, M.D. ANESTHESIOLOGY Georges Bean, M.D. GYNECOLOGY Marie P. Warner, M.D. Bernard Greenblat, M.D. Jack Cohen, M.D. RADIOLOGY Bernard Epstein, M.D. Paul S’teinhorn, M.D. PODIATRY William Rieder, Pod.0. OPTOMETRYSERVICE Edward Steinherg, OJDf. Professional and Non-Professional Employees We wish to express our appreciation to the following professional employees, who helped make our progress possible. and non- professronal PROFESSIONAL EMPLOYEES ACTIVITIES THERAPY Judith Conrad Karen Diaslo Laura Dunlap Ann Elliott Miriam Gozali Phyllis Holland Mona Jones Mary Marrone Lila Martin Marion Sheffer _ Richard Thaler Joan Tucker Yaeka Umemura Alida Vasquez CLINICAL LABORATORY and x41" Kathryn Boone carolyn siegel DENTAL Bertha Sckipp MEDICAL RESEARCH Stephen Deckoff, M.D. Laura Zaves, R.N. PHARMACY Eleanor Palais RESEARCH IN BIOCHEMISTRY PSYCHOLOGISTS Howard Bogar'd, Ph.D. Eugene Friedman, Ph.D.. Benjamin Lapkin, Ph.D. Ira Rosenblatt, Ph.D. ‘Formerly Member of the Medical Board Allen Sapolsky, .Ph D‘. Stanley Schlff, P D.'-. Eelix Steiner, P Leonette V‘anderhost”. Florence Volkman‘ TR'es‘igneJ Robert Burnett . Vivian Fishman Ph. D. ' Audre Heater) Michael Rabinowitz; Daniel [White- wgeeasea‘? . �RESEARCH IN EXPERIMENTAL PSYCHIATRY Ira Belmont, Ph.D. Romeo .Cartolano llana Goldschmidt Abraham Kaplan, M.D. Eric Karp, M.A. Donald Klein, M.D. Jean Kolodny John C. Kramer, M.D. Hanna Mosquera Max Pollack, Ph.D. Arthur Willner, Ph.D. REGISTERED NURSES Marie Cafiero Isabelle Copeland Ann Dispensa Carol Enggasser Maureen Rolston Rose Schulbaum Helen Stein Zelda Feigenbaum Evelyn Feminella Marion Fitzgerald Millicent Goldberg' ‘Ilse Hurst Ann Kelley Joseph Kelly Patricia Kenney Elaine Kirs’chenbaum Ann Klemballa Mar'y' ‘Kohnke Kathleen Le'eFlora McCartney Joann Mastrole Martha Morey Janet Moses _ NanCy Steinhardt Gladys :Stokes‘ .Cfa‘therine' Szakmary Hele‘n Thrasher EditthitoIo Dorothy Urban Helen Zeigler LICENSED PRACTICAL NURSES Mar-y Corrigan Maud Drun'canson Heathlean English Theresa Homrd Betty Ann Kelly Luverne Reeves Mary Nigro Myra Pesk0witz MYrtle‘Re‘mbe‘rt Shirl‘eyi Piot’nic‘k Gloria Swan Ruth Thiele‘ Catherine Wall Sylvia :Riback Nancy Rosenbaum Lita Schmidt S'eymotir Silverberg Gisela Tauber Alice Thompson Ellen weinstein Isabelle Young; SOCIAL SERVICES Casework Division "Robert F ishman BeatriCIe Freeman “Sally Gold Regina G‘oldstein Beatrice 'Hartley Grace HaWKi‘ns Mildred Heller Connie Israel SarahKlionsky Sondra Match Anita Mehr :SOCIAL se‘nwces Group Work DiVision Ellen Brathwaite Deugla‘s‘Glangw Barbara ‘Goldstein Robert'Handman Elaine Heyman Geraldine’Lauter Beverly Luther Adele Orlinsky SERVICE AND NON-PROFESSIONAL EMPLOYEES BUILDINGS and GROUNDS Adam Biali'k Edward Brady John R. CivinSkas Edward Fitzgerald Gustavo Greco Frank Greene George Jungk Bernard Keena Salvatore Lav Manna George Loblein Nero Moyd Stanley Novak Walter Roland Jr. Albert Schmid Joseph Seagren’ Albert Senese John-Skinder Thomas- Slaton Ignazio Taormina Leroy Watkins CLERICAL and BDOKKEEPING Accounting Department Arline Fle’ischmann Lillian Ingbe‘r Lillian Schaeffer Ethel Siegelman Jeannette Silver Dorothy Streir Office Services Irene Attinson Mary Benesta’d John Borgner Diane Brafm'an Jane Buckley Elizabeth cox Irene Djinkin Claire Dubin Leonora Edelstein Eugenia Fievss Marlene Forman ,Norma’Friedman. Shirlee G'alanty Sara Gingold EdWard Golove Frances Gullo James Hand Norberto Medina Adele Harris Grace Hyams Ida NoVick Martin Novick Gaspari Orlando SyIVI'a Hymo‘witz Belle Kapner Edna Kappes. Rose Landgarten Esta Levy Dorothy McClary Inge Mai Yetta Mintz Catherine Muff Florence Offsie Aileen Olton Elinor Paur Mary Pignoni Regina Pi'lchick Gloria Podrid Rita Rodon Joseph Ryan Dorothy Saults, Rose Sa‘vader Dorothy ‘Schnirman Belle Schultz Charlotte Sinovoi B'ettyStarr Edna Telesca Walter Theisen Crannie Weinstein Edna Weis'sman Lott‘e Wollman BIanche-Zaitz rooo seninces Francesco Ca‘nnetto Emma Casamassima Walter Davis, Jr. Arthur DWyer Pardo Faro Alphonse’Gross Ella Jacobs Jimmy Knight- Barbera Alfred Lemaire Gustavo Lescouflair Sarah Littles Anna Lueatorto Michael McDonough Arthu’r Martin Fortunate La Arthur Pitts Irwin Powell B'azil Allen Rivers Walter Rodney Eva Schwartz Helen Thompson Tindel Thompson HDUSEKEEPINC Low‘ell Booker Louis Burgie George Cables Jesus Cora James Cuozzo Jimmy Lee Dasher Nathaniel Glover Charles T. Hill Gerard Honore Joseph Hope ‘ William Hyman Heie'n Jackson, Ruby Jackson Marion Johnson Ernest King Harry‘Lewis August Lo Piccolo Annie Miller Roosévelt Mitchell Robert Reddick Agnes Schuster Willie Lee Skinner Ray Warren Blanche White William Wood PSYCHIATRIC AIDES Olga Allen Marion Bell Althea Bing; George" ‘Bi n‘gha‘m William Black, Jr. Beatrice Blake Annie Bo‘n'd Joseph Britt Joan Brown Lawrence Burger Raymond Burger Frances Butler Sylvester campbell Malcolm carter Annie Clements Alma Clinton Frederick Coley May Conrad Teresa Cooney Hatti'e'Cummings Catherine Eames Annie M. ‘Ervin Ellen Es‘aw' Guillaume Esse‘rs Irish Ford Herbert Franklin Idella Gaston Nettie Gordon Dolores Griffin Juliet Haipern Mabel Harper Essie Harris Linda Hart George Heller Alberta Hopkins Ethel HopWood June Johnson Anna Mae JonesThomas Kelson, Jr. A‘s‘a’lee‘Kirby Helen Olsen Clemmie Palmer Joseph Petty Ida Pulliam Elizabeth Rodriquez Dorothy Schrantz Carltdn Scott Lessie Mae Scott MildredShaw Grace Shieh Virginia'Smith Chauncey smokton Henrietta Strachan Bessie Sumner Louise Thiell Marion Thomas Walter T. Thomas Clyde Trotman Jean Trotman Clarence Tully Thomas Valentine, Jr. Martha Visalli Martha Welch Hazel White Leona Willett LaWrence Williams Anna Wolfberg Leon Wolfberg Clarence Young Edgar Zephyrine . Barbara Knight Doris Kraemer Josephine Lafayette Arthur Lanier Leslie. Lee Miriam Lee .Alic‘e'Leliukevicz Georgina Lohman Grace Lozano Thel‘matMac‘k Mildred March Laura Matthews Dolores Mitchell waiter Moore Ronald Myles designed and IIIUstrated by VISUAL SERVICES Inc. �HILLSIDE HOSPITAL .. is licensed by the New York State Department of Mental Hygiene. g .. is approved for resident training by Council on Medical Education, American Medical Assmiation. American Board of Psychiatry and Neurology. . . is .. .. accredited by American Psychiatric Association. Joint Commission on Accreditation of Hospitals. is a member of American Hospital Association. Hospital Association of New York State. Greater New York Hospital Association. Greater New York Fund. Unite'd'Hospital Fund. Welfare and Health Council of New York City. National Conference of Jewish Communal ServiCes. cooperates with Adelphi College. Altro Workshops. Federation Employment and Guidance Service.Jewish Community Service of Long Island. Jewish Family Service of New York. Long Island Jewish Hospital. New York City Board of Education. New York State Employment Service. New York State Department of VacatiOnal Rehabilitation. Queens College of the City of New Yerk. The Educational Alliance . - _ is .. a partieipating hospital in Master Plan for Hospitals and Related Facilities: for The Hospital Council of Greater New York. A ‘ ~ ‘ A ‘ » Hillside Hospital is a constituent agency of the Federation :of Jewish: Hiii'li'aothirepies .of‘Neinork �for psychkunk:ﬂeaﬂnent haﬂﬁhg and research January 19, 1962 Dear Fellow Employee: of the Hillside Hospital's Progress Attached to this letter is a c read this As and 61. 1960 family your you the fiscal for Report year made toward have we that reminded of the be progress Report, you will the establishment of Hillside as a leading hospital for psychiatric treatment, training and research. been have would possible not which Speaks, Report of this progress, without the dedication, loyalty and effort which you and your fellow would we For few shown the have this, last during years. employees like to extend our thanks. The Cordially, W X. ”m4/69/ Lewis L. Robbins, M. D. Medica1.Director ', Maurice Bachrach Administrator LLRﬁMB/SD/mb �32nd Annual Report HILLSIDE HOSPITAL Glen Oaks,Queens,N.Y. �Hillside Hospital is a nonprofit, nonsectarian mental hospital for the treatment of voluntary patients, suffering from early and curable mental symptoms and admitted regardless of ability to pay. The Hospital is a pilot institution, pioneering in and advancing the scientific frontiers of the human and efficacious application of psychiatry to the mentally ill. Hillside provides organized training for physicians in postgraduate psychiatry and psychotherapy. Major emphasis is placed on advanced research in all phases of treatment. ��........... REPORT OF THE MEDICAL DIRECTOR ................... PROFESSIONAL AND ADMINISTRATIVE STAFF MEMBERS. 5 6 TREATMENT 8 REPORT OF THE PRESIDENT OF THE HOSPITAL 3 SOCIETY OF THE HILLSIDE HOSPITAL BOARD OF TRUSTEES. 4 . . . ...................................... 11 TRAINING ........................................ RESEARCH 14 ....................................... STAFF PUBLICATIONS PRESENTATIONS 16 ............. REPORT OF THE PRESIDENT OF THE 18 ...... MEMBERS OF THE 19 .................... REPORT OF THE ADMINISTRATOR 20 ..................... PROFESSIONAL NONPROFESSIONAL AND MEDICAL BOARD MEDICAL BOARD AND EMPLOYEES ...... 1959 32nd Annual Report HILLSIDE HOSPITAL Glen Oaks, Queens, N.Y. �______WHM._.._» This is my ﬁfth and last annual report as President of the Board of Trustees of Hillside Hospital, and I am happy indeed to be able to state that during this last L. Robbins Lewis Dr. of service, my year has become Medical Director of the Hospital. His broad gauged plans have been submitted to our Board, and accepted for the future development and general planning of the treatment, teaching and research programs of the Hospital. There have been many changes here at Hillside since the death of our founder, Dr. Israel Strauss in 1955, and my election as the second president. I am confident that the original ambitions of our founder to improve treatment, to instruct as many as we can, and above all to attempt to really learn the “why” and “what” of mental illness have been furthered. I believe that my able successor, D. Herbert Beskind, will follow these same general pathways. During this past year, among other interesting incidents, may be mentioned the adoption by Hillside of the personnel policy of the Greater New York Hospital Association, the conversion of our insulin recovery dormitory into offices and conference rooms for research, and the raising of the basic rate of compensation by New York City from $16.00 to $20.00 per day. Costs continue their unbroken upward course, and the day of the “lowcost” hospital seems doomed. Adequate service combined with low cost appears to be a paradox. The need for additional buildings is, of course, generally present with most progressive hospitals, and we are no exception. During this year it has become apparent that we simply must have an Activities Therapy Building, since we just do not have enough room for our patients in the present quarters; and a specialized research building is really necessary since research is so obviously demanded to improve treatment results. Both of these buildings will, hopefully, begin construction in 1960. We have been granted $125,000 from the estate of our former Trustee, Edwin Elson, for the Activities Therapy Building; and we have been able to match this amount with a grant of $150,000 from the United States Public Health Service, for a research building. An incidental, but most important effect of the construction of these buildings will be to create space which may be used for critically needed living-in quarters for our personnel. Such quarters will improve the well-being of our staff, something which has always been of great importance to us. Dr. Joseph S. A. Miller, our former Medical Director, resigned during 1959 with plans to enter private practice; he continues, fortunately, to serve the hospital as a consultant and teacher. We all wish him every success in the years to come. In closing this, my last report, I wish to refer to two principles affecting com— munity activities which to me seem important. One that has guided me in my own decisions, is that it is important to rotate top board ofﬁcers. Such action not REPORT OF THE PRESIDENT OF THE HOSPITAL Alvin E. Coleman only affords opportunity to more individuals 'to serve, more variety in ideas, but probably, more efﬁciency, on the basis of the old adage that “a new broom sweeps clean”! The second principle is possibly more important since it refers to the motivation of why “we seek to serve.” Laymen who donate their time and thought to community affairs do so, of course, to be of service to those less fortunate than themselves. However, an important additional motive is the gain of ego gratiﬁcation from having a controlling part in decisions vital to their institution. Such emotions bring satisfaction to us, and are no doubt an important part of the broader life. It is this drive which makes the boards of or— ganizations so effective, and I believe that the autonomy of each board of each organization is absolutely essential to maintain this effectiveness. It seems to me that any serious interference with this autonomy would greatly weaken organizational actions, would make board memberships a mere fiction, and would soon cause board members to lose interest and drop active participation in institutional activities. This would be calamitous. It is with mixed emotions that I pass along the gavel of leadership. Mine is not only a sense of great satisfaction and pride in having been able to serve such an outstanding institution, but also is a feeling of humility at the vastness of the horizon and the smallness of the job accomplished thus far. May I express my deep appreciation and friendship to the professionals of the hopsital, and to the members of the Board of Trustees who have worked with me and so greatly helped me, and with whom it has been a privilege and a pleasure to serve. �OFFICERS‘ President Alvin E. Coleman Chairman of the Board Roy Foster Honorary Chairman of the Board Leon Lowenstein Vice Presidents Dudley Shoenfeld, M.D. D. Herbert Beskind George W. Galinger Secretary Manuel Lee Robbins Assistant Secretaries A. Jacob Abrams M. Victor Leventritt Treasurer David Finn Roy Foster George W. Galinger Assistant Treasurer Arthur Garson Members: A. Jacob Abrams Jonas Adler Alfred Appel Meyer Goldstein Arnold S. Askin Arnold S. Askin John M. Bendheim D. Herbert Beskind David Bunim Alvin E. Coleman Martin Coleman Morris David Thomas Epstein Arthur C. Fatt David Finkle Arthur Gar-son Maurice Glinert Jacob Epstein Katz Carl L. Kempner Harold P. Kurzman M. Victor Leventritt Budd Levinson Morris L. Levinson Milton B. Loeb Sandor Lorand, M.D. Leon Lowenstein Charles H. Meyer Arthur Murray Charles Revson Manuel Lee Robbins Irving Rosenbaum S. H. Scheuer Walter Scheuer Dudley D. Shoenfeld, M.D. Harry Silverson John W. Straus Irving Weisglass Nathan Wigod Morton S. Wolf Walter D. Yankauer Morton S. Wolf Walter D. Yankauer CHAIRMEN OF STANDING COMMITTEES Executive Committee Roy Foster Medical Affairs Committee D. Herbert Beskind Finance Committee Arnold S. Askin House & Grounds Committee George W. Galinger Nathan Wigod Legal Committee Charles H. Meyer Social Service Committee Hilda N. Strauss, Honorary Chairman M. Victor Leventritt, Chairman Personnel Committee Meyer Goldstein Nominating Committee Walter Yankauer Gifts Jr Legacies Committee Walter Yankauer Committee On Administrative Savings Arnold S. Askin Building Committee D. Herbert Beskind, George W. Galinger, ‘As a/ Novenlber 15, 1959 Honorary Trustees: Saul Blickman Hilda N. Strauss Executive Committee Members Arnold S. Askin D. Herbert Beskind Alvin E. Coleman Arthur C. Fatt Roy Foster George W. Galinger M. Victor Leventritt Leon Lowenstein Charles H. Meyer Manuel Lee Robbins S. H. Scheuer Dudley D. Shoenfeld M.D. SOCIETY OF THE HILLSIDE HOSPITAL BOARD OF TRUSTEES A4. ‘,.. A �The function of an annual report is to look backward brieﬂy in order to assess how well one is looking ahead. Much that took place during this past year indicates that Hillside Hospital has been making steady progress toward achieving the best clinical program that current knowledge permits in order to provide a base for achieving its research and training goals. During the year, the staff was reorgan— ized into sections consisting of members of each of the professional disciplines: phychiatry, psychology, social work, activities therapies, and psychiatric nursing—and each section was given responsibility for all the patients living in a particular ward and/or cottage. The patients are no longer being transferred from one living area to another; they now remain in contact with the same personnel throughout the length of their hospital stay. This plan permits the members of the staff assigned to each section to integrate and co-ordinate their efforts much more effectively, thus further facilitating our goal of individualizing treatment. Through administrative changes in our intake procedures, we have eliminated our long waiting list, making it possible for many patients to enter the hospital within twenty-four to forty-eight hours. All patients who are approved are admitted within two weeks. At the end of the year, Hillside Hospital was ofﬁcially approved by the Central Inspection Board of the American Psychiatric Association and by the Joint Commission on Accreditation of Hospitals. These organizations regularly inspect psychiatric hospitals to insure the maintenance of high levels of patient care. The detailed report of their inspection indicated that, on all counts, our treatment program, staff and physical plant met their higher standards. In April of this year the Children’s Out-Patient Clinic was opened and is now in full operation. In addition to providing treatment for disturbed children and their parents, this clinic offers supervised experience in child psychiatry for psychiatrists practicing in the community, as well as for physicians in our residency training program. This additional clinical activity will also serve as an important part of future research. Hillside Hospital has long accepted its responsibilities for training psychiatric personnel. In July, we increased the number of psychiatric residents in training from eighteen to twenty-ﬁve and have developed an educational program to teach residents in each of the three years of residency. In addition, training beyond the residency level is being added for psychiatrists in the hospital as well as in our out-patient clinics. During 1959, the Nursing Department instructed students from several hospitals and nursing schools. The Psychology Department provided instruction in Vocational Counseling; Occupational Therapy had students from Columbia University; the Department of Social Services maintained its training programs with the New York School of Social Work and with Adelphi College. The Department of Experimental Psychiatry has been providing research training in connection with the psychiatric residency. All these and other departments have been most active in many aspects of training, further details of which follow. Above all, the staff of Hillside Hospital has continued its interest in advancing our knowledge through research. A list of numerous presentations and publications indicating research being done at REPORT OF THE MEDICAL DIRECTOR Lewis L. Robbins, M.D. Hillside is included in this report. It should be noted that it is our determined philosophy to carry out investigations in all these three areas; psychology, biology and sociology and to share our ﬁndings with others in the hope that much-needed advances in our ﬁeld can be achieved. It is also gratifying to ﬁnd our judgments about the value of our research activities and the competence of our research staff conﬁrmed by several foundations and other agencies. Among those which have generously supported our research programs are the Nassau County Commu- nity Mental Health Board and the National Institutes of Mental Health. Numerous other developments have taken place during the past year. We have altered our former insulin unit to provide class rooms, conference rooms, a one-way viewing room, and ofﬁces. We have inaugurated a careful study of all of our physical facilities in order to meet our developing needs. Our volunteer program has been considerably augmented and staff has been added in several departments to further beneﬁt our patients. Co-operative programs with Long Island Jewish Hospital have added to both our treatment and training programs and give promise of valuable further collaborative activity. All that has been accomplished during the past year has been based on the ﬁne work of many people over many years. Outstanding have been the contributions of Dr. Joseph S. A. Miller, who after many years of distinguished service, retired in August from the position of Medical Director. To him, and to all the staff, past and present, the writer is indebted for providing such a solid base on which to build our future. Also, to the Medical Board and to the leadership of its President, Dr. Robert A. Savitt; and to the Board of Trustees which, under the leadership of its President, Alvin E. Coleman, has given advice and support—~the writer is gratefully indebted. �ADMINISTRATION Medical Director Joseph S. A. Miller, M.D.* Lewis L. Robbins, M.D. Associate Medical Director Simon Kwalwasser, M.D. Administrator Maurice Bachrach, B.S. Assistant Administrator Samuel Davis, B.A., M.S. STAFF PSYCHIATRISTS William Benjamin, M.D. Muriel Benton, M.D. Calvin Cheek, M.D. David Graubert, M.D. Henry Lefkowits, M.D. Zenos M. Linnell, M.D. Gerhard Schauer, M.D. Barbara Ure, M.D. Morton Wachspress, M.D. George Yessin, M.D. PROFESSIONAL DEPARTMENT HEADS Creative Therapy Ernest Zierer, Ph.D., Director Edith Zierer, Ass ’t Director Experimental Psychiatry Maximillian Fink, M.D., Director Internal Medicine Arnold Blumberg, M.D., Director Israel Strauss Pavilion for Adolescent Girls Alice Slater Stahl, M.D., Director Laboratories Harry Goldenberg, Ph.D., Director John Croghan, R.T., M.T., Supervisor Nursing Goldie Krupa, R.N., Director Nancy J eﬁries, R.N., Assistant Director Occupational Therapy Eileen Fisher, B.S., Director Out-Patient Services Robert R. Luttrell, M.D., Director Harvey Goldey, M.D., Assistant Director Robert Navarre, M.D., Assistant Director Aaron D. Weiner, M.D., Director Child Therapy Unit Psychology Abraham Levine, Ph.D., Director Social Services Abraham Lurie, M.S.S.W., Director Louise Pinsky, M.S.S.W., Assistant Director, Case Work Division Arnold Eisen, M.S.S.W., Assistant Director, Group Work Division CLINICAL ASSISTANTS Lester I. Abend, M.D. Edward R. Adelson, M.D. Romano Antonelli, M.D. Marion Axel, M.D. Howard Boskey, M.D. Stanley Brodsky, M.D. Daniel Chansky, M.D. Fred B. Charatan, M.D. Lionel Chertoﬂ’, M.D. Ralph W. Clemments, M.D. Frances Colonna, M.D. Stefano Fajrajzen, M.D. Irving J. Farber, M.D. Philip Friedland, M.D. Ruth Fuchs, M.D. Harold Galef, M.D. Harvey Goldey, M.D. Sumner I. Goldstein, M.D. Clara Gonda, M.D. Eugene Glynn, MD: Director Adolescent After-Care Unit Lebert Harris, M.D. Martin Hurvitz, M.D. Gunthar Jacob, M.D. Norman Levy, M.D. Zenos Linnell, M.D. Buck Luria, M.D. Howard Mele, M.D. Daniel Miller, M.D. Meyer Monchek, M.D. Beatric Nachtigal, M.D. Maurice Nadelman, M.D. Iris Orens, M.D. Joseph D. Rosen, M.D. J ehuda Rozanski, M.D. Leon Tec, M.D. David M. Tillim, M.D. Clara Torda, M.D. PSYCHIATRIC RESIDENTS Bruno Bellinfante, M.D. Reva Berstock, M.D. Richard Brown, M.D. Sevin Eker, M.D. Richard Frenkel, M.D. Robert Glauboch, M.D. Feridun Gunduy, M.D. Halldor Hansen, M.D. Harry Gonda, M.D. Paul Hansch, M.D. PROFESSIONAL AND ADMINISTRATIVE STAFF MEMBERS Sherwin Harris, M.D. Raymond Hollander, M.D. John Kramer, M.D. Leslie Langlois, M.D. Jay Lefer, M.D. Genesia Liu, M.D. Dorothy Lieberman, M.D. Harvey Mandel, M.D. Mark N essel, M.D. Richard Resnick, M.D. Alvaro Rozo, M.D. Mollie Schildkrout, M.D. Jack Schnee, M.D. David Steinman, M.D. Michael Trupp, M.D. Shirley Wallach, M.D. Daniel Weitzner, M.D. ADMINISTRATIVE DEPARTMENT HEADS Accounting Services Dorothy Croghan Buildings cf Grounds Thomas R. Lumley Dietary Services Angelina Canavan, B.A. Housekeeping Sarah Travers Oﬁ‘ice Services Lillian Dailey ’Resigned I959 ��The function of the Hillside Hospital InPatient Service is to provide treatment to patients suffering from the early and curable symptoms of mental illness. It is not the intention of Hillside Hospital to meet the overwhelming need of the com— munity for psychiatric treatment facilities. Limitations of funds and the inability to provide an expansive treatment pro— gram compatible with the Hospital’s training and research goals make limitation of the number of in-patients necestherathe if be the This case must sary. peutic community is to be a real treatment modality. It is therefore our purpose to provide a treatment program which is consistent with Hillside Hospital’s image of itself as a pilot institution in the field of mental health. Basic to the treatment of patients at Hillside Hospital is a concept of the therapeutic community. The effective relationships between patients and staff, as well as those between patients themselves is a basic element of the treatment program. Moving psychiatric patients from nursing unit to nursing unit, as their conditions improved, meant changed relationships as each move was made. This structure did not provide the best therapeutic situation for our patients. Therefore, in 1959, it was decided to reorganize the treatment service on the premise that patients remain in the units to which they are admitted throughout their entire hospital stay. This arrangement provides further advantages to the treatment program. Not only are staff psychiatrists, psychiatric residents and nursing person- nel able to develop sustained relationships as a therapeutic team, but the patients are also able to develop such relationships with each other, without having to face the problems associated with a constantly ’s patient environment. Further, changing self—government is stabilized by this arrangement. Finally, the entire administrative organization of the hospital has been facilitated by this organizational change in that sustained accountability for the total treatment program is now possible. In connection with this reorganization, several signiﬁcant changes took place within the Nursing Service during 1959. Provision of adequate nursing care within the revised organization required the restructuring of staffing patterns. A major segment of the nursing service was reassigned to provide the equal distribution of technical, semi-professional and professional nursing skills to all patient units. In the effort to improve staffing patterns, two new personnel categories were created in 1959—Counselor and Senior Psychiatric Aide. As a result of changes in the hospital treatment program, there have been corresponding changes in the assignment of the case work staff of the Social Services TREATMENT TRAl N l N RES EA Department. Two psychiatric social workers are now assigned to each administrative unit. It is now possible to co-ordinate work— social the of work the closely more ers with the work of other members of the team. The casework division has been making increasing use of group counselling. The group approach is now used by the case work in the Hillside Hospital After-Care Clinic. Social workers who function in connection with the InoPatient Service are supplementing individual contacts with visits with patient ’s relatives with group counselling. The admissions policy of the hospital in radically and reviewed changed was 1959. By making it possible to accept appointments for patients applying for admission during any week day, the delay in accepting patients has been drastically reduced. In addition, excessive waiting lists for in-patient admission have been virtually eliminated through the efforts of the Social Work Division, and the staff psychiatrists. Assessment of patient suitability for admission and rapid processing of patients who are accepted for admission is now possible. 1959 saw further expansion of the services of the Group Work Division of the Social Services Department in the provision of additional social and recreational facilities to the in-patient group. Patient government, social clubs, service groups, special interest groups and the the from comvolunteers for program munity were considerably expanded. �The Psychology Department in 1959 continued its program of diagnostic evaluation of the patient, in keeping with its function within the treatment team. The Vocational Counselling Unit of the Psychology Department continued to provide vocational counselling, training and placement services to our patients. The Vocational Counselling Unit joined with the Group Work Division in 1959, in the establishment of a secretarial skills program which was taught to patients by volunteers. The Occupational Therapy Department saw marked growth in 1959. To enable this department to treat the entire patient population and to eliminate waiting lists for this service, the staff was increased from ﬁve to twelve therapists. This permitted more intensive function by occupational therapists in the therapeutic team. Further, a high level of individualized occupational therapy is now possible. An Art Therapy program was also inaugurated in 1959. The Creative Therapy Department continues to perform its dual function as a diagnostic and therapeutic unit. _ Nonpsychiatric medical needs of Hillside Hospital patients are met through the Intramural Clinic. The Hospital Internist participates in initial and dis— charge conferences concerning patients whose physical problems are signiﬁcant in the planning of the total therapeutic program. Consultants in every branch of medicine give freely of their time to the support of patient care. Further, the services and facilities of the Long Island Jewish Hospital are utilized wherever indicated. An excellent Dental Unit is also provided to meet the particular dental needs of the mentally ill patients. This latter clinic is also fully staffed by dentists who serve voluntarily. The Hillside Hospital Out-Patient Department provides psychiatric care to residents of Queens, Nassau and Suffolk Counties who cannot pay for private psychiatric care. In 1959 an average of over one hundred persons were treated each week. In addition to individual psychotherapy, three group psychotherapy programs were established. 1959 also saw the staffing pattern of this clinic improved by the addition of more highly qualiﬁed doctors to insure the provision of a treatment program consonant with the goals of the Hospital. The out-patient selection process, too, was revised to afford immediate consultation Within twenty-four to forty-eight hours for all applicants. On April 1, 1959, the Child Therapy Unit of Hillside Hospital Out-Patient Department was opened with the help of a grant from the Nassau County Mental Health Board. A pilot project in the provision of psychotherapy for children, this clinic is further intended to provide the base for the expansion of future child care services at Hillside Hospital. The staff of the Child Therapy Unit consists of a psychiatrist in-charge, three clinical assistant psychiatrists, a psychologist and a social worker. Major emphasis is given to therapy or guidance for parents of children under treatment. Such treatment is usually focused on considering the parents’ reaction to the child’s prob— lems, or the parents’ role in the origin of the difﬁculty. In the nine months of 1959 during which this clinic was in operation, forty children plus their parents were seen in complete diagnostic evaluation. Fifteen children and their parents were accepted for treatment in this facility. A variety of after-care services have been developed for Hillside Hospital’s former patients. The Foster Home Care Project with the Jewish Community Services of Long Island; the After-Care Clinic which is part of our own Out-Patient service and is provided at Mt. Sinai Hospital; a supportive social case work service with the Jewish Family Services of New York; and a rehabilitation center, “The Bridge,” which provides a resocialization program and supports the Hilda and Israel Strauss League of former patients. �x» �The need for well-trained personnel in the ﬁeld of psychiatry cannot be overstated. Recent years have seen the devel— oping awareness of the assistance which psychiatric knowledge can bring to the broad spectrum of human problems. All of the specialties of medicine are becoming increasingly aware of the psychiatric elements in the etiology and treatment of physical disease. In the ﬁeld of public health, education, and welfare, psychiatry is playing a role of ever increasing importance. Further, public acceptance of the practice of psychiatry and the advances made in this ﬁeld make mandatory the provision of suﬂicient personnel to meet the nation ’s mental health needs. Hillside Hospital, because of its relatively small size and carefully selected patient population, is ideally suited to develop and share psychiatric knowledge. In accepting its responsibilities for the training of psychiatric personnel, Hillside Hospital is helping to meet the need not only for trained psychiatrists, but also for related professional personnel in the ﬁeld of mental health. In order to meet the increased need for psychiatrists, Hillside Hospital expanded its teaching program in 1959. The number of psychiatrists in training was increased from eighteen to twenty-ﬁve in a teaching program that is expected to require three years for completion. The residency pro— gram itself was improved by the inclusion of training in out-patient care and in research. Historically, the In-Patient Service of Hillside Hospital has not only provided quality patient care, but has also afforded the means for the training of psychiatric staff. The reorganization of the treatment service in 1959 provided for better patient care. The development of discreet administrative patient units affords the psychiatrist in training an opportunity to develop sound therapeutic relationships with an integral patient group. Furthermore, this arrangement allows the development of equally sound relationships between resident and supervising psychiatrists, resident and nursing staff, and resident and activities therapist, thus providing not only a good therapeutic milieu, but a more salutary training milieu. TREATMENT TRAINING RESEARCH To provide for the training of psychi- atric residents in the treatment of other than the hospitalized patients, the OutPatient Department now provides the resident with a learning experience which is similar to that which the psychiatrist has in his ofﬁce practice. This program, which was initiated in 1959, provides for the training of ﬁve psychiatric residents, who function part time during the third year of their psychiatric residency. Supervision by the Director of the Out—Patient Department and members of his staff obtains in planned individual and group conferences. To provide for the development of increased knowledge and skills by practicing psychiatrists in the local community, a planned program has been developed. Clinical assistants who are actively in the practice of psychiatry, receive further training under the supervision of the Director of the Out-Patient Department and members of the attending staff. The Child Therapy Unit which was initiated in 1959, also serves a signiﬁcant additional training function for practicing psychiatrists in the community. Three clinical assistants, who spend half their time in this clinic, receive individual supervision as a function of the Director of the Child Therapy Unit and from other highly trained psychiatrists. Clinical conferences, seminars and reading conferences, team meetings, planning conferences and psychiatric staff conferences provide further for the teaching program. ��Research at Hillside Hospital in 1959 was carried out not only in three departments whose function lies primarily with re— search, but in addition, clinical studies were carried out by individuals of various professional departments. EXPERIMENTAL PSYCHIATRY The study program in the Department of Experimental Psychiatry increasingly focused on the drug treatment process. Based on an extensive experience with newer drugs for mental illness, a detailed drug evaluation study was started in the fall. The selection of treatment, and behavioral, psychiatric, psychologic, neurophysiologic and sociologic aspects of change are being investigated. These examinations are undertaken to learn how drugs inﬂuence mentally ill patients, and to test a theory developed in this Department in 1956. In this theory, drugs are seen to affect behavior by changing both brain function and the psychologic attitudes of subjects. In the experimental psychology studies, increasing emphasis has been placed on individual differences in perceptual and cognitive behavior as related to the type of behavioral response with treatment. Study of these indices as predictors of change in addition to the usual use of indices of the effects of the treatment has demonstrated signiﬁcant relationships. The introduction of an electronic frequency analyzer of the Ulett-Loeffel type in August, 1959—a device to rapidly measure the various electrical waves recorded from the brain—signiﬁcantly expanded the electro-encephalographic 14 program. An analysis of changes in the various patterns in the EEG made possible the critical and more precise determination of neurophysiologic effects of various drugs. During the year, 404 records were recorded, and of these, 59 were clinical consultation requests. The sociologic programs undertook an analysis of the differences in patient attitude to treatment of the various staff groups, as the resident doctors, nurses, social workers, etc. ; tolerance of the staff for different types of emotional upset and referral for somatic treatment; and changes in the Hillside Hospital patient population between 1957 and 1959. In order to understand the relation of social factors to the treatment of mental illness, an elaborate tri-hospital study comparing sociologic characteristics, treatment referral rates and discharge ratings in the Menninger Foundation, the Massachus— sets Mental Health Center and Hillside Hospital was begun. TREATMENT TRAINING RESEARCH In language studies—an area that is receiving increased attention in psychiatry—the staff organized and participated in a unique seminar at the New York Divisional Meeting of the American Psychiatric Association. Various psycholinguistic experts employing their individual methods of study, analyzed two tapes of an analytic treatment, and compared their results. They showed the value of combined methods in providing an objective measure of the psychotherapy process. Eighteen reports were published during the year and eleven papers were presented before the national societies. The staff was instrumental in the organization of the New York Divisional Meeting of the American Psychiatric Association, and presented reports at four of its symposia. The staff also participated in the International Conference on Depression and Allied States that was held in March in Montreal. Changes in staff during the year included the appointment of George Krauthamer, Ph.D. as neurophysiologist, and Donald F. Klein, MD. as psychiatrist to the Department. Dr.' Robert L. Kahn, after ﬁve years of service, left to assume the position of Head of the Section of Psychology, Division of Psychiatry of Monteﬁore Hospital. Dr. Joseph Jaffe, while continuing as an Associate in Research in this department, assumed the position of Faculty Member and Associate Director of Research of the William Alanson White Institute. �Continuing support for the program was obtained from the Board of Trustees, extensive program support from the National Institute of Mental Health of the United States Public Health Service, and with grants from the Mental Health Board of Nassau County. BIOCHEMICAL RESEARCH Biochemical research was focused on aromatic substances in the urine of psychiatric patients and on the metabolism of the newer psychotropic and hallucinogenic drugs. For many years, the possibility that psychiatric patients excrete compounds not present in normal subjects has provided the basis for special studies. This program analyzes urine samples for a wide range of chemical substances which are similar to known hormones. It attempts to determine whether psychiatric patients from Hillside Hospital and Creedmoor State Hospital differ from normal subjects. With the widespread use of new drugs in psychiatry, it has been important to determine the way these compounds affect metabolism. One program has been devoted to tracing the changes which chlorpromazine undergoes in the body. For this study, special techniques of analysis for chlorpromazine derivatives have been developed. The focus now is in relating the kinds of derivatives and the rate with which they are produced to their clinical effects. The metabolites of adrenalin are the object of another study with the Medical Department. In patients receiving the Mecholyl Test, urine samples are analyzed before and after the test for various derivatives of adrenalin. Blood studies to determine the enzymes responsible for changing adrenalin are in progress. Recently, a special colorimetric technique for O-methyl transferase was developed. In experimental animals, as well as in the laboratory, the metabolism of hallucinogenes has been studied. Derivatives of lysergic acid related to the vitamin B complex and have been produced and are being tested for hallucinogenic activity and metabolic pathways. MEDICAL RESEARCH The major efforts of medical research in 1959 continued to be directed toward an understanding of the mechanism of the Mecholyl Test. The reliability of the Mecholyl Test, using newly developed equipment for recording blood pressure, ﬁrst was undertaken. These studies demonstrated that the two initial readings of the test were reliable measures. They, furthermore, established the limits of change in the test as a basis for continued studies. In addition, in co-operation with the Biochemistry Department, a study of the relation of metabolites of adrenalin to this test was begun. In the drug evaluation program, the Medical Department assumed control of new medications and of a variety of physiological tests. These included the electrocardiogram and liver and thyroid function studies, as well as the Mecholyl Test. CLINICAL STUDIES A study of the factors affecting the selection of somatic treatment, Drs. A. Kaplan and H. Lefkowits noted that the recommendations for special treatment were as often based on extra medical factors as on the type of behavior of the patient. They described various degrees of symptoms and tolerances for different behaviors. In the Out-Patient Department, Dr. R. Luttrell and his staff have been interested in the prognostic factors in selecting pa- tients for Out-Patient Department treat- ment. Mr. Lurie and Miss Pinsky of the Social Service Department have done a follow-up study of Hillside Hospital patients who have been referred to The Foster Care Program. The results of this study have been gratifying in terms of the evaluation of the program and of the indication of future direction. In clinical psychology a special study of the psychological characteristics of post-partum depressive reactions was instituted. Toward the end of 1959, an extensive review of the Pavilion for Adolescent Girls, a pilot program in this ﬁeld, was prepared for publication in the ensuing year. I5 �efforts of the Hillside Hospital staff in the area of research will be seen in the following listing of publications and presentations. BLUMBERG, A.—Use of An Automatic Sphygmomanometer in the Mecholyl Test, Journal of Hillside Hospital, Vol. 8, #3, pp 179, An index of the July, 1959 BLUMBEEG, A., ROSETT, and DOBROW, A.—Severe Holland, Amsterdam, pp. 238-239 PINK, M. KAHN, R.L. and KORIN, H.—Therapy of Schizophrenia: Role of Alteration of Brain Function on Behavior, Congress Reports, II Int. Cong. Psychiatry, II: 492-493 and KORIN, H.—Relation of Tests of Altered Brain Function to Behavioral Change Following FINK, M. KAHN, R.L. In’duced Convulsions, The First International Congress of Neurological Sciences (III: EEG, Clinical of Internal Medicine, Vol 51, Neurophysiology and #3, pp 607, September, 1959 Epilepsy), Pergamon, 613-619 London, M.——Effect pp. of an PINK, Anticholinergic Agent, PINK, M.——EEG and Behavioral Effects of Diethazine, on EEG and Tofranil, International Behavior; Signiﬁcance for Conference on Depression Theory of Convulsive and Allied States, Montreal Therapy. Biological Psychiatry, ed. Masserman, PINK, M.—Language J ., Grune and Stratton, N. Y. Patterns as Measures of pp. 184—194 Behavioral and Neurophysiologic Change, rINK, M.—Alteration of Brain Function in Therapy. American Psychiatric Association, Philadelphia Psychopharmacology Frontiers, ed. Kline, N., FISHMAN-GOLDENBERG, Little, Brown 85 00., Boston, v., SPOERRI, mar—Coloripp. 325-332 metric Determination of Dicarbozylic Acid rINK, M.——Signiﬁcance of Derivatives as Hydroxamic EEG Pattern Changes in Acids, Anal. Chem. 31: Psychopharmacology. EEG Clin. N europhysiol. 2: 1735, 1959. Hypotensive Reactions to Overdosage of MeprobamatHThe Annals 398 (abst.) rINK, M.—Electro- encephalographic and Behavioral Effects of Tofranil. Canad. Psych. Assoc. J. 4: 1668-1718 rINK, M. KAHN, R.L. and GOLDENBERG, 11., FISHMAN, v., WHIT’I‘IER, J., BRINI'EZER, W. —Urinary Aromatic Excretion Patterns in Schizophrenia A.M.A. Arch Gen. Psychiat., in press GOLDENBERG, H, WHITE, D.L.-- Colorimetric Determination Factors Affecting Individual of O-Methyl Transferase. Diﬁerences in Behavioral Presented at the 126th Response to Convulsive Meeting of the American Association for the Therapy, J .N .M.D. 128: 243-248 Advancement of Science, 1959 December 27, Chicago, and R.L. M. KAHN, PINK, KORIN, H.—Eﬂ’ects of Diffuse GOLDENBERo, H., FISHMAN, v. Altered Brain Function on —Chromatographic Studies Perception. Proc. X V Int. of Chlorpromazine Metabolism in Man. Presented at the 126th Meeting of the American Association for the Advancement of Science, Chicago, Dec. 27, 1959 POLLACK, M.—-—Psychologica1 of Threshold and Duration of Social Attitude to Psychiatric Seizures to Degree of EEG Treatment, N.Y. Divisional Meeting, A.P.A., New York Delta Activity Induced During Electroshock, EEG. KAHN, R. L., with WEINSTEIN, Clin. N curophysiol. 2: E. A. and BERGMAN, P.——Effect (Abst.) of Electroconvulsive Therapy on Intractable Pain. JAFFE, J.—-—Communication A.M.A. Arch. Neurol. and Networks in Freud’s Psychiat. 81 : 37-42 Interview Technique, Psych. Quat. 32: 456-473 KAHN, R. L., with WEINSTEIN, E. A.——Symbolic ReorganizaJAFFE, J.——Symposium on ‘‘ tion in Brain Injuries, in Psycholinguistic Analysis Handbook of Psychiatry, ed. of the Psychiatric Interview ’ ’, Divisional Arieti, S. Basic Books, N. Y., Vol. I, pp. 964-981 Meeting, A.P.A. New York KARP, E.—Behavioral Changes JAF‘FE, J.——Social Backwith Different Methods of ground and the DoctorPatient Relationship, Acad. Induced Cerebral Dysfunction, Eastern Psychoanalysis, New York Psychological Association, KAHN, R.L. and BLACK, M.— Atlantic City of Application Prognostic Psychological Techniques in KORIN, H. and FINK, M.— The role of Set in the Convulsive Therapy, Dis. N erv. Sys. 30: 180-184 Perception of Simultaneous A. Tactile Jour, Stimuli, and R. POLLACK, M., L., KAHN, 384-392 72: Psychol. M.—Sociopsychologic FINK, KRAUTHAMER, G.—Form Aspects of Psychiatric Perception Across Sensory Treatment in a Voluntary Mental Hospital; Duration Modalities, Am. Psychol. 14 : of Hospitalization, Discharge 396 (Abst.) Ratings and Diagnosis, KRAU’I‘KAMER, G.———Personality A.M.A. Arch. Gen. Psychiat. Correlates of EEG, 1 : 565-574 Metropolitan EEG Society, New York KAHN, R. L., and PINK, M.— Personality Factors in LEVINE, A.—A Comparative Behavioral Response to Evaluation of Latent and Electroshock Therapy, Overt Schizophrenic Patients J. Neuropsychiatry 1: 45-49 with Respect to the Concept KAHN, R. L.—Socioof Ego Strength. Journal psychologic Factors of Hillside Hospital, VIII, Affecting Therapist-Patient No. 4, Oct. 1959, pp. 243-266 Relationships, American LEVINE, A.—“App1'aising Academy of Psychoanalysis, ego-strength from the Philadelphia projective test battery” KAHN, R. L.—Socio——Society for psychologic Aspects of Projective Techniques, Psychiatric Treatment, New York, May 1959 Eastern Psychological Association, Atlantic City Cong. Psychol., Publ. North- GREEN, M.—Relationship of KAHN, R. L.—Re1ation STAFF PUBLICATIONS AND . . 16 .m_............,,.... PRESENTATIONS LEVY, E.—The Role of the Volunteer In The Treatment Program of a Mental Hospital, Social Work with Groups, 1959, (New York Natl. Assoc. of Social Workers), pp 109-119 LURIE, A., HIRSCH, 8.— Establishing a Hospital Social Service Department, Journal of Social Work (Vol. IV, No. 2—April 1959) ‘ A.-—‘ Structure of LURIE, Field Work Training” Workshop, Council on Social Work Education, Philadelphia, Pa., January, 1959 LURIE, A.—“The Use of Group Process Within Medical Settings”. National Conference of Jewish Communal Service, Pittsburgh, Pa., May 1959 ‘Forecasting the Place and Role of the Aging in our Society during the next decade”. Little White House Conference on Aging, sponsored by the Community Council of Greater New York, LURIE, A.——‘ December 1959 POLLACK, M.—Effect of Induced Cerebral Dysfunction in Man on Tachistoscopic Perception of Embedded Color Figures, Eastern Psychologic Association. Atlantic City POLLACK, M. with BENDER, M. B., and BATTERSBY, W. s.— Complex Visual Perception in Patients with Brain Tumor. Proc. XV Int. Cong. Psychol., Publ. NorthHolland, Amsterdam, pp. 236-237 POLLACK, M.~—‘ ‘ Comparison of Intellectual Functioning in Childhood,” Adolescent and Schizophrenics, N. Y. Divisional Meeting, A.P.A., New York STAHL, ALICE—”The Role of the Psychiatrist in the Adolescent Pavilion. ’ ’ Midwinter Divisional Meeting of A.P.A. ��The past years has been one in which the Medical Board has shared in the period of transition now in progress at Hillside Hospital. Acting in an advisory and consultative capacity, the Board has aided the Medical Director and the Board of Trustees in bringing into sharp focus the aims and aspirations of Hillside Hospital : to become a leading center for psychiatric treatment, training and research. In keeping with the current spirit of transition at Hillside Hospital, the Medical Board has done considerable soul searching in order to reappraise its role in the affairs of the hospital. The Board is comprised of people who are outstanding in the ﬁelds of psychiatry and psychoanalysis. Some of its members are training analysts on the faculties of the three Psychoanalytic Institutes in New York City. Others have achieved aca- demic distinction as members of medical school faculties and hospital staffs. It is expected that gradual evolutionary changes will take place which will enhance the value of this reservoir of psychiatric experience and knowledge. In the past it has made major contributions to the academic deveIOpment of Hillside Hospital. Together with the devoted membership of our chiefs of Medicine, Surgery and Dentistry, the Board is a source of expert advice in the major activities of the hospital. The year has brought other changes, too. Dr. Sidney Tarachow, the first editor of the Journal of Hillside Hospital, has retired as the Journal’s guiding light, after ten years of unﬂagging devotion. Under his direction the Journal has become an outstanding contributor to the body of scientiﬁc knowledge and literature. It is expected that in the near future an issue of the Journal will be dedicated to Dr. Tarachow, as a token of our appreciation, esteem and affection. Dr. Aaron Stein of our Board has succeeded as editor. The various committees under the able direction of their chairmen have continued to function energetically in the many areas noted in previous years. To them and to the attending and visiting REPORT OF THE PRESIDENT OF THE 18 MEDICAL BOARD Robert A. Savitt, M.D. staffs I offer deepest thanks for their advice and co-operation. I particularly Wish to express my compliments to Mr. Alvin E. Coleman, the President of the Board of Trustees, and to Dr. Lewis L. Robbins, the Medical Director, for their valued and rewarding relationship to the Board. Conferences with these men and their dedicated colleagues have always been stimulating, informative and constructive. In closing, I take extreme pleasure in welcoming Dr. Sidney Tarachow to the Presidency of the Medical Board. He will give it the energetic devotion it so much deserves. �MEDICAL BOARD President Robert A. Savitt, M.D.* President-Elect Sidney Tarachow, M.D.* Secretary Sidney L. Green, M.D.* Treasurer Paul Scheman, D.D.S.* Eat-President M. David Epstein, M.D.* Psychiatrists Samuel Atkin, M.D. Arnold Eisendorfer, M.D.* M. David Epstein, M.D.* Margaret E. Fries, M.D. I. Peter Glauber, M.D.* George S. Goldman, M.D. Sidney L. Green, M.D.* William Karliner, M.D.* Sylvan Keiser, M.D. Sarah B. Kelman, M.D. Emanuel Klein, M.D. Samuel R. Lehrman, M.D. Joseph S. A. Miller, M.D. Samuel Z. Orgel, M.D. Hyman L. Rachlin, M.D.* Lawrence J. Roose, M.D. Robert A. Savitt, M.D.* Martin Schreiber, M.D.* Isidor Silbermann, M.D. Otto Sperling, M.D. Sidney Tarachow, M.D.* Non-Psychiatrists Director of Department of Medicine Lester Cohen, M.D.* Director of Department of Surgery Sidney Hirsch, M.D.* Director of Department of Dentistry Paul Scheman, D.D.S.* CHAIRMAN OF STANDING COMMITTEES Adolescent Pavilion Sidney L. Green, M.D. Credentials Committee for Psychiatric Attending Staff Promotions Martin Schreiber, M.D. & Credentials Committee for Non-Psychiatric Visiting Staff & Promotions Paul Scheman, D.D.S. Education of Resident Staﬂ" Arnold Eisendorfer, M.D. Group Psychotherapy Samuel Z. Orgel, M.D. Manhattan A fter-Care Clinic Sarah B. Kelman, M.D. Queens Out-Patient Clinic Martin H. Orens, M.D. Sub-Committee for Child Guidance Clinic Isidor Bernstein, M.D. Research Committee Sidney Tarachow, M.D. Publications Committee I. Peter Glauber, M.D. Committee for Adjunctive Services I. Peter Glauber, M.D. Credentials Committee for Supervising Psychiatric and Resident Staﬂ‘ Lawrence J. Roose, M.D. CONSULTING, A‘ITENDING AND VISITING STAFF-'5 Consultants Psychiatry Leonard Blumgart, M.D.? Sandor Lorand, M.D. Nathaniel E. Selby, M.D. Dudley D. Schoenfeld, M.D. Medicine Alfred Angrist, M.D. Morris S. Bender, M.D. Oscar Levin, M.D. I. Jesse Levy, M.D. YNeurology A. M. Rabiner, M.D. Hans Strauss, M.D. I. S. Wechsler, M.D. Surgery David Warshaw, M.D. Gynecology Julius Jarcho, M.D. Dentistry Morris Fierstein, D.D.S. Attendings Attending Psychiatrists Samuel Atkin, M.D. Frank Berchenko, M.D. Isidor Bernstein, M.D. Arnold Eisendorfer, M.D. M. David Epstein, M.D. Margaret E. Fries, M.D. I. Peter Glauber, M.D. George S. Goldman, M.D. Paul Goolker, M.D. Sidney L. Green, M.D. William Karliner, M.D. Sylvan Keiser, M.D. Sarah R. Kelman, M.D. Emanuel Klein, M.D. Samuel R. Lehrman, M.D. Abraham S. Lenzner, M.D. Joseph S. A. Miller, M.D. Martin H. Orens, M.D. Samuel Z. Orgel, M.D. Hyman L. Rachlin, M.D. Lawrence J. Roose, M.D. Robert A. Savitt, M.D. Martin Schreiber, M.D. Isidor Silbermann, M.D. Otto Sperling, M.D. Aaron Stein, M.D. Sidney Tarachow, M.D. Associate Attending Psychiatrists Renato J. Almansi, M.D. Alexander J. Friedman, M.D. Soll Goodman, M.D. Louis Kaywin, M.D. Bruce Kendall, M.D. Geraldine Pederson-Krag, M.D. William W. Pike, M.D. Jay Stanton, M.D. Adjunct Attending Psychiatrists Edward R. Adelson, M.D. Herman S. Alpert, M.D. Alvin B. Balaban, M.D. Irving L. Bauer, M.D. Benjamin J. Becker, M.D. Julius Belinkoff, M.D. Milton M. Berger, M.D. Lionel H. Blackman, M.D. Rita M. Chalef, M.D.:t Isadore H. Cohn, M.D. Irving J. Crain, M.D. Joseph H. Feldman, M.D. Jules Glenn, M.D. Albert E. Goldberg, M.D. Michael Gould, M.D.i Albert Harrison, M.D. Thomas Hora, M.D. Wilbur Jarvis, M.D.i Abraham I. Kaplan, M.D. Eugene H. Kaplan, M.D. George R. Krupp, M.D. Peter Laderman, M.D. Myer D. Mendelson, M.D.* David Milrod, M.D. Helene Papanek, M.D. Henry Rosner, M.D.t Irving Salan, M.D. Frederick F. Shevin, M.D. Fred U. Tate, M.D. B. Frank Voge], M.D.* Leonard Weinroth, M.D. Herbert Wieder, M.D. VISITINGS Medicine Director Lester Cohen, M.D. Visiting Physicians George Sabrin, M.D. Louis Rosenblum, M.D. Arnold G. Blumberg, M.D. Associate Physician Jerome Weinstein, M.D. Adjunct Physicians Arnold L. Berger, M.D. Wilbur B. Brett, M.D. Associate Dermatologist Joel Schweig, M.D. Adjunct Dermatologists Norman Goldfarb, M.D. Eugene L. Bodian, M.D. Neurology Associate Neurologist Kurt Adler, M.D. MEMBERS OFTHE MEDICAL BOARD Gynecology Visiting Gynecologist Marie P. Warner, M.D. Associate Gynecologists Jack Cohen, M.D. Bernard Greenblat, M.D. Rodlology Visiting Radiologist Bernard Epstein, M.D. Associate Radiologist Paul Steinhorn, M.D. Optometry Staﬂ‘ Optometrists Edward L. Steinberg, O.D. Bernard Attinson, O.D. Podiatry Staﬁ’ Podiatrist William Reider, Pod.O. Surgery Director Sidney Hirsch, M.D. Adjunct Surgeon Stephen Deckoﬂ", M.D. Visiting Neurosurgeon Joseph Siris, M.D. Visiting Urologist Daniel Kaufman, M.D. Adjunct Urologist Albert Sutton, M.D. Visiting Orthopedist A. H. Lewert, M.D. Associate Orthopedist Julius Schneiderman, M.D. Visiting Proctologist Benjamin Warner, M.D. Visiting Ophthalmologist Edward Seretan, M.D. Associate Ophthalmologist Arthur Minsky, M.D. Visiting Otolaryngologist Sam Clayton, M.D. Visiting Anesthesiologist Georges Bean, M.D. Dentistry Director Paul Scheman, D.D.S. Associate Director J. Gordon Rubin, D.D.S. Associate Dentists Benjamin Schwaid, D.D.S. Bernard Lebow, D.D.S. Adjunct Dentists Henry Lewis, D.D.S. Samuel Plotnick, D.D.S. Elsa Friedman, D.D.S. Martin Protell, D.D.S. Leon Basson, D.D.S. Herbert Forman, D.D.S. *Executive Committee Member f Deceased 1959 IAppointed in 1959 19 �The body of our Annual Report indicates that 1959 was a year in which the Professional Development Program, introduced by Dr. Lewis L. Robbins, was launched. The goals of the program have been outlined and the beginnings of its implementation have been described above. Additional personnel required by this program were initially engaged as of July, 1959, and were gradually added during the second half of the year, so that the 1959 calendar year data does not show appreciable expenditures for the Professional Development Program as such. COMPARISON OF COSTS 1958-1959 1958 — TOTAL OPERATION 1959 % INCREASE 16. Salaries $1,241,350. $1,442,458. 3. Food 127,142. 131,083. Maintenance and Grounds ( 8.) 78,914. 72,408. Administration 29. Expenses 111,300. 143,860. Medical Supplies 55,217. 49,289. (11.) Repairs and Replacements 48,101. 41,727. (13.) 13. Total $1,662,024. $1,880,825. This table shows that the total expenditures for all operations increased by 13%; the percentage increase from 1957 to 1958 was 11%. Salaries and wages increased by 16%. This is in keeping with our experience of the past ten years in which this item rose by ten to ﬁfteen percent per year. Almost the entire rise in this ﬁgure was caused by increases in rates rather than by the addition of new positions. The chief factors in this increase were the across-the-board increase of about 13% to all nonprofessional employees and provision of time and one-half for overtime for all employees. These actions were taken by the Board of Trustees in accordance with the “Statement of Policy Regarding Personnel Practices” promulgated by the Greater New York Hospital Association and subscribed to by the Board of Trustees. Increased salaries were also provided for all categories of the professional staff. The impact of the Professional Development Program as such was hardly felt in 1959 ; its further implementation will produce a more appreciable impact during 1960. . 20 Food costs increased 3% in accordance with the rise in the food price index. Out-patient services expenses increased by only 6% as compared with 30% in 1957 and 21% in 1958. This reﬂects the stabilization of this operation after a period of constant growth dating back to 1954 when the large Queens Out-Patient Service was established. The largest increase was in administration expenses which rose by $32,000, or 29%. The following were the chief components of this increase: INCREASE IN DOLLARS ITEM Ofﬁce Equipment $3,500 Medical Care Prepayment for Employees 8,000 Social Security and Retirement Contributions 9,300 Personnel Expenses 6,300, Medical Care Prepayment for employees (Blue Cross and Blue Shield coverage for the employees and their families) was initiated in July, 1959 as part of our over-all improvement of personnel practices. Social Security and retirement contributions rose both as to rate and volume. Personnel expenses rose in accordance with liberalized policies as to travel and other allowances for professional staff. SERVICE DATA: IN-PATIENTS Total number of patients treated Total patient days Average income per patient day Average cost per patient day Average loss per patient per day 1958 1959 % INCREASE — —— 536 70,691 537 70,219 $16.58 $18.83 + 13.5% $18.73 $21.69 + 15.8% $ 2.15 $ 2.86 + 33% REPORT OF THE ADMINISTRATOR Maurice Bachrach �With total number of patients treated and the number of patient days virtually unchanged, average income per patient day rose by 13.5% while average cost per patient day rose by 15.8%. The average loss per patient day rose by 33% over 1958. Thus, In-Patient Service developed a gross operating deﬁcit of $200,826 for the year in spite of an increase of $4.00 in the per diem rate paid for indigent patients by the City of New York as of July 1. Without this increase, this loss ﬁgure would have been appreciably higher, since 75% of our In-Patient Service (50,000 patient days) is assigned to indigent patients. Most of our deﬁcit both for In-Patient and Out-Patient Services was met by a grant from the Federation of Jewish Philanthropies of New York, while an increasingly large deﬁcit is being met by our own trustees. Our Board of Trustees meets the operating deﬁcit for treatment and training programs as well as for research, which is their sole responsibility. As we continue to put more and more of the Professional Development Program into action, our gross expenditures for the In-Patient Service will continue to out-run foreseeable increase in operating income. Closest integration of planning and effort between the hospital administration, our Board of Trustees and the Federation of Jewish Philanthropies of New York can lead to construetive solutions of the support problems which lie ahead during the next few years. The most potent ingredient of such integration is close agreement as to the hospital’s goals as they have been expressed in the programs promulgated by Dr. Robbins in 1958 and 1959. These goals promise the provision of the highest attainable level of patient care and are so incontravertible, that they must stimulate all concerned to meet them in spite of the difficulties to be encountered. The growth of the professional programs must be accompanied by parallel development of administrative services. Careful application of sound administrative procedures to every phase of all of our programs will tend to make these programs more effective and to introduce elements of management that can decrease cost without impairing service. During 1959, Mr. Samuel Davis joined our staff as Assistant Administrator. We willnow be able to plan for increased appli- cation of administrative processes in the professional areas. More time and effort will be available for improvement and intensiﬁcation of personnel administration. An important function for administration during the next year will be to develop major projects in conjunction with Dr. Robbins and the professional staff and appropriate board committees, a master plan outlining the physical development of the hospital for at least ﬁfteen years ahead, a survey of existing plant and buildings and a comprehensive site plan leading to the development of a research building and an activities therapy building. The hospital’s administration will continue to maintain constructive relationships with community agencies such as the Nassau County and New York City Community Mental Health Boards and the various co-operating social agencies, as well as Long Island Jewish Hospital. Efforts to intensify and improve the areas of co-operation will continue. The board has already authorized the creation of an effective public relations program which will lead to wider and more productive community participation in the life of the Hospital and greater usefullness of the hospital in the life of the community. The task of administration during 1959 has been a great one. None of our accomplishments and none of our plans for the future would have been possible without the devoted and intelligent assistance of the department heads who worked so closely with us. It is therefore more than appropriate to state that Mrs. Angelina Canavan, Dietitian; Mrs. Dorothy Croghan, Accounting Supervisor; Mrs. Lillian Dailey, Ofﬁce Manager; Mr. Thomas R. Lumley, Superintendent of Buildings and Grounds; and Mrs. Sarah Travers, Executive Housekeeper supplied the basic day-to-day services which provided an essential foundation on which professional programs are built. They worked unceasingly with sometimes inadequate staff, to meet the challenge presented by the growing Professional Development Program of the hospital. 21 �The following professional and nonprofessional employees supported the treatment, training and research goals of the Hillside Hospital in 1959: PROFESSIONAL Biochemical Research Dr. Vivian Goldenberg Grace Kittel Susan Rea Dr. Bernard Searle Daniel White Creative Therapy Edith Zierer Dental Technician Sheila Berger Experimental Psychiatry Romeo Cartolano Dr. Robert Kahn Eric Karp Dr. Donald Klein Jean Kolodny Dr. George Krauthamer Hanna Mosquera Dr. Max Pollack Dr. Nathaniel Siege] Intramural Clinic Laura Zaves Laboratories Theresa Midulla Medical Librarian Ellin Resnick Nursing Service Registered Nurses Frances Anderson Susie Mae Behlmer Marie Caﬁero Kathleen Cliggett Mary Cressy Mary Ann Dalton Ann Dispensa Jean Hendry Nancy Jeff eries Mary Jones Sandra Kraner Grace Lyons Eleanor MacPhillips Flora Mae McCartney Catherine McCormick Helen Murray Yolande Paquet Lorraine Schaeﬂ’er Helen Schippicase Rose Schulbaum Suzanne Smith Barbara Steinbach Zurline Thornhill Edith Titolo Anna Urbach Helen Ziegler Licensed Practical Nurses Alma Clinton Mary Corrigan Hope Fox Theresa Howard Alice McDonough Isabell Pierce Rosemary Stevenson Gloria Swan Catherine Wall Delores Williams Psychiatric Aides Martha Adams Olga Allen Marion Bell Patricia Bell William Black, Jr. Beatrice Blake Annie J. Bond Joseph Britt Lawrence Burger Frances Butler Sylvester Campbell Frederick Coley May Conrad Teresa Cooney Naomi Cotter Hugh Cracker �Catherine Eames Annie Ervin James Faulkner Janie Ferguson Marion Flood Irish Ford William Godett Margaret Griller Katherine Hammel Mabel Harper Linda Hart Pauline Hawkes George Heller Sandra Heller Lawrence Hood Alberta Hopkins Ellen Kennedy Joan Kelley Asalle Kirby Carole Kornfeld Doris Kraemer Josephine Lafayette Ernest Lambert Grace Lau Leslie Lee Miriam Lee Alice Leliukevicz Ella Mae Leonard Lillian Leslie Anna Lewin Georgine Lohman Ellen Long James Merrill Edith Minor Bertha Monroe Helen Olsen Clemmie Palmer Elizabeth Rodriguez Barbara Sang Lessie Mae Scott Samuel Scott Mildred Shaw Nancy Smith Virginia Smith Marian Thomas August Tosi Martha Visalli Catherine Williams Thomas Wolf Anna Wolfberg Leon Wolfberg Edgar Zephyrine Occupational Therapy Karen Beutlich Joseph Chase J udity Conrad Laura Dunlop Martha Ittelson Mona Jones Deanna Levine Mary Marrone Doris Metzger Helene VViller Pharmacist Robert M. Frank Psychology Ira Rosenblatt Dr. Allan Sapolsky Dr. Stanley Schiff Charles Silver Dr. Felix Steiner Leonette Vanderhost Florence Volkman Social Services Case Work Division Ida Baumstein Anne Connery Barbara Fishman Robert Fishman Beatrice Freeman Evelyn Furman Sally Gold Regina Goldstein Selma Hornstein Sarah Klionsky Sandra Match Anita Mehr Sylvia Riback Esther Sanders Lita Schmidt Seymour Silverberg Sylvia Solovey Gisela Tauber Lewis White Group Work Division Aaron Beckerman Frieda Bradlow Denis Dryden Judith Duﬂy Edward Fitzgerald Geraldine Lauter Eli Saul Levy Evelyn Mason Naomi Miller Holmes Morrison William Pressman Frances Rubinstein Philip Schwartz Virginia Zaremba NON PROFESSIONAL Accounting Department Arline Fleischmann Lillian Ingber Henrietta Lyons Ethel Siegelman Jeanette Silver Dorothy Strier Buildings & Grounds Erich Brau Walter Foley Frank Groene William Hannigan Robert Hill George Loblein Nero Moyd Stanley Novak Edward Reeder Frank Reinlein Walter Roland, Jr. William Roland, Sr. John J. Rose Albert Schmid Joseph Seagren Albert Senese Dietary Services George Canavan Francesco Cannetto Emma Casamassima Flozell Clarke Hubert Cooke Thomas Duncan Arthur Dywer Pardo Faro Elaine Fields George Fields Alphonse Gross Ella Jacobs Fred LaBarbera Alfred Lemaire Gaetano Mandala Arthur Martin Ida Novick Martin Novick Gaspari Orlando George Perreta Arthur Pitts Walter Rodney Eva Schwartz Broadie Taylor Thomas Tucker Ester Watkins Leroy Watkins Housekeeping Cle Anderson Betty Bruckman James Cuozzo George Czinczinger Stanley Durant William Garland Fulgencio Gerena Nathaniel Glover Joseph Hope William Hyman Robert Jones Harry Lewis Charles McLeod Richard Newton Roosevelt Mitchell PROFESSIONAL AND NON PROFESSIONAL EMPLOYEES Dorothy 0 ’Berry Arturo Orengo Booker Richardson Rafael Salazar Agnes Schuster General Walker Ray Warren Blanche White Oﬁice Services Irene Attinson Celia Bernstein John Borgner Janet Bowie Diane Brafman Manuel Brown Irene Dinkin Claire Dubin Regina Freedman Lillian Freifeld Norma Friedman Edward Golove Frances Gullo Adele Harris Sylvia Hymowitz Joan Kase Edna Kappes Yetta Levitt Inge Mai Sylvia Marcella Fradele Marcus Yetta Mintz Catherine Muﬁ Dorothy McClary Margaret 0 ’Connor Mary Pignoni Gloria Podrid Frances Roth Joseph Ryan Dorothy Saults Charlotte Sinovoi Miriam Slater Jeanette Sobel Edna Telesca. Walter Theisen Edna Weissman Lotte Wollman Blanche Zaitz 23 ��HILLSIDE HOSPITAL is licensed by. . . . . The New York State Department of Mental Hygiene. is approved for resident training by... . . Council on Medical Education of The American Medical Association The American Board of Psychiatry and Neurology. is accredited by . .... The American Psychiatric Association The Joint Commission on Accreditation of Hospitals is a member of..... The American Hospital Association Hospital Association of New York State Greater New York Hospital Association Greater New York Fund The United Hospital Fund Welfare and Health Council of New York City The National Conference of Jewish Communal Services cooperates with. . . . . Adelphi College Altro Workshops Federation Employment and Guidance Service Jewish Community Service of Long Island Jewish Family Service of New York Long Island Jewish Hospital New York City Board of Education New York State Employment Service New York State Department of Vocational Rehabilitation Queens College of the City of New York is a participating hospital IWhIle no precnse form ..... and Related Facilities for essential for making a valid bequest to HIIISIde Hospital, the following may be used: give to the Society of the Hillside Hospital, the sum of $ TheHospitaICounciIof Gr t rN wY rk HI::;DEeHO:PITAL I ISAMEMBER OF . . . IS . . . . . , I land or any specn‘uc property, such as bonds, stocks, etcetera, IS given, a brief descrlpH tion of the property should be inserted instead .of the phrase "the sum of If . . . . . . $____. THE FEDERATION or JEWISH PHILANTHROP'ES' �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Progress and annual reports; research activities (folder title). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-007 Date A point or period of time associated with an event in the lifecycle of the resource 1960-1963 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Hillside Hospital Annual Report (published copies), 29th, 30th, 31st, 32nd; Hillside Hospital A Report of Progress, 1960/61; Letter; Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/e06d90c86c34900cbfbc862c755d6567.pdf 15ada951bb078ffb8bea42b5be5e0745 PDF Text Text IV: 10/113/60 Experieeutel Peyehietrie Presreue et niiieide neepitni A The Review veeieue prostate in the Department at Experineetei W Psychiatry have been devoted to en undereiending e: the node at W‘iherepiu “tie: or thrush undies or hreiu taxation. the principal techniieel have been edepted tree deeoriptive peyehieiry, uenrepeyehoiexy, electreeeeeyheiecrephy, linguietiee, phereeeelour, end eeeielecy. In initial etudiee It reaction were round cenvuleive iterepy. ehenzee in brain it reiete beth to iepreveuent retinge end to pro-treatment peyuhelecic variables. in our enderetendin; e: ceevuieive therepy develeped, e centre: neerephyeieiezio-edeptive view e: eaeetie therepiee eeerted ( ). In this Suuka» view psychiatric treeteente ereﬁtherepeutieeiir exteetive to the degree that brein function in nee-trebly’eitered. While ehense in brein tenetien neeeeeery to: behavioral change, the irpe e: edeptetiee, it however, veriee depending upon pre-treeinent peyoheleuiigend eeeieiecieag charecterietiee er the subject. Thee, the node at eotien ie not eeen ee eiiher 'ercenic' er 'peyehelexie' bet tether ee the intereotion at both eepeete in the individeel. further, while behevierei change in �-2- ralatad to chanson in brain function; and the adaptiva pattarn to paynhologiéﬂoharaatariatic!t praotraatnant avalaationa at 'inprovaaant'; baing spacial typan at avalnatian or ahanga, ara darivativa Jadgnanta baaad an start and tanily anpaatatiana and talarannaa. Thin hypothaaia was dovalapad and anatainad in a aariaa at atudiaa at onnvulaiva therapy. concurrant atndiaa of insulin tuna indicatad that behavioral changa hora, too. van ralatnd to tha anaat and dacraa o: prolancad cana a: rapaatad aaiauraa - than. bainx tho nanraphyaialogiélnhanaa nanixantatiana at principal prolansnd in thin thanany. Tho node at action of tha nan paychetroyic asanta anpraaaad within thin hypothaaia ( aganta would III all. ). It ran anxgaatad that thaaa b. attactiva to the dasraa that tho: indnaad paraiatant chanxaa in brain fanaticn' and that tha typa a: bahavioral raaponaa vanld ha ralatad to tha type at brain nhanza, and to pranorbid pnyehaloxigﬁ(para¢nality) pattarna. rho praaant proxrann in tha Bogart-ant an. danisnnd to atndy than. ralatianahipa in datail. Canvnlaiva Tharazz Prooana or variaua anaanraa at brain tnnatian, tha anannt of slow vat. activity in tho alantronncnphalacran and cantabnlatory and �-3H dontal languago pottorno attor aaohorbital ( ) oonottivo indiooo in oonvaloivo thorany oohaoeto. voro tho aoot In tho firot oxporioont, improvooont ratings ooro round to ho oorrolatod dirootly with tho appoaranoo or high dogrooo o: ohango indicoo ( ). 1n thoao rhooo oboorvationo woro tootod in a douhlo-hlind study in which pationto rotorrod for olootroohock woro randoaly ao~ aignod to coorooo or oithor oonvuloivo or auboonvoloivo thorapy undo: poutothal pronodioation. nigh dogrooo o: nourophyoiologie ohango ooro oboorvod only in tho aonvoloivo group; improvonont ratoo significantly highor in this group; '02. and than oubconvnloivo oohjooto uoro ro-troatod by convuloivo appliaationo, tho improvoaont rota was oinilar to tho original convaloivo group. In tho oihconvnloivo troatod oahjoota, oonoidorahlo anonnto o: oloetrieol corront paoaod hotwooh tho hitouporal oloetrodoo. It woo ooncludod, thorotoro, that tho thoropoutio agont total oloctrioal curront, or no, but an all woo not tho or nono quality aahitootod by tho grand nal ooiouro. rho otgniticaneo or tho grand nal ooiouro was turthor olahoratod 1n otudioo of tho inhalant convuloont, hoxatluorodtothylothor (Indoklon). 31-11ar dogrooo o: olootrographio ohaugo, iayrovoaont ratoo, typo: o: bohavtoral �‘hV, change and ohanxee in neuropeyohologio teak behavior were obaerved in the inhalant and in electrically treated :ronpa. It nae anon apparent, however, that not all anbjeote aaniteetin; high decreea of physiologic ohanga were rated on 'inproved'. In a deeoriptive typelogio atndy, rive patterne were doeoribed, eaperioally teraed ‘enphorio', 'hypoaanio', 'eoaatiaetien’, ’paraneid-Iithdraval', and 'panio'. While the tirat adaptive aedea were ratod ae 'nnoh inproved', the aeen ae ‘uniapreved' or 'verae‘ ( two or latter theae two were ). In etndiee of peyoholegio variablea, it nae reported that patiente rated ae 'anoh inproved' and ’reoevered' frequently aanireeted peraenality patterne similar to that deeoribod by Heinatein and Kenn ( ) an the explicit verbal denial personality. In language patterna, they expreeeed the language of denial, when dittnae brain change denial, was indnoed, exhibiting anoh aepeote an niniaiaation, diaplaoenent, oliohee,|g§g. aere treqnontly than unimproved enhaeote. high I Stale eoore ( Other indioee related to favorable ontoeae were ), and Rorschach deterninante or color, abeent aoreaent and abaent torn-oeler ( ). alao, :avorable ontoeae nae aaaooiated tith lea In thin population, educationalaohieveaont �and revels: birth ). ( Antlehellner lea and Convalelve there Seeking a way EEG slew wave eae given te eucaent the degree at peet-oeaveleive activity, an inn-anneal: at antlehelinercle cenpoand, diethaaine, vex-1e“ “sea at the eemalelve therapy preeeee. Contrary to expectatlene, diethaaiae eaueed an iaaedlate and entrained decreaee in EEG alerting. Patleitl with dental language patterae rellnxqalehed than; Instead of euphoria and well being, the eibjeete were irritable, anxieue and expreeelve a: nre-treateeet patterne. In eubjeete prior to cenvuleive or drug therapy, elethaalne induced exciteaent, tenelen, anxiety and lllaeery eeaeatlene. Sabaeqeent etadlee with ether eentral antlohelinerglo oeapeeade (VII-2299, JB-318,336, beeaetyaine) abated behavleral and electrezraphle patterns alaalar te diethaelae. Stellar deeynohrenieatien a! peet-eenvulelve EEG aleeing wee aleo noted with central eynpathealaetie hallucinogene (euphetaaine, aeeoallne, LSD-25). and baa been reported re: antihietaainee (dephanlydraalne). Theee obeervatlene led to the eaageetlea that an increaee in central ehellnergie activity eae a biocheaieal haste tor the eenvalelve �therapy process ( ). Pszshotrogic Drugs and During EEO this period,the drugs aroused interest. node of action of newer psychotropic Following the concepts derived from convulsive therapy, the neurophysiologis ohenges induced by drugs were tested within the experi-ents in an EEG Ill. experimental setting or acute setting. It was observed that phenothiasines (shlorprolasine, pronssine, triflnepronasine) induced isation and a shitting o: the spectra: to the ERG synchron- slow frequencies; leprobanate and barbiturates , en increased synchronisation and a shift of spectra: to fast frequencies; reserpine, an inoreased slowing with synchronisation at low dosages, and desynchronisatien at higher levels. Inipraaine induced desynohrenisation with a shift of frequencies to the slow bands. Other experinental oonpounds tested included phenyltoloxaline (Bristol), Deaner and (liker), wx-21h9 (Wyeth) and its vsrions BL-HlBB and oongeners trenquel (nerrill). For eaoh, no consistent electrographis.patterns energed. It teens use suggested that psychopharnaoelogio agents provide a ‘lr eliciting a variety or nenrephysielogio patterns in �.7contreet to the eingle pattern of induced oonvuleione. Furthermore, the typo of neurophysiologie alteration, ee reflected in synchrony and Iroquoooy petterns, or hehoviorel edoptetion. elow :roqnonoieo wee Inoreoein; EEG related to epooirio types EEG eynohrony and e shift to or. oeeooieted with trenquillisetion, eedetion deoreeeiog ogitotion; while deeynohronisetion and e end shift to test frequencies in eeeooieted with oxoitenent, illusions, end delnlionol idoetion. These observations orooeaeietont with hypotheeoo or Hikler ( ). The merit of such teohaiqoeo for the eeeey or psychotropic agents hoe been doeorihod ( ). new �-8Pszchcpharaacologz Evaluation Prograa The present pregraa, instituted in October 1959, is based these studies and is on designed to answer the following questions: Is there s relation between aeasurable alteration in brain function and behavioral change with psychotropic drugs on chronic administra- tion? Are there pre-treatasnt clusters of psychiatric, physiologic and psychologic variables related to the type of behavioral adanptation? - to the type and degree of physiologic change? Method: is an initial approxiaation, fixed a double-blind, dosage rendoa assignment drug study was undertaken. Based on clinical experiences with various psychotropic coapounds, three classes were selected on the basis of their patterns of :30 response. ‘The selected agents were those eith predoainent desynchronicing patterns; synchronising and slowing; or niniaal or no effect. Patients referred for drug therapy, after medical examination, and after all other medications have been discontinued are randoaly assigned to one of three classes of compounds. Patients are predoainantly middle class, urban, with high educational attainment. Hillside Hospital is a non-profit, philanthropic supported psychiatric institution, admitting voluntary �.9patients for extensive psychotherapentic treatment. of stay is seven months. are prescribed by Kean duration Convulsive and psychotropic drug therapies star! psychiatrists on referral to the Department. All treatment is adninistered by Departaental start, so that the experinentsl variables or drug dosage, route of administration, assignsent to groups, 333. are readily controlled. All patients in the hospital are available for study. all patients receive After a testing period, ho cc of medication daily tron individually labelled bottles. increased in fixed weeﬂy etepe until a nsxiaua at date, 1&0 the study period. Dosages are After weeks. reotestinz occurs. two weeks on maximum dosage, To h liquid subjects have been referred, and 110 have completed Preliainary analyses of the data are new in progress 0 avieral Chan e5 In a survey or the behavioral adaptations of patients receiving phenothiazines er iaipranine, various clusters at behaviors were developed. The typology was based on the pre~treatasnt psychiatric the treatnent reepenee and profile. In the present study, various measures of behavioral change are under study. Therapist referral questionnaires and six week evaluatione; therapist and �-10- patient two Clyde Heed Scales; Lorr Scale evaluations in interview by research psychiatrist, and Lorr ward scales; patient eelta ratings including the Johns Hopkins synpten check list and the Chicago Attitude Scalee are ancnget the neaenres being explored. lenropezchelcgz: Paychelcgic tasks are viewed both as change variables and predictive variablee. In convulaive therapy, changee ), tactile perception in aencry tasks ( ), crr ( ( or figuree ( ), rignre ground tasks ) have been ( ), Recheler«3ellevne ( and tachietcecopic recogniﬂcn , ) related to the degree of induced neuro- For each task, the degree or decrement in physiologic change. taek pertornance has been positively correlated with the amount of EEG slowing. lollcwing treatnent completion, with the return of physiologic indicee to pre-treatnent levels, performance in these peychclcgic taaka also returns to prewtreatnent levels, or higher a betternent of performance ascribed to practice eitect. Denial scores on interview ( ), Rorechack deterninante ), 1 ), auditory feedback ( ),and perception of the visual upright ( ) have been viewed ae predictive indices of the behavioral changes following nor. various tasks are new ﬁbeing Scale scores ), language patterns after ancbarbital ( ( ( Theee asseeeed with paychctrcpic agents. �.11. In the convulsive therapy studies; the lieetreencezhalogrsghzs degree of EEG slowing was measured by counting the consecutive waves in selected samples. were studied, it was When the more subtle changes or druggeftects necessary to apply less tediens techniques. Electronic frequency analysis was introduced in August 1959. By asasurenent e! the pen deflection for various frequencies free 3 to 33 cps in ten second epochs, rapid aeasnreaent of apparently saall changes in total activity and and frequency spectra are not obtained applied. Other physiologic variables include the response of £30 to intravenous chlerprcnasine; blood pressure response to sechelyl; EKG; radioactive iodine uptake, and analyses or various blood and urine element ordinarily conceived ac protective of the patient'e welfare. �Pnzghuliggualtion: rollcving thy studios at syntgotio Iguanas. pattorns ( ) in oonvnlntvo thnrspy, 0th.: anpoctu or Innguagc cﬁndind for worn their ralatiou as 1361... st «hung. in intrnporlonll with nonltdurabln nun: .xplarctlou attnr bcinvior. attic, (1T3) thn‘ typewtokoa-rutio augxoltod 11:;«1-t19 nounurOI, or connoautivo 33-pin: a: dyldic apcoch 1.: bu A useful lunar. tppliud to writing toxta or tho Hull. ran had previously buon hung. nmlu ¢ individuals, Jute intuit-d ﬂat the two index (dyad) at a ounnunieutioa an: sicniriuant not. portal tho ltttc at tho intaraction than snnlytcn or ltplrt‘. Innplnn or the participantl. tpplytn; ‘htv technique to couralsivo tiara»: pntiunta, august: in ran nonn and atnndnrd deviation worn rclntod both to tn. dogroo 0: induced use slow vuvo nctivity and to lyutaatic lan‘unxa puttorns obtained in indop-ndoat structurod iutcrvicvnc Bpocch boa... new. rupctttivc (lovarod nag: 223) and Iowa vurttblc in connocutivo canplou (inoronnod standurd dovistion) ( ). �In tnttrvidvt tutor. &nd aft-r 8h. intravunoul administration of coutrully .ctivo ngcnta, 11-11;: chtnguu rare obaorvtd. Axtntu with a prcdauinnnt lynehronisatiou ptttorn tn. on EEG uxhibttod n docroaao tn tutu 218 and inarcuao in Itnndtrd deviation or soorcs,vh11n ataynchroniliag compounds olicitcd grnttnr variability in apooch pa‘torus (lﬂOrOll. in and accrual: 13 varidbility at conntnntivo 133 noun) neuron (doeronlo 1n It;adnrd dcvistion). 0th.: 1:33:33. nasuuroo under study includu dintronln r0110: quottontl, colt-rotoronco, tad potion. It 1- aucxoutod are potont tuchaxquos to: and poyuholusie ultorttioa 1n tuna. and that than. paycholinsutstte nut-urns ﬁho operational unnlyiun a: phylialogta crises: at payohopharnuoologic acunta C ). �aotiolg‘io Studio: 2h. cuncral prdbiun 0: tbs rolatiuu at liaitl tautarl to choico tad rocuitu o: parchiatrio troutucnt. and tho Ipoeitic prdblun at tho rolnticn at it... taatars pittcrnn, within tun instieutioa. and to a cutie: at population ), uduoatiun, ago. place a: birth In on: tinny ( utmdioa. 13d ta in. rorcrrul learn .3 tau California I nail. var. nixnitieuntly rciatod to thc type .1 thnripr roe-iv'd ind tho utiliuntion o! ndaunctiv. hoapittl nitric... ndnantod hid paiinntl uh. var. old-r, poorly Than, night: I acorou und warn tar.i;n-horn, pnrtieuinrly Einicrn lnropo, utro ngat 11301: to be rotorrtd fur oloctro— shook. Thou. rnlntianahipl were pro-nail: iudupondcut a: diagnnlol. within tho crunp at cloctrolhock putiontl, rottrrnl {or In rclltod to 36? vac .100 g cocond Iﬁuuy at this tin. tor in... factora. group ( ). durstioa or hospituliaation, dilohurxu ovuluutina and dincnoa¢n wars :0lniod to the can. 000111 taetcru. Fur «suspic, patiunta hoapituliuod tar Sh. Ihnrtolt patina var. oidoat, had thi icast oducution, war. nest likely to hivc and had in. high I again boon tornign born scar... titular, nativoaborn, str- �uduoatod, lunar 1 real. Ilﬁrl pttiontn v'ro hospltnllscd tho lnagost. Inn's rolttsonuhipl bald trnu within tronincnt typo and had thn rithln diutunaﬁao 31330. On allohurxo, .14.: pttttutu not! tavurubli rttlngo. In not, valiant. rutad ti rooovcrod or IIOh luprovnd htd thq hlxhott F scarce, lunat odnuuttou :ad var. acct likaly to ho rarclxn born. In a study at patlont rtrulal a: 30!, 01:11.: ro- lutlonlhtpu wort obncrvcd ( ). that. rolgtlounhlpi If. no! undo: ntndr in tho out-pttlantxdopartnoat, sad in a trlw hospital cunpnrattvc Itaay. In tn. lnttor Itudr. th- population! or thrco hunptlalc in which :11 thrupltu are equally arullnbla to all p¢tluata, - sonniugor roundatlau lllplttl (Ippir-cltll, Protoltant), nascaohau-ttn unnttl Xcslth c ntnr (lavdroclnao Catholla) and 3311314. noopltll (nlddln-clnnn Jalluh) boin; alaoaacd. It but Etna postulntod that lhunc rcl:t1¢ulhlpl rctlact tho tntlncncu at .00131 bunksround on plynhologlcnl pronoun, nah u hubltul undo: at axprcsslon. tho putt-tn a: nontal action tr. undo: Ir. ”turn or Th. onutwibution emulation um 0: than. tactorc to antaru tho tad patsont-thtrnpttt lllnsal, atlﬁr. �Exporinuutal Plyohiatrio Progr;ul nt Hillside ﬁespitnls A Max Review rink, H.D. the Depurtneut of Experimental Psychiatry, Kill-id. Hospital, Glen Oaks, 1.1., l.I. From V: 11/60 �v: 11/22/50 Experimental Psychiatric Prograns at Hillside hospital: A Review various programs in the Department of Experimental Psychiatry have been devoted to an understanding or the node of action or psychiatric therapies through studies or brain function. The prin(ipnl techniques have been adapted tron descriptive psychiatry, nenropeychelcgy, electroencephalography, linguistics, pharaacology, and sociology. In initial studies of convulsive therapy, changes in brain function were found to relate both to evaluations of improvement and to pro-treatment peyohologic variables. is our understanding or convulsive therapy developed, a general neurophysiologicadaptive view of soaatic therapies emerged ( l ). In this view psychiatric treataents are therapeutically effective to the degree that brain tnnction in measurably altered. While change in brain function is necessary for behavioral change, the type of adaptation, however, varies depending upon pro-treatment psycholozic and sociologic characteristics of the subject (2). Thus, the node of action is not seen as either 'orgenic’ or "psychologic' but rather as the interaction of diffuse neurophysiologic changes and adaptive mechanisms. further, while behavioral change is related to changes in brain function, and the adaptive pattern to pre-treatnent psychologic characteristics, evaluations of 'inprovenent', being special types of evaluation of change, are derivative Judgments based on start and {anily expectations and tolerances (2). The �-2... amine series "or studies of convulsive therapy. concurrent etudiee of ineulin ccna indicated that behavioral change here, too, was related to the onset and degree e: prolonged cone or repeated seizures - these being the principal aanitestatiens or prolonged neurophysiologic change in thie therapy (3,h). The node of action or the new psychotropic agente was also expressed within this hypothesis (5,6). It use suggested that these agents weuld be effective to the degree that they induced persistent changes in brain function and that the type or behavioral response would be related to the type of brain change, and to preeorhid peycholegic (personality) patterns. the present prograne in the Department are designed to study these relationships in """""'m. hypS‘iEiSii‘ﬁ; a.‘+‘¢i3§.ia'gua‘ .. .. «'WIfahlr‘ehnebtn ”1.5"; detail. GOHVVLSIvg IBERAP! PROCESS or various neaeuree of brain function, the aecuut or slow wave actiéity in the electroencephhlcgraa (7,8) and contahulatcry and denial language patterns atter anoberhital (9,10) were the sensitive nest indices (11) in convulsive therapy subjects. In one experieent, improvement ratings were correlated with the appearance of high degrees or change in these indices (7,10). These observations were thsted in a double-blind etudy in which patients referred for electrcehcck were randomly assigned te ceureee of either convulsive or subccnvuleive therapy under pentothal prenedication. High degrees of neurophyeiclcgic change were observed only in the cenvuleive group; improvement rates were significantly higher in this grog); and when snbconvulsive subjects �-3- epplicetiene, the inprevcnent rete wee sieiler tn the originel convulsive group (2). In the enbccnvnleive treeted subjects, ceneiderehle emanate er electric current pessed between the bitenperel electrodes. It sppeered that the therepeutic egent use not the totel electrical current, ger es, but en e11 or none quelity eenitested by the grend eel seizure (8,12). the significsnce cf the grend eel seizure wee exenined in studies of the inhalant ccnvnleent, hexetlnorodiethylether (Indoklon). Sieiler degrees at electrogrephic cheese, iepreveeent retes, types at hehevicrel change end cheeses in nenrepsychclegic tesk behevier were observed in the inhelent end in electricelly treated groups (13). It wee seen epperent thet net ell subjects lenitccting high degrees 0: physielegic chenge were reted es 'iepreved'. In e descriptive typelegic etndy, rive petterns were described, eepirieelly tereed 'enphcric', 'hypeeenic', 'seeetieetien', bereneidovithdreeel', end 'penic'. While the first tee of these edeptive nodes were reted es 'nuch inpreved', the letter two were seen es 'uniepreved' er 'ecrse' (It). In stndiee of psychelcgic veriebles, it wee reported thet peticnts reted es 'ench improved' end ’reccvered' frequently menitested perecnelity petterns siniler to thet described by Heinetsin end Kehn es the explicit verbel deniel personelity. In lengnege petterns, petients expressed the 'lengnege or deniel', when diffuse brein chenge wee induced, exhibiting such aspects es explicit deniel, nininisetien, displeceeent, cliches, etc. eere frequently then nniepreved subjects. Other indices releted to revereble were re-treeted by convulsive �4,ontooae were high 1 Scale ecore (15), and Rorechach deterrinante or color, absent movement and abeent torn-color (16,17). In thie population, also, favorable outcome wee aeeociated with low educational echievenent and foreign birth (18). ilfICXOLIEERGIO courovlnc one GGIVVLSIVE 2323‘?! Seeking a way to augment the degree of poetoconvnleive activity, EEG anticholinergic compound, diethasine, was given intravenously at variene stages of the convulsive therapy proceee (19). Contrary to expectations, dietharine caused an innediate and sustained decrease in EEG slowing. Patiente with denial language patterns relinquished then. Inetead of euphoria nelow wave and well being, tho on ethecte irritable, anxione and expreeeive of pre-troataent patterne. In subjects prior to convulsive or drug therapy, diethaoine induced excitement, tension, anxiety and were illusory sensations. Snbeequeht etndiee with other central anticholinergic coapounde (WIH-2299, JB-318,336, benactycinc) ehoued behavioral electrographic patterne eiailar to dicthasine. Similar deaynchrenination of poetaoonvuleive EEG cloning wee also noted with central eyapathoniaetic hallucinogene (amphetamine, neecaline, LSD-2S), been and hae reported for antihietaainoe (diphenylhydraaine). These obeervatiene led to the suggeetion that an increaee in central cholinergic activity wae a biochemical basic for the convulsive therapy proccoe (20). and PSIOROERGPIG DRUGS AND EEG this period, the node of action of newer psychotropic aroused interest. Following the concept: derived from During drnge convuleive therapy, the nenrephyeiologic changes induced by drnge �-5- tested within the sane acute experimental franework of the EEG setting. It was observed that phencthiacinee (chlcrpronazine, proaasine, triftuopronanine) induced EEG synchronisation and a shifting of the spectra: to the slow frequencies; neprebanate and barbiturates, an increased synchronization and a shift of spectrum to fast frequencies; reserpine, an increased slowing with synchrono isatien at low dosages, and desynchronizaticn at higher levels (5,6). Inipraaine induced desynchronisatien vith a shift of frequencies to the slow bands (21). Other experinental oerponnds tested included BL-H188 and phenyltolexaaine (Bristol), Deaner and its various cengeners (hiker), wr~21h9 (Wyeth) and frenqnel (Merrill). For each, no consistent electrographic pattern was recorded. It was suggested that psychepharnacclogic egents provide a means for eliciting a variety of neorophysiclogic patterns in contrast to the single pattern of induced convulsions. Furthernore, the type of neurophysiologic alteration, as reflected in EEG synchrony and frequency oatterns, was related to specified types of behavioral adaptation. Increasing EEG synchrony and a shift to slow frequencies were associated with tranquillisaticn, sedation and decreasing agitation; while desynchronieation and a shift to fast frequencies was associated with excitement, illusions, and delusional ideaticn (6,20). These observations are consistent with hypotheses of Wikler. The advantages of EEG techniques for the assay of new psychotropic agents have already been reported (6). were V �-6PSYCHOPHARHACOLOGI EVALUATION PROGRAM besed on present progree, instituted in October 1959, is these studies end is designed to ensver the following questions: Is there e reletion between eeesureble elteretien in brsin function end behevierel chenge with psychotropic drugs on chronic edninistretion? Are there pre-treetnent clusters of psychietric, physiologic end psychologic veriehles releted to the type of behevierel edsptetien? And, ere such clusters related to the type end degree of physiologic ohenge?Method: is en initiel epproxinetion, e double-blind, fixed dosege rendon eseignnent drug study wes underteken. Besed on our clinicel experiences with verious psychotropic coeponnds tree 195k to 1959, three clessss were selected on the besis of their patterns of EEG response.' the egents selected were those with either predoeinent desynohronising petterns, synchronising end slowing, or mini-e1 or no effect. Petients referred for drug therepy, etter nedicel exeeination, end etter ell other eedicetions heve been discontinued ere rendonly essigned to e conpennd in one of these three cleeses. Petients ere predominently middle eless, urhen, with high eduoetionel etteinnent. Hillside Hospitel is e nonnprﬂtit, philenthropie supported psychietric institution, ednitting volantery petients for extensive psychetherepentic treatment. The noen duration or stey for petients is seven months. Convulsive end psychotropic drug therepies ere prescribed by stetf psychietrists The �.7. referral to the Departaent. All treatment is administered by Departaental start, so that the experimental variables of drug dosage, route of adainistration, assignment to groups, 232' are on readily controlled. All patients in the hospital are available for study. After a testing period, all patients receive he so of liquid aediestion daily tron individually labelled bottles. Dosages are increased in fixed weekly steps until a aaxiaua at h weeks. After two weeks on maxiaua dosage, ro~testing oeeurs. Io date, 1&0 subjects have been referred, and 110 have eonpletod the study period. Preliainary analyses of the data are new in progress. Behavioral Change: In a survey of the behavioral adaptations of patients reeeiving phenothiasines or iaipraaine during 1958-59, various clusters of behaviors were developed. The typologies were based on the treataent response and on pre—treatnent psychiatric profiles. In the present study, the typologies are being tested, and various measures of behavioral change are being studied. These include therapist referral questionnaires and six week evaluations, therapist and patient Clyde Hood Scales; Lorr Scale evaluations in interview by two research psychiatrists, and Lorr Ward Scales; and patient sel£~ratings including the Johns Hopkins syaptoa check list and the Chicago Attitude Scales. lenrogszehelegx: Psycholozie tasks have been viewed both as ehanze variables and predictive variables. In convulsive therapy, changes in aenory tasks (22), tactile perception (23,2h), WeehslerBollevne (13), CF! (13), figureagronnd tasks (25): and taehistoseopie recognition of figures (26) were related to the degree or induced 0% �.8neurophyeiolegic change. for each task, the degree of decrement in tank portornance was found to be positively correlated with the enount of EEG cloning. Following treatnent completion, with the return or phyeiologic indicee to pre-treatnent levelo, performance in these paychologic tacks aloe returned to pro-treatment levels, or higher - e hetternent of performance ascribed to prectice effect. Denial ecoree on interview (27), Rorschach determinante (16,17), I Scale coerce (15,17), language patterne after anoberhital (28), auditory teedheck end perception of the vienal upright have been viewed as predictive indicee of the behavioral chengee following 36!. Thole veriene tasks are now being eeeeeeed with psychotropic egente, for their capacity to chenge with verione agents, or their capacity to predict change. Electroencephelogrephze In the convnleive therepy etndiee, the degree of RIG cloning nae neaenred by counting the consecutive waves in selected eenplee (7). When the more subtle changes or drug effect- are etndied, it ie neoeeeary to apply leee tedious techniques. Electronic frequency enelyeie wee introduced in inguet 1959. By neaenrenent of the pen deflection for vaﬁione frequenciea from 3 to 33 ope in ten eecond epoche, repid eeeenreeent of apparently enall chengee in total activity and frequency epectra are new obtained and epplied. Other phyeiologic variablee etndied in thie progren include the reepenee er era to intravenous ohlorprenaeine; bleed preeeure reeponee to neoholyl; the EKG, radioactive iodine npteke, end analyeee o: varioue blood and urine elenente. E 5 �PSIGROLIHGBISIIGS series of studies in the Departnent have been devoted to ternal lenguege patterns. Following the etudies of syntactic lenguage petterns (28) in convuleive therepy, other espects of lenguage were studied for their relation es indicee or chenge in interpersonal behavior. darts; otter considerable exploretion with verious linguistic neesures, nuggested thet typeutoken-retioe (2!!) of consecutive senplos or dyadic speech nay be e enetnl index (29,30). While 213 hed previously been applied to written texts or the language senples of indiriduels, Jeffe indicated that the two pereon eonnunicetion (dyed) wee e acre significent index of the etete of the interaction then enelysee or concrete eenples of the participants. Ayplying this technique to convulsive therapy petionte, changes in 21! neon end etenderd deviations were releted both to the degree of induced ERG slow ueve ectivity end to syntactic lenguege petterne obteined in independent structured interviews. Speech heeene more repetitive (lowered nean 113) and nkre verieble in consecutive eenplee (increesed etenderd devistion)§(31). In Another interviews hetero end otter the intrevenous edeinistretion or centrelly ective egente, einiler chengee were observed. Agente with e predominent synchronization pettern on the EEG exhibited e decreese in mean or: and increase in standard deviation of scores, while deeynchronieing conpounde elicited greater variability in speech petterne (increase in TTR neon) end decreeee in veriehility of consecutive eoorss (decreeee in etenderd devietion) (32). Other lengnege neeeures studied included dietrese~relie£ quotients, self—reference, and elteretion in tense end person. �«10- It was luggontod that then. psycholingukatic nonsuroa tr. techniques for the opcrational annlyaoa or physidlagic and psychologic ctr-eta of psychopharuteologic ugcnts (32). potent �.11 .3001030910 STUDIES In the course or these psychiatric programs, considerable interest wee engendered in the tenily organization to which patients returning. Also, the general problem of the relation of social factors to choice and results of psychiatric treatment, and the specific problem of the relation of these factors to the referral patterns led to a eeriee of pepnletion studies. In one study (33), education, ego, place or birth and score on the California I scale were significantly related to the type or therapy received and the utilization of addonotive hospital services; Thus, patients who were older, poorly educated, had higher P scores and were foreignhorn, particularly Eastern Europe, were most likely to he referred for electroshock. These relationships were present independent of diagnoses. Within the group o: electroshock patients, the tire for referral for BC! was also related to these factors; In a second study (18), duration of hospitalization, discharge evaluation and diagnoses were related to the eaae social factors. For example, patients hospitalized for the shortest period were oldeet, had the least education, were most likely to have been foreign» born and had the higher 1 Scale scores. Younger, native-born, more educated, lower 1 Scale score patients were hospitalized the longest. these relationships held true within treatment type and within diagnostic close. On discharge, older patients had the nest favorable ratings. In 30?, patients rated as recovered or much improved had the highest 1 scores, least education and were most likely to he foresighorn. In another study or patient refusal of nor, similar relationships knee observed (3h). were �Theee reletionehipe ere new under etudy in the Out-Petient Depertnent, end in e tri—hoepitel conperetive study. In the letter etudy, the population: or three hoepitele with preveiling differing cliente, in which e11 therepiee ere equally eveileble to e11 petiente, - Kenninger Peundetion Hoepitel (upper-ollee, Proteetent), Hheeeehueette lentel ﬂeelth Center (leverceleee, Getholio) end Hilleide noepitel (niddle-eleee, Jewieh) ere being eeeeeeed. It hee been postulated that theee reletionehipe reflect the influence of eociel beckgrouud on peychologicel processes, such ee hebituel petterne of eennunieetien and nodes of expreeeion. The contribution of these factors to the pattern or mental illneee, end the petient-therepiet interaction ere under etudy. �-13SEHMAB! . on. Dopartnontal programs are a clustor of intsrrslatsd studios toonssod about common population sonplos. Within Hillside Hospital, rosoaroh laboratories in Bioohonistry, and in Hsdieino are aotiro; and other laboratorios in psychodynanic psychiatry aro boing dovolopod. In this Dopartaont, various disciplinos aro participants,rsprssonting a gradual growth of six ysars. Furthsr growth and tho dirsotions o: ensuing studios sro dopondsnt on tho results of tho studios doscribod bars; as wall as tho growing institutional avaronsss that roooaroh is an intogral part or the hospital's operation and budgots - as such as troatnont and staff training. �”lh‘ Reterenaea Authors at the {alleving references include the following staff nenbere: Hex Pink, Hex Pollack, Robert L. Kuhn, Joseph Jette, xertin 3. Green, Eric Kerp, Hyman Karin, Doneld F. Klein, George Ireuthener, Arnold G. Blnnberg, Ittheniel S. siegel, Abrehen Keplen end Henry 1. J. Hillside Reap. 113, 19583 3. J. lééa 18h6, 1958) A Go., 325, 19593 J. Letkewite. 2. Die. Harv. 8:1. 12: Eilleide Heepitel‘gt 13h, 1955) h. J.A.H.A. Q} 197, 19571 5. Pszehozhernecolegz Frontiers, Little, Brown 6. Heuregazehozherneeologz, Eleerier, hhl, 1960; 7. A.H.A. Arch. Neural. Psychiet. 1Q: 516, 19573 8. Die. Kerr. 5:3. 12: 227,19583 9. J. Hillside Heep. g. 3, 1955; 10. Arch. lenrol & Peychiet. 1g. 23, 1956. 11. First Int'l can . leurol. Sc1., Pergenon, 613, 1959: 12. Jeur. Herr. Kent. Die. $29: 117. 19603 13. A.H.A. Arch. Gen.Paychiet. (in press); lh. Unpublished nenneerﬁﬁtg 13. Jenr. Herr. & ' Bent. Die. ggg: 187, 1960; 16. J. leurepeyehiet. 1: 2&2, 19603 1?. Jour. lerv. Kent. Die. ggg. 2h3, 19593 18. A.H.A. Arch. Gen. Psychiet. 1; S65, 1959: 19. A.H.A. Arch. laurel. & Peychiet. ﬁg: 20. EEG Clin. Neurophyeiel. 15¢ 359, 1960. 380, 19583 21. Gened. Psych. Aeeee. J. A: 1668, 19591 22. Cent. Neural. 23. J. Hillside Hoep.‘§: 2&1, 1957; 1g: 88, 19563 2k. Am. J. Psychol. 13: 38h, 19593 25. A.H.A. Arch. Neural g: 5&7, 19601 26. Free. 1? Int. Pezehel., lerth-Hellend, 238, 1959; 1%. J. Heuropeyohiet. 1} hS. 19593 28. Pezehezethelegz of Guaranieetien, Grnne & Stretton, 126, 19583 29. J. Hillside Heep. g; 207, 1957; 30. Psyehiet. 3;. 2&9, 1958. Gong. �.1531. Jour. lorv. Hunt. D13. 120: 235, 19603 Pazchiutric Drug Thorazz, 0.6. that‘s, 29, 19603 3b. Unpublished Hannueript. Boap. g: 216, 195?) 32. ngnnieu at 33. J. Hillsid- �lap-rtnaltal Fuyuhtutrac 2701:... at 3:11:14. luapitcls A title: In: fink, Fran tau ntpnrtuaut ”’F‘ul. 91“ “kl. 7!: U I, 1;!50 K.B. a: sxpurtnuutnl Psychiatry, 1111.14. 10.1.; '0’. �/ [, ‘e VI //y 11/22/60 layoviunntal ruyuhtutrto Procrnnn u‘ [1113140 loapltnlu A Icvtou It. Virtoun program: 1: an. nupartnant of xxpcrtnantal Payoh‘airy 531‘ but: dcvutod to an underttnndtn: of tho sad. at ﬂl‘itl at payuh1n$r1¢ thnruptta through studina at brtiu tunetiun. rho principal inshnign¢¢ invo boon adapted {ran doneriptiv. plyuilutry.vnanrapiyuhology, oloetronnotphnlocrnphy. lingututtcl, phuruaaolﬂtyg and socinlocy. 1n chungoa brats convululvu thcrtpy, at initial attain: functian nova round ta rtlatc both to ovuluution- o: inpruvaucnt In ptywholaciéﬁznrinblca. Al 0‘? undarnttudtnu and to pru~tr¢3tncut or eonvulaivw thcrupy dovelupad, a genera: nouroyhynialozic1 ( usergnd slanttw ). In this via: thorapxos a! vita udtpttvc uiif‘i‘rxplnttonlly thy dogtoo to ottactivo troutueutn payihtntrtu this brain function 13 uncuurahly nl‘nrnd. will. Chung. in brain function 1- noatnsary tar bchuvtorul ch:u¢o, the twp. or nd:p$¢tton, paywhologiédnna hurtvnr, vnrtoo «avoiding upon pro-‘rontncnt Itoiuloxliﬂcharactnrtutio: 02 sh. cuhdoot (2). Thus, tho use. or uotlcn 1. not soon as ulthar 'oralnle' or *poynhologic' but rathcr and chaugua of nourophyaiologio distant tan lattruaticn a. adnptivo 3008331.... turthcr, uh$lo bohtvtirtl chins. 1a rnluted to ohnngns in brain ttnottaa,‘nnd the nanptivt patio!» t0 prt-triatuont psychologte thirtetcricttot, 07:1nat10nu a: ’1Iprovcunat', but»: npuottl $79.! or uvlzuntiou or chnnxo, arc atrtvutivs stagnant. hated an :tatt and £1.11: oxpootutions and inlcrtaonu (2). �n2- ?hiu hypothuain Ill dovulopca and nuntstncd an a £021.! a! ntuditl qt cunvulstvn thnrnpy. ctncurrcnt aﬁudios a: tuuulia can. tnd1¢utod taut hohsvtor¢1 chant. horn. too, wua.r¢1ntod to tn. lutot ind accrue or piniongut can: a: ropaatod stature. - that. b.1uc tho prinaxpul manifestations at proloncod nonrcrhysioloctcaﬂ an that»: (ink). chm: in It: made if aoStoa of tho new pcyahotropio «goat; vac also nithta thin hypothesis (5,6). It nan ouggontod that ﬁhouo tgan%a would ho affectivc to tho 403:0. that ghoy induced paratatant ch:ugau 1a brgtn fanatian and that the typo at bchaviur;l rampaano Inuld to rolttud to tho typo or brain ohaagc, and to prcaorbtd payohologit (paruunultﬁr) patturnt. Tho prisont pruxruan in tin Btpartltat ‘20 4331¢u§d to study th.ue volitianuhipt in unprosuud _d¢tti1. E E III 13‘ £88 a: turtou: nanutrnn at brain tunusiaa, thc alount a: slaw var. atttvity ta ta. cinctrcunoupphagzrin (1,8) tad contcbulutary and 60.1.1 Inasmuch pattora: nttur unobarbital (9.10) not. thu unit uoaca‘:vc that... (11) 1a .0I7‘101VD thorny: subjects. In on. naportnont, tapruvclnnt ratings wire ctrruxttod with the upponrnacc .1 itch dgcrooa or change in thou. inexact (7.10). dtnbin-bltnd 1a 1n abnorvntiana tkntot a a‘udy ”‘2. it... Itiuh patiohta rotorrod for clootrguhock var. rand-n1: nustgncd to court‘s o: otthor ocnvulutvu 0r aubconvulttvo therapy under anurophytlologiénchaagt pqntothnl prcnodtonttal. nigh dugrtul or v!ra obuarvod only in tun convulitvn grnupg inprcvon-nt rutct varnixuitiouutly higher in this ﬁriﬁtj and vhaa subconvuluiv: nubjoeto �U). * v.20 ru-trontad by couVIInivo upyliuutiona, ﬁlo tuprovcnnnt rut. um: lintzsr to the orictual convtlaivt group (2). In the anboouvulaivo treated Inhannta, uuuutdar;b1¢ Quaint. or altntria «arrout yauaca hotuocu tho hitanporul cluotrodoc. It Ipptﬂrtd that the thorupautic taunt wan not tho total cloatrle.1 currunt, aggugg, but an :11 or non. quality nan££.ctnd by thc grand In: lotuuru (8,12). Th. algnittenuao at ﬁhc grand In! I'liir. van~cxan1uod in etudiat of tho inhalant aouvnlsnnt, insurlugrodtothylcth¢r (13692105). ﬁinilur 4.3!... of alsetro~ graphic ehsngc, ﬁngvovwnaut tutti, typos or bghgviortl ahtugo and changes In nourvysyuholoxtiﬂgatk bahavivr nﬁro observcd in tic tnhallnt tn ulcatrieally treatud groups (13). It at. anon npyaroat $hat act :11 tubjaats Ianiroatins high tugraou or physiologxc chnngo warn rttod ts '1npravod'. Ia a dcsaripttva typolngtn study, :31. ptttarna wire doacrihad, impartcnlly turned 'ouphnrlu', 'hypounnio', 'sonlttnatiuu', $0!!ﬂ.1£¢'1‘hdtlﬂl1'. and 'punlo‘. ﬁhtlo the ttrat tun of than. udnpt11¢ .04.: nor: rttud I. 'nugh taprovod', ¢ho latter two were noun as 'Iuinprovvd' or 'uoraa' (1%). In station a: ysyuh01031£#VIrinb1on, it run vaportod that pctxnnta rntcd as 'I‘ch improvud* and 'reaovurad' frequently ltnituntcd puruonnltky puttcrut liuillr ta that diaeribod by ﬁctuutnin and Ink: is ﬁhu laplacit vorbal 4.31.1 pornonality. 'In 1!:zunxo ynﬁtoras, patiantn capraastd thu 'lnazuugu a: doninl', than ditthln brain ohnagc In: Indueca, txhiblttus anon napocﬁa an txpltctt dintsl, Izaiuisataun, ditylne¢noat, cliches, g§g&_uorc traqu.ntly thug untuwravcd cubaoctu. Other 134130: taint-d to tnvorsblo and �.3. hash I 5341. acct. (15), and Roruuhaeh dotarnintnts «Olav, nbsaut novunaat and nbaont t-rn-calor (16,17). In thia popu1&tttn, also, :avurablo outatuu at. taaoctntod with 10v uduaattgnnl uahxuvannnt tad {truism birth (18). tutu... it?! at sitting a way to nuancat tun digit. of pentatonvulitvu :39 $1.! utvu nitzvity, ta anttahozanorciu coupltnd, «totEutzno, was giro: tutrnvonoualy at various :tngos or tht ccavulutvc thor‘py - proutll (19). doa$r¢ry to oxyaetntiaal, ditthnlinc eaunod In lunadiatd and «attained ¢aer¢aan in EEG cloning. Patiunta with donstl lagging. putt'ruu rulaaqntshad than. Inttcud or atphorin aha wall hasng, thc lubjoota vat. irritqblc, anxious and prrO181V. or pramtrnatnnnt patterns. In aubaastv prior ta eonvulaiva a: drug thnrapy, diothantnu andueod uxaitanont, tan-ion, anxiety and illusory nontatsunc. ﬁuhaoqncht ntndica with 9th.: «antral antioholinurutc ae-paunda (VII-8299. 33-318,336g hanaotyttno) aboucd behavioral sad cloctrogruvhlc pattarau elitist to daoth‘xino. atnilnr datynahrontnnttau o: postuconvulaivt 330 niacin; was ‘10. notod with «Mt-'11 amnion-tutu: hunuinnuo (nphounno, «suntan, nan-as). Ind ht: been rcpur‘od for tatihiatantnoa (diphunyihylrauinc). that. thiarvaticnu 10d $a tut mugxultion thtt «a incrtano 1n coutrnl ottltnargia activiiy VQI a btoahouscal haul: for thy convulaivc ttorapr greats: (26). rsmgonauo nma an no During this parted, tho mod. 0: sctlaa cf ucv¢r psychotrepic drug. trout-d intnrnst. rollcving tho caaouptc doravca tron ' J2 otavulntvu ‘harupr, thu nc‘rophgwiologio outage: inanood by drug. �.5... f tutti! I1th1n tun 3.x. aautc oxpcrinautu1 trunnuork at th. E39 usttinx. It It: thaurvod thtt phonothitslnos (ohlorpronasiac, any. prangnlnc, tritanaprolaaxna) :nduood axe ayauhrontauttou and a oh£tt1ng of tho upcetrun to tho .10! frequaaotts; Improbaghtc cad barbiturates, an incrouuud IyuchrnaxsatSOB and a shirt 0: spoctrnn to inst (recitation; roanrpiuo, an Inorouood ulcvtns with Iyaohrouw inattua at . dying... and douynchronisatioa at night! 10'010 (5,6). 2.133.313. tainted ﬁctynohrtnisnttua with a ah1:% ct :rcquauaicu fa the a!” but: (21). ”‘ng Gina: expirtnnatal annpounda tul‘cd inaludod nz~uxaa and phtnyaioltlslino (ariatol), nectar tad its variant aoneaaors (33:99), wtatlh9 (37"h) and trﬁnquol (lorrill). tor cash, an I0|tiutcut olnctrucraphia putters it. recordta. psyuhoyhnrtnollaciéwazoats wgu that staccatod It pruvtd. u nearaphyuiolotiéﬂpat§cran u for of 1a nasal eliciting varicty ctutraat t¢ tho sags}: psttura or induced scavalnionu. furthtrnouroyhyntolugidJtlttrttion, sh. a! type .02., I: rotlon$ad in as: aynohrcny and IFC‘ICRGI ynttcrna, nun rolnt.‘ to apoottiud typo: a: behavioral stuptntsdn. InorOtttuc nae aynchrony tad a shirt GO aluu fvnqncactou aura nauoatttud with trangutlltzn‘tua, notation uni docrnﬁatng agitatious stilt angynohraatua£tua and a shirt tn tu't tragucncloa It: antacxntta with excitouaut, tlluuionu. tad dolnntcntl ilcatton (6.20). than: aha-trutionu are conclt‘aut with hypothaloa o: Hitler. 2h. advantagon at are tuchntquco tn: the 300.7 or not payuhntropzc ugcntu haw. nlroady b¢0u reportcd (6). low �2h. presuut progrnn, instttnﬁod in Outabcr 1959. 1a banal an sh... attitua and in 6.113304 £0 .3380? $8. I’llavinc quantlultu In £3.90 t rolutlon hotutcn Innuurublo altovtttua in 53:13 tunc‘ian and bohnvtoral «hung. with payuho- airbus. unnaatatrttian? 120 that. proeﬁrtntnoatfqlua§oru gt paynhxatrao, ptyctulcciéinnd ptyuhmlc¢1£&variahzoa rolgtud to in. tropic drugs an typa 0: hohnviornl adiptntttn? And, art such cluntora rolntod to the typo and 403200 at phyutologle ohuuxo?# ‘gggaggs AI ua.1n1t1n1 ayproxinattcn, a doublnuhlind, sized Gonna. random Isntgnncnt drug study clinical In. undertnktn. luccd on our varitu' piyuhctropto coup-sud; tron 195k to 1959, thrco clan... unto 0.100%04 an tho 5‘31! or that: patﬁnrun or 310 ro‘ponao. tho slant. scloutnd wit. that. rich oxpcrzoncoa with caﬁhcr proloninan‘ dunynuhrouiutax pattcrnu, Irhahrontutng and nlyvinc, or nintnal or no errant. Pattoutu r-rorrud in: drug therapy, IItOf nudist: tun-auntaon. and art-r :11 other nodicntiouu hay. boon diucoattuucd are randomly usutgacd to ‘ compound.1n an. or that. ‘hrio «lacs... Pa‘icnto are pvodonlnnuﬁly Ilddlo eluot, urban, utﬁh high oiiontaonnl :t‘linlont. 1111.14. 80-pita1 1a a nou-pritit, philanthtopie supported psychiatric tnutttutton, .duitttng voluntary pattoutn {or txtonntvn puyuhothurcpoutie troitntut. fin loan duration or its: fer patients in novon months. convuiaivc and puychotropao drug thnrnpics It. pronortbud by star: payuhxntriota �.1. A11 thc trlatnnut in aduluintorad by to naparﬁutu‘. rottrrll Da’artniatul stuff, no that the axpcraanutal vartthlta or drag daoaco, rant. 0! adutaictrnttua, aaotguunut to groupu, 333, &r¢ roadtly controllod. 111 patiantu in thc hoapttal arc «v.113blu for titty. Attor‘a tutti»: ptrtod, 111 puticnt: rocuivc he so or liquid ‘nndtogttoa daily tron 1nd:vtd:ally inhallcd bettlco. Dos;¢o: at: incrcnscd in ttxnd tOIIII atop: tutti a u.x:uun at h ucnku. Artur tun wank: on nixtnau 4.111., ro—tnatlnx ¢o¢ura. to dn‘o, 1&0 vuhjaoto but. hon: rtturtod, and 110 have outplatod tn. study period. Proltniunry analyst: of tho data At. an: in on prozroau. Ichuvigral GhlI‘Oi In a tutti: u: tho bnhnviorul adnptnstonu of pt‘tuuta rcaoiviag pitucthiasiutl or inipruutua during 1958-59, variauc clustorn at bchnvtora var. duvolopad. 1h. typalocton wore but-d on tho trontatut rcapiaat and on pr0~trlntauut ptyuh1&tr1c protilus. In $3. pruncut sitar, tho typoloxint at. being tested, and variant scalarot at behavtoral ahtug. at. being atudtod. It... inaluac thorlyitt ritorrnl quortiouuairoc I1: cvaluntiono) therapiat tad puts-at Glyn. Road s¢nlang burr aoglu .valuntiona 1n int¢rviov by two rnutnrch psychiatrtnta. and Lorr Hard Scale.) and puttout unit—ratings 15013413: ‘ho Johan toutinl symptul about lint and the stints. Attstnda 50:10:. boon both vtcvod I‘Vl tank. as Psycholnglc lutrggangglogzg thing: vsrtnhlou sud pradlcttvo variablou. In convulsivo thorgpy, chingo¢ in Inner: tanks (22), tactile paraoption (23,2h), wcohnlcro Bolltvu‘ (13). err (13). flatro‘3rocnd talk. (25). ‘nd tachlntQUQOptu recognition a! figure: (26) war. relatcd to thy Court. or induocd and ﬂ‘Ok am �neurophyutczogaggihnngu. In: 9.03 tack, tn. dcxroo at docruuont tn rouui ta b. poatttvny ocrr'lutod with the ‘llk vortoruuncn nus assist a! :36 closing. lollewaac trout-oat aonalation, with the rotur: a: phybitloxialiaaauca t. prootroatnnnt lovnln, performing. payahologidﬁkasku in than: also raturnud to pro-trontnont lcvuln, or higher ~ a buttarntnt 02 purrornnnco ascribed to practi¢o afloat. Donia: start. on interviﬁw (27), aoroohach dotorl1nuntn (16,17), r 8.11. Idﬂvit (15,17), ltngunzu pntﬁarns attnr tnobnrbttal (28), andatary toodbuck and porcuption if the 11:ua1 Iyrscht have bcan v10v0d a: prcdlattvu attains at tho hchavioral outages following 362. fhauo vurinuo tank. are at: being Isa-anon with paychctropio :.£?:1.1p agon$s, alpncxty capacity to prudiot chaago. t. cling. wl‘h vurtona anout319igfﬁhotr §;I¢§ronniqggg;o‘gughzg In tn. convulttvn therapy ntndlnt. the intro. of as» slaving was latsurod by counting tho oonncauttv. wave- 1» lolcotad :unpi:a (7). lab.» ta. not. nubtlchohuazoo at uttoetl arc ltudiod, it in uooclaury to gyply lula'ttdionn toohntquoa. Iltctroulc Iroqutncy nnnlrlia wt: introduacd 1h Angint 1959. 8y nauaurounat 0: th. pun doticetion for vaﬁﬂoal rrnquoneius Iran 3 ta 33 8?! 1n ttn ataoaa epochs, rapid nanuurcnnat o: upptrintly nlnll august. in total activity nnd troguoncy aptctrl arc new obtatnnd drug tad applied. ethn- play-1.1.316" in thin program include tha rtlpautn I: :36 to iatrnvontua chlorpronnsinzj blood protauro reapnunu to the nut, pullout!" 1041” mute, and a: turtouv blo.d and urin. elegantl. man" “at“ ”any” “an“ w: 9! 115‘ 8 �tho atadlco in napnrtuont hurt beta dovctoa .: to torn;1 1.33133: puﬁtcruu. iylzoving it. stutits ct syntactic lung‘tgu pattern: (:8) tn asavulitvo ihsrapy, uﬁhor capogts at 11:51:30 vuru Ituaxod for tkcir r01:$£on an iudSQIa of change in intovpornonnl bohtvtor. .Jattc, urtnr oonoiiertblc omnlorutian with Various linguistic consecutivn or that suggcitaa typo~tokoa~rtttol (I?!) lilltrit, ho t 1nd»: (19.30). man. «mm: at and“ apneh it! hid prtvionoly §ncn npplicd tn urittua $311: or en. 1:ngungo nanplou of indivﬁdulil, 3.1!. indicated that the two pcrnou cou~ nuatcttton (47") was 1 nor. liznitignnt indox at tho itttn at tho interacting than auulylou or i¢paratu snnpxoa of tho ptrtitiplutl. tpplying than toohutque ﬁt convulltvu shtrnyy patients. chanson 13‘!!! noun and atundnrd «aviation. var. r01¢tnd both to in. deavco or induced 3:3 ulot wire aat1viti and to uyutnet1c lunxttxo pattern. ob$ttnca 1n indopondtut atruatnral interviouu. apauah 5.01:. no»: rupo‘tttvc (lowered noun If!) and nor. vartnhlo in coautcutivu nunplon (in-ruaI04 utnndurd d¢v1at10n) (31). In intarvtawl but-r. and alter tho mutrtvvaonu aduanlatrtttoa at ecutrally activa astutu, 31:11:: Ihlngil Int. obnurvod. taint. with n yrcdouinant lynchruatxgtion pnttorn on tn. £86 oxhibitcd a 4.120ntt in net: 191 cud inﬂfilti tn itandnrd duvxatioa o: necros, viii. dotynchrouising ealputuda 01101106 groatcr variability in tyccch pattcrus (1:090... in RI! Inna) tad dtcrunan in v.r1ub111%y of coauoeutiva scorn. (duorouun 1n ntandnrd deviatian) (32). 6th.: languaga notnnrnl atudiod includod diatroccurolior quttt¢ata, uclt-rutcruncc, and alttrntion 1n tunnu and paracn. Antﬁhar 30:10. m tutu �.19. nu: sagsoaﬁcd that ﬁt... yuywhcltnxutstta Inaiurcs tgo pa‘cat incantqutl for sh: operational unnlytns o: phyaiologig%und yi:¢h¢1¢¢1€?£ttactn a: ycychopharanaolugse taunt: (32). It �aggggaggzc $233133 It ta. court. at ‘ thou. plyuhta%r1e protraaa, comaidartblo InﬁnrOtt Ian unguudarcd in at. tantly organisation to which pttttnto turn rcturntnc. Also, its ginornl problem at tho ralntiou or stein! M chase. and a: pnychutric treat-out, and the Ipttifia prathn a! the rnlutiau of thtli factor. in tht rarogrul puttarna lad to a aortic at papulatian studsus. In on: study (33). ﬁduaattua. ﬂgi, plus: ct birth cud score on tho Galltarnia r Iallc wort ticnttioaatly ralctad to the may. at therapy rocoivod und the utilatniton at adainottva hotpttnl aortic... rhui, pgttont; aha var. older, pearl! uduantcd, had hishar I neuron And aura tarnishhnru, ptrtiuularlyranstnrn invent. wart neat ltkuly to be 90:0rfﬂd tar ¢ls¢trouhooh. that. rclationahlpl worn proaont indopiadont or atlxntnoa. within tic sunny 3: cluo‘ronhack patiuntu, $3. tins for rotttrnl for 3a: 3:: ulna rolntnd to ﬁhoau factora. In t nocand ntud: (18), dnru‘ton a! harpitnliantion, discharge uvnluattan and asucnoun: vova rolniod ta tho Ian. social flotara. fur uxauplo, patient: harpitlltuna for it. uhortcnt ported EOE. oldest, had in. lcaaﬁ education, v¢ro punt llkcly ta hnvc baou farcicaioru and had the hiahﬁr t ﬁnal. user‘s. Younger, uttivowborn, not. nénuatod, lava: ! 89.10 a¢oro yuttonta worn hospit.11sod thu taunt-t. I)... rnlntinanhipl htld trnc within troutlant typt and within diagnoatic 0131!. on dinohargt, 014.: patients had tan unit tavorablc ratings. In :61, patients rated as renovated or sunk improvod had tho highoat r 3.0!... lasat aduantion and war. moat 113.1: ta b. rurattg* born. In anoﬁhcr study or p;t1cat textual a: new, 01.11;: rolattun~ ships tutu obsorvad (3h). an». nun: �.12“ ‘ thc under antarctiout in study not volatiiauh1pa If. It... Dtpnrtutnt, and in I triuhtnpttnl coupura‘tvo study. In tho 133%.: utuﬂy, tho pcpn1n%1ona at ﬁbre. haupttclu uttk provatltac dittcvtng $0 .11 pttaoutt, :11 wits! aquully in thoruptcs arc I'lillhlt cltuutu, - Ionian:- muauw Iowan (mu-«nu, run-mu, hunk» nottn lontil ﬂunl‘h cantor (lowiroclnns, ctthnlta) ‘34 ltllllio loaptt&1 (naddzcvcliuu, icwioh) It. ﬁning tanouacd. It ha. bcon thy rotlooﬁ antlntnco .2 social rolutiandhtpt it... ha011ruund on payth.lo¢1all prrcanuou, such ll habitual pnttnraa or contagiouttun and gods: of «sproutioa. {ha cantrthlﬁton 0! than. tnotara to tho patﬁorn o: ncaﬁal 111303., and thy ptticIt-thnrtpiot intoruottou are undo: atnﬁy. postultttd that �.13- may; it. nipnr$uoat:1 99032.3: are a oluutar a! interrolntod studios tocuunod about cannon pnpulntauu annplcu. within ltllltdo Iblpttnl, restart! ltboratoricu 1a niaehauiltry, and in nadtctno if. aattVQ; and 0th.: inbnrntorina 1a puyuhodyulnto puynhtntry Ar.hmaac aqvolcpud. In tat; Dtpnrtnont, various diacipllnoo tr. vartttayaats,roprtuoatzn: a gradual cravth a: :1: 33.3.. tartan: grcuth and t8. ﬂirtation. a: tanning 31341.. tr. dapoudont .a tau rostlta at tho attain. dotcrahtﬁ hart; no will a: th§ (rowing £Il$1titt¢ll1.nilrin031 that ruaonrch in an tutogral part of thy httpitul't opcrnttcu and budgu‘n . II that ll trcntnnat and otutt training. �~13:- kahuna” fauna: uni-cue“ that“ m £0.11.ng rut: hum" m rink, ﬂu hunk. “but 1.. tum, Jinnah um, Int-u I. Erna, 3”,. Km, In" mu, ma: 3'. £1.13. Guru Imam, ”and a. auburn. “that“ 8. 33.301, abun- Inn: at! nary J. Mint“... Aim" at tho J. “11.1“ lap. 93 197, 1957; .3. J. mun. Hospital at 1958; 2. Ms. 3.. .113. In". 81.. 3:2: h. 4.1.11.1. 1.1m... Iron 131;. 1955; h 5. ms h “mule 1min”, a c... .325. 1339; 6. ¢h02m00§2u. naval". Mal, 19603 7. Add. not. loan)... a 1-31.31». ﬂ: $16, 1957: 0. Mn. In". an. '33: ”7.19563 9. J. i111.“- llup. g: 3, 1955: 19. Arab. 18116, 1958; ”my; 1.956. :3, rennin. t ﬁt 11. nm In“). 3” In“ 1. Sci. , Penman, 613. u. “an Em. that. 31!. 122' 117. 19691 13. 1.3.1:. Int-.1 Mm“. 1959) arch. Gun. pan); ﬁnalist“ autumn 15. Jar. low. but. ml. ms 15?, 1960: 16. a. lunpuehut. 3,: an, 1960; 1?. am. it". lat. M... m; 11:). 1959: 18. Mid. Arch. on. ”want. .13 555. 1959; 19. Add. Auk. Int-1. I: "youth £9: no. 1958; 21. g: (in 1h. can“. 8!, 1,563. usual. can Emlyn“. 9,3: 359. uni. Anna. 3. A: 1668, 1959: to. no 13. 3. Hanna. luv. g: 1950. 2:. 21:1, 1957: car. lmol. 2h. a. J. luau: g: Shh 1m; 8&. 17.19%: Gong. 238, 1959] 901350;” law-mama, m, 335. 4. 28. 19593 lmopoychiu. u. chhgzﬂhclaa at y «1-. 35.11.14. Buy. 5 1953; 126, Gun 29. Mutton, cwuuia, g: 207. 19573 30. urchin. 3.2») 2139, 1958. 1?} 381:. 19593 25. MILL. Arch. �. «150 ‘1-.. O 3'1. :"9: ‘.".¢ "”‘o ﬁt‘t > ‘ ‘ hip. g: 216, 195'!) g 31:. w! ”5’ 1,69} M', uranium-a Mnuonph 3.6; 2’. 196°, 3!. W 33. ‘¢ 31.11.14. �Experimental Psychiatric Programs at Hillside Hospital: A Max Review Fink, MnD. the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, L.I., N.Y. From VI: 1/61 �Experimental Psychiatric Programs at Hillside Hospital A Review various programs in the Department of EXperimental Psychiatry have been devoted to an understanding of the mode of action of psychiatric therapies through studies of brain function. The principal techniques have been adapted from descriptive psychiatry, neuropsychology, electroencephalography, linguistics, The pharmacology, and sociology. In initial studies of convulsive therapy, changes in brain function were found to relate both to evaluations of improvement and to pre~treatment psychological variables. As our understanding of convulsive therapy developed, a general neurophysiologicadaptive view of somatic therapies emerged (1). In this view psychiatric treatments are seen as therapeutically effective to the degree that brain function is measurably altered. While change in brain function is necessary for behavioral change, the type of adaptation, however, varies depending upon pre—treatment psychological and sociological characteristics of the subject (2). Thus, the mode of action is not seen as either "organic" or "psychologic" but rather as the interaction of diffuse neurophysiologic changes and adaptive mechanisms. Further, while behavioral change is related to changes in brain function, and the adaptive pattern to pre-treatment psychologic characteristics, evaluations of 'improvement’, being special types of evaluation of change, are derivative Judgements based on staff and family expectations and tolerances (2). �-2This hypothesis was developed and sustained in a series of studies of convulsive therapy. Concurrent studies of insulin coma indicated that behavioral change here, too, was related to the onset and degree of prolonged coma or repeated seizures - these being the principal manifestations of prolonged neurophysiological change in this therapy (3,h). The mode of action of the new psychotropic agents was also eXpressed within this hypothesis (5,6). It was suggested that these agents would be effective to the degree that they induced premorbid psychologic (personality) patterns. The present programs in the Department are designed to study these relationships in detail. CONVULSIVE THERAPY PROCESS 0f various measures of brain function, the amount of slow activity in the electroencephalogram (7,8) and confabulatory and denial language patterns after amobarbital (9,10) were the most sensitive indices (11) in convulsive therapy subjects. In wave one experiment, improvement ratings correlated with the appearance of high degrees of change in these indices (7,10). These observations were tested in a double-blind study in which patients referred for electroshock were randomly assigned to courses of either convulsive or subconvulsive therapy under pentothal premedication. High degrees of neurophysiological change were observed only in the convulsive group; improvement rates were were �-3- significantly higher in this group; and when subconvulsive subjects were rc-treated by convulsive applications, the improvement rate .was similar to the original convulsive group (2). In the subconvulsive treated subjects, considerable amounts of electric current passed between the bitemporal electrodes. It appeared that the therapeutic agent was not the total electrical current, per sez but an all or none quality manifested by the grand mal seizure (8,12)o significance of the grand mal seizure was examined in studies of the inhalant convulsant, hexafluorodiethylether (Indoklon). Similar degrees of electroThe graphic change, improvement rates, types of behavioral change and changes in neuropsychological task behavior were observed in the inhalant and in electrically treated groups (13). It apparent that not all subjects manifesting high degrees of physiologic change were rated as 'improved’. In a descriptive typologic study, five patterns were described, empirically termed 'euphoric', 'hypomanic', 'somatization', 'paranoid-withdrawal', and ‘panic'. While the first two of these adaptive modes were rated as 'much improved', the latter two were was soon seen as *unimproved' or 'worse' (1h). variables, it was reported that patients rated as 'much improved' and 'recovered' frequently manifested personality patterns similar to that described by Weinstein and Kahn as the explicit verbal denial personality. In language patterns, patients expressed the 'language of denial', when diffuse brain change was induced, exhibiting such aspects as In studies of psychological �-h- explicit denial, minimization, displacement, cliches, 222. more frequently than unimproved subjects. Other indices related to favorable outcome were high F Scale score (15), and Rorschach determinants of color, absent movement and absent form-color (16,17). In this population, also, favorable outcome was associated with low educational achievement and foreign birth (18). ANTICHOLINERGIC COMPOUNDS AND CONVULSIVE THERAPY Seeking a way to augment the degree of post-convulsive slow wave activity, an anticholinergic compound, diethazine, EEG was given intravenously at various stages of the convulsive therapy process (19). Contrary to expectations, diethazine caused an immediate and sustained decrease in EEG slowing. Patients with denial language patterns relinquished them. Instead of euphoria and well being, the subjects were irritable, anxious and expressive of pre-treatment patterns. In subjects prior to convulsive or drug therapy, diethazine induced excitement, tension, anxiety and illusory sensations. Subsequent studies with other central anticholinergic compounds (WIN-2299, JB-318,336, benactyzine) showed behavioral and electrographic patterns similar to diethazine. Similar desynchronization of post-convulsive EEG slowing was also noted with central sympathomimetic hallucinogens (amphetamine, mescaline, LSD-25), and has been reported for antihistamines (diphenylhydraminc) These observations led to the suggestion that an increase in central cholinergic activity was a biochemical basis for the convulsive therapy process (20). �PSYCHOTROPIC DRUGS AND EEG During this period, the drugs aroused mode of action of newer psychotropic interest. Following the concepts derived from convulsive therapy, the neurophysiological changes induced by drugs were tested within the same acute experimental framework of the EEG setting. It was observed that phenothiazines (chlorpromazine, promazine, trifluopromazine) induced EEG synchronization and a shifting of the spectrum to the slow frequencies; meprobamate and barbiturates, an increased synchronization and a shift of spectrum to fast frequencies; reserpine, an increased slowing with synchronization at low dosages, and desynchronization at higher levels (5,6). Imipramine induced desynchronization with a shift of frequencies to the slow bands (21). Other experimental compounds tested included BL-M188 and phenyltoloxamine (Bristol), Deaner and its various congeners (Biker), WY-21h9 (Wyeth) and frenquel (Merrill). For each, no consistent electrographic pattern was recorded. It was suggested that psychopharmacological agents provide a means for eliciting a variety of neurophysiological patterns in contrast to the single pattern of induced convulsions. Furthermore, the type of neurophysiological alteration, as reflected in EEG synchrony and frequency patterns, was related to specified types of behavioral adaptation. Increasing EEG synchrony and a shift to slow frequencies were associated with tranquillization, sedation and decreasing agitation; while desynchronization and a shift to fast frequencies was associated with excitement, illusions, �and delusional ideation (6,20). These observations are consistent with hypotheses of Wikler. The advantages of EEG techniques for the assay of new psychotropic agents have already been reported (6). �97PSYCHOPHARMACOLOGY EVALUATION PROGRAM _______an.._________.__u~m._______. present program, instituted in October 1959, is based on these studies and is designed to answer the following questions: Is there a relation between measurable alteration in brain function and behavioral change with psychotropic drugs on chronic administration? Are there pre-treatment clusters of The psychiatric, physiological and psychological variables related to the type of behavioral adaptation? And, Method: As an are such clusters related to the initial approximation, a double-blind, fixed dosage random assignment drug study was undertaken. Based on our clinical experiences with various psychotropic compounds from l9Sh to 1959, three classes were selected on the basis of their patterns of EEG response. The agents selected were those with either predominant desynchronizing patterns, synchronizing and slowing, or minimal or no effect. Patients referred for drug therapy, after medical examination, and after all other medications have been discontinued are randomly assigned to a compound in one of these three classes. Patients are predominantly middle class, urban, with high educational attainment. Hillside Hospital is a non-profit, �-8- philanthropic supported psychiatric institution, admitting voluntary patients for extensive psychotherapeutic treatment. The mean duration of stay for patients is seven months. Convulsive and psychotropic drug therapies are prescribed by staff psychiatrists on referral to the Department. All treatment is administered by Departmental staff, so that the experimental variables of drug dosage, route of administration, assignment to groups, 323. are readily controlled. All patients in the hospital are available for study. After a testing period, all patients receive no cc of liquid medication daily from individually labelled bottles. Dosages are increased in fixed weekly steps until a maximum at h weeks. After two weeks on maximum dosage, re-testing occurs. To date, 1ho subjects have been referred, and 110 have completed the study period. Preliminary analyses of the data are now in progress. Behavioral Change: In a survey of the behavioral adaptations of patients receiving phenothiazines or imipramine during 1958-59, various clusters of behaviors were developed. The typologies were based on the treatment response and on pre-treatment psychiatric profiles. In the present study, the typologies are being tested, and various measures of behavioral change are being studied. These include therapist referral questionnaires and six week evaluations; therapist and patient Clyde Mood Scales; Lorr Scale evaluations in interview by two research psychiatrists, and Lorr Ward Scales; and patient self-retina including the Johns Hopkins symptom check �-9- list the Chicago Attitude Scales. Neuropsychology: Psychologic tasks have been viewed both as change variables and predictive variables. In convulsive therapy, changes in memory tasks (22), tactile perception (23,2h), WechslerBellevue (13), OFF (13), figure-ground tasks (25), and tachistoscopic recognition of figures (26) were related to the degree of induced neurophysiological change. For each task, the degree of decrement in task performance was found to be positively correlated with the amount of EEG slowing. Following treatment completion, with the return of physiologic indices to pre-treatment levels, performance in these psychological tasks also returned to pretreatment levels, or higher - a betterment of performance ascribed and to practice effect. Denial scores on interview (27), Rorschach determinants (16,17), F Scale scores (15,17), language patterns after amobarbital (28), auditory feedback and perception of the visual upright have been viewed as predictive indices of the behavioral changes following ECT. These various tasks are now being assessed with psychotropic agents, for both their capacity to change with various agents and their capacity ts predict change. Electroencephalography: In the convulsive therapy studies, the degree of EEG slowing was measured by counting the consecutive waves in selected samples (7). When the more subtle changes of drug effects are studied, it is necessary to apply less tedious techniques. Electronic frequency analysis was introduced in �August 1959. By measurement of the pen deflection for various frequencies from 3 to 33 cps in ten second epochs, rapid measurement of apparently small changes in total activity and frequency spectra are now obtained and applied. Other physiological variables studied in this program include the response of EEG to intravenous chlorpromazine, blood pressure reaponse to mecholyl, the EKG, radioactive iodine uptake, and analyses of various blood and urine elements. �-11PSYCHOLINGUISTICS series of studies in the Department have been devoted to formal language patterns. Following the studies of syntactic language patterns (28) Another in convulsive therapy, other aspects of language were studied for their relation as indices of change in interpersonal behavior}. Jaffe, after considerable exploration with various linguistic measures, suggested that type-token-ratios (TTR) of consecutive samples of dyadic speech may be a useful index (29,30). While TTR had previously been applied to written texts or the language individuals, Jaffe indicated that the two person communication (dyad) was a more significant index of the state of the interaction than analyses of separate samples of the participants. Applying this technique to convulsive therapy patients, changes in TTR mean and standard deviations were related both to the degree of induced EEG slow wave activity and to syntactic language patterns obtained in independent struuctured interviews. Speech became more repetitive (lowered mean TTR) and more variable in consecutive samples (increased standard deviation) (31). In interviews before and after the intravenous administration of centrally active agents, similar changes were observed. Agents with a predominant synchronization pattern on the EEG exhibited a decrease in mean TTR and increase in standard deviation of scores, while desynchronizing compounds elicited greater variability in samples of speech patterns (increase in TTR mean) and decrease in variability �-12- of consecutive scores (decrease in standard deviation) (32). other language measures studied included distress-relief quotients, self-reference, and alteration in tense and person. It was suggested that these psycholinguistic measures are potent techniques for the operational analyses of physiological and psychological effects of psychopharmacologic agents (32); �SOCIOLOGIC STUDIEE In the course of these psychiatric programs, considerable interest was engendered in the family organization to which patients returning. Also, the general Problem of the relation of social factors to choice and results of psychiatric treatment, and the specific prohlem of the relation of these factors to the referral patterns led to a series of population studies. In one study (33), education, age, place of birth and score on the California F scale were significantly related to the type of therapy received and the utilization of adjunctive hospital services. Thus, patients who were older, poorly educated, had higher F scores and were foreignborn, particularly in Eastern Europe, were most likely to be referred for electroshock. These relationships were present independent of diagnoses. Within the group of electroshock patients, the time for referral for ECT was also related to these factors. In a second study (18), duration of heapitalization, discharge evaluation and diagnoses were related to the same social factors. For example, patients hospitalized for the shortest period were oldest, had the least education, were most likely to have been foreign-born and had the higher P Scale scores. Younger, nativeborn, more educated, lower F Scale score patients were hospitalized the longest. These relationships held true within treatment type and within diagnostic class. On discharge, older patients had the most favorable ratings. In ECT, patients rated as recovered or much improved had the highest F scores, least education and were most likely to be foreign-born. In another study of patient were �refusal of similar relationships were observed (3h). These relationships are now under study in the Out-Patient Department, and in a tri-hospital comparative study. In the latter study, the populations of three hospitals with prevailing differing clients, in which all therapies areenually available to all patients, - Menninger Foundation Hospital (upper-class, Protestant), Massachusetts Mental Health Center (lower-class, Catholic) and Hillside Hospital (middle-class, Jewish) are being assessed. It has been “postulated that these relationships reflect the influence of social background on psychological processes, such as habitual patterns of communication and modes of expression. The contribution of these factors to the pattern of mental illness, and the patient-therapist interaction are under study. ECT, �SUMMARY Departmental programs are a cluster of interrelated studies focussed about common population samples. Within Hillside The HOSpital, research laboratories in Biochemistry, and in Medicine are active; and other laboratories in psychodynamic psychiatry are being developed. In this Department, various disciplines are participants, representing a gradual growth of six years. Further growth and the directions of ensuing studies are dependent on the results of the studies described here; as well as the growing institutional awareness that research is an integral part of the hospital's operation and budgets - as much as treatment and staff training. �~16- References Authors of the following references include the following staff members: Max Fink, Max Pollack, Robert L. Kahn, Joseph Jaffe, Martin A. Green, Eric Karp, Korin, Donald F. Klein, George Krauthamer, Arnold G. Blumberg, Nathaniel S. Siegel, Abraham Kaplan and Henry Hyman J. Lefkowits. 1. J. Hillside Hosp. 6: 197, 1957; 2. Dis. Nerv. Sys. 12: 3. J. Hillside Hospital h: 13h, 1955; 113, 1958; h. J.A.M.A. 166: 18h6, 1958; 5. Psychopharmacology Frontiers, Little, Brown 6. Neuropsychopharmacology, Elsevier, hhl, 1960; 7. A.M.A. Arch. Neurol. & Psychiat. 18: 516, 1957; 8. Dis. Nerv. Sys. 12: 227, 1958; 9. J. Hillside Hosp. A: 3, 1955; 10. Arch. Neurol & Psychiat. 16: 23, 1956. & Co., 325, 19593 11. First Int'l Cong. Neurol. Sci., Pergamon, 613, 1959; 12. Jour. Nerv. Ment. Dis. 129: 117, 1960; 13. A.M.A. Arch. Gen. Psychiat. (in press); 1h. Unpublished manuscript; 15. Jour. Nerv. Ment. Dis. 129: 187, 1960; 16. J. Neuropsychiat. l: 2h2, 1960; 17. Jour. Nerv. Ment. Dis. 128: 2h3, 1959; 18. A.M.A. Arch. Gen. Psychiat. l: 565, 1959; 19. A.M.A. Arch. Neurol. & Psychiat. 82: 20. EEG Clin. Neurophysiol. 13: 359, 1960. 380, 1958; J. g: 1663, 1959; 22. J. Hillside Hosp. 6: 2hl, 1957; 21. Canad. Psych. Assoc. 16: 88, 1956; 23. Conf. Neurol. 2h. Am. J. 25. A.M.A. Arch. Neurol. g: 5&7, 1960; Psychol. 13: 38h, 1959; 26. Proc. XV Int. Cong. Psychol., North-Holland, 238, 1959; 27. J. Neuropsychiat. l: h5, 1959; 28. Psychopathologx of �-17- m Communication, Grune ' & Stratton, 126, 19583 29. J. Hillside Hosp. 6: 207, 1957; 30. Psychiat. g3: 2&9, 1958. 31. Jour. Nerv. Ment. Dis. 130: 235, 1960; Psychiatric HOSp. Drug Therapy, C.C. Thomas, 29, 1960; 6: 216, 1957; 3h. Unpublished Manuscript. 32. ngamics of 33. J. Hillside �EXPERIMENTAL PSYCHIATRIC RESEARCH AT HILLSIDE Review and Prospect MAX FINK, M.D. Reprinted from JOURNAL OF THE HILLSIDE HOSPITAL Volume X ' Nos. 3-4 ° July-Oct. 1961 . �EXPERIMENTAL PSYCHIATRIC RESEARCH AT HILLSIDE Review and Prospect MAX FINK, MD. The dedication of Hillside Hospital as a Research Institute has been a dream of many of its students—a dream that may achieve realization in this decade. Dr. Tarachow was an early proponent of this view; and both in his sponsorship of the Journal, and in his encouragement of research studies, he presaged this development. He was also the inadvertent sire of the research studies in experimental psychiatry. While I was a resident in psychiatry in 1952, we collaborated in a study of the relation of the early separation of child from a parent to the adult choice of neurosis. Reviewing the hospital records of ﬁve previous years we concluded that there was, indeed, a relation— neurotic patients with obsessional neuroses had a signiﬁcantly, greater incidence of separation than patients with hysterical neuroses (2). This report was the beginning of the patient population studies described here. Since 1954 the various programs in experimental psychiatry have been devoted to an understanding of the mode of action of the psy- chiatric therapies of the hospital. The techniques have been adapted from descriptive and dynamic psychiatry, neuropsychology, electro— encephalography, linguistics, pharmacology, and sociology. This report reviews these studies and presents support for the creation of a Research Institute at Hillside. PAST STUDIES In our early studies of convulsive therapy, instituted with the 1 From the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, N. Y. The studies reported here have been aided by the Board of Directors Research Fund; the National Institute of Mental Health (Grants M-927; MY-2092,-27l5, ~4798; MF-12,033); Foundations Fund for Research in Psychiatry (FFRP 56-151); Kaufmann, and Dazian Foundations; and numerous pharmaceutical concerns including Geigy, Bristol, Wyeth and Smith, Kline 8: French Laboratories. 159 �160 MAX FINK aid of a grant award of the National Institute of Mental Health, evaluations of patient improvement were shown to be dependent both on changes in brain function and on psychological factors. As our understanding of convulsive therapy developed, a general neurophysiologic-adaptive view of somatic therapies emerged (6). A change in brain function was seen as a necessary condition for behavioral change, with the type of change varying, depending upon psychological and sociological characteristics of the subject (22, 25). Thus, the mode of action was not seen as either ”organic” or “psychological” but rather as the interaction of neurophysiological changes and individual patterns of response and behavior. This hypothesis was sustained in studies of convulsive and insulin coma therapies (21, 22); and the mode of action of the new psychotropic agents was expressed within this hypothesis. It was suggested that psychotropic drugs would be effective to the extent that persistent changes in brain function were induced; and that the type of behavioral response would be related to the type of brain change, and to individual premorbid psychologic (personality) patterns (6, 28, 40). l. Convulsive Therapy Process: Seeking a measure of altered neurophysiological change that was sensitive and suitable for repeated retests, various measures were studied including changes in the face-hand test (1, 10, 13, 35), memory tests (17, 35), amount of slow-wave activity in the EEG (16, 23) and confabulatory and denial language patterns after amobarbital (3, 15). The latter two, EEG and amobarbital tests, were the most sensitive indices of change in convulsive therapy subjects. In one experiment, clinical ratings of improvement were correlated with high degrees of change in these indices (15, 16). These observations were tested in a double-blind study in which patients referred for electroshock were randomly assigned to either convulsive or subconvulsive therapy. High degrees of electrographic slow-wave activity and positive amobarbital tests were observed only in the convulsive group; improvement rates were signiﬁcantly higher in this group, and when subconvulsive subjects were retreated by convulsive applications, the improvement rate was similar to the convulsive group (22). In subconvulsive applications, considerable electric current passes between the electrodes. It was postulated that the therapeutic agent was not the total electrical current per se, but the “all or none” quality manifested by the grand-mal seizure (9, 23, 42). The signiﬁ- �EXPERIMENTAL PSYCHIATRIC RESEARCH 161 cance of the grand-mal seizure was examined in a comparative study of the inhalant convulsant, hexaﬂuorodiethylether (Indoklon), and electrically induced seizures. Similar degrees of electrographic change, improvement rates, types of behavioral adaptations, and changes in neuropsychological task behavior were observed in both the inhalant and in the electrically treated groups (49). However, not all subjects manifesting high degrees of physiological change were evaluated as “improved.” In a descriptive typologic study, ﬁve adaptive modes were described, empirically termed “euH H phoric,” “hypomanic,” “somatization, paranoid-withdrawal,” and “panic.” While the ﬁrst two patterns were rated as “much improved,” the latter two were seen as “unimproved” or “worse” (50). In studies of psychological variables, it was reported that patients rated “much improved” and “recovered" frequently manifested personality patterns akin to the explicit verbal denial personality type (37). These patients expressed the “language of denial” more frequently than unimproved subjects, exhibiting such aspects as explicit denial, minimization, displacement and clichés (27). Other psychological indices also related to favorable outcome included high F Scale score (42), Rorschach determinants of color, absent movement and absent form-color (30, 45), and low educational achievement and foreign birth (31). 2. Anticholinergz'c Compounds and Convulsz've Therapy: Seeking a way to augment the degree of postconvulsive EEG slow-wave activity, an anticholinergic compound diethazine, was given intravenously at various stages of the convulsive therapy process (20, 24). Unexpectedly, diethazine caused an immediate and sustained decrease in EEG slowing, which was associated with marked changes in language and mood. In patients with denial language patterns (27), these could no longer be elicited. Instead of euphoria and wellbeing, the subjects became irritable, anxious, and complaining. In subjects prior to convulsive or drug therapy, diethazine induced excitement, tension, anxiety, and illusory sensations. Subsequent studies with other central anticholinergic compounds and sympathomimetic hallucinogens showed behavior and electrographic patterns similar to diethazine. These observations led to the suggestion that an increase in the cholinergic activity of the central nervous system was the biochemical basis for the convulsive therapy process (38). 3. Psychotropic Drugs and EEG: Following these studies, the neurophysiological changes induced by drugs were tested within an �162 MAX FINK acute experimental EEG setting. It was observed that phenothiazines induced EEG synchronization and a shifting of the frequency spectrum to the slow frequencies; meprobamate and barbiturates, an increased synchronization and a shift of the spectrum to fast frequencies; reserpine, an increased slowing with synchronization at low dosages, and desynchronization at higher levels (18, 26, 28, 40). Imipramine induced desynchronization with a shift of frequencies to the slow bands (33, 34). Each active psychotropic compound was thus shown to have a characteristic frequency pattern. Various other experimental compounds were also tested, and for these no consistent electrographic pattern was recorded. These compounds have since been shown to have either no or very limited clinical psychotropic activity. The absence of behavioral change with these compounds lent further support to the assumption that brain change is a necessary condition for the action of psychotropic drugs. These observations suggested that psychopharmacological agents provide a means for eliciting various types of altered brain function in contrast to the single pattern following convulsive therapy. Furthermore, the type of neurophysiological alteration, as reﬂected in EEG synchrony and frequency patterns, was found to be related to speciﬁed types of behavioral adaptation. The advantage of EEG techniques for the assay of new psychotropic agents and the technical merits of electronic frequency analysis were assayed and described (47, 52). 4. Insulin Coma Therapy: In our insulin coma studies we con- firmed earlier observations that persistent alterations of brain function were related to prolonged coma and spontaneous seizures; and saw in this relationship support for a neurophysiologic-adaptive hypothesis. With the availability of the new psychotropic agent chlorpromazine, a controlled chlorpromazine-insulin coma study was undertaken in September, 1955. As patients were referred for insulin coma they were randomly assigned to courses of either oral chlorpromazine for at least three months in doses adjusted to fall short of toxicity; or insulin coma, induced by a standard technique at least ﬁfty times in each patient. While a number of minor differences were noted in comparing the two therapies, the results at time of discharge showed no statistical difference in the effectiveness of both treatments. Neither treatment seemed to affect the basic schizophrenic process, but chlorpromazine had the advantage of being safer, easier to administer, and better suited to long-term management (21). Concurrently, following the suggestion by the Creedmoor workers that �EXPERIMENTAL PSYCHIATRIC RESEARCH 163 divided insulin doses were superior to single insulin doses, Blumberg and Laderman (39) essayed this problem and demonstrated no signiﬁcant merit to the multiple-dose technique. (In 1958, following the general conﬁrmation of these observations, insulin coma therapy was discontinued at Hillside). 5. Neuropsychology: Various psychophysical tests were adapted from neuropsychology, where their signiﬁcance in brain-damaged subjects had been demonstrated. The early studies assessed these tasks as indices of altered brain function (35), and measured the range of performances of psychiatric patients, who are generally assumed not to be brain-damaged. Thus, memory function was assessed on immediate recall, after various interpolated learning tasks (17, 35), as well as during convulsive therapy (17). Tactile perceptual tasks were ﬁrst examined in the clinical population (1). Later, with more sensitive electrical tactile stimuli, Korin (10) observed the range of thresholds in different body parts, the changes with altered brain function (10), and the inﬂuence of set (instruction) on performance (36). We also studied the perception of embedded geometric ﬁgures (43), tachistoscopic presentation of embedded color ﬁgures (55), perception of the visual upright (55), critical ﬂicker frequency (49), and interference in reading time by delayed auditory feedback (55). For each task, the degree of decrement in task performance was found to be positively correlated with the amount of EEG slowing. Following treatment completion, with the return of physiological indices to pretreatment levels, performance in these psychological tasks also returned to pretreatment levels, or higher—a betterment of performance ascribed to practice effect. Concurrently, assessment of various psychological measures as indices predictive of behavioral change during convulsive and drug therapies led to studies of the Rorschach determinants (30, 45), California F Scale scores (30, 42), language patterns after amobarbital (27), denial scores on interview (37), and the perception of the visual upright and auditory feedback (55). 6. Psycholinguistics: Concurrent with the syntactic language studies (27), analyses of other language patterns were undertaken, both in a search for more objective indices of behavioral change and to gain experience in the technical problems of tape analysis for psychotherapy research. An index of variability in the vocabulary of speech, the type-token ratio (TTR) of consecutive samples of dyadic speech, was extensively studied (7,41, 44, 46, 56, 57). In convulsive therapy patients, signiﬁcant changes in TTR mean �164 MAX FINK and standard deviations were related both to the degree of induced EEG slow-wave activity and to syntactic language patterns obtained in independent structured interviews. It was noted that speech became more repetitive (lowered mean TTR) and more variable in consecutive samples (41). In interviews before and after the intravenous administration of centrally active agents, similar changes were observed. Agents which produced predominant synchronization patterns on the EEG were related to a decrease in mean TTR and an increase in the standard deviation of scores, while desynchronizing compounds elicited greater variability in speech patterns and decrease in variability of consecutive scores (44). Other language measures studied included distress-relief quotients, self-reference, and alterations in tense and person. It was suggested that these psycholinguistic measures are useful techniques for the operational analyses of physiological and psychological effects of psychopharmacological agents (44, 46). 7. Brain Damage and Schizophrenia: Following his studies at Ittleson Center, Pollack reviewed the relationship between age of hospitalization, intellectual functioning and prognosis in schizophrenic children and adults. He noted that initial hospitalization in childhood and adolescence was related to I. Q. scores in the subnor— mal range, deviant performance on psychomotor tasks, and more frequent ratings of “unimproved” at hospital discharge than was initial hospitalization as an adult. The early and insidious onset of the behavioral syndrome “schizophrenia” was thus related to brain dysfunction (54). Findings suggest that different subgroups of schizophrenia may be classiﬁed on the basis of neuropsychological deviancy. 8. Sociological Studies: Considerable interest in the family organization to which discharged patients were returning, the relation of social factors to choice and results of psychiatric treatment, and the specific problem of the relation of these factors to treatment referral patterns led to a series of population studies. In one study (8), education, age, place of birth, and score on the California F Scale were signiﬁcantly related to the type of therapy received and the utilization of adjunctive hospital services. In a second study (31), duration of hospitalization, discharge evaluation, and diagnosis were related to the same social factors, while in a study of patient refusal of ECT, similar relationships were observed (51). These observations suggested a comparative interinstitution study, and among three hospitals the relationships between social class and other demographic variables (age, sex, education) to the clinical �EXPERIMENTAL PSYCHIATRIC RESEARCH 165 variables of patient classiﬁcation (diagnosis), duration of hospitalization, selection of therapy, and discharge evaluation have been assessed. Three teaching institutions were selected in which all therapies are equally available to all patients—Menninger Foundation Hospital (upper-class, Protestant), Massachusetts Mental Health Center (lowerclass, Catholic), and Hillside Hospital (middle-class, Jewish). In such a comparison we have found the differences in designations of treatment, diagnosis, and discharge evaluation so marked as to make comparisons difﬁcult. While many relationships between social variables and clinical variables were observed in each hospital, no social variable was found related to the clinical variables in every hospital (53). In an outpatient department study, sex, age, and marital status were found to be related to the acceptance and rejection of patients and failure to complete the application process (55). These observations in population samples led to concurrent studies of staff attitudes in the selection of therapy (ll, 12). In a series of ward observation studies, Kaplan and Lefkowits indicated the signiﬁcant role of staff attitudes (especially nursing personnel) in the referral for subjects for somatic therapies, and in the transfer of patients from one ward to another. (To study the inﬂuence of staﬂ attitude on patient selection for drug therapy, we requested one ward be designated as a “no-movement” unit. This was adopted in September, 1959 and shortly thereafter by the whole hospital.) PRESENT STUDIES During the period of the convulsive therapy studies, many new psychotropic compounds were assessed clinically (5, 21), electrographically (34, 40, 48), and psychophysically (48). The present psychopharmacology evaluation program, based on these studies, was designed to answer the following questions: 1. Is there a relation between measurable alteration in brain function and behavioral change with psychotropic drugs on chronic administration? 2. Are there pretreatment clusters of psychiatric, physiological, and psychological variables which are related to the type of behavioral adaptation? 3. Are such clusters related to the type and degree of physiologi- cal change? As an initial approximation, a double-blind, ﬁxed dosage, ran- �166 MAX FINK dom assignment drug study was undertaken. Based on our clinical experiences three types of compounds were selected on the basis of their EEG patterns. In this study, 203 subjects were referred, and 149 have completed the testing program, from October, 1959 to July, 1961. l. Behavioral Change: In a survey of the behavioral adaptations of patients receiving various psychotropic compounds during 195859, a behavioral typology based on the treatment response and on pretreatment psychiatric profiles was developed (55). In the present study, the typologies are being tested, and various measures of behavioral change studied, including therapist ratings, self-ratings, and various ward observation scales. 2. Neuropsychology: Psychological tasks have been viewed both as indices of behavioral change and as predictive guides in convulsive therapy. Each of these tasks and a selected group of motor tasks are now being assessed for both their capacity to reveal change with various drugs and their capacity to predict change with the drugs in this program (48). 3. Electroencephalography: In the convulsive therapy studies, the degree of EEG slowing was measured by counting the consecutive waves in selected samples (16). When the more subtle changes of drug effects are studied, it is necessary to apply less tedious techniques (48), and electronic frequency analysis was introduced in August, 1959. By measurement of the pen deﬂection for various frequencies from 3 to 33 cps in ten-second epochs, rapid measurement of apparently small changes in total activity and frequency spectra are obtained (52). Other physiological variables studied in this program include the response of EEG to intravenous chlorpromazine, blood pressure response to mecholyl, the EKG, radioactive iodine uptake, and analyses of various blood and urine elements. 4. Data Analysis: To analyze the data generated in this study, we have sought the aid of complex statistical methods and computational facilities. Analyses of covariance, correlation matrices, factor analyses, and discriminant function analyses are computations now in progress with these data at the NIMH Psychopharmacology Service Center’s Biometric Laboratory in Washington. THE NEXT STEPS Favored by a national research climate and a cooperative hospital staff, these studies have proceeded vigorously. The assets for research in this setting have been great—a selected, intelligent patient popula- �EXPERIMENTAL PSYCHIATRIC RESEARCH 167 tion resident from six to twelve months, without individual economic limitation of hospital stay; a sophisticated administration tolerant of controlled studies; and approval of a Board of Directors who desire “research” as an institutional function. As Dr. Lewis Robbins noted in his ﬁrst hospital report in 1959, a specialty hospital can make little impact on the mental illness problems of the community by treatment alone. The successful treatment of 350 patients a year is but little comfort to the 40,000 resident patients in the state hospitals of Long Island. Nor will the annual training of twenty or thirty physicians in the arts of psychotherapy do much to help these unfortunates or the many thousands of ambulatory mentally ill resident in the nation. No, a therapeutic goal alone is salutary but inadequate to our needs. As he proposed, the answer may lie in the dedication of a “research hospital,” as it is here that a specialty hospital can truly excel. The charter has been written in the Board’s assertion of research as a hospital goal. With the assets of an exemplary therapeutic facility, such rededication can provide the stimulus for the continuous study of the cause of mental illness and of methods of therapy. Such dedication would provide the stimulus for comparative and controlled assessments of different therapeutic techniques. Continued study is urgently required of the selection of patients for various therapies; the application and mode of action of the therapies; and the role of social and milieu factors in supporting the effects of our therapies. Assessments require a meaningful classiﬁcation of subjects. The behavioral variables alone, which are the basis of our present diagnostic schemata, are unsatisfactory. Study is urgently required of the applicability of social and demographic variables; psychological task performance proﬁles; typologies based on behavioral response to deﬁned stresses or drugs; and physiological reactivity measures. Such classiﬁcations are also essential for any biochemical, physiological, or evaluative study to provide homogeneous samples and comparable controls. Assessments also require meaningful indices of evaluating change. Present global “improvement” ratings and socialization measures are inadequate. Whether the intervening variable be milieu therapy, psychotherapy, drug therapy, or time, the criteria of behavioral change require deﬁnition. The applicability of rating scales, language tasks, self~ratings, psychophysical change scores, family assessments, etc., require study and evaluation. Recent studies of psychotic subjects have provided the suggestion �MAX FINK 168 that there is a neurologic factor in a group of the schizophrenias. The high incidence of electrographic and neurologic dysfunction, the lack of behavioral response to all therapies, and the relentless course of the illness suggest an “organic” involvement in this cluster. Such a substrate must be clearly sought by the application of biochemical, neurophysiological, and epidemiological techniques to various clusters of young psychotic subjects. These are broader views of some of the questions studied in the programs in experimental psychiatry of the past seven years. These programs, and the contemporary projects in biochemistry and in medicine, provide models of bootstrap studies undertaken with limited support. A dedication of Hillside Hospital as a Research Institute will provide the needed focus and impetus for the scientiﬁc and humanitarian forces of the community to join in a common endeavor to resolve the problems of the mentally ill. Acknowledgment: Participants in these programs include the present members of the Department of Experimental Psychiatry: Ira Belmont, Martin A. Green, Abraham Kaplan, Eric Karp, Donald F. Klein, John C. Kramer, Max Pollack, and Arthur Willner. Former associates included Karl Andermann, Joseph Jaffe, Robert L. Kahn, Hyman Korin, George Krauthamer, Nathaniel Siegel; and Research Fellows Barre Alan, Fred Coleman, Harold Esecover, Stanley Friedman, Henry J. Lefkowits, and Robert Shaw. The cooperation of Arnold G. Blumberg of the Department of Medicine in the present program is gratefully acknowledged. The reports listed here are the result of the collaboration of these workers and the professional staffs of the hospital who gave unstintingly of their time and their good-will. REFERENCES (1) ' This Journal, 1:21, 1952; (2) ibid., 2:67, 1953; (3) ibid., 4:3, 1955; (4) ibid., 4:134, 1955; (5) ibid., 5:67, 1956; (6) ibid., 6:197, 1957; (7) ibid., 6:207, 1957; (8) ibid., 6:216, 1957; (9) ibid., 6:229, 1957; (10) ibid., 6:241, 1957. (13) Neurology, 4:211, (15) ibid., 76:23, 1956; 1956; (18) EEG Clin. (20) ibid., 10:207, 1958. (21) ]. Am. Med. Assn., 166:1846, 1958; (22) Dis. Nero. Sys., 192113, 1958; (23) ibid., 19:227, 1958; (24) Arch. Neurol., Psychiat., 80:380, 1958; (25) ibid., 80:73, 1958; (26) Neurology, 8:682, 1958; (27) Psychopathology of Communication, New York: Grune 8c Stratton, 126, 1958; (28) Psychopharmacology Frontiers, New York: Little, Brown, 325, 1959; (29) Proc. XV Int. Cong. Psychol, North Holland Publ., 238, 1959; (30) J. Nero. Ment. Dis., 128:243, 1959. (31) Arch. Gen. Psychiat., 1:565, 1959; (32) EEG Clin. Neurophysiol., 11:398, (11) This Journal, 10:84, 1961; (12) ibid., 10:97, 1961; 1954; (14) Arch. Neurol., Psychiat, 72:233, 1954; (16) ibid., 78:516, 1957; (17) Conf. Neurol., 16:88, Neurophysiol.,9:180,1957; (19) ibid., 10:162, 1958; �EXPERIMENTAL PSYCHIATRIC RESEARCH 169 1959; (33) ibid., 12:243, 1960; (34) Canad. Psychiat. Assn. ]., 4:1668, 1959; (35) Proc. Int. Cong. Neurol. Sci., Pergamon, 613, 1959; (36) Am. J. Psychol., 72:384, 1959; (37) J. Neuropsychiat., 1:45, 1959; (38) EEG Clin. Neurophysiol., 12:359. 1960; (39) Am. ]. Psychiat., 116:839, 1960; (40) Neuro-Psychopharmacol., 1:441, Elsevier, 1960. (41) J. Nerv. Ment. Dis., 130:235, 1960; (42) ibid., 1302187, 1960; (43) Arch. Neurol., 2:547, 1960; (44) Dynamics of Psychiatric Drug Therapy, Springﬁeld: Thomas, 29, 1960; (45) J. Neuropsychiat., 1:242, 1960; (46) Am. J. Psychother., 15:46, 1961; (47) Neuro-Psychopharmacol., 2:30, Elsevier, 1961; (48) ibid., 2:381, 1961; (49) Arch. Gen. Psychiat., 4:259, 1961; (50) ibid., 5:30, 1961. (51) ]. Nerv. Ment. Dis., 132:153, 1961; (52) Medicina Experimentalis (in press); (53) VA Conf. Psychopharmacology (in press); (54) Arch. Gen. Psychiat., 2:652, 1960; (55) Unpublished manuscript; (56) Psychiatry, 21:249, 1958; (57) Comparative Psycholinguistic Analysis of Two Psychotherapeutic Interviews. New York: Int. Univ. Press, 1961. ° Due to the length of this Bibliography, it is presented in an abbreviated form. ��IIIIIIII, IIII III IIIII, IIIIII I mill‘iﬂﬁl IIIIIIIIII IIIII 3,963.4. 16"”1WI m3 “It W “WI IIII. 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III III III. IIIII. IIII PIIIIII. II. XIIia II IIIIIIIIII IIIIIIII I: IIII IIIIIIIIIIII* IIIIIIII IIII ~ I ., . “t “I; _ .I I. "In”. IIIIIII II ’ I I ' IIII I IIIIIIIIIIII A “I; IMIS, '1’ ‘ I mm a“; IIIII_IIIIIIIIII II ‘4‘. MI, “I IIIIIIIII IIIIIII ', gIIIL L;_ ’IIIIIIIé;, ”If! I tit _.. �grnnnrnxnr 0! lggllillll&L PBIBlItYI! [I‘LSIDI SPIIA ngoontattoso 1261 cornbrul tutoriality and the BIG in Iolntton to Psynhtltry, lbtropolitan :no Socioty, Jan. Audurnnan, [.3 89:. run ﬂhnugtu on twat. and chronic Janin1-trat10u of Pagwhatropie Aconts 1n ’ayahittrie Subaootl, cont. on 136 3:! Hanan Payohapharnaaology, Ubrld 6:33:00. 92 Puyugintry, lentrtal, Juno. 1n 02 loo-grub luturo Puyuhtntrio Plunntnc, u.: lolrink, coat. on “Future trend: in Hospital and con-unity faith:lie-pun, April. any“, nun-.1 1-11,. rank, n.: Prciautton 01 Individual rataout Increas- to convulV; Baccarat cont. eta-tunati. Annual ct '1 atvahrhorcpy. unto . Round in At‘ttudou Pros-nu, tbs troutnont Stat! rink, 3.: lab}. on lbnnnru; 1321:0300: on ’uynhophnrnnaologia hut-wt, AH, ensue, my. link, 3.: BilB‘lIiOl a: Ptythologicnl and ltoohcnietl Synthosou Occurring Duran: 10907097 tron Parana-cl, by lagoon, 8., Andornnnn, K.: It“. ABA, III. rank, n.: laurophyuiologic«Adaptive 1:0! or canvulutvo rhorupy Bound table on 'luarophyutological chin... with iloetroconvulsivo rhurapy', ARA, chioaao, ”by. rank, u.a chn1runn, coat. on Ila tad Eula: Paychcpharnnaoloxy. World CongrOII of Plyuhlutry, Houtrutl, Juno. rink, u.: 336 troqnoucy tad rnynhotropio Bras Activity, nautuchn Arbuitoaunoxnschttt tit luurnpnychopharnukolozio, hub-r: , Supt. rank, n.: In. convulsive thorapy Press-a, Itstoru nil-our: Paynhtntrtc Sacioty, at. tonic, ectobar. rink, 1.: Ila and lulnn rayohophlauaaolony, 2.1a notioutl Ioaosrch contoronoo, lovonhor. :14 lohuvtor, link, n.2- Plyohotrtplc Brunt, train Function ancona county 8.010%: a: Icurology 33¢ Puychintry, Duct-bar. �Q .2“ 5195.9’ and :39 r11okcr rruqnaaay 3.: critical x»rp 3911:511Sty ; Study, Sulturl Payohaiuztcnl Lauoutu‘tul, Pundnlphu , lurch. 11.13, 3.: rypolou at thnviorsl Gunman with Ph¢ngthtuuiao ﬁndicntlan, Gout. nu auhtsophrcutn, at. Elisabeth' a lcupztal, J;n., W‘shingtan. Pollack, n.:' 3.1. a: ltur01&¢tea1 Dyntunotlon 1n tho childhood schizophraninn, Lynx. arthapuyohiatric Auioc., 8.3., Burah. in Pollack, n.: scatnl £Ipo¢ta of Paytltnirtc Ironinout YA V1 Aunnnl Problcnn, Hothtdologia loupst‘la: first nsonareh can:., Bantinuaﬁt, Karen. “ or Sinnlﬁantous StimulaPullnck, H.s attordcrcd Pgraopt1¢n ttou a: rsoc-aad Hand: A Ravine and thaory, Sac. 3101. Payohtnt., Atlantic Gity, Juan. 810301, 1.: Diagnosis and truatnon‘ 1n Thrao Pnywhtntrto noapitala, An. Saelologtcal Lss¢o., 8%. Louis, Aug. �\ PUBLICATIONS OF DR. MAX FINK 1950 1. 2a. Subdural Hematoma Developing During Hospitalization, Amer. J. M. 1950 Dr. (With Green). 107: 381-383, Pszchiat. Patterns in Perception of Simultaneous Tests of Face and Hand, Trans. Amer. Neurol Assoc. 72: 250, 1950 (with Drs. _' Ereeni. & Arch. Neurol. ibid, Pszchiat. ﬁg: 355-362, 1951. M.B. Bender and M. .... 3. 1952 Test as a Diagnostic Sign of Organic Mental Syndrome, Neurologz, 2: h6-58, 1952 (with Drs. M.B. Bender and M. Green}. Tactile Perceptual Tests in the Differential Diagnosis of 1952 21-31, Hillside J. Hosp. 1: Disorders, Psychiatric (with Dr. M.B. Bender). A Clinical Evaluation of Carotid Angiography, Conf. Neurol. 13: 181-195, 1952 (with Dr. J.M. Stein). Exosomesthesia, or Displacement of Cutaneous Sensation into 1952 Amer. Assoc. 1Q: Neurol. Trans. Space, Extra-personal .B. Ben er . (with Drs. M.F. Shapiro an & 1952. h81-h90, Neurol. Arch. éﬁ: ibid, Pszchiat. .... Order of Dominance in Cutaneous Perception, Trans. Amer. Neurol. Assoc. 7h: 238-2h0, 1952 (with Drs. M.B. Bender and M. Green}. Patterns of Perceptual Organization with Simultaneous Stimuli, Arch. Neurol. & Ps chiat. 13: 233-255, l95h (with Drs. M.B. The Face-Hand '- Bender and M. areani. 1953 8. 9. HeDeielopment of Perception of Simultaneous Tactile Stimuli in 1953 (with Dr. M.B. 27-3h, 3: Neurologz Normal)Chi1dren, Bender . Perception of Simultaneous Tactile Stimuli by Mentally Retarded Adults, J. Nerv. Ment. Dis. 117: h3-h9, 1953 (with Drs. M.B. Bender and M. Green). �-210. 11. Spinal Fluid Findings Following Cerebral Angiography, Neurol— ( 1953 with Dr. J.M. Stein). 137, ogz'g: A Statistical Study of a Psychoanalytic Hypothesis: Absence of a Parent as a Specific Factor Determining Choice of Neurosis J. Hillside Hosp. 3: 67-71, 1953 (with Dr. S. Tarachows. 12. 13. Effects of Barbiturates on Perception, Trans. Amer. Neurol. Assoc. 15: 1953 (with Drs. M.B. Bender, P. Bergman and M. Nathanson). Homosexuality with Panic and Paranoid States (Case Report) J. Hillside Hosp. 3: 16h-19o, 1953. l95u Standardization of the Face-Hand Test, Neurology, h: 211-217, l95h (with Dr. M. Green). 1955 Test in Patients with Mental Illness, J. Hillside Hosp. 3: 3-13, 1955 (with Drs. R.L. Kahn and E.A. Weinstein}. Delusional Reduplication of Parts of Body after Insulin Coma Therapy, J. Hillside Hosp. A: 13h-1h7, 1955 (with Drs. R.L. Kahn and D. Graubert). The Amytal 16. 195 O\ 17. 18. 19. Relation of Amobarbital Test to Clinical Improvement in Electroshock, Arch. Neurol. & Ps chiat. 16: 23—29, 1956 (with Drs. R.L. Kahn and E.A. Weinstein). Evaluation of High-Dose Reserpine Therapy for the Relief of Anxiety, J. Hillside Hos . g: 67-77 (April) 1956, (with Drs. M. Wachspress, 1.5. Blumberg and J.S.A. Miller). Relation of Changes in Memory and Learning to Improvement in Electroshock, Conf. Neurol. lé’ 88-96, 1956 (with Drs. H. 20. Korin and S. Kwalwasser). Denial of Blindness Following Cerebral Angiography, J. Hillside Hosp. 5: 238-2h5, 1956. �-321a. Quantitative Studies of Slow Wave Activity Following Electroshock, EEG. Clin. Neuro hysiol. 8: 158 (abst) web.) 1956 (with Dr. §.E. Kahn). Relation of EEG Delta Activity to Behavioral Response in Electroshock: Quantitative Serial Studies, A.M.A. Arch. Neurol. & Psychiat. 18: 516-525, 1957 (with Dr. 5.5. Kahn). 1957 22a. Clinical Response to Megimide, EEG. Clin. Neurophysiol. 2: 180, 1957 (with Dr. M. Green). Clinical and Electroencephalographic Effects of Megimide in Patients without Cerebral Disease, Neurology 8: 682-685, EEG and 1958, (with Dr. A Green). Unified Theory of the Action of Physiodynamic Therapies, J. Hillside 26. M. Hosp. é: 197-206, 1957. Perception of Embedded Figures After Induced Altered Brain Function, Amer. Psychol. lg: 361, 1957 (with Dr. R.L. Kahn). Social Factors in Selection of Therapy in a Voluntary Mental Hos . g: 216-228, 1957 (with Drs. Hospital, J. Hillside R.L. Kahn and M. Pollacﬁ}. Role of Stimulus Intensity in Perception of Simultaneous Cutaneous Electrical Stimuli, J. Hillside Hosp. é: 2h1-250, 1957 (with Dr. H. Korin). 1958 27. Changes atholo grune & 28. 29a. in Language During Electroshock Therapy, in Psycho- of Communication, Ed. Hoch, P. and Zubin, gtratton, 1958, {with Dr. R.L. Kahn). J., Lateral Gaze Nystagmus as an Index of the Sedation Threshold, EEG. Clin. Neurophysiol. 12: 162-163, 1958. Effect of Diethazine on EEG and Significance for Theory of EEG. Clin. Neurophysiol. 19: 207-208, Therapy, Coggulsive 19 . Effect of Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy, A.M.A. Arch. Neurol. & Psychiat. 82: 380-387, 1958. �-uidem, Biol. Psvchiatr THE-195. 29c. New 30. 31. ‘ 32. 33a. b. Bha. b. YorE, ed. Masserman, , J., Grune & Stratton, Experimental Studies of the Electroshock Process, Dis. Nerv. Sys.. 12: 113-118, 1958, (with Drs. Kahn and Green}. Comparative Study of Chlorpromazine and Insulin Coma in the Therapy of Psychosis, J. Amer. Med. Assoc. 166: 18h6-1850,1958 (with Drs. R. Shaw, G. Gross, and E.§. Coleman). Electroencephalographic Correlates of the Electroshock M. 1958 Green). Dr. Nerv. (with Dis. 227, Bye. l2: Process, Experimental Studies of Convulsive and Drug Therapies in Theoretical Implications, A.M.A. Arch. Neurol. Psychiatry: & 1958 (ﬁEtE‘ﬁ?§T'§TE?'EEEE‘ 80: 733-73h (abst.), PSﬁchiat. an . . reEK). Alteration of Brain Function in Therapy, in Ps & N. Brown Co., Ed., Frontiers, Kline, Little, cho harmacolo y BosEon, 1958, Pp. 325‘3320 Effect of Anticholinergic Compounds on Post-Convulsive EEG Behavior, EEG. Clin. Neurophysiol. lg: 776 (abst.). Effect of Anticholinergic Compounds on Post-Convulsive EEG and Behavior of Psychiatric Patients, EEG. Clin. Neurophysiol. 13: 359-369, 1960. and 1959 35. 36. 37a. b. Effects of Diffuse Altered Brain Function on Perception, in Proc. XV Int. Con . Psychol., North Holland Publ., Amsterdam, [959, PP. 238-259 (with ﬁrs. R.L. Kahn and H. Kojéﬁ)..lk~u-Al Diff rences in Psychological Factors Affecting Individual Jwﬁfgvﬁt Behavioral Response to Convulsive Therapy, 2h3-2h8, 1959 (with Drs. R.L. Kahn and M. Po ac 128: Significance of EEG Pattern Changes in Psychopharmacology, EEG. Clin. Neurophysiol. 11: 398 (abst.) 1959. EEG and Behavioral Effects of Psychopharmacologic Agents, Neuro-Ps cho harmacolo y, ed. Bradley, P., Elsevier, REE-HES, T950. Amsterdam, 38ayr / Electroencephalographic and Behavioral Effects of Tofranil: Canad. Psych. Assoc. J. h: 1668-1713., 1959. v.9w. �-5; (abst.), 38b. Idem, EEG. Clin. Neurophysiol. 13: 2h3-hh 39. Relation of Tests of Altered Brain Function to Behavioral Change Following Induced Convulsions, The First International Con ress of Neurolo ical Sciences (III: EEG, Clinical Neuro— and EEIIepsyi, Pergamon,‘fondon, 1959, pp. STE-519 physiology W a n and H. Korin). ran 1960. . a of Set in the Perception of Simultaneous Tactile Stimuli, Am. Jour. Psychol. 13: 38h-392, 1959 (with Dr. H. The Role Korin). Personality Factors in Behavioral Reaponse to Electroshock l: J. Neuropsychiatrz Therapy, Kahn . h5-h9, 1959 (with Dr. R.L. Wm: Sociopsychologic Aspects of Psychiatric Treatment in A Voluntary Mental HOSpital: Duration of Hospitalization, Discharge Ratings and Diagnosis, A.M.A. Arch. Gen. Ps chiat. """ _1_: 565-571., 1959 (with Drs. R.L. and M. Pol ac . 1960 h3. Efficacy of Divided and Single Dose Schedules in Insulin Therapy, Coma J. Am. P8 Drs. A.G. BlumEerg and hh. h5. h7. h8. 1960 (with Eaderman). in Verbal Transactions with Induced Altered Brain Function, JNMB-IBO: 235—239, 1960 (with Drs. J. Jaffe and R.L. Kahn).: S;uw.UUub‘Jua'but Drug Induced Changes in Intervi w Patterns: Linguistic and Neurophysiologic Indices, in ‘__Dynamics of Psychiatric Drug Therapy, ed. G.J. Sarwer-Foner, C.C. Thomas, Springfield Changes 9“ pp. h6. 116: 839-h0, chiat. %. ’ Jaffe 1960, (With Drs. Jo Social Attitude (California and R.L. Kahn). Scale) and Convulsive Therapy -JNMB 130: 187-192, 1960 (with Drs. R.L. Kahn and M. Pollack). 5.“,"wllua-Du‘ Figure-Ground Discrimination After Induced Altered Brain Function, A.M.A. Arch. Neurol. 3: 5h7~551, 1960 (with Drs. R.L. Kahn and M. PollacES. F Prognostic Value of Rorschach Criteria in Clinical Reaponse to Convulsive Thera 1960 2h2-2h5, J. Neuropsychiatrz y, l: Kahng. (with Dr. R.L. r .2” //£ .'V ' '.. / «n: Ln 1 I aré/a /->" -'- f, 4' _.” ‘. a“ ’34 45.114.” 7;” gay” n)/m / (j " 6.. ff) ,1"? ' "'4 K p (1 ‘ H y ,y /" m; «1" (rm *4 I 3 . , w V if“. r 51:3 ‘ /7w,« 5mm... x {5" ‘ ‘*' 4'" /‘ (a 3.1;,' A A.' g ”z " e, p/fivJ’J‘ “l ' W. “if 3 f/ a 3 (f ‘- , / ’5 K £9 / 3%» u �- 1961 h9. Modification of Psychotherapeutic Transactions by Altered Brain Function, Amer. J. Psychother. 1E: hé-SS ( with R.i. Kahn). Neuropsychologic Response Patterns of Some Psychotropic Drugs, Neuro-Psycho harmacology 3: 38l-38h, ed. E. Rothlin, Elsevier, Amsterdam (with M. Pollack, E. Karp, G. J. Jaffe, SO. H. Esecover and Krauthamer and D.F. Klein). 51. Problem of Antagonists to Psychotropic Drugs, 30-320 ibid, Inhalant-Induced Convulsions, A.M.A. Arch. Gen.Psychiat. h: 259-266, (with R.L. Kahn, E. Karp, M. Pollack, M.A. Green, B. Alan and H.J. Lefkowits). 53. Behavioral Patterns in Convulsive Therapy, A.M.A. Arch. Gen. Psychiat. E: 30-36, (with R.L. Kahn). Sh. Sociopsychological Characteristics of Patients Who 132: Refuse Convulsive Therapy, Jour. Nerv. Ment. Dis. —' """"“"“"""""""" M. 153-157, (with Pollack). SS. EEG Techniques in Study of Psychotropic Drugs, Acta of on Techniques for Study of Psychotro ic Int'l Meeting Drugs, Soc. Tipografica Modense, Modena, 1951. Withdrawal Symptoms Following Discontinuation of Imipramine Therapy, Amer. J. Psychiat. 118: 5h9-SSO (with J.C. Kramer and D.F. Klein}. 52. Experimental Psychiatric Research at Hillside: Review and Prospect, J. Hillside HOSEital 19: 159-169, 1961. Prediction of Individual Patient Response to Convulsive Therapy, VA Coo erative Chemothera y Studies in Psychiatry é: 317-325, 1951. Social Aspects of Psychiatric Treatment in Three HospiVA Coo erative Chemotals: Methodological Problems, 202-205, 1951 (with Studies in thera Psychiatry é: M. PoElack, N. Siegel and R.L. Kahn). Quantitative Electroencephalography and Human Psychopharmacology: Frequency Spectra and Drug Action, Medicina Experimentalis i: 36h-369, 1961. '7 -.\,A.-r-w, . -ﬁm... , _. ,, .1 . um.» . .4 m A~ a ‘R .1.” �1961 c" h9. Modification of Psychotherapeutic Transactions by Altered Brain Function, Amer. J. Psychother. 15: h6- SS ( with J. Jaffe, H. Esecover and R. f. Kahn).“ Neuropsychologic Response Patterns of Some Psychotropic Drugs, Neuro-Psycho harmacology 2: 381- 38h, ed. E. Rothlin, Amsterdam (with M. Pollack, E. Karp, Elsevier, G. Krauthamer and D. F. Klein). Problem of Antagonists to Psychotropic Drugs, 30'320 ibid, Inhalant- Induced Convulsions, A. M. A. Arch. Gen.Psychiat. h: 259- 266, (with R. L. Kahn, E. Karp, M. Pollack, M. A. Green, B. Alan and H. J. Lefkowits). 53. Behavioral Patterns in Convulsive Therapy, A.M.A. Arch. Gen. Psychiat. E: 30-36, (with R.L. Kahn). 5h. Sociopsychological Characteristics of Patients Who Refuse Convulsive Therapy, Jour. Nerv. Ment. Dis. 132: 153-157, (with M. Pollack). 55. 56. Techniques in Study of Psychotropic Drugs, Acta of Int’l Meeting on Techniques for Study of Psychotro ic Drugs, Soc. Tipografica Modense, Modena, 1951. Withdrawal Symptoms Following Discontinuation of Imipramine Therapy, Amer. . Psychiat. 118: Sh9—SSO (with JKlein}. EEG J. C. Kramer and D. F. CriticalEEGFlicker Frequency and EEG Alpha: A Reliability Clin. Neuro hysiol. (with E. Karp and Study, M. Pollack}. ‘ Neurophysiologic-Adaptive View of Convulsive Therapy, J. Neuropsychiat: Disordered Perception of Simultaneous Stimulation of Face and Hand: A Review and Theory, Biological PsychiaM. IV: (with Pollack). try, Factors Associated with the Selection of Applicants for Out- Patient Psychiatric Treatment, Social Issues. (with The N. Siegel and R. L. Kahn). �1962 I..— 61. 62. Critical rlicker Frequency and Alpha: EEG Olin. lenroghzeio1., __c Study, EEG and x. Pollack). A Reliability 1962 E. Karp (with , of Action of Convaleive Therapy: The Neurophysioe logic-Adaptive View, J. Neurogezchiats, ;; 231-233, 1962. The node Disordered Perception of Simultaneous Stimulation of Pace and Hand: A Review and Theory, Biolo icel Pe chiatr , IV Ede Jo 6h. Hortil, Ch‘pe 31, (With He P011.Ck)e Tachietoeoopic Perception After Induced Altered Brain Function: Influence of Hental Set, J.l.H.D., : , 1962, (with 1!. Pollack, 11.1.. Kahn and E. Kerp). Psychiatric Reaction Petterne to Inipraline (Torranil), 1962 D.F. Au. Jour. Pezchiat., __: (with Klein). , 66. Behavioral Reaction Patterns with Phenothiasinee, A.M.A. 1962 D.F. Arch. Gen. Pczphiat., __: (with Klein). , Quantitative Electroencephalography and Hanan Peychopharaacology. II: Drug Patterns, in EEG Correlate of Behavior, ed. 6. Glaser. 68. Iniprenine an an Adjunct to Phenothianine Therapy, Cong. Pezchiatrz, __c , 1962 (with J.c. Kramer end D.F. Klein). �69. Motivation in Psychotherapy, (with 70. H. Co . Po ohintr , z , 1962 Siogol). Rating Sooloo as Bohoviorol cpango Hoaauroo in Payohophorna1962 cology, v.1. Coon. Chonothor. St. in Pozchiat., 1: , (with DJ. Klein) . ��1. 195“ ~- 1 ‘ .3)... Standardlzatlm of the Faee=~Hand Test, 1H1 . 1. . . ~..‘-.~-:- 1- _. 1.1,..1 "9:“ .1: (mthM. _Neumlog:’21'1=12'17*,~ if} ‘ -.1955 ; 157° 1.'i That 1n Patlents w1th Mental Illness, J1 .axld . (With . R9 Ed A01m; 126111). Kahn Ly} of ‘Deltslmal Redupllcatlm of Parts Insuhn after «)1...’ R1 13911147 Kahn L1 D1 and (mth H0321“; i151 Coma Therapy, - . ' A I ' . - .3 . of ' Relatmn E17 1 ' 1 ~ . . f;-';tal ____ 19.1 mmlxla 201 . Denlal S1. _ = ' of Bhndness Pollowmg Cerebral Angh , cal .2231 1”” 'bo ‘ ’ Response ' ; to Meglmde, ﬁle ”j 1197:206 r 213-1 f; '1' ; 1. . 1... =1. ‘ 3. 1 1 1 ’ 3 , of Megumde in Patlents mthout (mth M1 Greenl1 »"."I_phalog'aph1c Effects Cerebral Insease, Neum'Ly 18;". 682-685, A Umfled Theory of the Aenm of PhysL; . 231 5.; ‘ 1957? - . «11 ‘ . 1 111111111311, .. J1 ,~ » 1 . . ; . 1 1 1. _ . Percep'aen of Enbedded ﬁgures After Induced Altered Iram hmctlon, Arlen -_Ps »12 361, (with R1 L1 Kahn)1 ‘“‘ﬁf_= _ . , 1 . E ' '1 2511 i 1 261: Soclal Factors 1n Selectman of - 3 17'.“- ‘3 " 3 , ‘ Quantltauve Studlee 80f Slow Wave Act1v1ty Follcmno Electroshock, 158 (Feb1) Absmct (with R1; L1 Kahn)1 . :,li .‘7 ' Evaluatlcm Of High-Dose Fez-35': Therapy for the Rehef of Annety, J1;;H:LlJ.81de_ M1. A1 G1.B (mth (Apml), Wadxspress, .1 3057515 57.77, 'Relatlcn of Changes 1n Learnmg to Improvement in Electroshodt, and ("3.11.12 'arld '85:." K' waSSer) (mm Hﬁ 88"96 '18” - 5? ~1 Test to Chnlcal Improvement 1n Bleetmshock,‘ Arch New?“ Psichlat1; Chmagoﬂﬂe23-29, (w1th R1 L1 Kahn and E1 A1 Welnsteln) 1 . 1955 ' .” ‘ lay an . a Voluntary kntal Hospltal, J 1 H11151de:. "i 3 �, _ j, . ,R-Pwmmgw;wwﬁssuu 955.3,umnm'», a. . . ,_ . hock ' fef'lheor‘y sP: Con " '- 4 ,l 5x2 Therapy, Po Koch and Jo Zubin (Edltors), {Gr-me s‘ Stmtton, New. .p 125-139, '1; wt, methazme, on EEG and Behavmr- SIgmfIcance unease . , g3; 380-387 . Q Q . ‘ :1:- . . ,s \‘..:- '- 1‘s u.“ I, ILJMMJI-L‘LL . ,' ' a . . : u QL‘_=A-uzca-m‘:& :‘ﬁ'u was '.Q“ ‘ ,.Q.- .ijhV‘. 19 227 ' , . ‘ (w1‘th ’Ms I ‘n)s, .“v Q Bwemnental Studles 'o‘f Oonvuls1ve and Drug Theraples In Psyclua} 'Inphcanons, Arch Neurol“ Psychlato, meaty, 80 733-734Abstract, (mth Alterauon 1:, of Emu Functlon in Therapy, Em s C00, mule, :uezs Effect of ArrtIcholmec No pp‘325-332 1959., and BehaVIor of 19600 359=339. "101ﬁ12 as an Post-Oonvu131ve Psyehla' a'ilfie Panents , Electr-éeneeﬂ f: ,. L EEG 1959 I ‘ ' 35-0) I as "Effects In Proc. ‘XV Into Kalm Ro and 238-239 Austerdam), L; Holland, pp Amt}: en Percepuon, 1:0 BehaVIoral Response IndIVIdual DIfferenees In Rio Psyduologleal Factors Affectmg Ls Ka‘r-m and 'Convulswe Therapy, J]° new mento msquzsjzuaszua (szth Mo was of mffuse Altered Bram thctlm Pode) 9 , I. \ SIgnIeranoe of EBG Pattern Changes In Psychhanralogy, Neum 111.551010» 11k. 398 Abs ' . H ' 1: ��1951 (tmued) ' M031”Kahn)e 1 is Who Refuse Cmvulswe Therapy, Somyeheloglcal maractemstlcs of Patlents M, Pollackh J3, mm n‘ento (mth 153457 2132 Tea‘zmqmu 1:: Study of Psyebopm Draws, 3x3, £13.,”31103 EEC 360: _; 7" 1 ‘ 5;; ' ‘EJS'EID . : '- Masque ‘ * _, one Pollemng mcontlnuauan C46 51‘9‘9550 (With - 159631:sta . insauz, E . Ele ' 60;; E Jo - ..-. _ ,. . :é'. « ,1 I ’* « :1 E? 1629; i. /63 1 Eggs ijhActlm elol wlswe of _N_:;3:3c::ruat13 23133233 The Mode (21": gist}; ‘ .j.-_. 650 - ilj. 1%.th 31,-- Mp 362-36 J o , : . 1 . _ ;~' , A 1:29 Fa Klemh " ' The NemphysmloglesAdaptlve View, . of Face and Hand: A ;{~i‘;:"_‘"fw5at':0n‘ " 7'" : “22"430, (Wlth Mo Renew " Press, Inc;..,_ (Elenmn "(-2 . 0n: Pellack, 3 rehens Inﬂuence Of Ra Lo Kat-1n ~3PM1;]th4!a“.179-173 (szth 1 1"*0. Reactim Pattems 1:0. Im:.jjf;":;i‘:: 2132:4138, (mth ‘ Rehablllty Study, Electroence’ho M‘. Pollack). and Karp 'Z‘iiMy: -i; _‘ _ 3'4“ 3...»... i: '7 -5' . ’ , 1 . 2 :Tadustoscoplc Perception After Induced Altered Brain Mental Set, :Lonerve '65:) KIM)9 "‘ ' Alter-o ' 80u63 (nth E0 and Theory} «Jo-worn" 3 ~ 3111- 'Dlsordered Perceptmn Of 51ml1‘1_‘{-Ifi; E61!» ' F0 sane-3690 "anneal Fucker Frequency and EG Alpha New York)Chapta E Impnamme Therapy, and 13-0 -» : - 1962 . 2* dMe- «maﬁa -Quant1tauve Spectra and Drug Acum, Mada . g 61 off. _, Expemnental Psychlatmc Research at Hlllslde Renew and Prospect, Ja Hlllszlde _ Ej’V j:.at £118 ‘ r ;-;- +2 {j - ’“V Nu and Slegel)‘, ��Publications - 1963 and Human Psychopharmacology, (Abstracts, 1961 Meeting, Mbntreal), Electroenceph. clin. Neurophysiol. lg; 133-137. 7/~ EEG 72. Multiple Item Factors as Change Measures in Psychopharmacology, Psychopharnacologia M: #3-52, (with D. E. Klein). 13‘ Quantitative Electroencephalography in Human Psychopharmacology II: Drug Patterns, In: G. Glaser (Editor) EEG Correlates of Behavior, (Basic Books, New York), pp l77~197. 74; Comparative Studies of Chlorpromazine and Imiprandne, I: Drug Discriminating Patterns, In: P. B. Bradley (Editor), NeuroPs chopharnacolo , Vol. III, (Elsevier Publ. Co.), (With KL—Pollack'rD-r—EizKlein, A. G. Blumberg, I. Belmont, E. Karp, (In Press) J. C. Kramer and A. Willner). Vii Comparative Studies of Chlorpromazine and Imipramine, II: Psychological Perfornance Profiles, In: P. B. Bradley (Editor), Neuropsychopharmacology, Vol. III, (Elsevier Publ. Co.), (with M. Pollack, E. Karp, I. Belmont, and A. Willner). (In Press) wia’ and Human Psychopharmacology, III: Changes on Acute and ChronicnAdministration of Chlorpromazine, Imipagmine and Placebo (Saline), :W. P. Wilson and G. A. Ulett (Editors), Applications Quantitative 76. SS (In Electroence ofHEEG‘andWHumaﬁ"Psychopharmacology, h. Bibliography clin. Neurophysiol., Supplement 23, (in preparation), (With L. 77, * “ﬁg. 7" .. EEG w» Bouthilet E. Cromwell, and M. Brown). and Im1pram1ne of Chlorpromaz1ne on Perceptual Analytic Effects Ability, Perceptual Responsivity and Memory as Revealed in Rorschach Responses, J. nerv. ment. Dis., (with I. Belmont, M. Pollack and A. Willner). (In Press) �Nm~£xpcrim1ts1 B. ‘9. 1. BookRevimdeattm 23m" use, 33 W W3 Diffcmtial Trcctmnt and R. D. Win: and w. Simon, 1:. c. sispringficld. Illinois); 1959." 121-122. in Schizoplmmic. m. Revicwqé' Amh. Experimental Studies of the Mode of Action of Electroccnvulsivs Therapy Jun-Otto. Ottosoon (Editor) . get; pm KIWI c ("ET—MW, {swam Scam. 6'39 PM The i A Symbol Wo_ ” V“ .. 3"me m 1 clin. .3. Will J. Hillside (Bateugf’: “' R. 001m 1956. 111.7. Home 8101. 1952, Psychiatry H. Bruin (Editor), Pittsbm‘gh‘ﬁ 1961. ENG. 11093., 1962, 31;: Review“? .. W Doomtraliutim of Psychiatric Services and Ccntinuity Milbcnk of Md, 1961, CmL3thliM Pictorial Fund, Na York. 1982. Ravi“. ”of mm of. mm: cad m._ War, 1963, 3.: Jm» Intmticncl Dicticnm ' ’ in Clinical Medicine, harm KUniv. Pittsb‘n‘gh Press, on 0 (Esmgfyﬂwkgaﬁi 1361. E: :52. MMMHMNWNL '15.!) Psychic Graphs-M. of Pour “yﬂxginsgiﬁwﬂmiﬂﬁ V 78-79. ”W, Us 1;)“, C. C. Homology and WWW, cog, . a“ Wit: for Electra; Indicgtdgrs QumtiStctua cmvulc wk 'Ihcmpy. latter to the tar. {an};m. of ﬁg. 23: 292-293. P " mm Mt m, Emmi/1953. in of Inubmctim to Physical chiam,"w: Scrgcnt and E. Slctcr ”"W, An» 4 ' a; 1983*; and Wilkins new, 1mm“ (In mas) Review-dahntcl Mitch. ' , Cap 42.: ! ”1/ @3234 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource [Hillside] Hospital annual report (folder title). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-008 Date A point or period of time associated with an event in the lifecycle of the resource 1956-1960 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Experimental Psychiatric Programs at Hillside Hospital - A Review (several). Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/2f72d717289d05cb684207e823cb7f30.pdf 566433f2c3abf4221015fe305a951903 PDF Text Text Psychopharmacology erVicc Center ulletin N IMH-Sponsored Collaborative Study of Phenothiazine Treatment of Acute Schizophrenic Psychoses, p. 1 January 1961 NIMH Grant Support for Early Clinical Drug Evaluation Units, p. 3 NIMH—PSC Outpatient Study of Drug-Set Interaction, p. 4 Research Conference on Drugs and Community Care, p. 7 Conference on Information Needs of Psychopharmacologists, p. 13 The Psychopharmacology Research Unit at the Downstate Medical Center, Brooklyn, N.Y., p. 15 Experimental Psychiatric Programs at Hillside Hospital, ' p. 18 Coca-Leaf Chewing in the Andes, p. 22 Publications, p. 25 U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE - Public Health Service �Inquiries about the Psychopharmacology Service Center’s program are invited. Please write to: Dr. Jonathan 0. Cole Chief, Psychopharmacology Service Center National Institute of Mental Health Bethesda 14, Md. Correspondence regarding the Psychopharmacology Service Center Bulletin should be sent to: Dr. Lorraine Bouthilet Head, Scientiﬁc Information Unit Psychopharmacology Service Center National Institute of Mental Health Bethesda 14-, Md. The Psychopharmacology Service Center Bulletin is distributed at irregular intervals by the Psychopharmacology Service Center, National Institute of Mental Health, Bethesda l4, Md. It is issued for information purposes to investigators interested in psychopharmacology. It is requested that the Bulletin not be considered part of the scientiﬁc literature, and not be cited, abstracted, or reprinted. �NIMH-Spemered Collaborative Study of P/eemtbz'drz'ne Treatment of Acute Se/ez'gopbrem'e Pylcboyef The National Institute of Mental Health, through its Psychopharmacology Service Center, is sponsoring a collaborative study of phenothiazine treatment of acute schizophrenic psychoses. The comparative efﬁcacy of thioridazine (Mellaril) , fluphenazine (Permitil, Prolixin), and chlorpromazine (Thorazine) in the treatment of a large group of hospitalized acute schizophrenic patients will be evaluated at nine psychiatric institutions. Investigators at the collaborating hospitals applied for, and have now received, N IMH research grants which will support their participation in the study, which is expected to begin in February 1961 and to continue for 2 years. The grants were awarded to the following investigators and institutions on the basis of their interest and research experience, the availability of patients, and the geographical location and type of hospital organization: Principal Investigators Edwin M. Davidson Melvin M. Kayce Institutions Boston State Hospital Dorchester, Mass. Richard Steinbach Bernard Levy Georgetown University and D.C. General Hospital, Washington, D.C. Robert R. Knowles Edgar A. Moles Kentucky State Hospital, Danville, Ky. Kathleen Smith Washington University and Malcolm Bliss Mental Health Center, St. Louis, Mo. James H. Ewing Harold H. Morris University of Pennsylvania and Mercy-Douglass Hospital, Philadelphia, Pa. Frederic F. Flach Charles I. Celian Cornell University and Payne Whitney Clinic, New York, N.Y. Guy M. Walters Christopher F. Terrence Rochester State Hospital, Rochester, N.Y. Springﬁeld State Hospital, SykesVille, Md. George A. Ulett Martin Gross Irene L. Hitchman John Donnelly Francis J. Braceland Bernard C. Glueck, Jr. The Institute of Living, Hartford, Conn. The study is under the overall supervision of Jonathan O. Cole, Chief of the Psychopharmacology Service Center. Gerald L. Klerrnan, PSC Research Psychiatrist, *Prepared by Gerald L. Klerman, Research Psychiatrist, Psychopharmacology Service Center, National Institute of Mental Health, Bethesda l4, Md. will serve as project coordinator. Other members of the PSC staff who are involved in the study are Eva Y. Deykin, Research Social Worker, Martin M. Katz, Research Psychologist, and C. Jelleﬂ' Carr, Chief of PSC’s Pharmacology Unit. The Planning Committee, composed of the principal investigators in the collaborating hospitals and the participating members of the PSC staff, provides for the coordination and execution of the speciﬁc projects. Because of the parallels with the Veterans Administration Cooperative Studies of Chemotherapy in Psychiatry, the committee maintains close liaison with the VA Central Neuro-Psychiatric Research Laboratory at Perry Point, Md. The Committee on Clinical Psychopharmacology, a group of outside consultants appointed by the NIMH, serves as the advisory and consultative body to NIMH on this project, as Well as on other aspects of the Center’s clinical program. Members of this committee are Henry Brill (Chairman), Deputy Commissioner of the New York Department of Mental Hygiene, Albany, N .Y. ; Sol L. Garﬁeld, Professor of Medical Psychology, Nebraska Psychiatric Institute, Omaha, Nebr. ; Goldine Gleser, Associate Professor of Psychology, Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio; Leo E. Hollister, Chief, Medical Service, Veterans Administration Hospital, Palo Alto, Calif.; and George D. Ulett, Associate Professor, Department of Psychiatry, Washington University Medical School, St. Louis. Mo. DEVELOPMENT AND DESIGN OF THE STUDY The Committee on Clinical Psychopharmacology and the PSC staﬂ' designed this research project during the spring of 1960. Following general approval by the National Advisory Mental Health Council of the principles of the study, the Center staff discussed it with a number of clinical investigators who had previously expressed interest in such a project. In June 1960, representatives from more than a dozen institutions met to plan and clarify the research methods and aims of the study. A number of the investigators who attended the meeting subsequently submitted applications for an NIMH research grant to support their participation in the study. Thus the ﬁnal design and methodology of the study resulted from the combined efforts of the Committee on Clinical Psychopharmacology, members of the PSC staff, 1 �In psychiatry, cooperative research has been slower to and the principal investigators. The staff of the Biometric Laboratory of George Washington University, which operates under contract to the NIMH, will provide ongoing consultation on matters of research design and statistical techniques and will analyze the data from the study. The primary aim of the project is to evaluate the effects of two new phenothiazine derivatives, thioridazine (Mellaril) and ﬂuphenazine (Permitil, Prolixin) on schizophrenic symptoms and behavior by comparing them with the effects of chlorpromazine (Thorazine). Each of the 9 hospitals will study 40 patients (10 in each of the 4 treatment groups) . Newly admitted schizophrenic if the for selected will be 16 study 40 to aged patients they present two or more of the following types of symptoms or behavior: Thinking and speech disturbances, catatonic motor behavior, paranoid ideation, hallucinations, delusional thinking, disturbed affect and emotion, and disturbances of social behavior and interpersonal relations. The patients will be on the prescribed research treatment regimen for 6 weeks. A double-blind procedure will be used throughout. Improvement during the hospitalization phase will be assessed by the Lorr Inpatient Multidimensional Psychiatric Scale, the Burdock Ward Behavior Rating Scale, the Clyde Mood Scale, and clinical judgments. In addition to the primary aim, evaluating the efﬁcacy of the drugs, the study will also allow for the followup of 2 least for of at cohort patients schizophrenic a large made will be assessments 6-month At intervals, years. of the patients’ discharge status, psychopathology, social performance and adjustment, and treatment program. Social workers will interview family members for their perceptions of the patients’ progress, home conditions, and attitudes toward treatment. COLLABORATIVE AND COOPERATIVE RESEARCH Since World War II, collaborative and cooperative research, in which a number of institutions follow a common research design, has been successful in many areas of medicine. The trials of antimalarial drugs during World War II, the extensive studies of antituberculous drugs now in their 17th year, and the British-United States research on cortisone and aspirin in acute rheumatic fever are some examples. NIH experience with cooperative research includes the current extensive cancer chemotherapy program of the National Cancer Institute and the Collaborative Study of Cerebral Palsy, Mental Retardation, and Other Neurological and Sensory Disorders of Infancy and Childhood being conducted by the National Institute of Neurological Diseases and Blindness. 2 _ in of studies extensive penicillin the although develop, CNS syphilis during the 1940’s stands out as a notable AdministraVeterans the effort. In recent early years tion has developed its Cooperative Studies of Chemodemonhave studies VA now The in Psychiatry. therapy strated the value of cooperative studies as a means of clarifying important issues in psychopharmacology. From the scientiﬁc point of view, there are two major reasons for collaborative studies of psychiatric drug therapy. First, such studies allow one to increase the generalizability of ﬁndings. If the only question being asked is whether drug X is better than placebo, then the 40 of 20 with to obtained be often pagroups answer can tients. However, much larger groups of patients are discriminareﬁned make wishes to if (a) one necessary tions between compounds which are closely related chemically and pharmacologically, such as the phenothiazines; (b) to increase knowledge of predictors of drug response; whom for of a the patients deﬁne speciﬁc types to (c) or particular drug is best suited. Multihospital studies allow for comparisons among institutions. In the mental health ﬁeld there has been much discussion of the possible differences in the effectiveness of drugs given in varying hospital and clinical settings. A multihospital study provides both the number of hospitals and the number of patients needed to clarify these complex drug-environment interactions. The pros and cons of conducting large-scale, multihospital cooperative studies of psychopharmacological its and NIMH by been have weighed carefully agents advisory groups during the 4 years of the Institute’s proPSC. the administered by in psychopharmacology, gram The NIMH ﬁrst developed a wide program of basic and clinical studies in psychopharmacology, and has until now centered its major efforts upon the stimulation and support of individual research projects. While this program has resulted in a great deal of clinical drug research, it has not met the need for large-scale evaluation of widely prescribed psychiatric drugs. The several Cooperative Studies of Chemotherapy in Psychiatry which have been developed by the Veterans Administration in recent years have provided a great deal of useful information about some of the newer psychiatric drugs. The generalizability of these ﬁndings has, however, been limited by the special characteristics of the clinical material available to the Veterans Administration. The NIMH Collaborative Study of Phenothiazine Treatment of Acute Schizophrenic Psychoses has been designed to provide information on the effectiveness of new drugs in a population which will include female patients. The patients will, in general, be more acutely ill and will be treated in a wider range of hospital milieus than could be the case within the Veterans Administration. In addition, the study is designed speciﬁcally to explore possible interactions between hospital milieu and has than in systematic manner more a drug response �been possible in the earlier studies conducted by the Veterans Administration. The success of the Collaborative Study, a complex research endeavor, will depend upon close and continuing cooperation and collaboration between the research teams in the participating hospitals, the staff of the Psychopharmacology Service Center, and the advisory bodies of the National Institute of Mental Health. As this project develops, it is hoped that the participating groups will undertake a continuing series of investigations of the treatment of acute schizophrenic psychoses. NIMH Grant Support for Early Clinical Evaluation Unity Drag In November 1960, the National Institute of Mental Health announced the establishment of special grants for early clinical investigations of psychiatric drugs. The primary purpose of the grants is to broaden the present scope of early clinical trials of promising new compounds and to make it possible to screen more new drugs for effectiveness in the treatment of psychiatric disorders. The grants will be awarded to a limited number of carefully selected clinical units to support trials of promising compounds in patients to determine the safety, appropriate dose ranges, and side effects of the drugs, preliminary studies of their clinical effectiveness in the treatment of particular symptoms or syndromes, and small controlled comparisons of new drugs with known standard drugs or placebo. Because of the need for ﬂexibility in tailoring a clinical research design to ﬁt the types of drugs and types of patients under study, an attempt will be made to achieve an adequate balance between careful observational studies and small-scale comparative and controlled studies. This particular area was chosen for expansion because NIMH considered it to be more seriously in need of further support than either of the other two major stages of new drug development; i.e., (a) preliminary screening of new drugs in animals to determine safety and pharmacological activity, which is being adequately supported by the drug industry and by National Institutes of Health grants for basic research, and (b) deﬁnitive clinical drug research (controlled clinical trials and hypothesis-oriented clinical investigations), which is amply provided for by the existing NIMH research grant program in psychopharmacology. Expansion of support for early clinical drug evaluation was therefore recommended by the Advisory Committee on Psychopharmacology and by the National Advisory Mental Health Council, and the Congress subsequently provided funds for the establishment of special grants in this area. The program will be administered by the Psychopharmacology Service Center. �NIMH-PSC Outpatient Study The National Institute of Mental Health has recently awarded research grants to Karl Rickels, of the University of Pennsylvania, Philadelphia, Pa., and E. H. Uhlenhuth, of the Johns Hopkins University, Baltimore, Md., to support their participation in a special research project initiated by the Psychopharmacology Service Center. The study is a double-blind, placebo-controlled investigation of the effects of an active psychopharmacological agent (meprobamate) and physicians’ attitudes on a carefully deﬁned sample of neurotic outpatients. It is one of the ﬁrst known attempts to control experimentally the communication of differential attitudes by physicians when administering medication. The project is to be conducted at three clinics simultaneously, the Henry Phipps Psychiatric Clinic of the Johns Hopkins University, the Functional Clinic of the Hospital of the University of Pennsylvania, and the Neuropsychiatric Clinic of the Philadelphia General Hospital. The study was designed by the staff of PSC’s Special Studies Unit in collaboration with the two principal investigators, Drs. Rickels and Uhlenhuth, and was approved by the Committee on Clinical Psychopharmacology and the Advisory Committee on Psychopharmacology, both of which are appointed groups of consultants who serve the National Institute of Mental Health in an advisory capacity. The two principal investigators subsequently applied for and received, on recommendation of the National Advisory Mental Health Council, research grants to carry out the study. Coordination of the project will be handled by the Center’s Special Studies Unit, whose members are Seymour Fisher, Seymour H. Baron, Mitchell B. Balter, and Elizabeth Hackett. Under contract with the National Institute of Mental Health, the Biometric Laboratory of George Washington University, Washington, D.C., will assist in the analysis of the data. RESEARCH DESIGN AND METHODS The Outpatient Study of Drug-Set Interaction is part of a larger special program which is concerned with the effects of psychological set and social interaction upon drug response in both patients and normal subjects. The study has three main purposes: *Prepared by Seymour Fisher, Chief, Special Studies Unit, Psychopharmacology Service Center, National Institute of Mental Health, Bethesda 14, Md. 4 of Drug-Set Interaction“ To determine whether meprobamate, administered for a 6-week period at a ﬁxed dosage, is more effective than an inert placebo in the treatment of neurotic outpatients. (See Laties and Weiss, 1958.) 2. To determine whether patients’ expectations or set (as induced by contrasting behavioral roles by the doctors participating in the project) have a signiﬁcant effect upon treatment course. Set will be varied by training one group of doctors (the “T” group) to maintain a positive, consistent, enthusiastic, “therapeutic” approach to their patients; another group (the “E” group) will be trained to manifest a more aloof, uncertain, “experimental” approach in relating to their patients. The “T” therapists will attempt to convey the belief that they are treating the patient with a known, efﬁcacious agent; the “E” therapists will attempt to convey the belief that they are evaluating the agent. 3. To determine whether a signiﬁcant drug-set interaction exists; i.e., to test the hypothesis that a “T” set will potentiate response to the active drug. Following a pilot study of 24- patients, a total of 200 patients will be treated for a 6-week period, 50 patients being assigned to each of the following 4 treatments: Meprobamate combined with “therapeutic” set; mepro— bamate combined with “experimental” set; placebo combined with “therapeutic” set; and placebo combined with “experimental” set. The basic research design is in the form of a 2 x 2 factorial analysis, with each of the two independent variables being varied in two ways. Table 1 shows the four-cell design, which permits an exact statistical test (by analysis of covariance) of the three 1. hypotheses. Patients will be seen biweekly for 6 weeks. In order to rule out the effects of the personality characteristics of the doctors in the study, a total of 12 physicians will participate, 4 psychiatric residents at each of the 3 clinics. Thus, interclinic‘ comparisons will be possible. An attempt will also be made to validate the role behaviors in the doctors. TABLE 1.—-Researc}z Design Medication (N=200 patients) Set Meprobamate ......... ........ “Therapeutic” “Experimental” 50 patients 50 patients ....... ....... Placebo 50 patients. 50 patients. �The dependent variables are ratings—patients’ selfratings as well as doctors’ ratings—on a symptom-distress checklist, on the Clyde Mood Scale, and of overall change. Dropout rate will also be considered. BACKGROUND OF THE STUDY The impetus for this study stems from the Psychopharmacology Service Center’s interest in various methodological problems involved in the clinical evaluation of psychiatric drugs, in particular the problem of attitudinal variables and their effect upon drug response. The basic thinking underlying this approach was presented in a draft paper prepared some months ago (Fisher, 1960). That paper also pointed out the kinds of speciﬁc research designs which would test for any unique interactive effects between medication and set (i.e., attitudes and expectations) . A review of the literature has revealed much clinical suspicion that patients’ expectations may interact with medication to produce differential clinical effects, but supporting evidence for such speculations is rather tenuous. Sabshin and Ramot (1956) note that: “Often the patient may interpret a change in his internal milieu in the context of being a change in the expected direction. It is thus possible for a subtle type of communication to take place . . . and this may potentiate the drug effects. Hence a relatively speciﬁc effect can be geometrically increased.” However, the investigators do not present empirical evidence. That a particular drug can have one effect under one psychological condition and a quite different effect under another psychological condition is well documented experimentally. This holds for animals (e.g., Brown, 1958; Chance, 1946; Gunn and Gurd, 1940) and for humans. In an elegantly designed experiment, Hill, Belleville, and Wikler (1957) clearly demonstrated a signiﬁcant interaction between incentive conditions and drug response in human subjects. Nowlis and Nowlis (1956) and Starkweather (1959), in studies of normals, report complex interactions between drug response and the subject’s perception of other subjects’ behavior. In the clinical setting, Feldman’s paper (1956) indicated that the physician’s attitude toward medication is reﬂected in his report of degree of improvement in psychiatric patients. However, that is not conclusive evidence for an interaction effect, since placebos were not employed for comparison, and evaluation of the patients was badly contaminated by the fact that each of the participating physicians made his own overall estimate of change The latter comment also applies to a clinical study reported by Kast and Loesch (1959), who similarly argue that the action of a psychopharrnacological agent can be made disproportionately more effective than an inactive placebo when the medication is administered within the context of a positive set (i.e., a given set can potentiate drug response). While their theoretical formulation is quite ingenious and heuristic, their experimental design does not afford a valid test of their hypothesis. A more dramatic study concerned with potentiation was published by Uhlenhuth et al. (1959). In a doubleblind, cross-over design using meprobamate, phenobarbital, and placebo, two physicians obtained signiﬁcantly different rates of drug-related improvement in their patients. One physician (who was “therapeutic” and enthusiastic) obtained signiﬁcant differences between the active drugs and placebo, while the other physician (who was more skeptical and “experimental”) found no signiﬁcant differences among the three agents. The results of this study are certainly suggestive, but they are difﬁcult to interpret since one cannot state deﬁnitively what the effective differentiating characteristic(s) between the two physicians was (i.e., in addition to “attitude,” they obviously differed in an inﬁnite number of ways), and because of the complication introduced by using a three-way cross-over of drugs. In March 1960, Irvin S. Wolf, of Denison University, and PSC’s Special Studies Unit tested the interaction‘ hypothesis on normal subjects who were given dextroamphetamine and placebo under three different attitudinal sets (consistent, uncertain, and inconsistent expectations). Analysis of covariance for a 3 x 2 factorial design on subjective and psychomotor dependent variables revealed a number of signiﬁcant or near-signiﬁcant trends (all in the anticipated direction) suggesting a drug-set interaction. The signiﬁcance of this research approach is perhaps revealed in the following considerations. When reference is made to a “place-b0 response,” it is evident that the concept is a complex one. In a placebo-controlled experiment, not only is there a general set of expectations associated with the symbolic value of receiving medication from a prestige authority, but there are also undoubtedly speciﬁc expectations about the nature, purpose, and action of the medication. These different kinds of expectations have been discussed elsewhere (Fisher, 1960), but one important implication is worth repeating here. The most frequently used model in controlled evaluations of drugs assumes that the “placebo response” (i.e., the amount of change attributed to nonpharmacological factors) is a type of “error” involved in assessing the pharmacological effects of the active drug: If one can accurately measure the degree of placebo response, that effect can be subtracted from the total effect, thus giving the pharmacological component. This assumes that the psychological (i.e., general and speciﬁc expectations) and the pharmacological components are additive in nature. As shown in ﬁgure 1, speciﬁc expectations 5 �CLINICAL IMPROVEMENT SET A FIGURE 1. SET B Hypothetical Data Illustrating Additive Model. (sets A and B) do affect the response, but essentially equally for subjects who receive the active drug and for those who receive placebo. Irrespective of the set under which the drug is evaluated, the conclusion is the same—— the drug is X units more effective than placebo. CLINICAL IMPROVEMENT PLACEBO\ SET A FIGURE 2. \\\ O SET B Hypothetical Data Illustrating Interactive Model. A quite different possible model, however, can be built on the‘ assumption that the pharmacological and psychological components are interactive. As shown in ﬁgure 2, the speciﬁc expectations in set A potentiate the drug response, and one cannot generalize the effect of the drug without taking into account the set under which it was administered. Note in ﬁgure 2 that if the drug were evaluated in an experiment in which only set B was operative, one would conclude that the drug was no more effective than placebo—a conclusion which, though 6 correct, would have to be limited to the conditions of the experiment. Figure 2 also shows, however, that under set A the drug was obviously superior to the placebo— an equally correct conclusion for the given conditions. Thus, if it were established that the interactive model is more appropriate for certain kinds of clinical evaluation, one would run the risk of rejecting as ineffective a treatment which really does have an effect (type II error) whenever the clinical trial is conducted under inappropriate conditions of set. A great deal has been written about the need for controls in clinical research. It has often been noted that new forms of therapy are enthusiastically received on the basis of early uncontrolled clinical impressions, only to be laid to rest by subsequent controlled evaluation (Cornell Conference, 1954) . Recent papers by Foulds ( 1958) and Astin and Ross (1960) show that a signiﬁcantly greater number of uncontrolled studies in psychopharmacology yield positive results than do controlled experiments. Undoubtedly, this difference can be partly attributed to such factors as lack of controls, faulty or biased measurement, faulty design, etc., in the uncontrolled studies, or to insufﬁcient dosage or duration of medication, or sampling bias, in the controlled experiments. On the other hand, it is possible that this difference is not all due to various kinds of “error.” If some genuine interaction effect should exist between physicianmilieu and drug action, that would go a long way in accounting for many of the apparent discrepancies between the ﬁndings of hardheaded researchers and those of equally hardheaded clinicians. In uncontrolled clinical trials, the patients may be exposed to a quite different “attitudinal” atmosphere: They more often see themselves as being “treated” rather than “researched,” and that might provide a quite different setting for drug action. In many controlled experiments, the patients are deﬁnitely aware that they are participating in a research project (implying “Let’s see if the drugs will help you”), and such a perception is probably reinforced whenever patients ﬁnd themselves periodically being observed, tested, and probed. The overall aim of the Outpatient Study of Drug-Set Interaction is to attempt to create experimentally these two contrasting attitudinal sets within the context of a controlled clinical evaluation. REFERENCES Astin, A. W., and Ross, S. Glutamic acid and human intelligence. Psychological Bulletin, 1960, 57, 429—434. Brown, B. Inﬂuence of inter-animal and environmental stimulation on action of central nervous system drugs. Proceedings of the Western Pharmacological Society, San Francisco, January 27—28, 1958. Chance, M. R. A. Aggregation as a factor inﬂuencing the toxicity of sympathomimetic amines in mice. Journal of Pharmacology and Experimental Therapeutics, 1946, 87, 214—219. �Cornell Conference on Therapy. How to evaluate a new drug. American Journal of Medicine, 1954-, 17, 722—727. Feldman, P. E. The personal element in psychiatric research. American Journal of Psychiatry, 1956, 113, 52—54. Fisher, S. Milieu controls in psychopharmacology. Manuscript, 1960. Foulds, G. A. Clinical research in psychiatry. Journal of Mental Science, 1958, 104-, 259—265. Gunn, J. A., and Gurd, M. R. The action of some amines related to adrenaline. Cyclohexylalkylamines. Journal of Physiology, 1940, 97, 453—470. Hill, H. E., Belleville, R. E., and Wilder, A. Motivational determinants in modiﬁcation of behavior by morphine and pentobarbital. A.M.A. Archives of Neurology and Psychiatry, 1957, 77, 28—35. Kast, E. C., and Loesch, J. A contribution to the methodology of clinical appraisal of drug action. Psychosomatic Medicine, 1959, 21, 228—234. Laties, V. G., and Weiss, B. A critical review of the efﬁcacy of meprobamate (Miltown, Equanil) in the treatment of anxiety. Journal of Chronic Diseases, 1958, 7, 500—519. Nowlis, V., and Nowlis, Helen H. The description and analysis of mood. Annals of the New York Academy of Sciences, 1956, 65, 345—355. Sabshin, M., and Ramot, J. Pharrnacotherapeutic evaluation and the psychiatric setting. A.M.A. Archives of Neurology and Psychiatry, 1956, 75, 362—370. Uhlenhuth, E. H., Canter, A., Neustadt, J. 0., and Payson, H. E. The symptomatic relief of anxiety with meprobamate, phenobarbital and placebo. American Journal of Psychiatry, 1959, 115, 905-910. Research Conference on Drugs and Community Care“ In September, the Psychopharmacology Service Center sponsored a “Research Conference on Drugs and Community Care” to bring a number of investigators together to discuss problems of research on the use of drug therapy in the care of psychiatric patients living in the community. The conference, held in Washington, D.C., dealt with studies of both acute and chronic patients, evaluations of home-treatment or day-hospital care, maintenance therapy, treatment speciﬁcally designed to prevent relapse in previously hospitalized patients or to treat relapsed patients in the community, and followup studies. The primary objectives of the conference were (a) to permit investigators whose research in this area is supported by NIMH to discuss problems and to exchange ideas and experiences related to solutions to problems; (b) to provide the Center, its consultants, and the participating research investigators with an overview of the nature of the research now being supported; (c) to determine what has been learned from these studies about the role of drugs in the community care of psychotics; and (d) to assess progress in dealing with the technical aspects of these kinds of research; e.g., the establishment of criteria and the development of methods for classifying patients and for evaluating change and adjustment. In addition to NIMH grantees conducting research on drug therapy in the community, the participants included investigators whose interests and experience were compatible with the aims of the conference and several who are just entering research related to this general ﬁeld. The conference was organized by Martin M. Katz, PSC research psychologist. The formal participants *Prepared by Martin M. Katz, Research Psychologist, Psychopharmacology Service Center, National Institute of Mental Health, Bethesda l4, Md. were Dean J. Clyde, Washington, D.C.; Jonathan 0. Cole, PSC; Joel J. Elkes, Bethesda, Md.; David M. Engelhardt, Brooklyn, N.Y.; Leon Epstein, Sacramento, Calif; Seymour Fisher, Houston, Tex.; Norbert F reedman, Brooklyn, N.Y.; Sol L. Garﬁeld, Omaha, Nebr.; Goldine Gleser, Cincinnati, Ohio; Bernard Glueck, Hartford, Conn.; Milton Greenblatt, Boston, Mass.; Martin Gross, Sykesville, Md.; Leo E. Hollister, Palo Alto, Calif. ; Martin M. Katz, PSC; Else B. Kris, New York, N .Y.; Jordan Lawrence, Sykesville, Md.; Mark Lefton, Columbus, Ohio; Samuel B. Lyerly, Washington, D.C.; David Mann, Brooklyn, N.Y.; Richard D. Morgan, Sacramento, Calif.; Benjamin Pasamanick, Columbus, Ohio; Leonard Pearlin, Bethesda, Md.; Seymour Perlin, New York, N.Y. ; George A. Ulett, St. Louis, Mo. ; and Joseph Zubin, New York, N.Y. The ﬁrst half of the program was devoted to reports on six research projects, each of which was related to some aspect of drugs and community care. The papers reporting the projects emphasized aims and general research design, methodological and operational problems, and plans for future work. The second half of the conference was devoted to theoretical and practical problems of methodology. In many cases, new methods and methodological problems mentioned brieﬂy in the research reports were presented in greater detail and discussed more fully during the second half of the meeting. Some of the points made in each paper are summarized in the following paragraphs. These summaries do not, of course, cover all of the points covered by the speakers, but it is hoped that they will provide at least enough information to convey some impression of the overall content of the meeting and of the major issues which were considered. �SIX RESEARCH PROJECTS Home Versus Hospital Care for Schizophrenics. Presented by Benjamin Pasamanick, Department of Psychiatry, Ohio State University Medical School, Columbus, Ohio. This study is designed to test the hypothesis that acute schizophrenic patients can be treated at home when proper public health care is combined with appropriate drug therapy. All ﬁrst-admission schizophrenic patients referred to the Columbus Psychiatric Institute are to be considered for the study. Those who are suicidal, homicidal, or so violently disturbed that it would be impossible to keep them in the home will be dropped from further consideration. The remaining patients will then be randomly assigned to one of the following three treatment groups: (a) A group treated at home with drugs plus frequent visits by a public health nurse; ( b) a group treated at home with placebo plus frequent visits by a public health nurse; and (c) a hospitalized group treated with the usual methods of the hospital. The three groups are to be evaluated before treatment, after 1 year, and after 2 years by psychiatric and psychological examinations, and by reports and ratings from nurses and social workers (including interview data from patients and their families). Quality of housing and general home environment of all three groups will also be rated. A public health nurse, working in consultation with the psychiatrist and social worker, will frequently visit each home-care patient to give nursing guidance and counsel to the patient and his family. Patients in the home-care groups will be hospitalized when that is recommended, on the basis of previously established criteria, by a diagnostic council from the Institute. The hospitalized group and the home-treatment groups are to be compared for total length of hospitalization, psychiatric condition, and family reaction and receptivity. The two home-care groups—one on placebo, one on drug—will be compared for rate of hospital admission. Discussion of this study was devoted to such matters as control of medication in the home-care groups, degree of comparability of the hospitalized and home-treatment groups, and problems related to hospitalization of patients assigned to home treatment. Later in the conference, Lefton, also from the Columbus Psychiatric Institute, presented a detailed discussion of the interview schedules which will be used in the study. A Study of Ataractics in Outpatient Schizophrenia. Presented by David M. Englehardt and Norbert Freedman, State University of New York, Downstate Medical Center, Brooklyn, NY. This project was described as a longitudinal study of the effects of tranquilizers on the community adaptation of schizophrenic outpatients. Questions of interest in the study are whether continuation of medication after an initial gain will prevent relapse, whether further improvement is noted when med8 ication is continued, and, when there has been no initial gain, whether improvement will occur after prolonged administration of drug. Changes in symptomatology and in social behavior associated with drug therapy will be assessed after a brief time and after sustained administration of drug. The following criteria of outpatient adaptation are being used: Maintenance of outpatient status (i.e., avoidance of hospitalization), reduction in psychopathology, freedom from functional decrement, reduction in social dysfunctioning, concordance between social adaptation and psychopathological changes, and stability of clinic course during a prolonged period (up to 24 months) of continuous treatment with drug or placebo. Baseline psychiatric and psychological data are obtained during the ﬁrst week. The patient is then placed on promazine, chlorpromazine, or placebo. Dosage levels are ﬂexible and medication is administered doubleblind. Supportive psychotherapy is given, but the emphasis is on medication. Patients are seen in the clinic at frequent intervals. Detailed re-evaluations are conducted after 3 months and at the end of 1 year. Preliminary ﬁndings reported by Engelhardt show that the rehospitalization rate is signiﬁcantly lower in the drug groups than in the placebo group. Also, the number of patients showing clinical improvement at 6 months is much higher in. the drug groups than in patients on placebo, as is the rate of improvement of a group of patients who demonstrate severe thought disturbance on initial evaluation. Further, the amount of social dysfunctioning as reported by the relative has been found to be greater in the placebo group than in the patients on chlorpromazine. A detailed report on the accumulation and analysis of the data on social behavior was presented later in the meeting by Mann and Freedman, participating investigators in the study. Freedman also discussed the problem of dropout, which has been one of the major difﬁculties thus far. Attempts to distinguish clear-cut differences in personality or psychopathological features in the patients who drop out have not been successful, though the speculation is that there may be a complex interaction between the patient’s expectation concerning treatment and what he actually experiences in the clinic. Discussion of this project centered around the speciﬁc kinds of information obtained from the patient’s relatives, the handling of such data, problems of following up patients who drop out of the study, possible reasons for dropping out, side effects (which have not been a problem), the ethics of using placebos, and the possible relation between degree of social dysfunction and level of drug dosage. Drug Therapy in a Daycare Facility for Relapse Control. Presented by Else B. Kris, Manhattan Aftercare Clinic, New York, NY. The aims of this project are to evaluate �day hospital care plus drug therapy as a means of controlling relapse and preventing rehospitalization of formerly hospitalized psychotics, primarily schizophrenics. Acutely disturbed (relapsed) patients who would ordinarily be rehospitalized are randomly assigned to one of two treatments: (a) Rehospitalization and usual hospital care, or (b) drug therapy in a special day hospital afﬁliated with the Research Unit of the Manhattan Aftercare Clinic. At the time of assignment to a treatment group, the psychotic condition of each patient is determined by use of the Wittenborn Psychiatric Rating Scales. Patients assigned to the day hospital are immediately started on intensive pharmacotherapy, with drug dosage individualized according to patients’ needs. Length of time between onset of relapse and subsequent remission in the two treatment groups, and community adaptation following remission, are being compared. After patients are released from either the hospital or the day hospital, the investigators will study the patients further to determine whether remission achieved in the day hospital is temporary or lasting. Community adaptation is being measured by a set of scales developed by Katz, who described them more fully later in the conference. Kris reported that the most remarkable ﬁnding thus far has been the rapid achievement of remission in the day hospital patients, who return to their jobs far sooner than patients who were rehospitalized. She also noted that treatment in the day hospital seems to promote better community adjustment and that patients seen in the day hospital seem to have learned that they can discuss recurrence of symptoms without fear of being rehospitalized. Questions about the details of handling patients at the day hospital were discussed, along with comments about the liaison betwen the day hospital and employment agencies or vocational rehabilitation centers, possibilities of using the center as a training facility for physicians and psychiatrists in private practice, criteria for admission to the study, and the stafﬁng and physical layout of the day hospital. Termination of Treatment With Ataractic Drugs. Presented by Martin Gross, Springﬁeld State Hospital, Sykcsville, Md. This project, begun in 1958, investigated the importance of continuing chronic psychotic patients on medication after their release from the hospital. All patients in the study were ﬁrst stabilized on one of six drugs and then randomly assigned to either (a) a control group which was continued on active medication, or (b) an experimental group which was gradually transferred from drug to placebo under double-blind conditions. Patients who relapsed were removed from the study and placed on medication if they had been receiving placebo or were rehospitalized. The criterion for relapse was the clinical judgment of the treating psychiatrist. A rating scale developed to permit objective determination of the ' psychiatric condition and social adjustment of the patients was described by Lawrence during the second half of the conference. During the preliminary phase of the study, and at intervals thereafter, patients were evaluated by psychological tests, and their families or the people with whom they were living were interviewed by the social workers. Frequency of relapse while on active medication was compared with that which occurred while patients were on placebo. Summarizing some of the ﬁndings from the study, Gross reported that relapse occurred signiﬁcantly more frequently during the withdrawal or placebo period, the relapse rate being approximately three times as high during the placebo period as during the period on medication. He also noted that three-fourths of the patients who relapsed while on placebo did not require rehospitalization but were able to regain stability after medication was resumed. Among the problems of methodology and design which Gross enumerated were the difficulties experienced in dealing with six different drugs rather than with a single drug. He noted also that the generalizability of the ﬁndings was limited in that patients in the project—— chronic psychotics who were free from alcoholism and organic brain damage and who were able to attend the clinic regularly—could not be considered representative of the general outpatient clinic population. In reply to a question, Gross stated that he felt the low incidence of dropout was due to the personal contact between the patients and the social worker and physician. Other points discussed were the difficulties of maintaining double-blind conditions and of objectively determining the point of relapse, procedures for determining whether the patients took their medication, and techniques for switching patients from drug to placebo. Drugs and Social Therapy in Chronic Schizophrenia. Presented by Milton Greenblatt, Massachusetts Mental Health Center, Boston, Mass. This study was initiated to determine (a) how much of drug effectiveness is due to the drug per se and how much to other causes, and (b) whether there are signiﬁcant social and environmental differences between hospitals which may account for the differences between drug effects in one setting and another. Sixty chronic schizophrenics were transferred from a State hospital to an intensive treatment center (the Massachusetts Mental Health Center), where 33 received drug in addition to other therapy and 27 were not given drug. Comparison groups were composed of 55 patients remaining at the State hospital, of whom 25 were assigned to drug treatment and 20 were not. In neither setting were the patients assigned to “research wards.” The criteria on which patients in the four groups were compared were clinical improvement and discharge rate. �Findings reported by Greenblatt showed only slight differences between the State hospital groups and the MMHC groups after 6 months. At 18 months, however, there were differences which suggested the possibility of a beneﬁcial carryover of milieu effects in patients who had originally been transferred to the MMHC. In commenting on discharge rate, Greenblatt indicated that the State hospital criteria for discharge are much more stringent than those of the MMHC. He also noted that discharge rate was affected by the availability of a family or a transitional facility to which the patients could be released. Among other special problems which he discussed were the difﬁculties of incorporating chronic schizophrenic patients into MMHC treatment routines without changing the environment of the Center, the reasons for having decided not to attempt double-blind administration of drugs, and the possible signiﬁcance of any effects of “transfer trauma” in patients moved from one setting to another. The Eﬂeet of Ataractie Drugs on Hospital Release Rates. Presented by Richard D. Morgan and Leon Epstein, California State Department of Mental Hygiene, Sacramento, Calif. This project is one aspect of a much broader study of population movement in the California State mental hospitals. Morgan’s paper was devoted to the overall study, and Epstein’s to the parts of it which are speciﬁcally concerned with drug therapy. Morgan ﬁrst brieﬂy explained the system of cohort followup analysis which is being used, noting that it is essentially the application of individual followup analysis techniques to a group of patients who have one or more characteristics in common—cg, age, year of admission, sex, diagnosis, etc. Having set July 1948 as the beginning point for the collection of data, the California State Department of Mental Hygiene is now systematically coding and punching onto IBM cards detailed information on all ﬁrst-admission patients in the State’s 11hospital system. The records are not restricted to the period of ﬁrst admission, but cover residence during subsequent readmissions in the same hospital or in a different one within the State system. A wealth of information is collected for each patient: Vital statistics, diagnosis and details of treatment, and data covering current hospital entry, previous hospitalizations, leaves, etc. Thus, a patient’s complete record of hospitalization can be examined in great detail at any point during the followup period, and cohorts can be constructed on the basis of any combination of a large number of descriptive characteristics. Morgan observed that this technique permits analysis of the frequency or the likelihood of occurrence of changes in status during any speciﬁed interval in the followup. The status of a given cohort of patients can be examined for any period of time. Data being collected in this study are proving valuable in studies of current administrative policies and investigations of the 10 effectiveness of new or expanded programs. This system is also valuable in providing retrospective control data which may be used in lieu of a control group in evaluations of speciﬁc programs. Following Morgan’s report, Epstein discussed a particular set of analyses of these data in which the aim is to evaluate the role of tranquilizing drugs in the recent decline in State mental hospital populations, a decline which has occurred in California as well as in other States. For the period from July 1, 1955, through December 31, 1957, additional information (i.e., additional to that routinely obtained for all patients) on details of drug therapy was recorded for each patient in the State system who had received treatment with drugs. Name of the drug, total amount of drug administered, number of days on drug, and the reason for stopping drug treatment were among the additional data recorded. By looking at signiﬁcant subgroups—for example, ﬁrst-admission male schizophrenics between the ages of 25 and 4-4—the investigators hope to be able to draw certain conclusions about shortened periods of hospitalization and their association with drug therapy. Data concerning drug usage during the period of the study are now being analyzed. Epstein stated that investigators participating in this study are “painfully aware” that the data involve a variety of physicians, drugs, settings, and timings of drug treatment in relation to admission, as well as a variety of discharge policies among the 11 different hospitals. Despite such problems, the data do provide some reﬂection of what may be associated with drugs as they are used in a total system. A number of the conference participants were particularly interested in certain speciﬁc applications of data being recorded in the California studies or of cohort analysis techniques generally. Others expressed concern about the use of release rates as a criterion in studies such as these, questioned the comparability of present-day schizophrenics with those of a few decades ago, or asked whether the current “decline” in certain hospital populations might not be in part a reﬂection of the decline in birth rate which occurred during the depression. RESEARCH METHODS The section of the conference which dealt speciﬁcally with methods was devoted to technical and theoretical problems which arise in carrying out research on drugs and community care. In accord with evidence that drugs in combination with other psychiatric treatments are contributing signiﬁcantly toward. maintaining formerly hospitalized patients in the community, investigations have been initiated which are aimed at specifying the nature of these treatments and their effects. For purposes of the conference, the question of speciﬁcity was seen as having two major parts. The ﬁrst was concerned with the problems of specifying the kinds of �patients who are helped by a given treatment, identifying the clinical, personal, and social characteristics of patients which are associated with response to treatment, and identifying the “types” of patients who are most likely to respond to a given treatment. In addition to the question of types of variables which merit study with regard to this problem, the technical problems which arise here, such as coding and the application of multivariate analysis procedures, were also considered in separate papers. The second part of the section on methods was concerned with the problems of specifying the effects of a given treatment, of measuring clinical change and the various aspects of adjustment. Several approaches to these problems were described. Population Speciﬁcation Three papers were concerned with the search for signiﬁcant variables in clinical history, sociological characteristics, or personality of the patients. Clinical history was discussed by Bernard Glueck, of the Institute of Living, Hartford, Conn. Although several clinical and social variables have demonstrated some general predictive value in studies of response to treatment, Glueck observed that the search for speciﬁc prognostic factors in these areas has not been very successful. He reviewed some of the clinical history variables which have been linked to response to insulin therapy, electroshock, and lobotomy, and commented to the scarcity of such information in relation to treatment with drugs. His major criticism was aimed at the continuing lack of a common language to describe psychiatric conditions. Following a description of Q-sort techniques which he and his associates are applying to this problem, Glueck suggested that Q-sort methods provide a means of standardizing language and making comparable the ﬁndings from different clinics or hospitals. Sociological variables were covered by Leonard Pearlin, of the National Institute of Mental Health, Bethesda, Md. Arguing for greater speciﬁcity in this area, Pearlin observed that generic variables such as social class, age, and sex role are too global to be of much value in understanding the relations among variables. The need, he maintained, is for greater emphasis on description of the social context—i.e., the family, the community—and a descriptive system in which the “social characteristic in context” is the unit of analysis. The role of personality in the prediction of response to treatment was the topic of the paper by Seymour Fisher, of Baylor Medical School, Houston, Tex. His review of previous work in the personality area and his own experience led him to the opinion that the more simple personality variables have not been very helpful in the past as predictors and are not likely to be too helpful in the 580375—61—2 future. Increased emphasis should, he felt, be placed on theoretically derived conﬁgural measures of personality. Several possible conceptual dimensions were described. He acknowledeged, however, that the linking of personality variables to response to treatment is subject to a number of pitfalls, some of which he enumerated. The discussion which followed focused upon the issue of the single variable versus the conﬁgural approaches in attempts to relate personality and treatment response, and resulted in some clariﬁcation of the roles of each. The issue, however, was not resolved. Methods for dealing with population variables were discussed by Samuel B. Lyerly, of the Society for Investigation of Human Ecology, Washington, D.C., and Dean J. Clyde, of the Biometric Laboratory of George Washington University, Washington, DC. Lyerly, in a paper entitled “Interview Data: Coding, Scaling, and Selection of Potentially Useful Variables,” emphasized the differences in hospital and community situations which affect the collection and analysis of data, the characteristics of information which are essential to statistical analysis of data, and the importance of insuring that information collected is comparable from subject to subject. With regard to coding, he discussed different types of data and classiﬁcation systems, the role of the pilot study, ways of handling of “free responses,” and the application of simple mathematical procedures to patterning problems. Problems of weighting, suggestions for dealing with “does not apply” responses, and the application of different types of validity models were also considered. Clyde’s paper, “Multivariate Problems: Clustering Variables and Classifying Patients into Types,” focused on the role of multivariate models in drug research. He described the following three approaches and presented examples of the application of each: (a) Analysis of covariance, whose use was exempliﬁed in a study in which control of the pretreatment level of severity of illness was required; (b) factor analysis, which was used, in the example presented, to reduce a large number of items in a rating scale to two independent dimensions and thus served to clarify the composition and meaning of the instrument; and (c) discriminant function, which was applied to a problem of separating out groups of patients on the basis of their differential response to drug treatment. The relevance of the latter procedure to the problem of etiology was also considered. In discussing these papers, Goldine Gleser, of the University of Cincinnati, Cincinnati, Ohio, elaborated upon several approaches to separating subjects into meaningful groups. Three statistical models for accomplishing this kind of separation were described. She stressed that the state of knowledge in the ﬁeld is not sufﬁciently advanced to permit the prediction beforehand of the best way of separating groups, but pointed out that study 11 �of the outcome of such empirical separation can yield hypotheses which can then be cross-validated in other studies. Methods for Measuring Improvement Papers presented in this section of the conference described methods which are being used or developed to evaluate the adjustment of the patient and to specify ways in which improvement is manifested. Norbert Freedman and David Mann, of the State University of New York, Downstate Medical Center, Brooklyn, N.Y., described the manner in which they are attempting to measure psychopathology and social behavior. Emphasis within the clinic is on the psychiatric rating scale approach, and in their community studies emphasis is on a “naturalistic” approach. They have, through preliminary analysis of their psychopathology ratings, identiﬁed factors which improve with drug treatment and which predict drug response to treatment. In the area of social behavior, development of an extensive interview schedule covering such areas as family history, work history, and social pathology was described by Mann. He also discussed in some detail their coding procedures, the progress of their approach to studying the “typical day in the patient’s life,” and the dimensions of classiﬁcation which have been derived from the social data and which will contribute toward deﬁning “social remission.” It was pointed out that the deﬁnition of social remission is one of the central aims of the project. The details of a rating scale for measuring the improvement of outpatient psychotics treated with drug and placebo were discussed by Jordan Lawrence, formerly of Springﬁeld State Hospital, Sykesville, Md. The scale, which is completed by a psychiatrist or psychologist and a social worker following an interview with the patient, has three sections, one covering major psychopathology, one describing neurotic symptoms, and one concerned with social adjustment. Lawrence reported that the more reliable items in the scale have been factored and have yielded tentative dimensions of “schizophrenia” and “depression.” He also indicated that the three subscores and the total score have been found to discriminate well between pre-relapse and relapse conditions, but noted that further, better controlled validational studies need to be carried out. Progress on the development of a set of inventories designed to assess clinical and social adjustment was reported by Martin M. Katz, of the Psychopharmacology Service Center. He noted that the instruments are based on the need to integrate two points of view, the patient’s and the relative’s, in assessing the adjustment and per- 12 of the patient. The inventories represent atobtain objective estimates of (a) the amount of home and free-time activity in which the involved, and (b) the patient’s and the relative’s level of satisfaction with the patient’s functioning in the clinical, work, social behavior, and free-timeactivity areas. A validity study was described in which relatives were shown to be in very high agreement with psychiatric assessment (based on intensive clinical study of the patient) with regard to the level of psychopathology present and the extent of home, social, and free-time activities of the patient. Several trends in the data were noted: The relative is capable of providing accurate, objective information in certain areas; the sheer quantity of activity as reported by patient and relative reﬂects the level of adjustment; and the relative’s level of expectations at the time of assessment correlate highly with adjustment. More detailed study of the composition of the instruments and their general applicability is in progress. Mark Lefton, of Ohio State University, Columbus, Ohio, described his implementation of the interviewschedule approach, which had some similarity to others with regard to the areas of functioning sampled. Separate schedules were designed for the patient and the relative. The variables of prime interest in Lefton’s assessment of community adjustment are social participation, work performance, psychological functioning as measured by a relative’s ratings on a list of psychopathological indices, performance as a homemaker, and meas» ures of the relative’s expectations and tolerance of deviation. He reported that several measures have been found to discriminate between patients who were returned to the hospital within 6 months and those who remained in the community, as well as between patients who function well and those who function poorly in the community. During the discussion of these papers, one participant commented on the salutary effect that commitment to a particular approach has in this area, but he cautioned against inﬂexibility at this early stage in the development of the ﬁeld. The use of clinical judgment as a criterion‘has its advantages, but it was noted that areas of disagreement among raters can be just as important for understanding the nature of the problem. formance tempts to and kind patient is In an area that has seen only scattered attention in the past, the conference participants agreed that the diversity and extent of efforts now being directed toward assessing the clinical and social effects of various psychiatric treatments are very promising developments. �Conference on Information Needo A conference on scientists’ need for information, sponsored by the Psychopharmacology Service Center under contract wtih the Matrix Corp., of Arlington, Va., was held on November 25 and 26 in Washington, DC. It was a small, invitational conference of scientists active in research in psychopharmacology, documentalists, and other information storage and retrieval specialists. The aims of the conference were several: To learn whether the conference method of face-to-face interchange would reveal more relevant data about scientists’ needs in the ﬁeld of information and. communication than has hitherto been revealed in questionnaire and interview studies; to learn whether bringing the generators and users of information into direct contact with the experts in documentation would yield information of value to both; to obtain speciﬁc information about needs of scientists working in psychopharmacology; and, as a byproduct, to help the PSC’s Scientiﬁc Information Unit plan its future activities. The meeting was very informal. There was no prearranged agenda, nor was any attempt made to arrive at speciﬁc recommendations. Under the chairmanship of Roger W. Russell, of Indiana University, Bloomington, Ind., three speakers presented papers as starting points for the discussion. Robert J. Hayes, of the Electrada Corp., Los Angeles, Calif., reviewed the whole ﬁeld of information storage and retrieval, emphasing new methods and machines. He brought out that there are now machines that can be applied to almost any problem or situation in the ﬁeld of information storage and retrieval. Emphasizing the team approach to the problem, the cooperative efforts of users, operators, and machine experts, he observed that the application of machine methods to information problems is successful only when the machine specialists and documentalists have a clear understanding of the users’ requirements. Daniel X. Freedman, of Yale University, New Haven, Conn., discussed the use of information in his own research, reviewed the development of his research program and the role of information in the program, and mentioned ways in which information could be more useful. Murray E. Jarvik, of Yeshiva University, New York, N.Y., also reviewed the sources of information that he employs, including journals, monographs, books, reprints, review articles, conferences, the public press, science writers, drug company literature, textbooks, and other materials. In addition to these three speakers, several other participants described their uses of information, covering of Pyye/oop/onrmneologz'rtx kinds of information used, how it is used, and ways in which they would like to have it improved. Interspersed among the papers was lively and varied discussion from most of the participants. The following summary attempts to convey some of the ideas presented in the discussions, but it does not cover all the points that were made. Throughout the meeting one recurring theme was concern about the quality of scientiﬁc information. Commenting on the many problems of so-called scientiﬁc writing, one participant observed that much scientiﬁc writing occludes more than it illuminates. Most participants felt that many experiments were poor to begin with and should never have been published. They pointed to the need for editors of scientiﬁc journals to evaluate work more carefully and more critically before accepting it for publication. On the other side of the question were emphatic comments that strong efforts in this direction could lead to stultifying and untenable orthodoxy in science. One of the participants maintained that the problem was too much information, and that steps should be taken to cut it off at the source; i.e., to induce the scientist himself to be more selective in reporting his work. Another took the opposite point of view, saying that, as with farm surpluses, the real problem is not that of having too much information but of distributing and using information more effectively. A frequently recurring generalization was that scientists do not make maximal, or even good use of the many sources of information available to them. As each participant mentioned kinds of information he used, others remarked that they did not know of those sources. Similarly, when speciﬁc needs were mentioned, other participants often retorted that such needs were now being satisﬁed and the scientist had only to take advantage of available services. One of the questions raised was whether centralized, or even decentralized, information services could ever serve all the needs of scientists. One participant suggested that much of the seeming dissatisfaction with present information and communication is due to the unrealistic expectations of scientists, who often want answers to research questions that they themselves should submit to research. Information at the forefront of knowledge must be obtained by the scientist; readymade answers do not exist. A related comment was that information needs differ from one stage of research to another. A point that could be generalized from the discussion was that scientists perhaps do not know what they want 13 �in the way of information, and that it is, therefore, the duty of specialists in the information area to provide scientists with a wide variety of information presented in many different forms. If that were done, the scientists could then select what they need from what is offered to them. The usefulness of critical reviews of the literature was discussed in some detail. Although all agreed that critical reviews are valuable, they noted that ﬁnding really eminent scientists to write the reviews constitutes a major problem. Handbooks and other compilations of factual information that would be of particular value to the applied scientist were also felt to be of great importance. Many participants cited reprints, rather than journals, as one of the most useful forms of information, and felt that much could be done to make distribution of individual articles more feasible and more effective. In discussions of systems of handling information, it was noted that a scientiﬁc discipline is itself an informational system, and that some disciplines are, at different times, much more tightly organized systems than others. Physics and chemistry, for example, are at present rela- 14 tively more “organized” than the biological sciences and, therefore, in a sense, present fewer information and communication problems. This discussion, which occasionally bordered on excursions into the philosophy of science, brought out the paradoxical observation that as a body of knowledge or science develops and overthrows old concepts and formulations, it is in a continuous cycle of creating chaos out of order and then creating order out of chaos. In general, the conference participants agreed that the most important and effective means of disseminating and exchanging new information are by personal contacts at scientiﬁc meetings, by the “ﬁrst” type of scientiﬁc communication—the letter—and by visits with other scientists. In discussing the value of this kind of direct, personal interchange, it was suggested that tape recorders, which are now available in most laboratories and university departments, might be used to simplify and speed up the informal exchange of information. The practical value of directories of scientists and of indexed compilations of ﬁlms and other audiovisual aids was also stressed. �The Pylebep/aarmacolegy Rerearcb Umt State Unevem'ty of New Yer/e Dowmtate Medical Center" The Psychopharmacology Research and Treatment Unit of the Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, N.Y., was established in October 1957. From its inception, the Unit has been concerned with the study of the effects of long-term psychopharmacological treatment on the community adaptation of schizophrenic outpatients. In the selection of ambulatory schizophrenic patients as our study population we were guided by the wide use to which psychopharmacological treatment is put with such patients. By setting community adaptation as the criterion of treatment outcome we hope to emphasize that change in these patients must be deﬁned in terms of performance at home, at work, and in the community, as well as in terms of the usual criteria of psychological and psy— chiatric functioning. By assessing the effects of longterm, sustained drug action (1 to 5 years of continuous drug administration) we expect to determine to what extent such treatment may prevent relapse or lead to further improvement after an initial stabilization has been attained. The Unit thus focuses on the behavioral (i.e., psychological as well as social behavioral) correlates of drug treatment and tries to apply the method of controlled investigation to the clinical setting. Considerable effort is also being extended to the methodology of outpatient drug assessment and to the basic research task of developing objective assessment techniques which will allow for the tracing of changes in the qualities of community adaptation. These overall research objectives are discriminated into the seven speciﬁc studies outlined below. The overall project is in part supported by Public Health Service grant MY—1983. In addition to these long-term studies of chronic schizophrenic outpatients, a section of the Research Unit is speciﬁcally concerned with the testing of new drugs. In the course of the short-term studies we have an opportunity to test the validity of some of the assessment techniques developed in the longterrn studies. Finally, the staff of the Research Unit also engages in teaching psychopharmacology to undergraduate medical students and psychiatric residents. A *Prepared on request by David M. Engelhardt and Norbert Freedman, Psychopharmacology Research Unit, State University of New York, Downstate Medical Center, Brooklyn, N .Y. research fellowship program is carried out by the Research Unit with second- and third-year medical students who are expected to conduct their own experiments in psychopharmacology. The present staff of the Unit includes David M. Englehardt, Director, Norbert Freedman, Associate Director, Leon D. Hankoff, Research Psychiatrist and Director of the Treatment Unit, David Mann, Research Social Psychologist, and Reuben Margolis, Research Clinical Psychologist. The research design of the principal (long-term) project has the following essential features: (a) A free-clinic population of chronic schizophrenic patients is studied. Some patients come with a history of prolonged hospitalization, some with a history of brief recurrent hospitalization, some without previous hospitalization. The population is ethnically heterogeneous, evenly divided between males and females, and draws upon the lower socioeconomic groups. (b) Patients are given one of three commonly used agents, chlorpromazine, promazine, and placebo, and are seen in a setting which emphasizes a supportive doctor-patient relationship. The drugs are given under double-blind conditions, and drug assignment is made randomly. (6) Assessment of treatment effects is made by psychiatric ratings and psychological tests, as well as by detailed social behavior interviews administered to key relatives of the patient according to a predetermined schedule. Psychopathology and social behavior are thus independently evaluated, the former in the clinic by a psychiatrist and psychologist and the latter by the report of a relative. It is planned to assemble a cohort of 500 patients who have completed 3 months of treatment and a smaller number of patients who have completed 1 to 2 years of treatment under these relatively standard conditions. Study 1: The Role of Ataractio Treatment in the Maintenance of Community Status Treatment may affect both incidence of hospitalization and clinic dropout. Preliminary ﬁndings show that drug treatment (chlorpromazine) is associated with lower incidence of hospitalization. Our next goal is to determine the role of drug treatment in preventing hospitalization by separately studying certain criterion groups. 15 �Thus, we hope to deﬁne incidence of hospitalization on the basis of diagnosis, socioeconomic status, the relative’s tolerance for the patient, and previous hospitalizations, and to ascertain the probability of hospitalization for each of these criterion groups separately, for drug andplacebo conditions. Clinic attrition for reasons other than hospitalization is also being studied systematically. Analysis of dropout patients relative to patients remaining represents an important methodological task because of the potential bias that early attrition may introduce in the interpretation of results of change. Drug treatment does not appear to affect dropout rate. Instead, dropout appears to be affected by factors in the patient’s motivation toward treatment and certain factors in the treatment situation. Social (group membership) determinants also appear to be implicated. Study 2: The Measurement of Social Behavior and Social Behavior Change Emphasis is placed on the development of quantitative and qualitative indices of community adaptation. The instrument used is a detailed focused interview. This interview elicits from a relative a reportorial description of the patient’s activities at home and at work, covering a speciﬁed timespan. These detailed reportorial accounts by the relatives provide measures predictive of change as well as measures denoting changes per se over the course of drug treatment. Preliminary data have shown that the effects of drug treatment can be discriminated by a relative reporting on the patient’s behavior. This preliminary study has involved the use of a simple checklist of social dysfunctioning ﬁlled out by the relative. Patients on drug showed greater reductions in dysfunctional social behavior than did the patients receiving a placebo. Relatives having no awareness of the speciﬁc treatment the patient was receiving were able to make this discrimination. The meaning of these differential changes must await the detailed coding of qualitative behavioral descriptions. Study 3: Changes in Psychopathology and their Concordance with Social Behavior Changes Changes in psychopathology are evaluated by the coding of the doctors’ clinical judgments (progress notes), a detailed psychiatric rating scale, and certain psychological test performances. Psychological tests are used primarily to elucidate the meaning of changes observed on psychiatric and social behavior indices. A cluster analysis of psychiatric ratings suggests that psychiatric changes may be described in terms of two relatively independent dimensions of change, a cluster called thought disorder and a cluster called change in anxiety and treatment contact. There is a trend for patients on chlor16 promazine to show greater reduction of thought disorder than for patients on placebo. Once the social behavior indices of change are sufficiently developed, we expect to determine the degree to which psychiatric judgment and relatives’ observations concur or diverge. Speciﬁcally, we expect to inquire whether relatives and psychiatrists concur on speciﬁc aspects of the patient’s behavior (i.e., belligerence) or whether both concur that change has taken place but are in fact referring to different areas of change. Preliminary data so far indicate greater concordance of change on certain speciﬁc variables for patients on drug than for patients on placebo. Basically, this study seeks to attack the question of generality of the treatment effect. Is the treatment effect limited to change observed in the doctor’s office, or does it extend to the patient’s functioning in the community as this is perceived by a representative of the community? Implicitly, we are studying variations in the conceptions of mental health and illness as these are held by different observers. Study 4: Freedom from Functional Decrement The possibility that sustained treatment with psychopharmacological agents may bring about a decrement in the effectiveness of the patient’s functioning is especially important for outpatients, on whom the demands for effective performance in a community are greater than for inpatients. Psychiatric ratings and relatives’ reports on such variables as sluggishness, apathy, inertia, etc., are especially relevant here. Equally cogent in determining functional decrement are psychological test performances on measures of inertia and perseveration* and the Porteus Maze Test. Data on about 100 patients treated with drug or placebo for a 3-month period have been analyzed for changes in maze performance; so far we have not been able to substantiate Porteus’ general ﬁndings of a decrement with chlorpromazine treatment, but we have observed a decrement in one speciﬁc subgroup. The subgroup was characterized by a “more complex” level of cognitive organization. (See the following description of study 5.) Study 5: Prediction of Clinical Course Underlying our studies of the community adaptation of a heterogeneous group of schizophrenic patients being treated with drugs is the assumption that outcome is modiﬁed by factors within the patient and within his social mileu. Preliminary data suggest that several parameters other than drug must be considered in predicting clinical outcome: (a) The patient’s motivation toward treatment, (b) his cognitive organization, and (c) the attitude of the family toward the patient’s illness. The patient’s cognitive organization as gleaned from *See Cattell, R. B. On the measurement of perseveration. British Journal of Educational Psychology, 1935, 5, 76-92. �Rorschach responses (based on a scoring derived from Werner’s concepts) has been especially helpful in elucidating a “pattern of drug effects”: the direction of change in response to a given medication depended upon the patient’s cognitive organization. Study 6: Incidental (Nondrug) Treatment Factors In addition to the prognostic indices just enumerated, the role of several nondrug factors within the treatment situation has been observed. We have explored the signiﬁcance of the initial response to placebo and the doctorpatient relationship as they may affect the patient’s clinic attendance (dropout or hospitalization), as well as qualitative changes observed by the psychiatrist. Scoring procedures for the assessment of both doctor-patient relationship during the initial interview and response to placebo have been devised. These studies have emphasized the importance of nonverbal communication in the psychopharmacological treatment of schizophrenic outpatients. They have also delineated the contributions of the active agents to the treatment effect in some patients, but have suggested that in other patient groups the nondrug factor was prepotent. Study 7: Long-Term Drug Action Patients remaining in treatment for 12 to 24- months under drug and placebo conditions are observed at monthly intervals and their progress is then graphically charted. Our approach to long-term studies has been to select one of the more reliable change indices (psychoticism) and trace the patient’s status at successive intervals. In analyzing the time trends we have found it useful to distinguish two baselines, one at intake and a second after approximately 3 months of treatment. This second baseline permits the comparison of any further improvement or worsening in the patient’s adaptation after allowance for the initial drug effect has been made. It must be emphasized, however, that this study is always limited to patients willing and able to remain in treatment for such a long period of time. We are continually assessing differences between remainers and dropouts, so as to be in a position to detect bias introduced by the selective attrition of the sample. These long-term studies will also be corroborated by intensive case studies. Study 8: New Drug Testing The major efforts of the Unit are devoted to the study of long-term drug responses of chronic schizophrenic outpatients. Three relatively commonly used agents are employed. However, one section of the Unit is concerned with exploring the suitability of newer psycho— pharrnacological agents, speciﬁcally as they may be applicable to outpatients. Assessment methods which have proved to be useful in the larger study are also employed with the relatively brief trials of new drugs for outpatient use. With the study of new drugs we also hope to extend our information about the behavioral changes among outpatients in different diagnostic groups such as depressed patients. Studies of the following compounds have been completed or are in progress: fluphenazine (Prolixin), isocarboxazid (Marplan), imipramine (Tofranil) , and pyrbenzindole (IN—461, or 4-(1-benzyl-3-indolylethyl) pyridine hydrochloride) . In the course of conducting these studies we are accumulating a body of information about the methodology of outpatient drug testing; i.e., we are beginning to delineate the relative advantages and limitations of double-blind procedures in long-term assessment, the merits of simultaneous appraisal of an agent by the multiple clinic-community-member criteria, the utility of at least two baselines in the study of long-term trends, and the advantages of a drug spectrum of chemically similar agents which vary in presumed clinical intensity. Future Plans The ﬁndings so far support the view that the hospitalization rate tends to be lower for schizophrenic patients on active medication than for those on placebo; that psychotic symptomatology among these patients tends to be reduced by the drug; and that the adequacy of social behavior as judged by the relative appears improved, although we are not able to specify the quality of behavioral changes implicated here. Preliminary data on such variables as “psychotic thinking” also suggest that with prolonged administration of medication there tends to be less relapse with drug than with placebo. F urthermore, the data suggest that signiﬁcant variations in the effectiveness of drugs depend on the patient’s cognitive organization and his motivation toward treatment. In certain criterion groups, incidence of remission tends to be high regardless of drug treatment. In other criterion groups whose improvement is lower, the remission rate for patients on active drug exceeds the expectancy of improvement attributable to nondrug factors. Our next step in the project is to place these ﬁndings on a more solid foundation: We expect to study a sample of 5-00 patients who have received 3 months of treatment; we expect to cross-validate some of the speciﬁc predictions drawn from the initial sample; we expect to specify the meaning of the qualities of treatment outcome, particularly in the area of community behavior, through qualitative coding of behavioral descriptions by the relative; we expect to conduct certain control studies on the source of dropout, the patient’s condition after separation from the clinic, and changes in a sample of “isolated” schizophrenic patients, i.e., those not living with relatives. Finally, we hope to describe changes in subjective experiences among those patients judged by 17 �psychiatrists and relatives to be in remission. Thus, we hope to describe improvement from three vantage points, the community’s, the psychiatrist’s, and the patient’s. In most general terms, it is hoped that our Unit can contribute to the knowledge of the effectiveness of psy— chopharmacological treatment of schizophrenic outpatients by developing and delineating criteria of treatment outcome, by specifying expectancies of clinical change for speciﬁc patient groups, by indicating the role of the drug and nondrug factors in outcome, and by tracing the long-term consequences of treatment. Once this information has been derived from a large heterogeneous group of schizophrenic patients under relatively standard treatment conditions, it is hoped that newer agents can be tested more effectively; i.e., that the larger sample can be used as a reference group and that inferences can be drawn from smaller patient groups seen over briefer periods of observation. Finally, we hope that the accumulated data will increase our knowledge of the schizophrenic outpatient. Experimental Pay/chiatric Program: at Hillside Hospital, located in Glen Oaks, Long Island, N.Y., is a nonproﬁt, philanthropically supported psychiatric institution to which patients are admitted voluntarily for extensive psychotherapeutic treatment. Patients are from a predominantly middle-class, urban population, and most have high educational attainment. The programs of the Department of Experimental Psychiatry are a cluster of interrelated studies focused on common population samples. Other research laboratories in biochemistry and in medicine are active, and laboratories in psychodynamic psychiatry are being developed. The programs of the Department of Experimental Psychiatry have developed over 6 years, and are devoted to understanding of the mode of action of psychiatric therapies through studies of brain function. The principal techniques have been adapted from descriptive psychiatry, neuropsychology, electroencephalography, linguistics, pharmacology, and sociology. Members of the staff, representing various disciplines, are Max Fink, Director, Karl Anderrnann, Ira Belmont, Martin A. Green, Abraham A. Kaplan, Eric Karp, Donald F. Klein, George Krauthamer, Joseph Jaffe, John C. Kramer, Max Pollack, and Nathaniel Siegel. Former associates who contributed to these programs are Harold Esecover, Robert L. Kahn, Hyman Korin, and Henry J. Lefkowits. In initial studies of convulsive therapy, changes in brain function were found to relate both to evaluations of improvement and to pretreatment psychological variables. As our understanding of convulsive therapy developed, a general neurophysiological-adaptive view of somatic therapies emerged. In this view, psychiatric treatments are therapeutically effective to the degree that brain function is measurably altered. While change in brain function is necessary for behavioral change, the type of adaptation varies, depending upon pretreatment psychological and sociological characteristics of the subject. Thus, the mode of action is not seen as either “organic” or “psychological,” but rather as the inter18 Hz'ZZJz'de HarpiMF action of diffuse neurophysiological changes and adaptive mechanisms. Further, while behavioral change is related to changes in brain function, and the adaptive characteristics, psychological to pretreatment pattern evaluations of “improvement”—being special types of evaluation of change—are derivative judgments based on staff and family expectations and tolerances. This hypothesis was developed and sustained in a series of studies of convulsive therapy. Concurrent studies of insulin coma indicated that behavioral change here, too, was related to the onset and degree of prolonged coma or repeated seizures, these being the prin— cipal manifestations of prolonged neurophysiological change in this therapy. The mode of action of the new psychotropic agents was also expressed within this hypothesis. It was suggested that these agents would be effective to the degree that they induced persistent changes in brain function, and that the type of behavioral response would be related to the type of brain change and to prernorbid psychological (personality) patterns. The present programs in the Department are designed to study these relationships in detail. Convulsive Therapy Process Of various measures of brain function, the amount of slow wave activity in the electroencephalogram and confabulatory and denial language patterns after amobarbital were the most sensitive indices in convulsive therapy subjects. In one experiment, improvement ratings were correlated with the appearance of high degrees of change in these indices. These observations were tested in a double-blind study in which patients referred for electroshock were randomly assigned to courses of either convulsive or sub' *Prepared on request by Max Fink, Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, Long Island, N.Y. �»n-s,ww.- . . E convulsive therapy under thiopental (Pentothal) premedication. High degrees of neurophysiological change were observed only in the convulsive group; improvement rates were signiﬁcantly higher in this group; and when subconvulsive subjects were re-treated by convulsive applications, the improvement rate was similar to the original convulsive group. In the subjects given subconvulsive treatment considerable amounts of electric current passed between the bitemporal electrodes. It appeared that the therapeutic agent was not the total electrical current per se, but an all-or—none quality manifested by the grand mal seizure. The signiﬁcance of the grand mal seizure was examined in studies of the inhalant convulsant hexaﬂuorodiethylether (Indoklon). Similar degrees of electrographic change, improvement rates, types of behavioral change, and changes in neuropsychological task behavior were observed in the Indoklon group and in the electrically treated group.- It was soon apparent that not all subjects manifesting high degrees of physiological change were rated as “improved.” In a descriptive typological study, ﬁve patterns were described, empirically termed “euphoric,” “hypomanic,” “somatization,” “paranoid-withdrawal,” and “panic.” While the ﬁrst two of these adaptive modes were rated as “much improved,” the latter two were seen as “unimproved” or “worse.” In studies of psychological variables, it was reported that patients rated as much improved and recovered frequently manifested personality patterns similar to that described by Weinstein and Kahn as the “explicit verbal denial personality.” In language patterns, patients expressed the “language of denial” when diffuse brain change was induced, exhibiting such aspects as explicit denial, minimization, displacement, cliches, etc., more frequently than unimproved subjects. Other indices related to favorable outcome were high scores on the California F Scale, and Rorschach determinants of pure color, absent movement, and absent form-color. In this population, also, favorable outcome was associated with low educational achievement and foreign birth. Anticholinergic Compounds and Convulsive Therapy Seeking a way to augment the degree of postconvulsive EEG slow wave activitiy, an anticholinergic compound, diethazine, was given intravenously at various stages of the convulsive therapy process. Contrary to expectations, diethazine caused an immediate and sustained decrease in EEG slowing. Patients with denial language patterns relinquished them. Instead of feeling euphoric and experiencing a sense of well-being, the subjects became irritable, anxious, and showed symptoms expressive of pretreatment patterns. Prior to convulsive or drug therapy, diethazine induced excitement, tension, anxiety, and illusory sensations. Subsequent studies with other central anticholinergic compounds—WIN—2299 (2-diethylaminoethyl-a-cyclo- pentyl-a-(Z-thienyl)-glycolate HCl), JB—318 ( l-ethyl3-piperidy1 benzilate HCl), JB—336 (N-methyl-3-piperidyl benzilate) , and benactyzine—showed behavioral and electrographic patterns similar to those of diethazine. Similar desynchronization of postconvulsive EEG slowing was also noted with central sympathomimetic hallucinogens (amphetamine, mescaline, LSD—25), and has been reported for antihistamines (diphenylhydramine). These observations led to the suggestion that an increase in central cholinergic activity was a biochemical basis for the convulsive therapy process. Psychopharmacological Agents and EEG During this period, the mode of action of newer psychopharmacological agents aroused interest. Following the concepts derived from convulsive therapy, the neurophysiological changes induced by drugs were tested within the same acute experimental framework of the EEG setting. It was observed that phenothiazines (chlorpromazine, promazine, triﬂupromazine) induced EEG synchronization and a shifting of the spectrum to the slow frequencies; meprobamate and barbiturates induced an increased synchronization and a shift of spectrum to fast frequencies; reserpine induced an increased slowing with synchronization at low dosages and desynchronization at higher levels ; and imipramine induced desynchronization with a shift of frequencies to the slow bands. Other experimental compounds tested included BLM188 (which is 4-dimethylamino-3,4,5-trimethoxybenzanilide) and phenyltoloxamine, deanol and its various congeners, WY—214-9 (which is tropin-4-chlorbenzhydryl ether HCl), and azacyclonol. No consistent electrographic pattern was recorded for any of these compounds. It was suggested that psychopharmacological agents provide a means for eliciting a variety of neurophysiological patterns in contrast to the single pattern of induced convulsions. Furthermore, the type of neurophysiological alteration, as reﬂected in EEG synchrony and frequency patterns, was related to speciﬁed types of behavioral adaptation. Increasing EEG synchrony and a shift to slow frequencies were associated with tranquilization, sedation, and decreasing agitation, while desynchronization and a shift to fast frequencies were associated with excitement, illusions, and delusional ideation. These observations are consistent with hypotheses of Wikler. The advantages of EEG techniques for the assay of new psychiatric drugs have already been reported.* Psychopharmacology Evaluation Program The present psychopharmacology program, instituted in October 1959, was based on the studies described in the *See Fink, M. EEG and behavioral effects of psychopharmacological agents. In P. B. Bradley, P. Deniker, and C. RadoucoThomas (Eds), Neuro-psychopharmacology. New York: Elsevier Publishing Co., 1959. Pp. 441—446. 19 �preceding paragraphs. It is designed to answer the following questions: Is there a relation between measurable alteration in brain function and behavioral change with psychotropic drugs on chronic administration? Are there pretreatment clusters of psychiatric physiological and psychological variables related to the type of behavioral adaptation? And, are such clusters related to the type and degree of physiological change? Method. As an initial approximation, a double-blind drug study was undertaken in which subjects were randomly assigned to a ﬁxed-dosage schedule. On the basis of our clinical experiences with various psychotropic compounds from 1954 to 1959, we selected three classes of drugs according to their patterns of EEG response. The agents selected were those with either predominant desynchronizing patterns, synchronizing and slowing, or minimal or no effect. After medical examination and after all other medications have been discontinued, patients referred for drug therapy are randomly assigned to treatment with a compound in one of these three classes. Convulsive and drug therapies are prescribed by staff psychiatrists on referral to the Department of Experimental Psychiatry. All treatment is administered by the Department staff, so that the experimental variables of drug dosage, route of administration, assignment to groups, etc., are readily controlled. All patients in the hospital are available for study. The mean duration of stay for patients is 7 months. After a testing period, all patients receive 40 cc. of liquid medication daily from individually labeled bottles. Dosages are increased in ﬁxed weekly steps until a maximum dosage is achieved at 4‘ weeks. After 2 weeks on maximum dosage, retesting occurs. To date, 140 subjects have been referred, and 110 have completed the study period. Preliminary analyses of the data are now in progress. Behavioral Change. In a survey of the behavioral adaptations of patients receiving various agents during 1958— 59 a number of clusters of behaviors were developed. The typologies were based on the treatment response and on pretreatment psychiatric proﬁles. In the present study, the typologies are being tested and various measures of behavioral change are being studied. These include therapist referral questionnaires and 6-week evaluations; therapist’s ratings of patients on the Clyde Mood Scale; the Multidimensional Scale for Rating Psychiatric Patients, used for evaluations in interview by two research psychiatrists; the Lorr Psychiatric Behavior Rating Scales for ward behavior (AAMI: Level of Anxiety, Level of Activity, Mental Disorganization and Interpersonal Relationships); and patients’ self-ratings on the Johns Hopkins symptom checklist, the Chicago Attitude 20 Scales (self-perceptual scales devised to elicit attitudes of dependency, ﬁght, ﬂight, and pairing), and the Clyde Mood Scale. Neuropsychology. Psychological tasks have been viewed both as change variables and predictive variables. In convulsive therapy, changes in memory tasks, tactile perception, Wechsler—Bellevue, critical ﬂicker frequency, ﬁgure-ground tasks, and tachistoscopic recognition of ﬁgures were related to the degree of induced neurophysiological change. For each task, the degree of decrement in task performance was found to be positiVely correlated with the amount of EEG slowing. Following treatment completion, with the return of physiological indices to pretreatment levels, performance on these psychological tasks also returned to pretreatment levels or higher, a betterment of performance ascribed to practice effect. Denial scores on interview, Rorschach determinants, F scale scores, language patterns after amobarbital, auditory feedback, and perception of the visual upright have been viewed as predictive indices of the behavioral changes following ECT. Psychopharmacological agents are now being used to assess these various tasks, their capacity to change with various agents, or their capacity to predict change. Electroencephalography. In the studies of convulsive therapy, the degree of EEG slowing was measured by counting the consecutive waves in selected samples. When the more subtle changes of drug effects are studied, it is necessary to apply less tedious techniques. Electronic frequency analysis was introduced in August 1959. By measuring the pen deﬂection for various frequencies from 3 to 33 c.p.s. in 10-second epochs, rapid measurement of apparently small changes in total activity and frequency spectra are now obtained and applied. Other physiological variables studied in this program include the response of EEG to intravenous chlorpromazine, blood-pressure response to Mecholyl, the EKG, radioactive iodine uptake, and analyses of various blood and urine elements. Psycholinguistics Another series of studies in the Department has been devoted to formal language patterns. Following the studies of syntactic language patterns in convulsive therapy, other aspects of language were studied as indices of change in interpersonal behavior. Jaffe, after considerable exploration with various linguistic measures, suggested that type-token-ratios (TTR) of consecutive samples of dyadic speech might be a useful index. While TTR had previously been applied to written texts or to the language samples of individuals, Jaffee indicated that the two-person communication (dyad) was a more signiﬁcant index of the state of the �interaction than were analyses of separate samples from the participants. Applying this technique to patients receiving convulsive therapy, changes in TTR mean and standard deviations were related both to the degree of induced EEG slow wave activity and to syntactic language patterns obtained in independent structured interviews. Speech became more repetitive (lowered mean TTR) and more variable in consecutive samples (increased standard deviation). In interviews before and after the intravenous administration of centrally active agents, similar changes were observed. Agents with a predominant synchronization pattern on the EEG exhibited a decrease in mean TTR and an increase in standard deviation of scores, while desynchronizing compounds elicited greater variability in speech patterns (increase in TTR mean) and a decrease in variability of consecutive scores (decrease in standard deviation). Other language measures studied included distressrelief quotients, self-reference, and alteration in tense and person. It was suggested that these psycholinguistic measures are potent techniques for the operational analyses of physiological and psychological effects of psychopharmacological agents. Sociological Studies In the course of these psychiatric programs, considerable interest was engendered in the family organization to which patients were returning. Also, the general problem of the relation of social factors to choice and results of psychiatric treatment, and the speciﬁc problem of the relation of these factors to the referral patterns, led to a series of population studies. In one study, education, age, place of birth, and score on the California F scale were signiﬁcantly related to the type of therapy received and the utilization of adjunctive hospital services. Thus, patients who were older, poorly educated, had higher F scores, and were foreign born, particularly those born in Eastern Europe, were most likely to be referred for electroshock. These relationships were independent of diagnosis. Within the group of electroshock patients, the time of referral for ECT was also related to these factors. In a second study, duration of hospitalization, discharge evaluation, and diagnosis were related to the same social factors. For example, patients hospitalized for the shortest period were oldest, had the least education, were most likely to have been foreign born, and had the higher F scale scores. Younger, native-born, better educated patients who had lower F scale scores were hospitalized the longest. These relationships held true within treatment type and within diagnostic class. On discharge, older patients had the most favorable ratings. In ECT, patients rated as recovered or much improved had the highest F scores, least education, and were most likely to be foreign born. In another study of patient refusal of ECT, similar relationships were observed. These relationships are now under study in the Outpatient Department and in a trihospital comparative study. This study is assessing the populations of three hospitals, each of which has a prevailing patient population which differs from that of the other two. In each of the three hospitals, all therapies are equally available to all patients. The participating hospitals are the Menninger Foundation Hospital, whose population is primarily upper class and Protestant; the Massachusetts Mental Health Center, whose population is primarily lower class and Catholic; and the Hillside Hospital, whose population is predominantly middle class and Jewish. It has been postulated that the relationships mentioned in the preceding paragraphs reﬂect the inﬂuence of social background on psychological processes, such as habitual patterns of communication and modes of expression. The contribution of these factors to the pattern of mental illness and to the patient-therapist interaction are being investigated. Plans for Future Work Further growth and the direction of ensuing studies will depend upon the results of the investigations described here, as well as upon the growing institutional awareness that research is as much an integral part of the hospital’s operation and budgets as are patient treatment and staff training. 21 �Angler" the in Com-Leaf Chewing For many centuries, at least as far back as 1000 B.C., the inhabitants of the highlands in the Andean region have been habituated to the consumption of the leaves of Erythroxilon coca, a shrub growing in the Andean mountainsides at an altitude between 1,500 and 6,000 feet above sea level. At present, the production of coca leaves in Peru is estimated at 10 million kg. per year; approximately 40,000 acres of cultivated land are used, empIOying 25,000 workers (approximately 2 percent of the population devoted to agricultural tasks). The leaves of this shrub may be cropped on the second or third life-year, and the plant continues to produce for 20 years, yielding from three to six crops per year. The leaves are dried in the sun for several hours and then kept in cool, shadowed places until sold for human consumption. Marketing is essentially free, being only under the necessary controls for proper taxation and to avoid illegal exportation. Coca leaves are sold all over Peru, in any requested amount, from a few grams to several th0usand kilograms. Human consumption of the leaves, as such, is unrestricted. Industrial processing for the production of cocaine is forbidden by law, although frequent disclosure of illegal factories and cocaine rings calls for improved. methods of ﬁscal control. Coca leaves contain 0.60 to 1.80 percent of cocaine and 0.03 to 0.90 percent of ecgonine, according to calculations from different laboratories and varying also with the region and method of cultivation. Mention is also frequently made of the fact that coca leaves contain vitamin B1 (6 to 8 mg. per kg), riboflavin (10 mg. per kg.) and vitamin C (150 to 200 mg. per kg.). The high content of cocaine in the coca leaves becomes more meaningful if one realizes that the Peruvian people consume an estimated 9 million kg. of coca leaves per year, representing an average of 90,000 kg. of cocaine per year. The legally approved medical requirements of all the rest of the world amount only to 2,500 to 3,000 kg. per year. (This does not include the legally approved consumption in the United States. According to ofﬁcial information from Peruvian sources, the Coca-Cola Co. imports from Peru 140,000 kg. of coca leaves per year. These coca leaves are decocainized and the decocainized product is used in the manufacture of the Coca-Cola bevis turned obtained cocaine The as subproduct a erage. over to the proper authorities for legally approved consumption, the surplus being incinerated. The United States, thus, does not import or export cocaine.) The 90,000 kg. of cocaine contained in the 9 million kg. of coca leaves are consumed by approximately 2 million of the total 10 million inhabitants of Peru. These 22 million people represent 90 percent of all adult males in the highlands, 20 percent of all adult women in the highlands, and a large, but undetermined, percentage of male children over 12 years of age in the highlands. Consumption of coca leaves at lower altitudes is exceptional. The amount of coca leaf taken daily per individual varies from 10 to 100 gm. The average adult man takes approximately 30 gm. daily, but there are exceptional chewers who will take as much as 200 to 300 gm. every day. Although one speaks usually of “coca chewing,” the act of consumption may not properly be called chewing, at least in its complete process. The habitual chewer usually takes a handful of coca leaves and carefully cleans it from dirt, debris, and the main nerves of the leaf. He puts the clean leaves into his mouth and chews on them for 3 or 4 minutes until a bolus is well formed. Then he takes the bolus in his ﬁngers and pricks it deeply and repeatedly with a pointed stick which carries an alkaline powder, to be described below. The bolus is thereafter put back in the mouth and kept there, under the cheek, without chewing, for about 1 or 2 hours, during which the “chewer” sucks on it while he goes about his business. Finally, the bolus is either discarded or 2 swallowed. Usually, this process is repeated with 10 gm. of leaves every 3 to 4 hours, with interruption of current activities for about 45 minutes in order to prepare the bolus, in what might be called a “coca break.” It is exceptional to ﬁnd “chain chewing,” which brings up daily consumption to about 300 gm. per person. The addition of an alkaline substance to the bolus is a rather intriguing subject. The composition of this powder varies from region to region, ranging from plain quicklime to ground seashells or ashes of different plants. In exceptional cases, chewers do not use the alkaline subshow that evidence is to there but archeological stance, in one way or another it has been used for as long as coca has been known to man. One might speculate that this procedure increases the yield of alkaloid in the mouth, but there is conﬂicting evidence that this is a real fact. Gutierrez Noriega, one of the authorities on this subject, claims that the yield is increased by only 4 percent. Other explanations have been offered—improvement of taste, breaking up of the cellular membrane, etc.—but there is an obvious need for further research in this direction. *Prepared by Fernando Cabieses, Professor of Neurosurgery, San Marcos University, Lima, Peru. Mailing address: Talara 655, Lima, Peru. �It is generally accepted that cocaine is liberated in the mouth, being extracted from the bolus. Actually, that should not be a very difficult point to settle, but nonetheless different observers have reported very conflicting data. The actual yield, which should result from subtracting the amount of cocaine in the discarded bolus from the content of a similar amount of leaves, is difficult to obtain because of the rather frequent spitting, the swallowing of part or all of the bolus, and the different methods of titration. Published results vary from a 10- to a 90-percent yield. Also, whether the saliva contains free or bound alkaloid is not well known. At any rate, some form of cocaine is swallowed and, again, not much is known about its fate on reaching the stomach and intestine. How much of it is destroyed or further activated by the digestive juices is also in question. F urthermore, we have no information about how much is absorbed into the bloodstream or about the behavior of the gastric and intestinal mucosa exposed to bound or free cocaine. Cocaine absorbed into the bloodstream reaches the liver through the portal system, but no one really knows much about its metabolism at this level. There is some evidence that liver tissue will detoxify cocaine in vitro, and this has led to the thought that only a minimal amount of the ingested alkaloid actually reaches the general circulation. Here, again, careful evaluation is needed, since it seems that blood itself will partly destroy cocaine added to it in vitro. And, to complicate matters further, the results of determinations of cocaine blood levels in coca-leaf chewers are riddled with very difficult problems of interpretation, mainly because of the lack of appropriate methods of titration. Even if this information were available, absolute ﬁgures on cocaine blood levels would have but little meaning, owing to the lack of information on the level of neural toxicity of this substance. How high a blood level of cocaine can be tolerated without nervous effects in a normal individual, in a cocaine addict, and in a coca-leaf chewer is thus unknown. In spite of all these important questions, it is quite evident that some cocaine, or a cocainelike substance, reaches the nervous system of the coca-leaf chewers. This is easily concluded from clinical observation. Cocaine is perhaps the best antifatigue substance known to man. And it is a well proved fact that coca-leaf chewing is an excellent means of combating fatigue, both in industrial work and under experimental conditions. The possible differences between the effects of parenterally or orally administered cocaine and those obtained by chewing coca leaves, in normal as well as in habituated persons, and the action of cocaine and coca leaves on different types of fatigue remain to be experimentally evaluated. Cocaine decreases hunger sensation, admittedly through its central action. And this is also a very well known effect of chewing coca leaves, brought about either through a similar mechanism or, as commonly assumed, through local anesthetic action on the digestive tract. Whatever the mechanism is, coca-leaf chewing kills hunger. And this effect has an obvious social implication. It is said, on the one hand, that because of this action coca chewing leads to malnutrition. Other groups of sociologists claim the opposite; that malnutrition leads to coca chewing. And a third factor is brought into play when one is reminded that the coca leaves contain a fair amount of certain vitamins which are ordinarily lacking in other constituents of the usual diet of the dwellers of the high Andes. A pharmacological problem thus becomes a problem of socioeconomics and of social anthropology. Malnutrition, poverty, low culture, and coca chewing all go together, and at times it becomes almost impossible to disentangle one from the other. And if to this mixture we add high altitude, the problem becomes more and more intriguing and complicated. One cannot but wonder why, if the coca tree is only cultivated at altitudes lower than 6,000 feet, the habit of chewing coca leaves is found mainly above that level. Very few communities in the coastal area show the habit, which is mainly concentrated in the high altitudes. Futhermore, the habit of chewing coca leaves, a habit carried on continuously for many years, is usually abandoned when the individual is permanently transferred to lower geographical levels. And one cannot dismiss the frequent claims of travelers and of cultured dwellers of the highlands regarding the beneﬁcial effects of coca tea or coca chewing against the acute symptoms of mountain sickness. Unfortunately, no experimental evaluation has been made of these observations, which have been subject to much literary discussion in years past. It is true, of course, that high altitude is only one of the factors of a very complicated problem seen through the narrow light of an off—habit, on-habit proposition. But only a careful experimental approach will tell us what the real importance of this factor is, especially in the presence of a drug with as many unpredictable pharmacological actions as cocaine. It is commonly accepted that cocaine has a deleterious effect on the central nervous system when taken chronically. And it is only logical that this concept has been used in the interpretation of the mental functions of the coca-leaf chewers. This assumption, however, may not be entirely justiﬁed, since most of the alleged “facts” lack experimental veriﬁcation. The so-called effects of chronic consumption of coca leaves are always related to the other factors of the socioeconomic complex sur‘ rounding the coca habit; poverty, malnutrition, low culture, poor educational facilities, high altitude, etc. And although coca may be an important determining cause, the alleged low mental output of the Andean dweller should not be blamed only on this factor, as it frequently is. The appraisal of chronic coca-leaf consumption com23 �pletely separated from its socioeconomic constellation is, however, very difﬁcult to achieve. The acute action of coca-leaf chewing on mental processes also lacks sound and thorough experimental evaluation. A few experiments suggest that the effects are quite different in habituated and nonhabituated individuals, as would logically be expected. The extent and mechanism of these differences remain to be determined. There is also some indication that muscular activity during the process of coca chewing basically alters its mental effects. It is said that if the individual is resting, daydreaming and pseudohallucinations ensue, but that these mental effects can be prevented by physical activity. These observations need further experimental study, but this type of psychopharmacological study would meet with great obstacles in the markedly introvert personality of the Peruvian Indian, his resistance to participation in experimental studies of this type, the frequent language difﬁculties, and the lack of basic psychological and social anthropological studies in the Andean milieu. It is thus evident that there are many questions to be answered concerning the pharmacology of coca leaves and the socioanthropological aspects of this widespread habit. Differences between the chronic or acute effects of parenterally administered cocaine (a subject on which much remains to be settled) and the chronic or acute effects of coca-leaf chewing should be investigated. The 24 former leads to a rather well known condition: cocainism, i.e., addiction to cocaine. The latter leads to a habit, cocaism, which apparently does not follow the same psychopharmacological pattern, since a simple change in socioeconomic status or a change in geographical milieu leads to its spontaneous discontinuance; there is not a clear tendency to increase the dosage, as there is in cocainism, nor are there any evident withdrawal symptoms. Are these differences due only to the route of administration of cocaine? One certainly can provoke a clear syndrome of cocaine addiction in experimental animals (dogs, monkeys) by chronically administering cocaine by the parenteral route. But so far it has not been possible to obtain similar results by oral administration of this drug. Research Opportunities There are many stimulating areas for research on cocaleaf chewing. Facilities for research in this ﬁeld are potentially available at the Brain Research Center of the Armed Forces of Peru, of which I am director, and at the American Hospital in Lima, which has a good neurological and neurosurgical service. Investigators who wish to explore the possibility of conducting research related to coca-leaf chewing, or who wish to obtain further information, are invited to write to me at the following address: Dr. Fernando Cabieses, Talara 655, Lima, Peru. �Publications Tranquilizing and Anti-Depressant Drugs. Veterans Administration Department of Medicine and Surgery Medical Bulletin MB—6, September 12, 1960. Washington, D.C.: U.S. Government Printing Ofﬁce. This 19page bulletin is by Eugene M. Caffey, Jr., Leo E. Hollister, Alex D. Pokomy, and Jesse L. Bennett, all of whom are members of the Executive Committee of the Veterans Administration Cooperative Chemotherapy Studies in Psychiatry. It presents a general summary of current practices in the use of tranquilizers and antidepressives in psychiatry and in nonpsychiatn'c practice, and includes tabulations of generic names, trade names, and range of total daily dosage of drugs for outpatients and for hospitalized patients. The price of the publication is $0.15. Copies should be ordered from the Superintendent of Documents, U.S. Government Printing Ofﬁce, Washington 25, DC. Agressologie, an International Review of Physio-Biology and Pharmacology Applied to the Eﬁ‘ects of Agression, is a recently established journal that should be of interest to psychopharmacologists. In the preface to the ﬁrst issue, the title of the journal is explained: The commonly understood meaning of the word aggression is applied to the action of agents which harm the living organism by attacking it abruptly (from the outside or from the inside), including cold, heat, lack of air, surgery, disease, poisoning, and other causes of physiobiological disequilibrium which results in “more or less profound and lasting disturbances” in cellular metabolism. The purpose of the journal is to synthesize and integrate contributions which many basic disciplines are making to the study of the effects of “aggression” as previously deﬁned, and to the prevention and treatment of such effects. The journal is being published and edited by Henri Laborit, of the H6pital Boucicaut, 78 rue de la Convention, Paris 15, France, and P. Huguenard, of the Hopital de Vaugirard, Paris 15, France. Metabolism of, and Analytical Methods for, Phenothiazine Derivatives Used in Psychopharmacology; A Selected Annotated Reference List, compiled by the Scientiﬁc Information Unit of the Psychopharmacology Service Center. This list of approximately 65 references is made up primarily of articles concerned with analytical methods for the detection of phenothiazine derivatives used in psychopharrnacology, together with a few more general articles on the metabolism of these agents. The annotations are factual summaries of the articles, and are not evaluative or critical. The list is arranged chronologically. Copies may be obtained by writing to: Dr. Lorraine Bouthilet, Head, Scientiﬁc Information Unit, Psychopharmacology Service Center, National Institute of Mental Health, Bethesda 14, Md. 25 U. S. GOVERNMENT PRINTING OFFICE: 1961 0- 580375 �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Experimental Psychiatric Programs at Hillside Hospital, Psychopharmacology Service Center Bulletin, January 1961 (U.S. Department of Health, Education, and Welfare) Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-009 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Article based on Hillside Hospital annual report. One of nine articles in the Psychopharmacology Service Center Bulletin: NIMH-sponsored collborative study of phenothiazine treatment of acute schizophrenic psychoses; NIMH grant support for early clinincal drug evaluation units; Research conference on drugs and community care; Confernce on informaiton needs of psychopharmacologists; The psychopharmacology research unit at the Downstate Medical Center, Brooklyn N.Y.; Experimental psychiatric programs at Hillside Hospital; Coca-leaf chewing in the Andes; Publications. Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/ec4afc36e7130461e6211b8cf229b80f.pdf 15614c0aba92d94b8e5d0589849ccd08 PDF Text Text $57” 4’13 /?é,/~(22 ‘ may JUN HILLSIDE HOSPITAL Glen Oaks New 21 1961 York June 12, 1961 MEMORANDUM Victor Leventritt, Chairman, Medical Affairs Committee TO k Mr. M. FROM : Maurice Bachrach, Administrator WWW” SUBJECT: Proposed Research Request Budget for July'l, 1961 to June 30, 1962 income and the of proposed expenses Attached hereto is a presentation been has carefully Each 1961/62. request departmental research for for each schedule for There a is Robbins well myself. as reviewed by Dr. as Research Department. After the expenses are given for each department, we have Shown applicable and potential income from various sources that each of end At departmental the each department. for have been designated This the is "net deficit". shown the have department's we schedule, income that for designated less the for department, expenditure total department. will find the entire deficit picture which gives the from various income estimated each the of departments, for net deficit research the total to which Trustees applicable are the than sources other The research net departments". all and research "net deficit, program actual $53,250; our at was projected the for present year deficit Budget Research 1961/62 Request The $58,12h. estimated at expenditure is from this $h,250 of decrease net $h9,000, of a net deficit a projects actual from this year‘s decrease and $9,12h a Budget year's Request On page h you experience. �-2- June 12, 1961 HILLSIDE 1109131111, M wwnwm‘m 001. I Col. II - 1961/62 TENTATIVE REQEARCH BUDGET 1960/51 Budget I. 001. III 1951752" 1950731 Request Budget Experience est.) (2 mos. 001. IV Overage 001 III over 001. RE§EARCH IN EXPERIMENTAL PSYCHIATRY EXPEN§ES: l2 3 . . . 1 . Director . 7 . 8 . 9 . 1o. 11. 12. 13. 11. 19. 16. 17. 18. 19. 20. 21. 22. 1,500 3,100 3,100 3,113 2,163 600 600 600 3,311 11,011 2,817 10,126 25,000 17,000 3r. Assoc. Exper. Psychology 13,000 10,920 7,500 13,000 10,667 7,500 9,500 8,500 1,110 9,500 8,597 1,105 2,172 3,360 2,890 2,251 3,127 2,356 Assoc. in Psychiatry v - n n Assoc. EXPer- Psychology 6 . ‘Asst. Exper. Psychology S 25,000 17,500 9,000 11,000 13,331 8,100 7,218 10,000 1,120 1,800 3,600 2,185 3,192 2,710 1,500 3,000 3,600 3,000 25,000 16,116 u n (NEW) 11 Assoc. in Social Psychology Assoc. Exper. Psychology E.E.G. Technician, Sr. E.E.G. Technician Jr. (NEW) Psycholinguistic Technician Secretary Clerk Typist Technical Ass't. Equipment Travel supplies (office (NEW) & Medical) Director's Professional Expenses Training Expenses gocial security Overhead & Blue Cross Research in enses115351%§%151'9§23515177'7“' Total - - - - - — 251 1,838 3,500 11,010 - 1,081 9,000 1,000 2,111 (A) (B) (0) (B) 600 (C 7,218 (E) 500 (F) (7,080)(G) 390 (c) 3,600 (H) 313 (C) 132 (C) (150) 1,500 (I) (1,500) 200 (100) 1,838 (J) 186 2,999 ' 129,923 licable & Potential Income Researcﬁ in ExperimenEEI Psychiatry 122,839 7 159,797 29,871 A 23.'ﬁ?§7”565113 ﬁSEIEE‘EEFFTEE“"‘72,101 21. Drugs 25. Nassau County 26. Potential Income Total Applicable PotentiEI Income - 3,120 11,102 & Net Deficit, Research in EggerimenEEI PsycHIatry 78,000 1,800 - 111,708 5,089 - . 12,307 (K) 5,089 (L) (3,120)(M) (11,102)(N) 89,923 82,800 119,797 29,871 10,000 10,039 10,000 0 I �Memorandum re: preposed Research Budget June 12, 1961 ans-u. II. RESEARCH IN BIOCHEMISTRY 001. EXPEN‘EES: I 1960/61 Budget 27. 28. 29. 30. 31. 32. 33. 3h. .35 . 36. 3?. 38. 39. 80. Director 3r. Biochemist 3r. Biochemist Biochemist Biochemist Jr. Biochemist Jr. Biochemist 13,500 8,786 8,hlh 5,000 21, 500 8,168 h,000 gecretary (%) 1,680 Diener 1, 250 Laboratory Equipment 2,000 §upplies 7,000 Travel 1,000 3ocial Security & Blue Cross 2,h80 Overhead 2,h75 Col. II I96076I Experience (2 mos. 13,500 8,783 8,820 5,000 21,170 8,131; 3,972 1,692 1, 250 1,677 7,89h 1,000 1,776 h,2Bh est.) 001. III I96I752 Request Budget 13,500 9,883 1,816 5,300 8,600 8,868 h,h00 1,7h8 Col. IV Everage Col III over 001. I 697 (0) (6,998) 300 100 308 800 68 (o) (0) (0) 5,800 6,200 1,000 2,000 3,200 3,800 (Q) 300 (950) (800) 725 66,289 67,152 63,815 (2,83h) Applicable & Potential Income Research in Biocﬁemist MET—‘41:: 13"".9. Hea th service ET 82. Potential Income 18,162 26,087 111,317 - 37,900 6,515 19,738 hh,2h9 h1,317 hh,815 22,000 25,835 19,000 7,000 2,066 1,000 3,000 PatentiaI (19,572) & Woe Income h3. Net Deficit- Research in ems ry III. 166 (3,000)(R) MEDICAL DEPARTMENT RESEARCH EXPENQEE: 88. 85. 86. 87. 88. 1:9. Research Assoc in Medicine Research Associate Nurse-Technician supplies Travel & Publications 3ocial 3ecurity & Blue Cross w - 3,000 900 800 1160 - h,000 3,108 (7,000) 8,000 108 100 139 1,000 245 I425 (200) (35) 6,250 8,733 (3,027) - 200 Total Expenses - Medical Dept Research (0) (h80) Total E enses - Research in Biocﬁemlstry Total Applicable (O) 11,760 �Memorandum -h- re: proposed Research Budget £31. I 1960/61 Budget Applicable ,0. & Potential Income June 12, 1961 Col. II I95575I" Experience (2 mos. Est.) Col. III I§5I752 Request Budget Col. IV Overage III Col over 001. 1,510 5,000 u,000 8,733 h,223 (5,000) _2,510 h,000 8,733 (777) 2,250 2,250 - Net Deficits Forwarded §E§earc 1n . syc iatry Research in Biochemistry Medical Dept. Research h0,000 22,000 2,250 h0,039 25,835 2,250 h0,000 19,000 - (3,000) (2,250) Total Deficits 6h,250 68,12h 59,000 (5,250) 1,000 2,000 1,000 2,000 1,000 1,000 8,000 7,000 8,000 10,000 10,000 (1,000) 58912:: Egauw (E: 250) 51. 1c Potential Income . . Total Applicable PotentIaI Income .ervzce - & 52. Net Deficit Medical. Dept. ﬁesearcﬁ Unrestricted Research Income Henry Kaﬁfmann MemoriaI Funa scheuer Research Fund Contributions - Other than Trustees Total Unrestricted Research Income 11,000 NET RESEARCH - I DEFICIT; III‘DEEERTMENT§"‘“‘ 53, 250 (2,2SO)(31,_ - - (1,000) - _ �-Memorandum - - re: proposed Research Budget ane 1 1961 BUDGET COMMENTS I. RESEARCH IN EXPERIMENTAL PQYCHEgTRY EXPENSEB: projects total expenditures of $159,797, an increase of $29,87h over the approved budget for 1960/61. This increase is made up of the The Request Budget following items: Note A: Line 2-Associate in Psychiatry (Dr. Donald Klein)--Increase-----------—-—--$l,08h This increase represents tﬁo factors: a. Annual increment of $500 as of July 1, 1961 in accordance with stated increment plan. b. Salary adjustment made during the year in order to accurately reflect Dr. Klein's actual qualifications and experience. Note B: Zine §--Associate in Psychiatry (Dr. John Kramer)--Increase—---------------$9,000 During the current budget year Dr. Kramer divided his time between the research and clinical programs, being in charge of the Electro Shock Therapy services on the clinical side. He received part of his remuneration from the Operating Budget and the remainder of his salary was made up by a United 3tates Public Health Service Fellowship. His Fellowship terminates geptember, 1961 so that $9,000 of his total salary of $13,826 should be charged to the Research Budget. Note C: Line 5-- Senior Associate in Experimental Ps hole --------------------------- ncrease---~---------—-—-$1,000 Line 6--Assistant in Experimental Psychology (Eric Karp)—-Increase --------- $ 600 Line 10--EEG Technician Senior .................... Increase ................. $ 390 £§§§_}2--PS cholinguistic Technician -------------- Increase ----------------- $ 313 Line 13--‘Secretary-------------------------------- Increase----------—------$ 132 These repreEEnt regular increments for these positions. Note D: fine 5--Associate in Experimental Psycholo (Dr. Ira Belmont)--Increase---$2,hlh This increase represents two factors: Full year employment for 1961/62 against part year employment for 1960/61; increment from $12,500 to $13,500 as of September 1, 1961. �"Memorandum -6- re: prOposed Research Note E: Line 7--Assistant Budget June 12, 1961 erimental Psychology (NEW)--increase --------------- $7,2h8 personne? itEm grows out of two related factors in E This new in the program. 1. The volume of work in Experimental Psychology during the current year has risen to a point where it places a great strain on the two incumbents. In order to complete the number of psychological tests and experiments essential to the program it is necessary to add personnel able to do this work. This however would not require a full time worker. 2. This factor is related to the information given below in Line 11 which states that we have made a definite policy decision to make encephalographic studies of every patient admitted to the Hoapital instead of a selected sample of patients. This program of encephalography for each patient necessitates a corresponding increase in the number of associated psychological tests which are made concurrently with each encephalograph in order to complete the picture which we are seeking. These two added work loads qualified psychologist. will amply use the full time of a Note F: $ 500 Kelman)----increase (Dr. 8--Associate -----------in roial Psycholo Line or y the fact that the e 1 erence is accoun e new incumbent has higher qualifications than the present incumbent. Note G: Lin' e §--Associate in ppo n ment en 3 erimental Psycholo ugus , . w (Dr. Karl Anderman)-decrease--$7,080 Note H: fine IluEEG Technician Junior (NEW) -------------- increase ----------------- $3,600 The purpose of this new position is to enable the department to make complete encephalographic and associated psychological examinations of every admitted patient. At the present time we are making encephalograph studies on only a portion of the population related to our drug investigations. much found have we a however, these of studies, In the course been have we than abnormal of encephalograms incidence higher It has therefore been decided that it would be valuable and informative to make of instead each on patient study encephalographic a full selected patients in order to learn whether this high incidence of abnormal encephalograms will hold for the total patient population. In order to achieve this, it is necessary to add this position in to referred services additional psychological the well as as led to expect for our patient population. Line 7 above. �“memorandum -7- Note re: proposed Research Budget June 12, 1961 I: fine IS--Teohnical Assistant (NEW) ---------------- increase ----------------- $h,500 This positioﬁ‘is Being added in order to relieve higher paid professionals, psychiatrists and psychologists from statistical work and to provide a coordinating function in the department in the development of more efficient methods. This will give the top professionals more time and opportunity for the use of their higher skills. Note J: Eine 50~~Training Expenses ------------------------ increase ----------------- $h,838 Cost for didactic psychoanalysis, special courses, etc., for Dr. Donald Klein (Line 2 of budget); this expenditure is covered in full by United gtates Public Health Service‘Grant. Note K: line Income------ ------------~--~--a_~--increase—-------—--------$h2,307 Represents approximately $16,000 of additional funds for a con— tinuation grant from the United States Public Health 3ervice and $26,000 from the same source for a Career Investigation Grant to cover Lines 2 and 20 of the budget. 23--USEHS Note L: fine 25--Drugs ------------------------------------increase ----------------- $ 5,089 This {tam is for psychotropic drugs which the Hospital receives free of charge due to our extensive research studies. The cost of these drugs which the Hospital would normally purchase are charged to the Operating Budget and credited to the Experimental Psychiatry . Budget. Note M: Line 2S—-Nassau County---------------------------- decrease----------------- $ 3,120 Research projects supported by Nassau County have been completed and not renewed. Note N: Line 26--Potential Income ------------------------- decrease ----------------- $1h,h02 For I96I752 there are no pending grants or any other sources of potential income to be noted. II. REiEARCH IN BIOCHEMISTRY EXPENSES: Note 0: EIﬁes 58 and 30 through 3h------------------------ increase ----------------- $1,869 AII these increases totalling $1,869 are in accordance with the stated increment policy of the Hospital. the Line P: 29--§enior Biochemist------------------------decrease ----------------- $6,998 Kppointment ends August 31, 1961 �{Memorandum -8- Note re: prOposed Researdh Budget June 12, 1961 Q: ITEE‘36--Laboratory Equipment ------------------ ---increase ----------------- $3, 800 This expenditure is Toor one item of equipment covered Uhited States PUblic Health Service in full by Grant. a Note R: TEEE-E3--Net Deficit: Research in Biochemist ----decrease --------- - ------- $3,000 The decrease shown is the difference between the current year's budget and the budget for 1961/62. It should be noted that there is a decrease of $6,835 from our actual experience III. MEDICAL RESEARCH Note 3: Line §§--Net Deficit: Medical De Research-~decrease ---------------- $2,250 ent ¥or E? accountéd This decrease is the fact that Dr. Arnold Blumberg's full salary is carried in the Operating Budget as Hospital Internist and Employee Physician. All other expenses of this project are covered by a Federal Grant. �Memorandum OFFICE 01" 113E Frm The Mlmm June 30, 1961 Dr. Fink To: 1961-62 Mdget Re: is etateunt of the budget allowance for your departnnt for 1961—62; this is sent to you for your guidance The attached a during the coming year. If you have any queationa whatsoever, please feel free to see me about this femlation; I do not hear you I will assure that all of the figures and procedures are accepted by you. 1133130 Mel. if Ira �”7;” a Q ray—o“ meE 1961-62 WEARCH IN WTAL Salaries and Director Assoc. " nses " Sr. Assoc. Exper. Psycholoy Assoc. Exper. Psycholoy Asst. Exper. Psycholog I (new) I Assoc. in Social Psychology Assoc. Exper. Psycholog ' E.E.G. Technician, Sr. 15.3.0. Technician Jr. (new) Psycholinguistic Technician Secretary Clerk Typist 1961-62 Reguest (Kramer) 25,000. 17,500. 9,000. 25,000. 17,500. 9,000. (Belmont) (Karp) 13,33h. 8,100. (Fink) (Klein) (Pollock) "’ (Kellen) (Andersen) (Hosquera) (Kolo (Podrid Director's Professional Expenses Training Expenses Social Security & Blue Cross Overhead Research in Total nses ZﬁﬁeriggnEEE Egichiatii Potential Income licable & Research in EggngESEtal Pszghiatgz 3. Public Health Service Drugs Hess au County Potential Income Total tent Net licable Deficit Research in ﬁrﬁntg 111,000. 114,000. 7,2148. 7:2h80 Psichiat'i 1 r ,Afyc ﬂy}. ‘3 .. jar ~M" Deferred* 13, 33h. 8,100. 10,000. 10,000. h,800. 3,600. 2, h85. 3,h92. h,800. 3,600. 2,h85. 3,192. 2,710. 1,1120. 2,7110. 11,500. 1,1120. 11,500. 3,000. 3,600. 3,000. 600. 3,000. 3,600. 3,000. 600. h,838. 3.500. 1h,0h0. 3.500. 1h,oho. 159.797. 159,797. 11h,708. 11h,708. 119.797. 119.797. , 240,000. 110,000. . 5,0890 & ncome "? \ Approved 1961-62 Budget Technical Ass't (new) Equipnent (office & medical) Travel Supplies U. BUDGET \\\ {Lu [7/1, PSICHIATRI in" Psychiatry A HOSPITAL /' :1 11,838. 5,0890 cc: Dr. Fink Dr. Robbins Acctg. Dep . *These items requested may be restored to the budget during 1961-62 additional funds become available. if �Duﬂelmh C1707 9L“! v714x14 C 5. /£j>ur5r‘pf ~ "‘50 zaﬁ/ "‘.’U.'>V'“ ,I‘ June 12, 1961 HILLSIDE HOSPETAL TENTATIVE REsEARCH BUDGET Col. I. I - 1961/62 C01. II 1960761 1960/61 Budget Experience (2 mos. est. Col. III 195I75§* Request Budget ) Col. IV Overage 7001 III over Col. I RESEARCH IN EXPERDMENTAL PSYCHIATRY EXPENgES: 1 . 2 . Director Assoc. in Psychiatry 25,000 16,116 25,000 17,000 1 . 9r. Assoc. Exper. Psychology 13,000 7,500 13,000 10,667 7,500 9,500 8,500 1,110 9,500 8,597 1,105 n . 3 5 . 6 . 7 . 8 . u Assoc. Exper. Psychology “Asst. Exper. Psychology " (NEW) Assoc. in aocial Psychology Assoc. Exper. Psychology 1.13.0. Technician, Sr. E.E.G. Technician Jr. (NEW) Psycholinguistic Technician 9 . 10. 11. 12. 13. 9ecretary Clerk Typist '. 15. Technical Ass't. 16. 17. 18. 19. Equipment Travel supplies (office - & Medical) enses- Research in Ezgerzmeniéz Psychiagry licable & Potential 2'3. 21. Drugs 25. Nassau County 26. Potential Income Total Applicable FofenEIaI Income PS 0 rvice 3,113 2,163 600 600 - 1, 500 3,100 3,100 251 - - 1,838 3,500 11,010 2,817 10,126 . 1,081 9,000 1,000 2,111 (0) (D) 600 (C) 7,2118 (E) 500 (F) (7,080)(G) 390 (c) 3,600 (H) 313 (C) 132 (C) (150) 1,500 (I) (1,500) 200 (100) 1,838 (J) 186 2,999 129,923 atry 72,101 - 122,839 78,000 1,800 - 159,797 111,708 5,089 29,871 12,307 (K) 5,089 (L) (3,120)(M) (11,102)(N) - - 89,923 82,800 119,797 29,871 10,000 10,039 10,000 0 3,120 11,102 & Net Deficit, Research in EggsrimenfEI Psychiatry (A) (B) ' “Fawn .n erimen esearc U:.:S:.::m%c§ Income 7,2113 10,000 1,120 1,800 3,600 2,185 3,192 2,710 1,500 3,000 3,600 3,000 2,251 3,127 2,356 600 Expenses Training Expenses 30cia1 Security & Blue Cross 3, 311 Overhead 11,011 Total - 2,172 3,360 2,890 - (NEW) Director's Professional 20. 21. 22. An 10 920 25,000 17,500 9,000 11,000 13,331 8,100 ‘ �WWW Memorandum ~S- re: proposed Research Budget June 12, 1961 BUDGET COMMENTS I. RESEARCH IN EXPERIMENTAL PQYCHIATRY EXPENSEB: projects total expenditures of $159,797, an increase of $29,87h over the approved budget for 1960/61. This increase is made up of the The Request Budget following items: Note A: Line 2-Assgciate in Psychiatry (Dr. Donald Klein)--Increase-~~---—---—-~---$l,08b This‘fhcrease represen s we ac ors: a. Annual increment of $500 as of July 1, 1961 in accordance with stated increment plan. b. Salary adjustment made during the year in order to accurately reflect Dr. Klein's actual qualifications and experience, Note B: tine §--Associate in Psychiatry (Dr. John Kramer)~-Increase----------------$9,000 During the current budget year Dr. Kramer divided his time between the research and clinical programs, being in charge of the Electra Shock Therapy services on the clinical side. He received part of his remuneration from the Operating Budget and the remainder of his salary was made up by a Uhited States Public Health Service Fellowship. His Fellowship terminates September, 1961 so that $9,000 of his total salary of $13,826 should be charged to the Research Budget. Note 0: Line ﬁ~~§enior Associate in Experimgital Psycholo Drtéﬂax PoIIaCE--—-------------------—-::— ncrease ----------------- $1,000 Line 6--As§istant in;§§perimental Psychology (Eric Karp)--Increase 600 $ --------- Line lO--EEG Technician Senior-------------------- Increase ----------------- $ 390 Line 12--Psycholinguistic Technician -------------- Increase ----------------- $ 313 Eine 13--Secretagy -------------------------------- Increase--------~------~-$ 132 These repres§nt regular increments for these positions. Note D: fine §--Associate in Experimental Psychology (Dr. Ira Belmont)--Increase---$2,hlh This increase represents two factors: Full ytar employment for 1961/62 against part year employment for 1960/61; increment from $12,500 to $13,500 as of 3eptember l, 1961. �Memorandum -6- re: proposed ?esearch Budget June 12, 1961 Un- Note E: Line 7--Assistant erimental Psychology (NEw)--increase--------------- $7,2h8 personne§ item grows out of two related factors in E This new in the program. 1. The volume of work in Experimental Psychology during the current year has risen to a point where it places a great strain on the two incumbents. In order to complete the number of psychological tests and experiments essential to the program it is necessary to add personnel able to do this work. This however would not require a full time worker. 2. This factor is related to the information given below in Line 11 which states that we have made a definite policy decision to make encephalographic studies of every patient admitted to the Hospital instead of a selected sample of patients. This program of encephalography for each patient necessitates a corresponding increase in the number of associated psychological tests which are made concurrently with each encephalograph in order to complete the picture which we are seeking. These two added work loads qualified psychologist. Note F: will Line 8-~Associate in gocial Psycholc The difference is new incumbent has present incumbent. amply use the (Dr. full time of a Kelman)----increase--------~---$ at the iac accounts or y e higher qualifications than the 500 Note G: fine §--Associate in §%perimental Psychology (Dr. Karl Andermagl—decrease--$7,080 Kppointment en s ugus , /a . the H: Line I1--EEG Technician Junior (NEW) -------------- increase ----------------- $3,600 The purpose of this new position is to enable the department to make complete encephalographic and associated psychological examinations of every admitted patient. At the present time we are making encephalograph studies on only a portion of the population related to our drug investigations. In the course of these studies, however, we have found a much higher incidence of abnormal encephalograms than we have been led to expect for our patient population. It has therefore been decided that it would be valuable and informative to make a full encephalographic study on each patient instead of selected patients in order to learn whether this high incidence of abnormal encephalograms will hold for the total patient population. In order to achieve this, it is necessary to add this position as well as the additional psychological services referred to in Line 7 above. �Memorandum -7- Note re: proposed Research Budget June 12, 1961 I: EEEE'I§--Technical Assistant (NEW) ---------------- increase ----------------- $h,500 This position is Being added in order to relieve higher paid professionals, psychiatrists and psychologists from statistical work and to provide a coordinating function in the department in the development of more efficient methods. This will give the top professionals more time and opportunity for the use of their higher skills. Note J: Tine 20--Training Expenses ------------------------- increase ----------------- $b,838 Cost for aiHEE'icfEEychoanalysis, special courses, etc., for Dr. Donald Klein (Line 2 of budget); this expenditure is covered in full by United §tates Fublic Health Service‘Grant. Note K: Line 23"‘USH‘I9 In00me-----n-m-'~~—--——---ou—-~-.._..-a-increase—-—---—-—--------$b2,30'? Represents approximately $16,000 of additional funds for a continuation grant from the united States Public Health 3ervice and $26,000 from the same source for a Career Investigation Grant to cover Lines 2 and 20 of the budget. Note L: Line §E--Drugs ------------------------------------ increase ----------------- 3 5,089 This item is for psychotropic drugs which the Hospital receives free of charge due to our extensive research studies. The cost of these drugs which the Hospital would normally purchase are charged to the Operating Budget and credited to the Experimental Psychiatry Budget. Note M: Line §S--Nassau County---------------------------- decrease----------------- $ 3,120 Research projects supported by Nassau County have been completed and not renewed. Note N: Line 26-—Potential Income ------------------------- decrease ----------------- $lh,h02 For I95I752 there are no pending grants or any other sources of potential income to be noted. �T’Heﬁo ﬁranluh desk of 'L.ING.BE ‘ L Jun 21, 1961 to: Dr. Fink: of June 30, 1961, the changes you requested will be reflected in your net expenses. As will net expenditure of h0,000. at that time. we 114% show a M ”(M (L/ao/o/ 6’35? �Pg. 1 To: I Dr. Fink Director, Research in Experimental Psychiatry Fran: Accounting Dept. Re: Report of Expenditures 1 60 - H 31 1961 HOSPITAL 50331012110 ”Lac Fink Siege], Secretary Podrid Salaries 0 uses : Assoc. in Social Psychology Psycholinguistic Technician maize}! Kolodny Medical Equipment 113. Expense Account Total Expenses 1333: Income from Nassau County ' Donat i on of Psych 0 room Dru g s Net Expenses cc: Mr. Bachrach t 3,120. 2,172. 2,890. 1,500, Office Equipment Travel Supplies Social Security & Blue Cross Director's 25,000. to Hospital . 23,753' $33.?- :1 12, 3 . 18%. ES. 3’1“». 3 , hog. 920. 600. 1,0 . 2 38 . 143,120, 37,109- 3,120. 3:35;9 . {5%. 7 ' W, 0. ho,ooo, 31,859. �.1 Dr. Fink Pg. Director, Research in hcperhnental Psychiatry GRANT 2 141-2715 1/1/61 to 12/31/61 Grant. approved for $65,886. 1/1/61 to 12/31/61 Supplemental Grant 16 2 0 . approved for with: Amount hl,058.* 1960.61 to applicable hperience 1960-61 Budget . To Date ,. Grant. Balance 6/30/60 32,1105. 311,599- Additions: Amount applicable to 1960-61 1431053 -* bl 053. Starting Balance Salaries & ese nses: ssoc. n sychiatry Sr. Assoc. in Exp. Psychology Assoc. in Em. Psychology Asst. in Exp. Psychology Assoc. in 73,u63. Additions & Exp. Psychology Psycholinguistic Technician E.E.G. Technician Secretary Secretary 16 ,h16.~- \ Klein Pollock (Gittehnan 675. 6’8?” ’ 9’ 8,500. 7 ’ 890. 291. luhlo. 3,360. mm»... RM V . h 028 9,8112. " ’ 7'93: 106. ' Sspplies 2:5“). Medical Equipment Office Equipmnt Social Security 9 . 7.500. (Andermann Kolodny Mosquera Castalano ’ 10,920.-~r (Krauthamer % 15 583 6,1914.’ 7,333. (Belmont Karp v-1... 75 , 797 . 8: Overhead 382. 1,928. Blue Cross 9,681» " 1-1519‘ ,1 729. 3’ 259 1:100. “Iravel ”933' Total Expenses Unexpended Balance 530' - is 3!“an cc: Hr. Bachrach " Em 66,085. 9,672. if)? w, a 5, X“ I 3 41.3 6 7 3"? �Pg. 1 W m Director, Research in Ehperimsntsl Psychiatry To: Dr. From: Accounting Dept. Re: Report of Menditures J1EE}. HQ] .. 5323 39 mm HOSPITAL SUBSDIZED RESEARCH Experience To Date 1961-62 Budget SALARIES Fink Kramr 2% 6’25° Equipment Travel supplies 3. S. & Blue Cross Director‘s Expert“ Accmmt TOTAL EXPENSES IESS Donation of Psychotropic Drugs NET EXPENSES CC: Hr. Baohroch $313“ ' 3 233‘ 5 350 “65 5,089. 5 335 h0,000. 1 g �Pg. 2 To: Dr. Fink Director, Research in hperinantal Psychiatry cam 141—2715 Mariana To Date Grant Balance 6-30-61 ’ Addition: Starting Balance and Additions _S__ALARIES Klein Pollock Belmont Karp Andermann Kolodmr Mosquera Zoller & Schniman Cartolano xrlmr EXPENSES Winner Goldaclmidt Supplies Equipmant Travel S. S. 8: Blue Cross Overhead TOTAL EXPENSES UNEZPENDED BALANCE 00: Hr. Bachrach Sept. 30, 196; 6,810 .57 20 529, 2 72 .. 1,000. 3 ,500, 3,203, 2,025. 1, 771. 619. 1,133. 625. ho. 2 ’2500 610. 263. 133, 1,01h. 301. 2 ,676, 21,168. 6,201,, ., .. __ ..__.. ._.... �av~ ﬂh T6: Dr. Fink Director, Research in Mammal Psychiatry W Experience to Date 3.21;. 302 1961 Grant Balance 6-30-61 Additions -’\ Starting Balance and Additions SALARIES Klein Podrid 3,500, 861. EIPENSES 8.8. 8: Blue Cross W @1135 0 Supplies row. Emmszs mm ,. 8,166. p.500.) BALANCE « W 00: Hr. Bachrach 5" 64“ ”‘5 27’? 6‘ ﬂex/4’" ﬁb (I M / . �d To: . .‘Dr. Fink Director, Research in Experimental Psychiatry (RANT HI-hl98 to Date Sept. 30, 1961 Grant Balance 6-30-61 Additions ___6.ééé..________.____..___ Starting Balance and Additions M Klein Podrid 6.666. 3.500. 861. EXPENSES S.S. & Blue Cross Supplies Overhead TOTAL EXPENSES UNEXPENDED BALANCE CC: Mr. Bachrach 78. _______7_13‘_____________________ �"\ Pg. 1 x To W Dr. Fink Director, Research in Marianna]. Psychiatry From: Accounting Dept. Re: Report of Expenditures July 1 - October 31: 1961 HOSPITAL SUBSIDIZED RESEARCH Ebcperience ' To Date 1961-62 Budget SALARIES Fink Kramer 8.331.. EXPENSES Equipment Travel Supplies Blue Cross Director's Expense Account S. S. & TOTAL EXPENSES IESS Donation of Psychotropic Drugs NET EXPENSES 00: Hr. Bachrach 221;. 116. 13. 8,990. 1 “55 5,089. I 525. 140,000. �Pg. 2 To: Dr. Fink Director, Research in hperimental Psychiatry GRANT 141-2715 Experience To Date Oct. 31, 1961 Grant. Balance 6-30-61 July Oct. Additions . Starting Balance and Additions §5_LARIES ""‘"""" Klein Pollock Belmnt Karp Andermann Kolodny Mosquera Zoller- Schnirmn Cartolano Kramer Winner GOIdBChEidt EXPENSES 6,810.57 20,529. 20,529. 147,901.57 1, 333. 14,666. M333, 2,700. 1,771. 906. 1, 510. 879. ho. 3,000. 1, 277 . 550. Supplies we“ 3'“ S. S. Blue Cross Overhead & '7 215. 6 . l’iog. 3,568. TOTAL EXPENSES 2Q UNEXPENDI BALANCE 19.,hﬂs.._______________ 00: we mach mg. _... �.M W Pg. 3 Dr. Fink To: Director, Research in Experimental Psychiatry W herience to Date - Grant Balance 6-30-61 July Additions Oct. Starting Balance and Additions W October 31, 1961 6 666. 6:66h. 13,330. Klein Pcdrid h,667. 1,280. Travel 111;. EXPENSES 8.5. & Blue Cross Supplies Overhead TOTAL WSES UNEXPENDED BALANCE CC: Hr. Bachrach 10?. 15. 950. 7 ,133. 6,197. _ ��Pg. 1 ‘ EEEQEEEEE! To: Dr. Fink Director, Research in Emerimental Psychiatry From: Accounting Dept. Re : Report of Ehcpenditures July 1 to November 30: 1961 HOSPITAL SJBSIDIZED RESEARCH Experience To Date 1961-62 Budget SALARIES Fink Kramer 10,u16. EXPENSES Equipment Travel Supplies 808. 205. 53. Blue Cross Director's Expense Account S. S. 8: TOTAL EXPENSES LESS Donation of Psychotropic Drugs NET EXPHWSES CC 3 “re BacmaCh 235 11,767 . hég, 5,089. 10 302, 130,000. 1 __ , �Pg. To: 2 Dr. Fink Director, Research in Khmerﬂwntal PSyChiatry GRANT 141-2715 Merience To Grant Balance 6-30-61 July Additions Oct. Starting Balance and Additions SALARIES Klein Pollock Belmont Karp Andermann Kclodny Mosquera Zoller- Schnirman Cartolano Kramer EXPENSES Willner Gold schmidt 6,816.57 20,529. 20,529. h7,901.57 1,666. 5,333. 5,1633,375. 1 , 771 , 1,117. 1 , 888 . 1,111. ho, 2 ,250. 1 , 9&3 . 83 7 . Supplies 108. Equipment Travel S. S. G: Blue Cross Overhead TOTAL EXPENSES UNEXPENDED BALANCE CC 3 Mr. Bacmactl Date 1 . ’2?“ 11,1160- 3h 0h] 13,352.. ‘ ___-.- �To: Dr. Fink Director, Research in maximum Paychiotry mum HI-h 98 Exporience to Date Grant July Oct. Edam. 6-30-61 6 666. 61661;. Additions Starting Balmco and Additions p.330. SALARIES Klein Podrid 5,833. 1,575. Travel 209. 138. EXPENSES 5.3. a: Blue Gross mm: Overhead MAL MSES mm MCE 00: Mr. Bachrach 2?. 1,181. 8,969. 5361. �Pg. 1 To: Dr. Fink Director, Research in Experimental Psychiatry From: Accmmting Dept. Re: Report of icpenditmrea Jug: 1 to December 31I 1961 HOSPITAL SUBSIDIZED RESEARCH Experience To Date --__ 1961—62 Budget SALARIES Fink 12, 500. Kramer w Equipment Travel Supplies 629. 318 Blue Cross Director's Expense Account S. S. 8: 2683, 13,797. TOTAL EXPENSES IESS Donation of Psychotropic Drugs NET EXPENSES . 5,089. 2 ,295. 11,502. ho,ooo / 2K CC: Mr. Bachrach ; 1' a.) ,7“. ‘ .1 " .. �Pg. 2 To: Dr. Fink Director, Research in Experimental Psychiatry GRANT tax-2715 Experience Tb Date Grant Balance 6-30b61 July Oct. Additions Starting Balance and Additions SALARIES Klein Pollock 20 ,529 . 20,529. WI 901. 2 , 000. 7,000. 6,583. Belmont Karp Andermann Kolodny Mbsqnera Zoller - Schnirman 1,771. 1, 327 . 2,255. 1, 310. Kramer 3,000. Cartolano Willner EXPENSES 6,8h3.57 Gold schmidt Supplies those. hO. 2 ,652 . 1 , 1214 , 1108 . Equipment Traﬂel S. S. 8: Blue Cross Overhead 1 . ’23; 5,352. TOTAL EXPENSES 1 000 UNEXPENDED BALANCE ﬁIQQ], CC: Mr. Bachrach _ �To: Dr. Fink Director, Research in Experiments]. Psychiatry GRANT “1:5198 Meme to Date Grant Balance 6-30-61 July Oct. Additions Starting Balance and Additions W MNSES my) BALANCE cc: Mr. Bschrsch 13,330, 7,000. 1,870. Travel 350. 171. Overhead “FUSES 6,6611. Klein Podrid S.S. & Blue Cross Supplies TOTAL 6,666. . ho. ____J_’),L2)J_.________________,__ 102855. 2.2.15, �Pg. 1 Dr. Fink To: Director, Research Wu“). 1!: From: Accounting Dept. W62 Psychiatry Report of Expemﬂtures Re: . HOSPITAL w SUBSIDI- RESEARCH Experience To Date Fink 11bit”- Kramer 750. 21h. 333. Schnimn W" chin Equipment Travel Supplies S. S. gig" 1 ,1h9. Blue Cross Director's Ehpense Account & 359. TOTAL EXPENSES mss Donation of Psychotropic Drugs NET EXPENSES CC: Mr. Bachrach 1961-62 Budget m , 213 2 225 5,089. 15 213 1.0.000. �Pg. To: Dr. Fink Director, Research in Emperimental PsyChiatry GRANT MY-2715 Experience Tb Date W 6 ,8h3. 57 Grant Balance 6-30b61 Oct. Additions Starting Balance Jan. and Additions 68,906. Klein Pollock 2,000. 8 ,083. SALARIES Belmont Karp Andermann Kolodny Mosquera Zoller Cartolano Kramer EXPENSES Uillnnr Goldldhnidt Supplies Equipment Travel S. S. & Blue Cross Overhead TOTAL EXPENSES UNEXPENDED BALANCE CC: 20,529. 20,32 3. Mr. Bachrach 7, 628. h:6730 1,771. 1,522. 2,633. 1’3h3. 3,000. 3. 3061,389. 938. 3,315. 1,h37o 839. 6,100. 50 0h}. 2 �Pg. 3 To: Dr. Fink Director, Research in Mex-mental Psychiatry GRANT DIX-£1798 Experience to Date Additions July 6,666. Jan. 6,66h. Starting Balance and Additions 19 . 8 8. SALARIES EXPENSES Klein Podrid 21%;, Travel 350. Bur SOS. & Blue Supplies Overhead TOTAL EXPENSES UNEXPENDED BALANCE CC : Mr. Bachrach 60. Cross 2%. 0. 1, 3, 12 555, Lugs», �Pg. 1 To: Dr. Fink Director, Research in Experimental Psychiatry From: Accounting Dept. Re: Report of Ehcpenditures July 1, 1961 to February 28, 1962 HOSPITAL NBSIDIZED RESEARCH Experience To Date 1961—62 Budget SALARIES Fink Kramer Schnimn 2% Klein Equipment Travel Supplies Blue Cross Director's Expense Account S. S. & TOTAL EXPENSES LESS Donation of Psychotropic Drugs NET EXPENSES CC : Mr. Bachrach 15,371. 1,500. 1428. 666. M0. 1,329. 232. ['22 21,858. 2 1225 5,039. 19 5§2° h0,000. _ _. �Pg. 2 To: Dr. Fink Director, Research in Experimental Psychiatry GRANT 141.2715 Merience Date To Grant Balance 6-30-61 Additions 6,810.57 July - Jan. 62 ,062. Starting Balance and Additions SALARIES "" ' 68,906. Klein Pollock 2,000. 9,166. 8,673. 5,296. 1,771. 1,716. 3,000. 1,316. 66. 3,000. 1,694. Belmont. Karp . Andermann Kolodny Moequera Schnirman mm Cartohno Dramer Goldachmidt EXPENSES Willner Supplies Trave1 s. s. a. Overhead TOTAL EXPENSES UNEXPENDED BALANCE cc: Mr. Bachrach 3 , i460 . h, 2 95 . t 1 ) 1:353’1‘.. Blue Cross 7,01h. ‘4 ’ 9. 13,},62. �To: Dr. Fink Director, Research in Ewerimental Psychiatry GRANT DIX-M98 Mama to Date Grant Balance 6-30-61 Additions July - Jan. . -—————l9-,991+.——-——————————————. .___J.2;22L_.____.____.____.. Starting Balance and Additions SALARIES Klain Podrid EXPENSES 9 11 . falls» 2 Baer 212 . Travel 5.8. & Blue Cross Supplies TOTAL EXPENSES UNEXPENDED BALANCE CC: Mr. Bachrach 350- 319. 11h. 1h,h22. __§,_S7_g_._________________ �Pg. 1 MEMORANDUM To 3 Dr 0 Fink Director, Research in Experimental Psychiatry From: Accounting Dept. Re: Report of Expenditures Jnl3Al..l£ﬁl.tn.laznh.31,—1262 HOSPITAL SUBSIDIZED RESEARCH __ ...____~_._.._w-. __ Iii“ hramer Schnirnan Klein Experience To Date 1961-62 Budget 18,307. 2,250. 6h2. 1,000. EXPENSES Equipment Travel Supplies Blue Cross Director's Expense Account S. S. LESS r CC: & Donation of Psychotropic Drugs 4...: Mr. Bachrach 1 052. 1:971. 302. 509 ‘__~.w_____ 2' ““2 23 713. 5,0§3:~*WWM . 513,960. �Pg. 2 To Dr. Fink Director, Research in Experinental Psychiatry GRANT Mir-2715 Merience To 6,813.57 Grant Balance 6-30-61 Additions July - Jan. §2 m2 Starting Balance and Additions SALARIES 68 Qgé Klein Pollock 13:33: gm“ A”? ndermam Kolodm' Mosquera w! Krmr Ichnirnn Cartolano Winner EXPENSES Goldachmidt Supplies Eq‘li t Travel S. S. 8: Blue Cross Overhead TOTAL EXPENSES UNEXPENDED BALANCE CC 0 Mr. Bachrach Date 9,718. 5,919. 1 771. 1:911. 3,353. 1,310. 66 000: ﬁz6Sg. 1’36 . h,326o , i’gﬁ’ , 0 7,927. E] 555 ‘ �PSe 3 To: Dr. Fink Director, Research in herimental Psychiatry GRANT MI-h798 aperience to Date Chant Balame 6-30-61 Additions July to Jan. Starting Balance and Additions w EIPENSES 1‘1““ Podrid Baer Travel S.S. & Blue Cross Supplies Overhead TOTAL MSES UNEXPENDED BALANCE CC: Hr. Bachrach __J.9..22lL.__.__._.—_______ :2 22!: 10,173. 2,686. 352. I495. 397, 188. _____2.135.______________. 16,136. 3 68. �M Pg. 1 To: Dr. Fink Director, Research in Ehcpermental Psychiatry From: Accounting Dept. Re: Report of Ebcperaditures __EﬂaLJg—lﬁél_tn_hp=il_30,—1962 HOSPITAL sussmxzm RESEARCH Experience To Date _.._...._.__. 1961—62 Budget SHARES Fink 20,2m4. Kramer Schnirman 3,000. 81h. 1, 308.. Klein §§E§E§§§ Equipment Travel Supplies S. S. & Blue Cross Director's Manse i’éﬁi: 3% Account $99. TOTAL EXPENSES LESS Donation of Psychotropic Drugs NET EXPENSES CC 3 29 Hr. Bacm‘aCh ‘ . 2 8] 2 295 22 186 5,089. 140,000. __ _ �Pg. 2 To: Dr. Fink Director, Research in Experimental Psychiatry GRANT Mir-2715 Emerience To Grant Balance 6-30-61 Additions 6,816.57 July - April Starting Balance and Additions SALARIES Klein P°11°°k 29%“ ”P Andaman KOlOdW Mosquera MmSchnirman Kramer Willner Gold schmidt EXPENSES - Supplies Egamt 8“]. So So & Blue Cross overhead TOTAL EXPENSES UNEXPENDED BALANCE 00: Mr. Bachrach Date 8 3 , 065 . _.__...__..__. 52 292 1%??? 10,762. 6 , suz . 1 ’ 7 71 . 2 ’ 105 . 3 ’ 736 o 13%;: 3 , 000 . S . 3%; 2 o7 . , 1 12 O 3,315. 2 1468 1,h23. ’ O 8 ’ 8h0 . 52 212 22 5 3? . �Pg. 3 Dr. Fink 'Mmqum—‘m To: Director, Research in Ebzperimental Psychiatry GRANT PIX-M98 Experience to Date Grant Balance 6-30-61 Addiu‘ms July to April ‘ Starting Balance and Additions —-4515S8~————————————26 658 SALARIES K331“ 1. 2:9g9. 11 2 PM?“ EXPENSES Baer T 371“ 1 Sgt“; Blue Cross Supplies Overhead TOTAL EXPENSES UNEXPENDED BALANCE CC : Mr. Bachrach ﬂit . 188 . 2 312 18,072. 8 ~86 �’ To: Pg. 1 Dr. Fink Director, Research in Experimental Psychiatry From: Accounting Dept. Re: Report of Ebcpenditmrea Jugs! 1I 1961 - Max 2]“ 1262 HOSPITAL SIBSIDIZED RESEARCH Emerience To -.....___ Date 1961-62 Budget SALARIES Fink 22,179. 3,750. Kramer Schnirman W 1 , 028 . Klein 1,558. Equipment Travel supplies 8. S. & Blue Cross Director's Ishcpense Account TOTAL EXPENSES IESS Donation of Psychotropic Drugs NET EXPENSES U4872,032. 356. 519 22 262. Mr. Bachrach ho,ooo. 30.6%; * Transfers from Grants MY 2715 and MY 1:798 as per your to be entered on books as of June 30, 1962. CC: 5,089. 2 225 memo of 5/23/62 - �Pg. 2 To: Dr. Fink Director, Research it: Write; GRANT Psychiatry rib-2755 Ehcperience To We Grant Additions 6-30-61 LPN-1;! ~ . April """"" 89,909 . Klein Pollock 2,000 12,h16. 11,808. Behnont Kerp Andemm Kolodny Mos ere my: Certoleno Schnirman ramer 1mm. Travel S. S. 8: Blue Cross 2,601. 1,600. 9,753. Overhead UNEXPDJDED BALANCE 00: he WW 92. Supplies Gold schmidt EXPENS$ MOMS. 1,3}43 . Willner Equipment TOTAL 7,165. 1,771. 2,330. 3 ’ 000 , 6 , O36 . K EXPENSES 6,810.57 £33,063. Starting Balance and Additions SALARIES Date 2 A1; , 72 120, 11.112 . �To: Dr. Fink Director, Research in Mex-mental Psychiatry GRANT PIE-M98 Emerience to Data Grant Balance him Additions . Starting Balance and Additions _ 26,658 . 26,658, SALARIES Klein Podrid EXPENSES B8 er 12 ,36". 3,2h2_ 37h . Travel h9h. S.S. & Blue Cross Supplies Overhead TOTAL EXPENSES UNEXPENDED BALANCE 00: Hr. Bachrach 2481;. 188. g 692 12 256 g 202 �July 10, 1961 H830 re: ﬁre. Groghan Front Dr. Pollaak nleaae aet aaide the annual increaent approved for July 1, 1961 for retirement or other annuity pnrpneee attentive Jnly 1, 1961. I understand that the neniea withheld rill be nade available to me at my raqneet. Thank ynn. Would ynn Sincerely yours, Hrszp 33E FoIIacE, 55.5. �July 10, 1961 HERO To: Mrs. Croghan From: Dr. Klein please set aside tho annual increment approved for July 1, 1961 for retirement or other annuity purposes effective July 1, 1961. I understand that the monies withhold will be made available to no Would you at my requoab. Thank you. Sincerely yours, Drtgp I on . o n, . �g .I Wm [bur/m. a; !‘ ll L~O-h-b-C-* .0i ' 604’. a") “wt 6 ? 0 u-' ......... " ﬁ WW 4:~-5‘."4‘I-.0J.I«----'Q.OD.I'.II'.--.l“lC u-ov -.... n _ )J’ 4 I I! A / ” ll , I , 1 ”I. II i II II ‘ II II II II ll ‘ i "W“ II II || . ll ll ll r/. 03 nu». a A. V ['2411/ /€/ - �L\.‘\I-"-\ \y Q. �July 13, 1961 HERO To: Era. Dorothy Groghan Front Dr. rink Max Subject: Aaaignaout of salary Itaaa, 1961-62 Plaaao aaoign tho salary itaaa in tho Departaont of Exporirontal Psychiatry aa tolloval (a) lon-Govoroaant 1. Director 8. Social Psychologist 15. Toohnioal Aaaiatant (b) Dr. Fink To ho appointad To be appointod: H. NY-2115 2. 3. h. 5. 7. 9. 10. Payohiatriot (shooo) Lazoc. 8r. Expar. Psychology Aoaoo. Aoaiataut_ '” * ' - 0.1. Kloih John Kranar Pollack Dal-out Ira V Eric Earp Arthur Willnorﬁ streettvum9f6t-w Assoc. Expor.'Payoho1ogy Karl Andoraanui Ends 9/1/61 EEG Technician Hrs. Haaaah-Hooquora EEG Taohnioian ll. - Hrl. Ilano Goldoohaidtr Bagino 9/61 12. Poyoholinguiotio Toohoioian - Hrs. Joan Koloday 1h. Clark Typiat - 32f. fygiawzollor Max ‘ . (o) NI-h128 y 2. Payohiatriat 13. Soorotary . - D.F. Klltn - Hrs. Gloria Podrid Sinooroly youro, ﬁtter - ﬂax FIBEI 3.5?“ �July 19, 1961 HERO To: Hre. Croghen From: Dr. Ire Beleont pleeee set eeide the annual increment approved for Sept. 1, 1961 for retirement or other ennuity purposes effective July 1, 1961. I understand that the monies withheld will be made available to me Would you at my toque-t. Thank you. Sincerely yours, 1331p Ire EeImonE, 55.5. �Novenber 27, 1961 MEMO To: Mrs. Dorothy Groghan From: Dr. Max rink Subject: Revision of Salary Assignments, 1961-1962 Budgot. 2nd half, Please assign tho following salary itoms in tho Department of Exporinontal Psychiatry offectivo Jan. 1, 1962 to Juno 30, 1962 as follows: (a) Nen-Govornmont 1. Director - Dr. H. Pink 3. Psychiatrist ,- John Kronor (O$9000/annlb 8. Social Psychologist - To be appointod 1h. clerk Typist ”Us Do schnirlm '15. Technical Assistant - To be appointed (b) HI-2712 7 ' -21rPoychtatrist7**“‘““m“““‘””m““““”3“DTFT“ttetn“tO$kooo/annuo 8r. Assoc. lxper. Psychology - ﬂax Pollack 5. Assoc. I I - Ira Bolnont Assistant I 'I 3 I Assoc. Expor. Psychology EEG Technician EEG Technician Psycholinguistic Technician (c) HI-h798 C}. Psychiatrist 13. Socrotary - Eric tarp Arthur Willner To be appointed Hrs. Hannah Hosquera Hrs. Ilana Goldsohnidt Hrs. Joan Kolodny - D.F. Klein (Total loss $h000) - Hrs. Gloria Podrid Sincerely yours, Mllgp HIE'TIEEI'HTET' �MIMOIANDA ,“ �[13/ Memorandum From The OFFICE OF THE ADMINISTRATOR December 20, 1961 To: Dr. Arnold Blumberg v’Dr. Max Fink Dr. Harry Goldenberg 1962-63 Budget Re: I am working on the budget for the fiscal year - July 1, 1962 to June 30, 1963. Attached please find budget'forms with expense categories pertinent to your department. The first column shows the budgetary allowance for the current fiscal year; in the second column, kindly indicate the appropriation you feel will be needed for the 1962-63 fiscal year. You may append any data or schedules which you feel will be of assistance. For each item of salary and expense contemplated for 1962-63, kindly indicate in the appropriate column the source of support for the expenditure. Before you make your please confer with for next year. Thank you MB:DC Enclosure M:- 7254' final determinations for purposes of this budget, Dre Rebbins for your cooperation. as to your plans and budget prospectives �~T0: DEPARTWNT 0F MERIMENTAL PSYCHIATRY HILLSIDE HOSPITAL �L F; , . a , ,3 ,.. L: ....q. a a; mg 3. :m.‘ :2,‘ ,Fman .3, .35 n 1 a.»v. GM ,r I. , 4 Ahrwwm. a. H..4. H. ”a?” mh. 4 .3. . A». Vt. 1 can , H k ”21., ‘5‘.» K 3.: , _, L f. L H ‘ , . . l , f. : . , hm H 1+ ..'I {IIIII i'l'l'll «Inlgilillﬂllwll it‘ll-Illlllllllllllll «I'll'llll.wu,llllll"l “EIIIIIIII! .flllllllll I'lllnlll .,II|l|IIl|I:|-|lll|l.lll. IIIII'III...,.Illlll'l. Ill'lllll. «IIIIIIII! «ill-I'll! ,Illl'llllw ‘llllllllll .Ill'l'llllll ll! ‘ - , IlinllA ¢ A x . , 1, I x I.“ l z. , M I“ 1 . / , i. f lI < . . 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Y 5,. “lllll'lll'l'l'll IIIIIIIIIIIIIII , .. ‘ , \ I_ I ...... �ﬂFfBB’. 5% WA: I’wa N ”/7 ' x . ‘M. ”#7 11,1111; ’ ” 47%? 6’7? / Wu” 6/ ”F A203 /&:W - ��, . 31-. . _ km. Auoc. he. who . rod-aha up». an. .‘ kt" A“ ', Pooh-log , 7 m . Assoc. uni-w inn—- ~ rm ‘ roam Sea-our; mm. Club-mm . (ml-Ad» and run). nun-1) mun mat-01"! Put-utensil. Train“ up»... (0:. we; W W 3001.). & nu. an” ”7.”,— 4, an. 13.331» moon. 5,100. m7 :3: . A 7,50. 10.000. " 1.1.20. . Wu g b.000. 3.600. ' ' . 4.. (W) Us A .m‘ m. 2:12. n «a 2.1.65. 3,132. 2,1“. £500. . 3.000. 3,600. 3.000.. . w . ' - n4.) Cron- ‘ ~ . 3.500. ”MM. 7 ' 0.3. Public -. . a' m mm Hula; 1. M. 15,833. it"s-nu Tom lupus-a muscu- ram mu Scum-u . - . pun—L44 ’ lquimt (arm. .- lug-n ' 2.3.0. Yeoman, Jr. tholjnzuhuo . nrp . Auoc. 1n Soom’ V“ Bel-nut mug hpor. mm 3.x.o. rochucim, 8r.' . . We i ' 1.13.100. G tea! 8'!“- �81'. Anna. E190! Psychology Pollack Assoc. Bqu‘r. 3.01% Anya-.313)». p n new. in lung. 'E.E1.G. metal": thlby I a m W4 ‘ _ 30016. m1! . _ ~ Pmbloq Exp". thploq .7 Tahitian, Sr. E.E. a. nemoimn, Jr. Hams " ‘ ~ 1 mar-onngmtio technician ‘Stcutuy_ HINHW. ’ =j smm inert-Typist“ ' - . fwd/h‘wﬁﬁ $92:me mun) if Equip-Ont w-mia ”PM” ' . ’ ‘ ' W Wantor'a Prozac-10nd ruining Enigma (hasnun) "__Se¢1n «Emu Gm Wt! 1' ‘ m 'j: 2/1/11 " . .m in (/5: WW3: )7 * _ ‘ J47_-' r5“ ' ' ‘ �H1llside Hoqpitii 1962—63 Salaries Director & Budget - Research in Experimental Psychiatry Assoc. Exper. Psychology Asst. Exper. Psychology . Kramer . ’Pollock » Belmont ' Karp Assoc. in Social Psychology Assoc. Exper. Psychology E.E10. Technician, 3r. E.E.G. Technician, 4ﬁdhlﬂr Moaquera Jr. ,(L14‘.ALaQ»‘ (office and Medical) Training Expenses (Dr. Klein) Social Security & Blue Cross thioaw Total Expenses Anglicable & Potential Inca-o U. 5. Public Health Service «Mr—“whoa”, Ire.“ lions 7/4/4. a. 5».«~ " ﬁfe" . Fﬂclv 1“ 7 4/0 3 Director's Professional Expenses r. r- lbowr Scott/‘nual (éI‘M) 7 ?"',4]; : 3"” 47;: r: 417. Supplies W m-~.— C) agaao. Podrid 1‘rawel «- v 5-» [9‘100 ,.r, n.. ' A/vi Kolodny . mm. Drugs Request Anderman Psycholinguistic Technician Sacretnry Clerk-Typist ~Teohnioa1 Asst. gout/”‘4‘“ m... Budget .37 Klein Nil/Mr Overhead $1.1¢¢1Lc.z 1962-63 Egggnees Associate in Psychiatry n. I Sr. Assoc. Exper. Psychology Equipment 1961-62 F‘s-u ‘44. 7‘9 JI-A ?,h85. 3,h92. 2,7h0. h,500. 3,000. 3,600. 3,000. 6) >640 J 70 / 39/4. 7~fec — , /.(on Juo, 300 "' IOOo h,838. 3,5001h,ouo. V! 3! .3'00 [76yj'h' loco 153,797. /?3/:9. 113,708. 5,059. [4U .43 2! as. �” V‘r/‘f/ f‘ﬁf/ �7-5- H ”I ‘ I0“ V. .4 . ll . Mﬂzr Th ﬂ e, [ll—Yr» I ‘ . ll ll I! I Corr/biz} o‘7 ' I ‘ * - . ‘ " ~ “W ﬂﬂanoa‘ 1 t 1.- 6110 Q Afﬂéeméudz" ,, , .V 7!!) 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'@ 173,14’ A A ’31:. 0 ././wwa/«x..7 “'Mj/xm ?( ,0/L-7/f {u/y "A: hrs in lawn, / gruWMAiw 7% 7//v Jlnuﬁv’ {Mn‘ _ //.>" flu/no . ‘__..._.._._._ ��ﬂan—4‘ M/ 47/ 610..., 11; v J“. . K 39W ~ Chou. " ,7? ,, Mud ' o 0 Waﬁoc . ., �~24 Ioqu/ ‘ but and; /, a «1.1.x ”1.114.. /, 347.41” 447-4? ”4,1. p.441. 4%? 44' ’ 4,-3.30 47.3.30 .1,_‘ all" . ago .1“. 71-1. W 3. ’ .4 0 . . �c I 1&4 6.. ‘1‘” I‘ve : 4173.3v �H.’ 23’ 1962 \., HERO To: Mr. H. Bachrach Front H. Fink, H.D. Subject: Adjustment of Expenditures HI to MY 2715 and KY h798 1. Pleaao aeaeeign following expenditurae aaeigned 2715 to "non~government". a. Salary of lolodny, Jean Jan. 1, 1962 - June 30, 1962 Goldechnidt, Ilene Jan. 1, 1962-May 31, 1962 2. Pleaee reaeaign expenditures charged HY h798 by transfer to "non-government” of the following items: a. Gloria Podrid Charge 2/5 to MY h793 7/1/51 ‘ dtto BIS/to Ron-Govt. ' b. Mrs. Gertrude Baer Charge o. all salary to Non-Govt. Requiaitione dated: 11/61 ﬂax rink - expenaee 12/61 Max Fink - expenses 12/20/61 Max naailton 2/8/62 L.I. stenotape Co. (Royal Typita) 2/8/62 Joint Purchasing (aupplies) 9.75 b0.61 50.00 53.20 h6.55 W. ."' �oemnmtm or: arm» mcmm HﬂLﬂDEPKNFgﬂL Gumcnﬂhl99' May 23, 1962 MEMO To: Mr. M. ﬁachrach From: N. Subject: to MY Pink, M.D. Adjustment of Expenditures MY 2715 and July 1, 1961 - June 30, 1962 MI L798 Please reassign following expenditures assigned 2715 to “non-government”. 1. a. Salary of Jan. 1, 1962 - June 30, 1962 Jen. 1, 1962-Mey 31, 1962 Goldschmidt, Ilene 2. Please reassign expenditures charged HY h798 by transfer to “non—government" of the following items: a. Gloria Podrid Charge 2/5 to MY h798 7/1/61 - data lolodny, Jeen " 3/S/to Non-Govt. b. Mrs. Gertrude Beer Charge ell salary to Non-Govt. c. Requieitione dated: Fink - expenses Fink - expenses 12/20/61 Hex Hamilton 11/61 12/61 Mex Max 9.75 h0.61 50.00 53.20 2/8/62 L.I. Stenotape Co. (Royal Typite) 2/8/62 Joint Purchasing (supplies h6.55 Hex FInE, M.D. �6/11/62 Brain Function and Bohavior Rososrch Progoct Bud‘otagz Rocoonggggtiono -- 1262 ~ 62 - Rovisod 6/11/62 Following discussions or 5/22 and 23, a hudgst rooosnondation for oightoon months support was prosontod which did not lost tho Radical Diroctor's approval. In ossonco, it provided for an oxponditurs or $53.h10 for the first six months; $63,183 for tho next twolvo; and of those suns, 325.750 from Hillsido Hospital and $90,8h3 (including $9583 ovorhsod) from tho u.s.9.n.s. In lino with tho discussion of 6/11/62, tho following rovissd budgot is prosontcd for consideration. 1. It is tho intsntion of tho Director of tho Dopartnont or Exporioontal Psychiatry to resign fro- hia prsaont pooition' on July 1, 1962 to continue os Principal Invsstigator (Consultant) of tho Brain Function and Bohavior Rosoarch ProJoct (H! 2715) to Doc. 31, 1962. For this poriod, to Doconhor 31, 1962 his ssrvicos will ho conponsasod on a consultant stipond basis, tron funds providod by tho Board of Directors of Hillsido Hospital. 2. It is roconnondod that Dr. Belmont, boginning 10/1/62, bo continuod on a flat too stipond basic at an ostblishod rats oqnivalont in ootivity to ono day pot wash. 3. It is roconnondsd that tho following adjustnonts ho nadc in Dcpartnontal hudgsts to accomplish tho rsquostod soparation of tho Dopartaont into constituont unite. �-2- s. the expenses and activities of Dr. Donald Klein he continued under the direct supervision of Dr. Robbins, providing such secretarial and data processing services as his project may require. b. in EEG technician salary be provided by the hospital at a rate of $5,000/annuu for full tile. 1 would suggest 2/5 tine; but this should be based on s reconaendation of tho hospital Neurologist. For the period that Dr. Kramer is available, he will continue to read the records; but provision should be node for others to do this. 0. Dr. Kroner to continue in the sane relationship to end or 1962 continuing supervision or 30!, at Dr. Robbins' K! h798 and pleasure. 0. Present budgets (to 6/30/62) he re-ellocated to show estimated expenditure of approximately $30,000 in Board support, allowing the following a a) Estinsted balance 6/30/69 nr 2715 2000 Incone 2nd half 1962 h2001 stupoo 5. Budgets for six nonths 1962 and 12 nonths 1963, corrected for social security, blue cross and statistical expenses are shown on next page. These provide, exclusive or principal investigators 7/1/62 - 12/31/63 3h,260 Overhead 1/1/63 - 12/31/63 5,100 $38,960 50.500 �-36. Requeet 0.8.P.H.S.t $hh,000 a. 196? Income Expendituree 38.960 5.000 app. - carried forward b. 1963 50,500 -._.£&99_ hS.Soo Overhead 6.8gg $52,325 7. With theee adjust-cute, the budget ie reconnended inclueingt a. Continuation request or I! 2715 be aubaitted to U.S.P.R.s., requeeting the aaount of 52,325 to retain at Hillaide ﬁoapital for 1963 and the balance (app. 31.000) he made available for application of continuation at the Mieeouri Iuetitute or Paychiatry. b. iproval for transfer of EEG analyser and tape eyeten ee requeeted h/l/62 be approved. 6. Board of Directors approval tormfunde or 12,500 for period 7/1/62 - 12/31/62 aa continued aupport of Principal Investigator (Coneultant) on baeis outlined above. In the event coneultent tine 1- required in 1963, expenses and ccnaultation teee are to be paid by Hilleide Hoopital through {undo provided by the Board of Directore. A contingency fund in the amount of 86000 ie eugteeted for thia activity. a. U.3.P.H.s. be requested to approve Dr. Hex Pollack ea oouinveetigator. �7/1/62 - 12/31/62 1/63 - 12/63 1. Staff Psychiatrist I. Pollack, 8:. Res. Assoc. taper. Peychol. John Kroner, 3,956 - I. Bel-out 7,500 3,582 15,000 'Earn, Consultant 750 Res. Ass't. Expor. Fsychol. A. "illner, Res. Assoc. Expos. Psychol. B. Hosquereﬂ, EEO Technician 3. b.350 h,700 1,000 1,700 1,h57 1,315 0. Podrid, secretary Dr. schnirnanhe, secretsry J. Xolodny, technician 351 BC (OPP) 3,000 8,700 , 9,h00 2,000 3,800 ~ 2,600 950 Travel Supplies Conputaticn c Consultation ‘ Carried forward Net Overhead u.s.r.n.s. Total ' Board support Total Budgets: 18 nos. uspns Board 500 600 900 1;560& 1,200 1,800 1,500 3h,260 50,500 3h,260 5,000 u5,500 5.100 38,960 6,822 $2,325 12,599 16,000) $109,785 91,285 12,500 (¢ $6000 contingency). Notes 0 H. Hosquere: tins s 380 resesrch i and as ties statistician, clinicel EEO services recouaended by Allows one es Secretary-typistc Prograa (it sill Neurologist). not require second typist 1963. �6/11/62 I! Brain Function and Behavior Research Proaect Budgetarz Reconnendetions -- 1962 - 63 - Revised 6/11/62 Following discussions or 5/22 and 23, a budget reconnendation for eighteen months support was presented which did not nest the Medical Director's approval. In essence, it provided expenditure of $53,h10 for the first six nonths; $63,183 for the next twelve; and of these suns, $25,750 from Hillside hospital and $90,8b3 (including $9583 overhead) from the U.3.P.H.3. In line with the discussion of 6/11/62, the following revised budget is presented for for an consideration. 1. It is the intention of the Director of the Department of Experimental Psychiatry to resign from his present position on July 1, 1962 to continue as Principal lnvestigator (Consultent) or the Brain function and Behavior Research Project (M! 2715) to Dec. 31, 1962. 1962 December to 31. his services period, this will be cenpensaeed on a consultant stipend basis, tron funds provided by the Board of Directors or Hillside Hospital. 2. It is recon-ended that Dr. Belmont, beginning 10/1/62, be continued on-e flat fee stipend basis at an estblished rate equivalent in activity to one day per week. 3. It is recommended that the following adjustnente be node in Departmental budgets to accomplish the requested sepsraticn or the Departnent into constituent units. For �-2- a. activities of Dr. Donald Klein he continued under the direct supervision or Dr. Robbins, providing such secretarial and data processH! h798 and the expenses end ing services as his project require. b. in EEG technician salary be provided by the hospital at a rats of $5.000/annuu for full time. I would suggest 2/5 time; but this should be based on a reconnendation of the hospital Neurologist. For the period that Dr. Kramer is available, he will continue to read the records; but provision should be made for others to do this. c. Dr. Kramer to continue in the same relationship to end of 1962 continuing supervision of ICT, at Dr. Rohbins' pleasure. h. Present budgets (to 6/30/62) he re-allocated to show may estimated expenditure of approximately $30,000 in Board support, allowing the following: a) Estimated balance 6/30/6? NY 2715 2000 Income 2nd 5. half 1962 h2°?Z, thhpoo Budgets for six uonths 1962 and 12 months 1963, corrected for social security, blue cross and statistical expcnaes are shown on next page. These provide, exclusive of principal investigator: 7/1/62 - 12/31/63 Overhead 1/1/63 - 12/31/63 3h,260 - 3.100 838,960 50.500 �-36. Request U.S.P.H.s.s s. 1962 - Income Expenditures $bh,000 38.960 5,000 spp. - csrried forward b. 1963 * 50,500 §IOOO hS’SOO Overhead 6:825 $52,325 7. With these sdJustsents, the budget is recossended inelusing: s. Continustion request of I! 2715 be submitted to J.S.P.H.S., requesting the ssount or 52,325 to rensin st Hillside Hospitsl tor 1963 end the bslence (spp. 31,000) be nsde evsilsble for spplicstion of continuation at the Missouri Institute of Psychiatry. b. Aprovsl for transfer of EEG snslyser end tspe system so requested h/l/é? be approved. 0. Bosrd of Directors spprovsl forfﬂunds or 12,500 for period 7/1/62 - 12/31/62 ss continued support of Principal luvsstigstor (Consultsnt) on basis outlined above. In the event cousultsnt tine is required in 1963, expenses end oonsultstion tees sre to be psid by Hillside Hospitel through funds provided by the Bosrd of Directors. A contingency fund in the slount or 36000 is suggested for this sotirity. d. 0.8.9.3.8. be requested to spprove Dr. Hex Pollock ss eo-investigstor. �7/1/62 - 12/31/62 1. 1/63 - 12/63 Staff John Kraser, Psychiatrist Pollack, Sr. Res. Assoc. Bxper. Psychol. 1. Belmont Consultant I. tarp, Res. Ass't. Exper. Psychol. A. "illner, Ree. Assoc. Bxper. Psychol. H. Hosquerae, EEG Technician 0. Podrid, aecretary at. Schnirneneﬁ, secretary J. Kolodny, technician as, no (app) Travel Supplies Computation & Consultation H. ' ’ 3,956 - 7.500 3.582 15,000 750 3.000 b.350 8,700 h.7oo 1,000 1,700 1,h57 1,315 9,hoo 2,000 3,800 950 1,500 600 1,200 1.800 1,200 11500? Carried forward ,, Net ' . Board Support 03935 Board 50,500. 5,000 _., 3h,260 hS.Soo h,zoo 6,825 38,960 52,325 12,500 $6,000) 51,h60 58,325 Overhead Total Budgets: 18 nos. 9,600 900 3h,260 Total U.8.P.R.S. - $109,785 91.285 12,500 (+ $6000 contingency). Notes e i tine as research and i time as clinical statistician, EEG services (if reconaanded by Neurologist). so Secretary-typist: Prograa will not require second typiet 1963. H. Hosqueras Allows one EEG �Juno 12, 1962 Dr. Lowis L. Robbins, Hodioal Diractor Hr. Horbsrt Bookind, Prosidsnt, Board or Dirootors ﬁillsido Hospital Olon Oaks, !.!. Dsar Dr. Robbins and Hr. Bookind: It is with rogrst and with tondnsos for my stimulating and exciting ysars at ﬂillsids that I submit this lattsr of rosignation as Dirsotor of tho Dopartssnt or Exporiasntal Psychiatry stractivo Doooubor 31, 1962. I an aura you will ho ploaosd to know that tho prograss hora havo lad to tho invitation to ostahlish a rosoaroh and training program in a now cantor, tho Missouri Instituto of Psychiatry at St. Louis; as wsll as my appoint-ant as Rsssarch Protoosor of Psychiatry at Washington Unirsrsity School of Hodicino. I look back at thoss ysara with ploasurs, for I havo loarnod such and hats round snthusiastio and dodioatod co-worksrs. I as aratotul to tho contidonoo sxprosssd in my initial appointasnt by Dr. Israol strauss, and to tho Board or Diroctor's support during thoso yoars. During tho nsxt tow aonths, I should liko tho opportunity to coaplots as such o: my progras as possiblo hora, and for this roason hays askod to continua as projaot dirsotor or ths USPH3 grant H12715. is soon as tho studios hora psrait, I shall lsavs to ossuas my now dutiss in St. Louis. with my boot porsonal rogards, and assurancos of loyalty, I roaain. Rospoctfully yours, Hrsgp . ﬂax M IInE, 5.5. �HEHORAHDUH June 12, 1962 to: Dr. L. Robbins FROM: Hex Pink, M.D. With the disapproval of the proposed 18 nonth budget for the Brein Function and Behavior Project, and without a to submit the satisfactory alternative, I an conetreined enclosed letter of reeignation, dated Deco-her 31, with a recommended budget for the expenditures under HI-2715 during the renainder ot the grant period. I an dating the roaignation as of this time to permit the oonpletion of e major port or the progren. It in my intention to continue thie program of studies or the relation of brain function to behevior et the Hieaonri Institute of Poy‘ ehiatry, beginning early in September. For e treneition period or e few nonthe, while aone onelyeeo end write-up are in progress here, the continuation progrene will be eetabliehed there. AI noon on my tine is predoninantly in St. Louie, I will resign fully from the program here. I truet this is satisfactory to you. Roapeotfnlly yonre, Krzdto one. or M n , . . �June 12, 1962 Proposed Budget, Brain Function and Behavior Research Project Jnly 1, 1962 - December 31, 1962 Estimated Balance, 6/30/62 MY2715 Income 6/30-12/31 12,000 h2,007 $Sh,000 Expenditures l.2. Prin. Investigator Psychiatrist (Kramer) 3. Psychologist (Pollack) h. 5. 6. -7. 8. 9. 10. 11. 12. 13. lb. 15. ” EEG 12,500 3,956 7,500 3,582 (Belmont) 750 (Karp) '' (Willner) Technician (Moequara) Secretary (Podrid) (Schnirnan) Technician (Kolodny) Soc. Sec., Blue Cross Travel Supplies Cowputation and Consultation 0,350 h,700 2,000 1,700 1, h57 1, 315K ' Overhead 950 600 900 , ’ 1,500 h,700 $52,h60 Balance carried forward 1963 $ 1,5h0 �June 12, 1962 Proposed Budget, Brain Function and Behavior Research Project July 1, 196? - December 31, 1962 Estimated Balance, 6/30/62 H12715 Income 6/30-12/31 12,000 h2,oo7 $5h,000 Expenditures l.2. Prin. Investigator Psychiatrist (Kramer) 3. Psychologist (Pollack) h. So 6. 7. a. 9. 10. 11. 12. 13. lb. 15. (Belnont) 'I I . (Earp) (willner) ' £30 Technician (lacquers) Secretary (Podrid) (Schnirnan) ' Technician (Kolodny) Soc. Seo., Blue Cross Travel Supplies 12,500 3,956 7,500 3,582 750 13,350 ‘ h,700 2,000 1,700 1.h57 1,3155 . ' ‘ Computation end Consultation Overhead 950 600 900 1,500 ht7°° 3 2 h60 Balance carried forward 1963 ' 3 1,5h0 �June 1?, 1962 Propoeed Budget, Brein Function end Behevior Reeeeroh Project July 1, 196? - necenber 31, 196? V Settleted Belence, 6/30/62 HYZTIS Income 6/30-12/31 . 12,000 g2.oov $5h,000 Expenditures 1. Prin. Inveetigetor 2. Paychietriet (Ire-er) 3. Psychologist (Pelleok) * L. (Beleont) R S. 6. 7. 8. 9. 10. 11. 12. 13. 1b. 15. '' I (Earp) (willner) Technicien (Hoequere) Secretary (Podrid) (Schnireen) \ Technicien (Koladny) Soc. Sec., Blue Cross Trevel Supplies Coeputetion end Consultetion EEG ' Overheed 12,500 3.956 7.500 3.582 750 h,350 h.700 2,000 1,700 1.h57 1.315f 950 600 900 1,500 5&12Q 2 Belence carried toruerd 1963 h60 a 1,5h0 �glidilibﬂl Jan. 12, To. 1962 Dr. In Robbins ---.~-- -----”.-.-.with tho disapproval at the prchIod 18 nouth budget fur the Brain function and lohnvlnr Proaout, and without a tntlntuatory altornativc, I am eenstrainod to submit the with a Isolated lattar at rculznatlon, datod noun-bowII~5115 Jl roast-andod budgot for the Impoudlturuu and-r during tho ronnlndor or the grist porlud. I :m attlng rollcu:tlan In of ﬁhln #1:. to paralt the ounplo‘lon of a IIJOr part at in. progral. It 1- Iy intanllon to uoatlano tutubotavlor proxruu of It‘dlou of tho ralatlon or brain Pay— I1UIOIF1 tho or functlun $0 InstitutIt ohlntrr. bout-nan; early in Boptunhor. It: a truulttlou 902106 at I ran monthl, will. aqua analyacn and write-up are in prograan bars, the oonﬁlnnntlou prouru-l will be octablilhnd tiara. At noon an my tin. la produuiu:ntly 1a 3%. L§!1l. I will route: tall: from the progrum hcrc. I ‘rlnt til: 1. natiltlctozr to you. BprQoSShlly yours, ti. nmu “.0 n , . . �MEMORANDUM DEPARTMENT OF EXPERIMENTAL PSYCHIATRY June 1h, 1962 To: Mr. Bechrsch FROM: Dr. Hex Fink ..‘.~.“‘..--.-.“enclosed budget dated June 12, 1962 for 6 months under project support by MY-2715 is contingent upon the adjustments euthorised in my memorandum of 5/23/62, 3 copy or which is enclosed. The estineted belence or $12,000 for 6/30/62 may be in error by 10%, and if so, can be corrected by using the belenoe, or adjusting expenditures to conform with reality. Also, it is probable thst lines 1, 2 ere overestimeted. I have also indented this grent fully for Mrs. Mosquere (line 7). After Hrs. Croghen hes made the adjustments of 5/23/62, if she will give me e true balance, I will revise this budget statement. The Thenk you HFsdts for your cooperation. Sincerely yours, ﬁe: Fink, 5.5. �MEMORANDUM DEPARTMENT OF EXPERIMENTAL ?SYCHIATRY June 1h, 1962 T0: Mr. Bachrach FROM: Dr. Max Fink enclosed budget dated June 12, 1962 for 6 months under project support by MY-2715 is con— tingent upon the adjustments authorized in my memorandum of 5/23/62, a copy of which is enclosed. The estimated balance of $12,000 for 6/30/62 may be in error by 10%, and if so, can be corrected by using the balance, or adjusting expenditures to conform with reality. .Also, it is probable that lines 1, 2 are overestimated. I have also indented this grant fully for Mrs. Mosquera (line 7). After Mrs. Croghan has made the adjustments of 5/23/62, if she will give me a true balance, I will revise this budget statement. Thank you for your cooperation. The Sincerely yours, ﬂaw MF:dts Max Fink, M.D.' �MEMORANDUM DEPARTMENT OF EXPERIMENTAL PSYCHIATRY July 20, 1962 Pollack Co-Investigator M. Fink, M.D. T0: Max FROM: MI-2715 Project In answer to your question of 7/19, I plan to complete my active participation at Hillside on September 15 and shall request “vacation” time as terminal leave. For the past year I have accrued 16 days as of 9/1/62, and have carried forward 15 days from 1960-61. If my calculations are correct, my salary should be paid to October 26. Effective on your return from Europe in September, I believe you should assume full responsibility for the expenditures and management of MY-27lS. Until I leave for Europe, and in your absence, I shall continue to carry out these responsibities. I shall notify NIMH as to the transfer of responsibility as of September 15, and have notified Mr. Bachrach as attached memo indicates. In the event that you balieve my consultation will be of service to you, I shall be pleased to come to N.Y. However, reimbursement for expenses should be borne by the grant here. Good Hrtdts luck! Max Fink, M.D. �do ’ MEMORANDUM k DEPARTMENT OF EXPERIMENTAL PSYCHIATRY July 20, 1962 T0: Mr. Bachrach FROM: Max Fink, H.D. Principal Investigator, permit you to MI-2715 Project exact budget estimate for MI-2715 for 1962-1963, I should like to bring the following to your attention. At the completion of my duties in Europe I shall return to Hillside and complete such reports as may be necessary. This should be done by September 15. I shall ask that I complete my service on these programs as of that date, subject to reimbursement for accrued leave. is of September 1, 1962 accumulated leave time will be 31 days, which will be requested as terminal leave. Until September 15 I shall continue to exercise responsibility for the project activities, but shall relinquish these To make a more that date. Parenthetically, I would suggest a prudent bookkeeping measure for your consideration. is you know, the office of Director of the Department has never been supported by government funds. It is prudent to combine this course until the final termination of the office. As a record fully as of matter, if you exercise the prerogatives of your position you could so reassign items in MI-2715, and non-government for 1961-62 as to "carry forward” in non-government a sum necessary for the position. In the revised budget estimate you are planning to submit to NIMH, the item of principal investigator need no longer appear. Thank you for your cooperation. HF:dts ﬁax Fink, H.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource [Hillside] hospital budgets. (2/2) Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-010 Date A point or period of time associated with an event in the lifecycle of the resource 1961-1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Proposed Research request budgets; letters; report of expenditures Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/037717b3a94f66da3e9b2761caa9f3e2.pdf e23ad26e74d9d730dd0ebac94c7bdd05 PDF Text Text January 8, 1960. KIHORAIDUH 1803: 20: SUBJECT: Medical Director DOpartnent of Experimental Psychiatry Salary Scales for Professional Staff Over the past few years we have attenpted to establish reasonable salary scales based upon the conception of full tine work at the institution, without outside professional activity. By adninistrative pressures, a policy of equating Job positions both within the institution and between institutions has been grafted onto the full tine concept. This latter has been nade an integral part of the salary scales despite the awareness that so-called equivalent workers within the institution were not "full tine,’I and that institutional salaries are often different because of the nador.fringo benefits. Continuation of these fictions lakes further growth of this unit extrenely difficult. we are severely handicapped in recruitment; and the staff is restive, considering the opportunities they have elsewhere. We cannot provide university affiliation with graduate students as a source of new personnel; nor have we established an identification for staff persons with I the institution. For these reasons, among others, the following revisions of salary scale and work standards are reconnended for this Department, to be effective July 1, 1960. A. General Principles. 1. All appointments in Associate or Senior Associate categories are to be node on a full tine basis. �-22. All income tron ancillary eorvicee to accrue to the aeeeoroh Fund of the Hillside Hospital. 3. For Aoaooioto and Senior iseociate stat: neoboro ‘ aro in apeoial training toward graduate degree or oertitioatee, no enae to 83000 per anon: tor tour yoare lay bo approved by the Hadioal Director on roooaaondation o: the Director or the Dopartwho loot. h. aebbotioala Salary nay be paid up to .1: loathe after (it. years service and up to one year after oight yearoerrioa in the Dopartnont for etudy at another laboratory or ioatitotien. In the event that ouch eabbatioal in approved, travel and relocation expeneaa up to 3 looo nay be reqneetod. 5. Mentorohip in proteeaiooal eeoietiee and malpractice insurance oorerago to to providod by the Departnont. B. azeoifio Soolea 1e Pchhiﬂt’ye o. For accredited Alerioan Board or Peyohiatry, recent $13,000 - $20,000 with $1000 inoreaent, to 827,500; b. For :raduetoe, eligible for exaninatiooe, .16'000 ‘ .18,000a o. tor lellove (hth or 5th year) $12,000 “ ; ’1h3000 2. Payohelegy. a. Senior Reeearoh atatf ~ 31h,000 - $20,000 Ph.D. and ten or lore yoare orperienoe. .b. Pazaoaroh Aeaoeiate - $10,000 - $15,000 .D. o. Roeearoh iseietanae - $8,000 Phono G‘ndid.t..o ~ $10,000 �ca. 4. Roooorch Follow - $5,000 - $7,000 a. Job Sgociticotioa. 1. For itou la, b, ond to, b, o, tho doooriptiono in monotondun or ootobor 30. 1958, opply. i 2. For itolo 1n ond 24: ohoonto In tho or groduoto oohool otriliotion, tho troininc or our oqn otorr 1o Iondotory. With tho potontiol oupport of (routing ooonoioo oloo dooirono or providing troiaing tundo, thooo rongoo oro onggootod,'ond itouo oiil bo roquootod ‘in tho noxt budgot. 10. Poychiotriota Cooplotion or throo yooro in psychiatric rooidoacy, ond dooirono or otndyiatdhring hth ond 5th yoor. 2d. Ph.D. oondidoto or H.A. ooudidoto. Eorly in coroor, without thooio, would roquoot tnndo to pornit ouch oooiotont to oporoto within tho loborotorioo. \ Roopoettully onbnittod, IX ‘n, oo �\ Departaent of Experimental Psychiatry « April It, 1950. Director SUBJECT: Salary Scales fer Pretessienal Start. Correction of acne dated January 8, 1960. Here stands except for specified revisiens receanended: HEEORLIDUH Page 1. Page 2. T0: Medical General Princigles. 1. All appeiutsents er presetiens te senior Research Associate are made en a 'full'~tell-tiae basis. Appeintaents in ether categeriee are "fellotine" according to established standards of the Hospital. 2. All inceae Irea ancillary services of "full" full-tine start to accrue to the Research Fund of A. Eillsids Hospital. 3’ h, 5. B. 'tCte Sgecitic Scales 1. Psychiatry (a) Sr. Research Asaeciate: en agreeaent with the Medical Directer (b) Research Associates for accredited Aaerican Beard or Psychiatry, recent $18,000 . $20,000, with $1,000 increaent, to $27,500; for greauates, eligible for exasiuatiens, $16,000 - $18,000. (0) tellers: (hth & 5th year) - $12,000 - $1h,000 2. Psychology (a) Sr. Research Asseciate: stat. (b) Research Associate: Ph.D. and esperinental ,» experience $9,000 - $1h,000 (c) as. Research Assistant: x.i. or equivalent, three years experience, and candidate for Ph.D. at accredited university - $7,000 - 39,000 — (d) Research Assistant er Pelbw: H.i. or one year experience - $5,000 - $7,000 �Pug. 3 0. Job Sgociticatiana: while specificatians at 10/30/58 would apply, following changes arc rnqnvatnd. In original docignntion, Rcuoarch Lsaociata in Psychology was limited to Ph.D. and thrus ynnra or oxporicnec. this in hurdansonn, and :11 Ph.D. appointinbo designated 'Aaaociatc.' Assistant dasignation be subdividad to Sonia: Rnaonreh tall-tint and Roacurch Aaaintaut, as abovo pornittinx tho nmploynont or trainees 1nd aundidat-a, with origiu;1 cpcoificutiona applying. Roapodlully submitted, ‘EE§“FIEEI"HTET”~’"' 31:13 ��Pg. 1 Dr. Fink To: Director, Research in Emerimental Psychiatry Prom: Accounting Dept. Re: Report of Expenditures .131; 1 - October 21: 1960 HOSPITAL SUBSIDIZED RESEARCH 1960-61 Ebcperience To Date 25, We 8, 331e 3,167. 363. Dudet Salaries BC Assoc. 8c arises: Fink in Social Psychology Siegel Psycholinguistic Technician Secretary Medical Equipment Office Equipment Travel Supplies Social Security Director's Kolodny Podrid 118. ' Blue Cross Expense Account & Income from Nassau County Net Expenses cc: Hr. Bachrach h85. 1,500. Total Expenses Less: 3,120. 2 ,172. 2 , 890. 3,1t00o 3.1100. (67.) 920. 600. 119. 161. 237. 10,120. 12,796. 3,120. 1214. h0,000. 12 ,672. �Dr. Fink Director, Research in Experimental Psychiatry Pg. 2 GRANT biz-2115 5% to 12/31/61 Grant approved for $65,886. to 12/31/61 Supplemental Grant 16 2 O. approved for Amount applicable to 1960-61 6 151%: h1,058.* 1960-61 Budget quaerience Grant Balance 6/30/60 32,105- 3h,699. Additions: Amount applicable to 1960-61 1.12158 .* m, _ Starting Balance Salaries & Additions 8. nses: ese ssoc. n sychiatry Sr. Assoc. in Ehtp. Psychology Assoc. in Exp. Psychology Asst. in Exp. Psychology Assoc. in Exp. Psychology Psycholinguistic Technician E.E.G. Technician Secretary Secretary Klein Pollock (Gittelman (Bel-"nut Karp (Krauthaner (Andermnn Kclodny Mosquera Bowie Podrid To Date 73,1463. 3h,699. 16,1416. 5,667. 10, 92°. 7,500. 2 ’ 500. 2 ,500. 8,500. 2,931. h.l.10. 1,1426. 7,333. 3,360- 291. 1,123. 1.80. MM Supplies Iviedical Equipment Office Equipment Social Security 8: Overhead Blue Cross Travel Total Eutpenses Unexpended Balance cc : Mr. Bachrach 2,500. 382. 1,928. 101. 1196. 9,681.. 2,7hh. 563. 72,9330 20,8270 13,372. �1“ Director, Research in Experimm Psychiatry Dre mm Pg. 3 181-2092 Great. terminates 12/31/60; expenditurepicked up by Great III—2715 Supplement. mm m0 Starting Behnce 5 Additions We:PWIC" Salaries & Sr. Assoc. in Me Repairs to quipnent 800111 Security Overhead Tom & Blue Crone WW3 Wed We 6,&7e 7,h35e To Date 0 Additions Behave cc! Hr. Mhrech Wk be 1960-61 Bidet " 6/30/60 te 6,667. 7,h35. 5,667e 11,333. 130. 870. 1:3. 628. 6,667. 5,7080 0 7014. 1,727. �Pg. 1 ”MaDr. Fink To: Director, Research in kperimental Psychiatry Fran: Accounting Dept. Re: Report of Expenditures .1an 3 .. 393mm; 30, 1260 HOSPITAL SUBSIDIZED RESEARCH 1960-61 W'Lec Salaries nses: & Assoc. in Social Psychology Psycholinguistic Technician Secretary Medical Equipment Office Equipment 'l‘revel Supplies Social Security Director's Blue Cross Expense Account & Total Expenses Less: Income from Nassau County Net muses cc: Mr. Bachrach Experience Bidet Fink Siege). Kolodny Podrid 25,000. 3,120. 2 ,172. 2,890. To Date . 10, 338. 3,958. 5&6. 730. 1,500. 118- 3,h00- 3,1400. 920. 600. (55a) 173. 22h. 290. 10,120. 16,2014. 3,120,. 177. 130,000. 16,027. gm �M Director, Research in Experimental Psychiatry Dr. ( ' GRANT Pg. 2 111-27}; 1/1/61 to 12/31/61 Grant approved for $65,886. 1/1/61 to 12/31/61 Supplemental Grant approved for Amount applicable to 1960-61 W Grant Balance 6/30/60 Additions: Amount applicable to 1960-61 Starting Balance Salaries 8: ese uses: ssoc. n sychiatry Sr. Assoc. in Eng). Psychology Assoc. in up. Psychology Asst. in Assoc. Psychology Exp. Psychology Ebcp. in Psycholingzistic Technician E.E.G. Technician Secretary Secretary Klein Pollock (Gittelman Social Security a: Overhead 1960-61 Budget Experience 32,1105. 3h,699. 311,699. 16 ,hlé. 7,083. (Belmont Karp (Krauthamer 10,920. 7,500. 3,500,, (Andaman 8.500. 3,6140. Kolodny Hosquera h.h10. 1,783. 1,h06. 3 , 360. Bowie 2.500. 382. 1,928. Blue Cross Total Expenses Balance 5 d .- cc: n .n ﬁ.w ,...,..— I I Illll 291. 1:80. 165. 607. 3,130. 72,933. 26,185. 675: -IIIM' 530. ,. -Nv “A. 3,125... 9.681;. Travel "I'fn'expended To Date 73.h63. 7,333. Podrid Supplies Medical Equipnent Office Equipmnt h1,058.* 1413958 .* Additions 8. l "851%? 6 2 O. 8,51)» �..o~’ Drcl'ink Director, Research in mm Psychietry mm Pg. 3 III-2092 «when: 12/31/60; «podium» to be picked up by Great 141-2715 Suppl-lent Went 1960-61 Met Great Balance - 6/30/60 6.667. Belem. & mm» W Selene: I: Expense” 8r. Assoc. in Exp. Psychology S plies ‘greee Social Security Overhead Total To DI“ 7,105, 0 Additions mm Experience a Blue heme Wed Behme Pollock 6.661. 7,155, 5.567. S,h17. 130- SS. 725. 870. 785. 6,667. 6,982. 0 1:53. �' To: Dr. Fink Director, Research in Prom Accounting Dept. Re: Report of 119 Pg. 1 M mm herinentel Psychiatry nditures to December 31, 1960. A -._A -4tm ,.._ Assoc. in Social Psychol Paycholinguietic Technician Secretary Medical Equipment Office Equipment Travel Supplies Social Security ctor'e Tom Blue Croce Expense Account a: mews Less: Income from Nassau County Net Expenses Pink Siege]. Kolodnv Podrid 25, 000. 3,120. 2,172. 2,890. 112.3335. 14,750. 739. ”5. 1 500. ,118. (SS“ ) 3 ,hOO. 3,hoo. 920. 600. 233° 290’ 1‘3ng ”’566. 3.129.. 265. 130,000. ' ‘ ' �Dr. Fink Director, Research in Experimental Psychiatry GRANT Pg. 2 111-2715 approved for $65, 886. 1/1/61 to 12/31/61 Supplemental Grant approved for 1/1/61 to 12/31/61 Grant 1’20. ﬁg. Amount applicable to 1960-61 1960-61 Budget quaerience Grant Balance 6/30/60 32,105. 313,699. Additions: Amount applicable to 1960-61 1413958.!- ‘ Starting Balance Salaries & nses: Asst. in Exp. Psychology Assoc. in Exp. Psychology Psycholinguistic Technician E.E.G. Technician Klein Pollock 16,h16. 7,333. 8,500. Karp 10,920. 7,500. h,soo. 8,500. 31,3338. h.h10. 2,”.0. (61th (Belmont (Krauthaner (Aniormann Kolodny Hosquera 3,350- Podrid Supplies Medical Equipmnt Office Equipmnt Social Security 3h,699, Bowie Secretary Secretary 8: Overhead 2,500. 382. 1,928. Blue Cross Trml Total kpenses Unexpended Balance _ I cc : Hr. Bachrach To Date 73,h63. Additions & ese ssoc. n sychiatry Sr. Assoc. in Exp. Psychology Assoc. in Exp. Psychology _ hl,058.* ' I II. 3,750,. 291. 1,689. EEO. 278. 697, 9,68,4- 31,116. 72.933. 31,1170. 631. My 530- 3,229, Mum �Dr. Fink Director, Roam): in Experimental Psychiatry mm Pg. 3 31-2092 mus 12/31/60; Grunt picked up by Grant 141—2715 Wt. exp-Mite": to he 1960-61 that Balance - 6/30/60 ' 6,667. 3mm. 6 Additions W Salute: & Enema: $‘o To Date 71:35. 0 Additions Starting Met We “3°C. in m. won-m Supplies Social Security Overhead & 311:. Total. Expenses Unmanned Balance cc: Hr. Bum-ad: areas Wk 6,667. 71:35. 5,6670 6 Q a 130. 870. 63‘. 91-2. 6,667. 8,2138. 0 (813.) �W P80 1 W Dr. Fink To: ‘ Director, Research in Experimental Psychiatry Fran: Accmnting Dept. Re: Report of Menditures 1961 HOSPITAL SIBSIDIZED RESEARCH Salaries ec Assoc. & uses : in Social Psychology Psycholingulatic 'Dechnicien Secretary Medical Equipment Office Equipmnt Travel Supplies Social Security 8: Blue Cross Director's Expense Account Total Expenses Leas: Income from Nassau County Fink Siegel Kolodny Podrid 25,000. 3,120. 2,172. 2’890’ lb 181 5,5112. l ' ’912' D 220.0 _ 1,500. 118. 3,)400o 3,h00. 920. (SS ) 2714' 600. 397‘ 387: 10,120. 22,858. 34L 265. . l __________________________________._____———-——--——--—Net Expenses cc : Mr. Bachrach h0,000. 22,593 �Dr. Fink ‘ _.. ., Director, Research in 'hcperimental Psychiatry GRANT Pg. 2 IKE-2715 1/1/61 to 12/31/61 Grant approved for $65 ,886. 1/1/61 to 12/31/61 Supplemental Grant 16 2 0. approved for ‘B'iﬁi'ﬁ Mount applicable to Grant Balance 6/30/60 1960—61 .m Additions: Amount applicable to 1960-61 Starting Balance Salaries & Additions nses: ReseF-ch Issac. In Psychiatry Sr. Assoc. in Exp. Psychology Assoc. in Exp. Psychology . 1960-61 Budggt Experience 32,1105. 3h.699. ulzostm 20,529. 73,h63. 55,228. 16,h16. 7,333. 9 ,917. 1,083. 10,920. 7:500- 5,500, h,375. 8,500. 5,056., 291. To Date 8: Asst. in Ebcp. Psychology Assoc. in Exp. Psychology Psycholinguistic Technician W E.E.G. Technician Secretary Secretary Supplies Medical Equipment Office Equipment Social Security a Blue Cross Overhead Klein Pollock (Gittelman (Belmont Karp (Krauthamer (Ardemenn Kolodny Hosquera me Podrid 14,1th3 9 360. ‘ Total Ehcpenses Unexpended Balance Mr. Bachrach 2 ,517. 1, 972 ¢ 1:80. Cartolano 13s 2 ,500. 382. 1.928- 99681“ Travel cc : b1,058 .* 281;. 920. 5,009. 979. 72:933- 38,396. 530- 16 ,832. . �Pg. 1 Dr. Fink To: Director, Research in Experimental Psychiatry From Accounting Dept. Re: Report of Ehcpenditures 1: 1260 - Februagz 28I 1961 ng HOSPITAL SUBSIDIZED RESEARCH Salaries & 80 menses: Social Psychology Psycholinguistic Technician Secretary Assoc. 111 Medical Equipment Office Equipment Travel Supplies Social Security Director's Blue Cross Expense Account 8: Total Memes less: Income from Nassau County Net mpenses cc: Mr. Bachrach Fm Siegel Kolodny Podrid 25, m0 3,120. 2,172. 2,890. 1 500. ,118. 3,h00. 3,h00. 12,33: 1’09; ,, J £1455: 180' 13h. 61. 525. 920. 600. 1:17. 53:12“ 26,238. 3,120. “3,955. 10,000. 2 3 ,283. " ; 4-; A 3*) 7’ . �\ Dre Fink Director, Research in ﬁrperimental Psychiatry GRANT Pg. 2 PIX-273:5 1/1/61 to 12/31/61 Grant approved for $65,886. 1/1/61 to 12/31/61 Supplemental Grant approved Amount Grant Balance 6/30/60 Salaries & Eggnses: ese esoc. sychiatry Sr. Assoc. in Exp. Psychology Assoc. in Earp. Psychology Asst. in Ech. Psychology Assoc. in Earp. Psychology Psycholinguistic Technician E.E.G. Technician Secretary Secretary Electronics Technician Supplies Medical Equipnent Office Equipment Social Security 8: m Overhead Klein Pollock (Gittshnan (Belmont (Krauthamer (Andermann Kolodny Mosquera Podrid Cartolano Unexpended Balance cc : Hr. Bachrach Experience To Date 3h,699. M* 203529. 73,1163- 55,223. 16 hlbe 71333- 11 o 3:333. 10 920. 6 500. 3500- 5,765. 7:500- 5:000. 291. hyhloe 2.895. 2,255. 3’36“ 2480. ho. \a ’38:. 500. 295. 1,92 e\~\...1 9’68hN-h 5,3533.. Travel Total Ebnpenses 111,058.?!- 32’h05- 2 Blue Cross 11:15: 1960-61 Budget Additions 8: 16 230. applicable to 1960-61 Additions: Amount applicable to 1960-61 Starting Balance for 15029. 72,9330 [6,852. �Pg. 1 W MEMORANWH Dre Fink To: Director, Research in Merinontal Psychiatry From Accounting Dept. Re: Report of Ebcpenditnres 195] 3] 12m lamb 1. 3 Jul: W RESEARCH SUBSIDIZED HOSPITAL Salaries Assoc. uses: 6: in Social Psychology Psycholinguiatic Technician Siegel m Kolodny Secretary Medical Equipment Office Equipment Travel Supplies Blue Cross Expense Account Social Security Director's . Total Expenses less: Net Expenses 7’125' 1 500. 180' 3,1400. 151: 1’ 335‘ 1:681: ’118. 920. 600. . Income from Nassau County Donation of Paychiatropic Drugs 3,120. 2,172. 2,890. 3,h00. 8: Experience To Date 1960-61 Budget »» ~ x... ,, . 110‘ 626. 1117: 10,120. 2951.0. 3 ,120. 2,955. 2 :295: h0,000. 21:390. to Hospital ______________________________...——————————--- cc : Hr. Bachrach �Dre Fink Director, Research in farperimental Psychiatry GRANT Pg. 2 m~271§ 1/1/61 to 12/31/61 Grant. approved for $65,886. 1/1/61 to 12/31/61 Supplemental Grant 16 2 0. approved for T511137 Amount applicable to 1960-61 1_‘_‘_____ Grant Balance 6/30/60 Additions: Amount applicable to Starting Balance Salaries Essen 1960—61 Additions 3. nses: Issac. In Psychiatry Assoc. hp. in Psychology Exp. Psycholog Psycholinguistic Technician E.E.G. Technician Bud eet Experience To Date 32,1105. 3h,699. hl,058.* 20.5293 73,h63. 55,228. 16 ,h16. 12,750. M327. (Belmont Karp (Krauthamer 10, 920. 7,500. 7 , 5142 .. (Amiermann 8,500. 6,1173, Kolodny Mosquera , 7,333. h,h10. 3,360. & Overhead Blue Cross Travel Total Expenses Unexpended Balance Hr. Bachrach 5,625. 291. 3,272,, 2,592. 1:80. 93. Castolano Supplies Medical Emaipment Office Equipment Social Security Klein Pollock (Gittelman Em; Podrid Secretary Secretary cc : 1960-61 8c Sr. Assoc. in Exp. Psychology Assoc. in Exp. Psychology Asst. in h1,058.* 2,500. 382. 1,928. 9.968140" 3760 1,376. 6,1173n 14100" 72,933. 52,770.» 530. 2,158. �P30 1 Dr. Fink To: Director, Research in Emoriuontd Psychiatry W1 Fran: Accmnting Dept. Re: Report. of Expenditures w—WW m HOSPITAL wnsmxzm RESEARCH M Salaries ac Assoc. & gases: Fink in Social Psychology Siegel Psycholinguistic Technician Secretary Kolodmr Mics]. Equipusnt 1960-61 merience 25gme 19,7950 1,500. 180. 33’4me 5939 3,120. 2,172. 2,890. 118. Office Equipmnt bIVOI Supplies Social Security & Blue Cross 7,917. 1,57h. 1,906. 711, 3shme 920. 600. 163689. Total Expenses 1.3.120. 33, 308. less: Incaus 3,120. 2 ,955. Director's Expense Account from Nassau County Donation of Psychotropic Drugs to Hospital Net kpenses ~ 41;] cc: Hr. Backrest: 1417. 2: 295: 150,000. 28 ,058. �Dre Fink Pg. 2 Director, Research in "apex-mental Psychiatry GRANT ' a... 141-271; . $65,886. for Grant. approved 12/31/61 1/1/61 to 1/1/61 to 12/31/61 Supplemental Grant 2 0 6 1 . for approved 121115: Mat applicable to 1960-61 1960-61 Budget ... ’41, 058 .* Experience To Date Grant Balance 6/30/60 32,)405. 314,699 Additions: Amount applicable to 1960-61 glIOSBJ 111,058s 73,1163. 75,757. Klein Pollock 16,2116. lh,167. (30130111: 10,920. 7,500. 8,583. 6,250. 8 ,500. 7 , 181. Starting Balance & Additions Salaries &ﬁsoc.uses: In Psychiatry Sr. Assoc. in Exp. Psychology Hem Assoc. in hp. Psychology Asst. in Exp. Psychology Assoc. in Exp. Psychology Psycholinguistic Technician EOEOG. WWW Secretary Secretary 7,333. (Gittelmn Karp (Krauthatner (moment: Kolodny m W ughloe 3,360. HOWE 5,1111. 291. 3,6509 2,353.. LBO. 93o Oastslano ' Supplies pursuant Office Equipnnt 2.500. 382. 1,928. Medical Social Security 8: Overhead Blue Cross 9.681;. Travel Total MEMOS Unexpended Balance cc: Mr. Bechrach . 169. 1,5711. 7,366. $139.91 72,9330 593,458: 530. 16 ,299. ' �I [1W W Iu' [44/ : ~--—; I C. I / 1/ / ’W W K4444” ' LI“I X { ~//‘/. / I/L/ I I / 1 I, d — / / 7’ 'V e - ‘1 .__ �2.7 f 444/ Ms/ ,1. r a M dv //'. / .4 — ’ M1 h. 1 a... / 41%;»! / ’, [14,.” I If:/- (I t». AI'VA‘;_727 44' w W / .4 / / 4’15] / 5;! 1% ’ / {i I 440/ a a/ ”M7142: 72ﬁ;4h.&¢ igv M (A I» r], «Ac/47% ’ 3 I / (5300 if 1’ C II» a» W ﬁwm) 72. 13/ / one 53¢: 39 ace �5—0 90¢ �1/3/61 Dopartnont or lxpsriaantal Psychiatry 1961-62 Bndgot, Propoood I. 1960-61 Indgst (-ovsrhsad) $118,882 a. Inorsasos in salariss, annual inorsnsnts b. Additions in prograns: 1. Psycholingnist - to ba aotivatsd 2. Sociologist to tho proxraa 3, £80 technician Statistical tsohnioian, g.. Elootronio oqnipnsnt é. o. s. Status rslatinx to lndgst John [razors Irt. tron fallowship status to Rasaaroh Associats 9/1/61; snbjoot to approval of g. or‘g. Donald Klein: continnss as Isa. Assoc. but is to ba grant (Kh798) supported. that tho dittorsncs in It is axpsctod salary iton on grant and an lsvsl nay ha up to $7500. Grant providss 85000 additional for sscrotaria1 and othar sxpansss. Sabbatieal ~ lax link: 9/15/61-8/1/62 Visiting Soiantist support is roqnsstad. rhara is no salary ohangs during yaar. Amount is $15,000 par annnn. Expanss III. W %,650 1 000 Changas in 0. Souroas of Support (-ovsrhoad) a. Approved: 1961-62 1. HI2715 . ha P01161118: 2, nh798 rotal 0 12,000 170,732 12,000 182,732 72,231 - (323,000) out. 3. Visiting Soiontist c. To bs Raqnastads h. Snpplonantary H12715 126,282 10,000 10,000 6'800 tins tins llaetronios spacialist, II. 7.300 “17,000 13,500 30,000 r¢/~ gh,g§o �$0,000 a. Board or Daroetorl 1. it would Ilk the Board to apprevo I grant 0: $h0,000 to: {var ytara; with an lpyortunity to carry tarvnrd unoxpondod can: far 2 yn;rs. 2. WI wanld also ask for a credit tranltor tron operating budget funds of value of psychotropic drugs (to $10,000) roecivod in the progran. In 1959. the ' vulno was ontinntod as O11,000. Inconn Eutinato: 182,731 Exponae Estinatcs 182,732 ��V WWW—WM...‘ r L ///~/ 5 ”A Z 3%” ' IBKOO >3, W? + ' ————-'_f"——' I 23, We ’3 ’ (00 ‘ 2.00 ..—— I ~ I I v ’ 2“ 3f?” = ��May 5, 1961 Hrs. Croghan Departnent of Experieental Psychiatry Heme: Iron: Subject: Budget '1. In reviewing find budgetery expenses to date, I the following in the Beapitelised Subsidized Research: Expenditures 7/1/60 ¢ 3/31/61 $29,5h0 Less my credits (Nassau County) 5,250 (Drugs) Estimated Expenses nets sonths 3 $2h,290 I Salaries (3&00 x 3) Social Secutity Travel Other 10,200 300 1,000 _ 200 net: Less credit for teeching 900 Research Associete in Psychiatry (Klein) app. Secretary I! (Podrid) app. hSOO 82g $5,325 my calculations are in error, please call as. Thank yen. a Sincerely yours, HTzOP 11,100 35,990 ax n , . �5. 1961 May HOIO! Mrs. Croghan Irons Dapartaont of Expsriaantal Psychiatry Subdaota Budxat 1. In roviaviag a: budgstory oxpsusaa to data, I find tho following in tho lospitalisad Subaidisad Rasaaroh: nxpandituras 7/1/60 ~ 3/31/61 $29,5h0 Lass credits (lasoau county) 5,250 (Drug-v) __.______ not: $2h,290 lotiaatad xxoonsos 3 months salarios (JhOO x 3) 10,200 Social secuoity Traval ethar 300 1,000 200 not: Lass oradit for teaching 2. 11.100 35,990 200 I: this is iha approxiaatsly would you oorraot, ploasa assign following sxpandituras to this account, tron Grant l1-2715, attentiva April 1? nosoaroh Associats in Psychiatry (Ilain) app. ASOO Saoratary (Podrid) app. “33: I: ay calculations aro in Thank you. 85,325 error, ploaso call as. Sinosraly yours, IIsOP ax n , . . �Prcptlod ltdgot 1961-6! nevi-ad 5/22/61 Doparinont .: tsp-rtnonttl Plyuhtltry annuity: Exponloo 1961-62 $156,hh0 Inoolo warns _ Eonpttal eruditl 108,870 1.510 116.;50 lot Unuubcidisod ltloarch 8 ko,ooo �5/22/61 Bspcrt-sct ct lxpssissntsl Psychistry Prcpcscd 1961-62 ludxst (lsvtssd 5/22/61) Exp-uses: 1. Blrsctcr 2. Assoc. 1n rsychistry .AQE‘o/B. Assoc. 1n Psychistry h. is. Assoc. Expos. Psychology 5. Assoc. in lxpsr. Psychslcgy 6. Assist. in Expos. Psychslcgy ,rswo'7. Assist. in lxpsr. Psychc1cxy 8. Assoc. in Sosisl rsychclcgy 1960-61 1961-62 Apprsvsd hsqusst (3. link) 25,000 25.000 16,h16 17'500 Sllcta) lrsnsr) . 13.000 Pcllsck; lslncnt 10.920 1.500 Ksrp) . Villas!) 2'004' b‘; 1h,000 11,000 8.100 73200 (9) 9,500 10,000 (d) I,$oo 1,h20 (s) Elbsqusrs) lss) h:h10 k,aoo 3.600 (I) ) 12. rsychslingsistis rsshntc1sn élslcdn Psdridg 13. soot-tar: (Ibssclnsn) 1h. alcrkotyptst 1,172 3,360 2,890 2.300 - 2.700 3:500 16. [quip-cut (attics, nsdicsl 11. frsvsl 18. acrylics 19. nircctsr's Prstcsstscsl lxysnsss b.5oo 3,h00 3,hoo 3.000 3,600 3.000 3,31h 3.500 9. Assoc. 1s lxpcr. Psychology 33:6) Andsrssan) 8:. ”Eu/11. no lcchsicisn, Jr. 10. ans fschnicisn, AﬂE‘VlSs fcchnicsl Assistant 20. Social Bcccrisy/llns Gross (lcs) (sst.) 21. msrhssd «- 600 11.01;]. 20211 $129,923 33h80 (t) 600 11,200 kg 2,8h0 1 $156,hho �-2. Bopartnont at lxporincutal Prychiatry lxyoulon 1961~62 lacunae 0&56ikk0‘ ﬂ?{5.3,qzelo 1. warns 31.2115 (62) - 1/1/61»12/61 (1/2) Iroaght toﬁvurd (03%.) (1/2) (ca) - 1/1/62o12/62 h1,oso k,oeo 32.000 w 87,059 2. warns x.h795 natinutod 8.1.2: 1k,26h n.710 pr. 0701‘. 2.8!!6 21,820 (a) 3. 2cc¢htn¢ (But. he hrs. .181!!!) h. Bra: rrnnlror (13%.) ' 1,000 (k) 3,570 (1) 4E=4HHhIHHap6Iadtﬁ-GIaI-é-otalG~9010htt§rttt+jhﬂﬁﬂy4hér W ”3 Vs'ro lot lxpouaoa (Haunt-111104 lcncuroh) 3 ha,ooo �lgtoot Sagportod, in art, by l~h798, aa Garcon Iavoaticator, otfoctivo 1/1 61. Bixtoroaoc in inooao will to aooignod tron l1-27159 (b) loplncoo 3.). [loin in nx-avzs. In continuing onporvioion of la! prozroa would roqnoot continuation of clinical onpyott a! l/h otat: poychiatriot iton. low appointacnt, ottoctivo 9/1/61 at $8,500 for air nontho, $9,000 thoroottor. loo appointaont, to ho aado 9/1/61, at oatinatod $12,600 pot annna. ippointnont onco 9/1/61. Will not ho roplacod onlooBiroctor rocoivoa II! Vioiting acioatiat award. (t) (a) (h) (1) (3) (k) (1) Ion aypointnont to porait hoopital~uido onrvoyw plannod attor 9/1/61. low poaition to: ototiotioal ani onporviaory :nnotiono. lollovo a roooanondatioa at Aaoiotont idniniotrator, Hr. Bavio, tollowinc a Job convoy Icy 1961. evorhoad allcvoaoo on l1-2715. avorhood allowanoo on l-h798. n~h198 allowo $18,!1h for oalary ani roooarch cooto; $2,0h6 for ovorhood. rho-o'itoao aro applicablo to tho prograa. It aloo allovo Oh.838 opooitiod oo training cooto. Ihilo Dr. Kloin nay not ntilioo tho on: in tho conin; yoar, it nay not to nood for othor pnrpoooa without oxprooo provioion. It ia onticipatod that thio on: will to rotnrnod to tho warns. Incono ootinato boood on continuation of coarooo in Biological Paychiotry and in noooarch lothcdology. lininal oatiaato balod on 1959-60 and 1960.61 oxporionco. loqnoot continuation ot clinical crodit-tor clinical oorvicoo, followingll960-6l oxporionco. ‘ �5/!!I61 a.“ nupnrtuont at prorannatal Parnhtu‘vy ttovonod 19§1~62 nudgit (3011804 5/22/61) 196o~61 lupus-0.: 1. Blrootor H. fink) 2. assoc. 1a rnynhxntry x1013) J. Assoc. in Ptyuhtutvy tranor) Assoc. 8!. 8390!. Psycholtcy (Pollack) g. A‘s... in super. Psyuhnlocy (not-oat) . 6. Acoiut. 1n Savor. Puyehalogy Earp) 7. Alutlt. 1a Payah01n¢7* Willa-r) or. 8. Autos. 1: 3.0 :1 Payuholocy luv; 9. Assoc. in Expor. Psyuholncy Ila Ap’rovod 8:. Inna ' 15.133131», m 330 ruahaictna, Andlrllll) on) 25.000 15.h16 - 13.000 10,9:0 7.500 - . 8,500 10. 11. 1!. 13. 1h. 15. 47. ll! Pﬂytholtsgutattc rochniotna {301.43 ) 50ar¢$ary roarid Clark. 10% ftnuatlnan) rlahnie Lnatutaat 30v) . 2,112 16. 11. 18. 19. Equtpuunt (otttc..n¢di¢n1) traval Suppltca Dtruator‘c !rottultonnl lap-anon 800131 80¢n31$7llluo 0:03: (00‘) h.500 3.h00 3,hoo to. no: 21. Ovarhoau "f ﬁg?! {VFW 4‘ anf‘ <\ \J, a\. iﬂﬂﬂt 3,360 2,890 - $00 3.31h 11.0h1 $129,923 ‘155 0500 �“531.1190 Inna-0i 1. um :::: um 'mzz-wzzx . _ W , 01.059 I. um: MM “mm am “.000 10.850 3. latching (83%.) h. um.) S. m Wu- clilttti crolit (xerox/h 500 5.00.0 (a) Itttr plyth$n3rtnt1;‘ggg lit lliilill (I) (lhlniltltsod tinnitus) (a) \ W W ‘ 1505000 �(o) (d) (o) (f) (s) (h) sappurtod, in part, by u~h198. ll carter Invoc‘tcntcr. ottaottvt 7/1/61. Dittoronco in incon- v111 be assigned S!!! IY~2715. Inpltaoa 5.1. Xi'an in ur~2715. In contanuzn; unparttnion a: no: progran would mounts: aonttnuttton at tho 1/8 nt‘tt poynhxntrtlt. lav appcxntunut. «rtagtavo 9/1/61 at :0.500 for at: nontha, $9,000 ‘hnrunttur. lav appatatnnnt, t- be and. 9/1/61, nﬁ outiuttad $12,000 par gonna. Appointncnt and. 9/1/61. 3111 not he rnplnood talus: ntvactnr rﬁcctvbl III Vitittuc Scientiut award. luv appointuant.to pcrult hoapxtllavado survey: planatd utter 9/1/61. New position for azntintloni and aupnrviaurr tunotlcnt. Fallout 3 risen-audition of Assistant idlinistr¢‘ar. pr. navio, (allowing a Job I‘TVII law 1961. on continuation or court.- in Inc... ontinnto bland and non-arch nothodoloay. Bioloctonl Payohtutry (1) Kin1nnl catiunto based anti-stat. on 1959~60 and 1960~61 ' (3) noqscnt continuation or clinical credit for 01131301 suvvtauu. failurtuc 1960~61 o:pnr1¢n¢¢. �HILLSIDE HOSEFRHL WEGE & SALARY SCALES Scale # HIRING RATE SERVICE-MERIT INCREMENTS "‘if""‘i?“”"“"§"" MERIT INCREMENTS “ﬁf“"“‘3¢‘”"‘ l 185 193 201 209 217 225 2 205 21h 223 232 2&1 250 3 225 235 225 255 265 275 ,h 250 ‘261 272 283‘ 29h 305 5 275 2877 233' 311f 323‘ 335 6 305 318 331' 324, 357 370 T 320 355 320 385 hoo 215 385 200 his h30 nus 8 376 �9113 TITLES ﬁrm GRADES AND HOURLLRATES F0 a JON-PROFESSIONAL PERSONNEE #h #5 $250-$305 $275-$33é GRADE MONTHLY RANGE myTITLES ﬂed hr A JOB - $l¢55hr Accounting Clerk Busboy File Clerk §_; $1.32 hr Cook‘s Helper Housekeeping Dictaphone Operator II Asst. Gardener Counter Aide Leadman (days) Dishwasher 'Linen Asst. DriYBr [Store Keeper Haniyman Kitchen Man Maid C Room " $1.032 :Cook IV hr Clerk Iypist Mimeographer Receptionist Stenographer Telephone Operator B 'Porter Potwasher - $l.h5 hr Housekeeping Leadman(Nights) "Night Cook Linen Clerk watchman Painter N.B, All hourlz rates Room A - $1.71 hr Chief Telephone Operator Dictaphone Operator OPD Receptionist CaShier Seoretary,IIj Cashier B "' $1960 hI‘ Cook C III - $1.50 hr Licensed Practical Nurse Psychiatric Aide Maintenance Mechanic include 1 me§l_p§rﬂggz_§t_the rate of $10.00 per month I A - $1.8833 Jr. Laboratory Technician �SUPERVISORY & EWIEESSIONAL PERSOBYlé FOR RATES HOURLY AND GRALEE WITHIN TITLES JOB #6 GRADES , $37 $3110 - $h15§ $370 MONTHLY RANGE $05 - JOB TITLES A- $2.080 A- $2.31 Asst. Office Manager Bookkeeper Pay Master B- $2.02 Assistant Bookkeeper Registered Nurses ‘ hr hr A - Charge Nurse Supervisor $1.9h hr Asst. Superintendent Grounds Asst. Dietitian Gardener Housekeeping Supervisor 0- $1.82 hr Dental Hygienist N.B. All hourlz rates include 1 meal per day at the rate of $10.00 per (Nursing) Chef . Psycholinguistic Technician 8: §h10 ~ $510 $2.h2 hr Sr. Laboratory Technician Bldgs $1M $2.19 hr Executive Secretary B" #9 #8 #7 month �JOB TITLES WITHIN GRADES #2 #1 $15 - $235 , $1.20 hr. HOURLY RATE Ass't AND HOURLY RATES FOR NON—PROFESSIONAL PERSONNFL m $215 1§g§g Cook IV Gardener Busboy Counter Cleaner, File Clerk Housekeeping Cook's Helper Counter Aide II _ Man I Housekeeping Leadman Cashier Clerk-Typist Boiler Dictaphone Operator Chief Telephone Operator (days) Ass't. Leadman (nights) Maintenance Mechanic Dishwasher Linen Driver Psychiatric Aide II Painter Handyman Storekeeper Receptionist KitchenvMan ward Clerk Stenographer Maid Room II Mimeographer linen Attd‘t Room Room Supervisor Psychiatric Aide I Secretary II Cook III Dictaphone Operator Senior Telephone Operator Night Cook Porter Poiwasher *(Licensed Practical Nurses at_one incresent higher) *Watchman N.P. All rates include one meal per day at the rate of $10.00 per month. * Not included in Schedule A ' $235 - $31.5 Assistant Chef Accounting Clerk Housekeeping *Gateman . -, BET??? :. 9‘19? .51 s- 39.5.} Secretary I Jr. Laboratory. Technician � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource [Hillside] hospital budgets. (1/2) Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-001-0-011 Date A point or period of time associated with an event in the lifecycle of the resource 1960-1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Proposed Research request budgets; letters; report of expenditures Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/9060c539e20c3ba0581d3baa1fe2596c.pdf 225bfe4d17bc385ee38289963bbb494a PDF Text Text l...“ I 3% Protocol for Pilot Project. on Effect of Drug on Corebrsl Emotion ‘ 1. Object: (a) (b) on of dmgn To study the effect To observe the emotional responses to such ohangca and the perception of sensory stimuli; in function. first drug selected is LSD-25 (Sandoa) - on erect preparation which, in very minute doses, produces a time state with altered perceptions, emotional reactions and occasionally hallucinatory phenomena. Studies or porcep’onol change-s in the visual, amnion", an! anaesthetic senses are planned. Special enmhasis is to be placed on the more complex functions of spatial and temporal orientation; discrimination of size and shape; body may; and the perooption of multiple Simmons stimuli .111. (1) (2) (3) (h) In the emotional aphoro, the following questions are oonsidorud: Are the emotional responses secondary to or simultanemm with the perceptual changes? Are the “spams: consistent in repeated exporinonta in each In each class of oubjoabo? subject? Are the emotional moponooa related to personality structure in Hal? any predictable fashion? In there any relation of the mouse to drug aotim and tho ability of the subject to utilize the mohanisn of denial? In addition, there are thornpoutio oonoidorations: Dona 131) have org arrest on depressions? fl; 2 Does 15]) have am- valun in eliciting pmhiatrio material in bloom,- impressed subjects? 2. Subjects: (a) ‘ The subjects are in "Normal” controln~ at three groups: hospital yeraomol or hospitalized patients a general hospital. (b) Psychiatric subjects at Hillside Hog) (1 Depression a» psychotic anti (2 Scbimphronin (3 N9W1Co ital: “satin. (o) Neurological subjects at Mt. Sinai Hospital: (1) Cerebral (119%,me or diffuse. cord disease. Spinal £2) 3) Spinal root disease. 30 W05! subject is to be heated in a similar fashion prior to drug ingestion) during the period of drug activity; and after. Subjects Each tmatodhyESTandinsulinmtoboexanimddmingaxﬂaﬁortho Repeated sessions with each subject course of such treatments As the drug action has a duration 0: 2 to 5 hours, arc planned. The testing new be divided testing proceduren my be extensive. into three mops: Neurologcal. a) gb Modical. c) tholoacal. ‘\ �3a.. Neurological: 1. Routine neurological.- 2" Visual. Perception of color mixed and ambiguous figures taohistoscopi celly exposed; and cation ion or relative size and distance. . , ‘ 3. Tactile. he Double simultaneous stimulation or various Amt”. Perception modalities. of latrines” identification of sounds and estimation of time intervals. 5. Special studies of bochr image. Bbo Medical: Observation of the subjects by members of the Department of Medicine has been ”quested (Dr. A. Blmberg) and is under consideration. BiocheMcsl studios of hormonal studios secondary to drug activity is under consideration, with emphasis on the possible role of adrenal function in the reactions as measured to the pattern of wxﬂtosteroid excretion. 3c. Psycholouoalt Clinical psychological testing is considered an integral port 0 The cooperation of Dr. M. Ger-vita has been rethis survw. An evaluation 0:: personality structure and habitual quested, methods of reaction to stress will be studied in each subject. In addition, special testing procedures to study the mechanism of denial are under stuck ha a. member of the psycholomstafrz:,-;LC (lire Antinoph). Specific testing procedures include the following tests: a Rorschach. b Bender Gestalt. c d TvoTl Special tests for denial. he Supplies, Foods, Eton: The drugs have been made available to me for experimental purposes; Funds for the at no charge kw Sundae Pharmaceutical Company. equipmt moesssry for testing have been placed at my disposal by the Neurological Research Fund of the Mt. Sinai Hospital. The following items are requested from Hillside Hospital: (1) Office space and the use of one room in Treatment Dormitory during experimental days. (2) Availability of records and permission to request occasional coowration of Homing Department and of the Record Room staff. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Protocol for Pilot Project on Effect of Drugs on Cerebral Function, January 1953 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-1-001 Date A point or period of time associated with an event in the lifecycle of the resource 1953 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/d7a08df9cf0427fc8180966376064147.pdf df0afef232047bc6a8f732705fc32387 PDF Text Text USPHS M—927 Final Report ALTERED BRAIN FUNCTION FOLLOWING ELECTROSHOCK (Perceptual Changes Induced by Drugs and Electroshock) the Department of Experimental Psychiatry Hillside Hospital From Glen Oaks, L.I., N.Y. September 1, 1959 �September 1, 1959 FINAL REPORT weal Department of Experimental Psychiatry HILLSIDE HOSPETAL 1., Glen Oaks, L. N. Y. 235$! 1 1. Acknowledgment 2. Summary 3. Summary,Five Years, 195k - 1959 27 h. Publications, 195k 32 5. Presentations 195k - 1959 1959 37 195h #h, 6. Summary #1, September 1, 7. Summary 3,52, January 1, 1956 #3, April 8. Summary - February 1, 1958 1, 1957 September 1, 1959 - 2 January 1, 1956 hZA - April 1, 1957 55A - February 1, 1958 70A Fink, M.D. Principal Investigator max Research Associates (Experimental Psychology) Robert L. Kahn, Ph.D. Research Associates (Neurophysiology) EEG Technician Secretary Hyman Karin, Ph.D. Eric Karp, M.A. Martin A. Green,M.D. 195k 195h-1958 1958 1956 - George Krauthamer,Ph.D.1959 Hanna Mosquera Janet Bowie ' Associates, supported through other grants: Research Research Research Research Associate Associate Associate Associate (Experimental Psychol.) (Psychiatry) (Psychiatry) (Sociology) 1956—1959 Joseph Jeffe, M.D. Donald F. Klein, M.D. 1959 Nathaniel Siegel, Ph.D.l958 - Max Pollack, Ph.D. 1957 �Acknowledgment These studies would not have been possible without the of Founder of Hillside Hospital, and the support interest faith, Dr. Israel Strauss, the Board of Directors, and the Administrator, Mr. Maurice Bachrach, who sustained this program during its early vicissitudes. are also indebted to the Henry Kaufmann and the Dazian Foundations of New York, the Foundations' Fund for Research in and the Nassau Board County of Health Mental the Psychiatry, following pharmaceutical firms: Smith, Kline and French and Laboratories Bristol Geigy Pharmaceuticals, Laboratories, We Wyeth Laboratories, whose support is gratefully acknowledged. �September 1, 1959. M-927 Altered Brain Function Following Electroshock Progress Report #h Max Fink, M.D., February 1, 1958 - September 1, 1959 Director, Department of Experimental Psychiatry Hillside Hospital, Glen Oaks, L.I., N.Y. Associates: Robert L. Kahn, Ph.D.-Research Associate (Experimental Psychology. y) Psycholo Eric Karp, M.A.-Research Assistant (Experimental (Neurophysiology% Martin A. Green, M.D.-Research Associate Hanna Mosquera - Technician Janet Bowie - Secretary �-3ALTERED BRAIN FUNCTION FOLLOWING ELECTROSHOCK SUMMARY: In the past eighteen months, the various studies of the convulsive therapy process were completed and extended, and The begun. agents of psychopharmacologic an investigation framework for these investigations has been the neurophysiologicand 1955; Kahn, (Weinstein view convulsive of therapy adaptive Fink and Kahn, 1957) extended to insulin coma and drug therapies in psychiatry (Fink, 1957). The following aspects of the convulsive therapy process were studied: A Convulsion: comparative study the of 1. gignificance of the neurophysIoIogic, psychologic and behavioral effects of electrical and inhalant (Indoklon) induced convulsions. 2. S Eﬁe a tic Basis of Neuro h siologic Change: Further effects of acute administration of experimental studies of "normal" the both on and agents sympathomimetic anticholinergic and post—convulsive EEG. s There As Convulsive of ects ic 3. Sociopszcholo of the of factors Relation age, education, a. F Scale) the California by (measured and stereotypy nativity to the selection of therapy, duration of hospitalization, diagnosis and discharge ratings. b. Changes of F score with treatment, and relation of these changes to EEG indices. Thera : In supervisory chothera and Convulsive h. PsaIteratIons psychotherapeuggc in the relationship sessions, with convulsive therapy were observed. 5. Perception: Both patterns of change and individual differences on ac stoscopic figure-ground discrimination tasks and perception of the upright with induced convulsions. These studies were extended to drug therapies and the following studies undertaken: 1. Neurophysiologic: EEG of change on acute and chronic Relation a. administration of various psychopharmaceuticals to clinical behavioral change. III: 8/59 �potency. actiVityo b. EEG as a screening device for psychopharmacologic c. Relation of EEG changes to hallucinogenic effects of megimide. 2. Communication Patterns: Relation of induced neurophysiologic change to dyadic diversification and syntactic d. EEG language measures. 3. §pciopsychologic Studies: Aspects of the doctorpatient relationship affecting choice of somatic therapy. studies have supported and expanded the neurophysiologic-adaptive view of convulsive therapy, and demonstrated that such a hypothesis has applicability to our understanding of the mode of action of psychopharmacologic agents. These �~5- ‘mm PROGRESS REPORT A. THE CONVULSIVE THERAPY PROCESS; 1. Significance of the Convulsion: An earlier convulsive-subconvulsive control study had demonstrated that significant behavioral changes occurred almost exclusively in patients receiving grand mal convulsive therapy. The present report is an assessment of the neurophysiologic,behavioml, and clinical effects of two different methods of inducing convulsions - electrical and inhalant. Twenty-five consecutive patients referred for convulsive therapy were randomly classified into two groups with seizures induced in thirteen patients by the standard Medcraft alternating current instrument, and in twelve by the inhalation of hexafluorodiethyl-ether (Indoklon). In both groups treatment was administered three times a week for a total of 10 to 2b applications, determined by clinical criteria by the supervising psychiatrist. All patients were tested one to two days prior to the first treatment, following the 10-12th treatment, and two weeks following the last treatment. In addition to evaluations of behavioral change, tests included measures of intellectual function (five subtests from the Wechsler-Bellevue Intelligence Scale), perception (figure-ground discrimination using embedded geometric figures, the perception of pseudoisochromatic color plates at high speeds of tachistoscopic exposure, and the Street incomplete figures test), and social attitude (the Levinson revision of the California F Scale). An electro- �-6encephalogram was obtained during each of the testing periods, and measured for the per cent time slow wave (6 cps or slower) activity from a continuous 66 second sample. The results failed to show any significant intergroup test differences between the electroshock and Indoklon groups at each of the three test periods. Intragroup analysis, however, showed that during treatment both groups made increased errors on the intellectual and perceptual tests, and had higher scores on the F scale. By two weeks after the termination of treatment both groups returned to near pretreatment levels for most tests. Both groups were comparable for the degree of induced EEG slow wave activity after 10-12 treatments.v The per cent time slow wave activity for the Indoklon group was 51% and for the electroshock group h7.5%. Within each group individual differences in behavioral change were related to the degree of neurophysiologic change - those with the highest degree of EEG change showing the greatest behavioral change. Rank order correlations between changes in test performance and the degree of slow wave activity with treatment were positive for all procedures, except the comprehension subtest of the Wechsler-Bellevue, and reached a level of statistical significance for digit span (+ .61, p < .01), object assembly (+ .h6, pr< .05), F scale (+ .38, p (' .05), tachistoscopic perception (+ .67: P <: .01) and perception of embedded figures (+ .h3, p < .05). �-7Two different convulsant agents thus produced similar neurophysiologic and perceptual behavioral changes; and it was concluded that the behavioral change in convulsive therapy is related to the degree of altered brain function, and is non-specific for the type of agent used to induce the convulsion. (Presented, in part, at the Eastern Psychological Association, Atlantic City, April, 1959). 2. Biochemical“nu—On.“— Aspects of the Convulsive«non-mu...Therapy Process: The significance of high voltage EEG slow wave activity in the convulsive therapy process (Roth §t_al, 1951, 1957; Fink and Kahn, 19S?) and the report that this activity was blocked by the administration of such anticholinergic agents as atropine and scopolamine (Ulett and Johnson, 1957) provided the basis for these studies. As there were attendant unpleasant systemic effects with the administration of these agents, reports describing diethazine as an anticholinergic compound with potent neurologic but minimal systemic effects (Jenkner and Lechner, 1955; Lechner, 1956) led to studies similar to those of Ulett and Johnson using this compound (Fink, 1958). These observations with diethazine further led to the investigation of other experimental anticholinergic agents. Clinical and electroencephalographic responses to the intravenous administration of diethazine, Win-2299, benactyzine, JB-318, JB-336 and atropine in psychiatric patients at various �-8. stages of convulsive therapy were studied. Each is a potent anticholinergic agent in vitro. The subjects were ninety psychiatric patients referred for convulsive therapy, ranging in age from 18 to 67, with a A of diagnoses. total of 107 observations were made, variety as some subjects were studied with more than one compound. The observations were made in the EEG laboratory using a standard 8 channel instrument and needle electrodes. In each trial, the compound under study was administevhd intravenously at a set rate per minute until clinical behavioral or electrographic changes were observed. It was observed that administration of these anticholinergic agents was associated with a) desynchronisation of EEG rhythms with a blocking of post-convulsive delta activity; b) alerting, excitatory behavioral response with illusory, delusional and hallucinatory ideation, and c) systemic effects of muscular weakness, dryness of the mouth, dry skin and tachycardia. The electrographic, behavioral and systemic effects were concurrent. These observations are regarded as consistent with the suggestion that the physiologic basis of convulsive therapy lies in an increase in central nervous system cholinergic activity. Observations that LSD, amphetamine, mescaline and diphen- hydramine - sympathomimetic and antihistaminic agents - also induced EEG desynchronization, blocking of post convulsive delta �-9- activity and clinical excitatory activity support the suggestion that the behavioral and electrographic patterns of these compounds are also based on an alteration in synaptic activity. Increased synaptic activity (cholinergic, sympatholytic effects) is associated with EEG hypersynchronization, and clinical sedation and euphoria; while decreased synaptic activity (anticholinergic, sympathomimetic) is associated with EEG desynchronization and clinical excitatory and.ha11ucinogenic states, thus supporting a hypothesis initially described by Wikler (195h). It was also suggested in these studies that the discrepant observations of EEG slow wave activity after the administration of atropine was related to significant differences in dosage and to species specificity. (Presented, in part, at the Society of Biological Psychiatry, San Francisco, 1958 and awarded the first A.E. Bennett Psychiatric Research Award of that Society; and, in part, at American EEG Society, Atlantic City, 1958. Published, in part, A.M.A. Arch. Neurol. & 80: and 380-387, 1957; Psychiat. accepted for puﬁlication, EEG Clin. Neuropﬁisiol.) 3. Sociopsychologic Aspects of Psychiatric Treatmen : a. Duration of Hospitalization, Diagnosis and Discharge Evaluation. In an earlier study of the Hillside Hospital population (Kahn, Pollack and Fink, 1957), it was noted that age, education, place of birth and social attitudes as measured by the California F scale, were related to the selection of therapy. Those patients who were older, had less education, were foreign-born and with high stereotypy scores on the F Scale �likely to receive convulsive therapy. In contrast, who and who native-born better were educated, younger, patients were more obtained low scores on the F Scale, received psychotherapy as their sole form of treatment. This study was extended to determine the relations of these sociopsychologic factors to l) the duration of hospitalization, 2) the clinical evaluations at time of discharge, and was final diagnosis. The entire in-patient adult population on March studied. This consisted of 171 patients, 57 men 3) the 7, 1957 and 11h 68 16 from to in women, ranging age years, with a median of 35 years. Patients hospitalized for the shortest period (1-5 months) were noted to be the oldest, have the least education, were most likely to be foreign-born, and have the highest scores on the F Scale. Younger, native-born, more educated, lower F score patients were hospitalized the longest (10 or more months). The same relationship of these factors to length of hospitalization was found when separate analyses were made according to diagnosis and type of treatment (convulsive therapy or psychotherapy). Discharge evaluations of improvement were significantly related to age - the older patients having the most favorable ratings. Analysis of the data by type of treatment, however, demonstrated that among the convulsive therapy patients ratings of recovered or much improved were given to those patients with �the highest born. F scores, least education and who were foreign- Diagnoses of schizophrenia or psychoneurosis were associated with lower F scores, younger ages, more education native birth. older, less educated, foreign-born, high F score patients were more frequently classified as involutional or manic-depressive psychosis. It was postulated that these relationships reflect the influence of social background and psychological processes, such as the behavioral patterns of communication and mode of expression; and that these relationships contribute not only to the pattern of mental illness, but affect all aspects of the patient—therapist interaction. (Presented at the Eastern Psychological Association, Atlantic City, and the Academy of Psychoanalysis, Philadelphia, April, 1959. Accepted for publication, Archives of General Psychiatry.) b. Changes in Social Attitude with Convulsive and The Treatment. earlier observations that the California F Scale is useful in understanding the reason for referral for convulsive therapy and the evaluation of clinical response Following following such treatment, further studies were undertaken with this scale in regard to the following questions: 1) What does the F Scale measure in a psychiatric population? 2) Do F scores change with convulsive therqay? 3) Are these changes related to the degree of altered brain function? �-12- entire in-patient population of the hospital was given the F Scale, and one month later, was retested with The a "reverse" F Scale, in which each statement was changed to the opposite of the original. The "reverse" scale was scored in the same manner as the conventional scale, with high scores reflecting greater agreement. It was noted that those patients who made low scores initially, indicating a predominant disagreement with the statements, showed an increase on the "reverse" scale, indicating a high degree of agreement. In contrast, patients who made high scores initially showed little change on retesting, agreeing with the statements to the same extent even though the meaning was reversed. It is evident that low F score patients are more critical and discriminating persons, while those with high F scores are more undifferentiating and stereotyped in their reactions. This observation is related to the process of selection of patients for convulsive therapy. A high degree of stereotypy of thinking and communication is incompatible with the establishment of a conventional psychotherapeutic relationship, thus inhibiting the psychoanalytically-oriented psychotherapy stressed at this hospital. It follows that the high F score patients will be unsuccessful in psychotherapy and most likely referred for convulsive therapy. In another study, sixty-nine patients were given the F Scale before, during (at 10-12 treatment period) and after �-13convulsive therapy. Ten patients, selected at random, constituted a control group and received subconvulsive electroF in score of +5.7 mean There increase was a stimulation. during treatment in the convulsive group - a difference 5% the level. In contrast, the control group at significant showed an insignificant change during the same period (+0.5). The extent of increase in the convulsive patients was related to the degree of cerebral dysfunction as determined by slow (more The with EEG. delta high the on patients wave activity +8.6. of had mean increase a record) h0$ of the sample than Those patients with low delta indices, however, showed an F the treatment scores were Following +3.h. of increase comparable to the pretreatment levels. These findings support and elaborate previous observations on the effects of convulsive therapy. Greater agreement with show conventional treatment during statements Scale the F in Changes discrimination. and in difficulty stereotypy of changes language the characteristic thus score parallel cliche; and of use increased denial, evasion, qualification, and stereotyped expressions (Kahn and Fink, 1958). It is also comparable to the increased difficulty in complex visual F and 1957) figureKorin, tactile ground discrimination (Kahn and Fink, 1957). (Presented at the Eastern Psychological Association, 1958; and accepted for presentation at the Divisional Meeting of the American Psychiatric Association, New York, November 1959). and perception (Fink, Kahn and �-1hh. Psychotherapy and Physiodynamic Therapy: Previous studies indicated that patients referred for electroshock in this hospital are of two types. The larger older age who have limited education and are foreign born. They tend to be non-introspective persons, stereotyped in their language and thinking, and verbally uncommunicative. Symptoms of depression, agitation, withdrawal and somatization are prominent. The second, and smaller, group of patients are younger,native-born, bettereducated, and verbally communicative with a capacity for introspection. They characteristically exhibit thinking disorders and overactive behavior, with lesser degrees of somatization and depression. Four patients, two from each group described above were studied to determine 1) reasons for referral, 2) whether different attitudes were required in psychotherapeutic 3) the relation of the psychotherapeutic management, and approach to the patient's clinical response to convulsive therapy. It was concluded that these patients were referred for convulsive therapy because of difficulty in communication in the psychotherapeutic relationship. In two cases this was a reflection of the patient's limited verbal and introspective capacity related to educational and social factors. In two instances, however, the impaired communication was reflected in acting-out behavior. group are patients of an �-15Following treatment, the older, less educated patients were able to sustain the behavioral change with a reassuring, supportive technique, amplifying tendencies to minimization ‘In the better and denial developed during electroshock. educated patients, the decreased acting-out behavior was associated with increased interpretive psychotherapy. It was suggested that the relationship of psychotherapy to convulsive therapy various with the communication pattern and adaptation shown by the individual patient. Published in the Journal of Hillside Hospital, 1: 17-25, 19 58 ). 5. Perception: have of procedures test perceptual-cognitive variety been studied in patients receiving somatic therapies. a. The Tachistoscopic Perception of Embedded Colored Figures: This task was studied in an experimental group consisting of 35 consecutive referrals for convulsive therapy, and "control“ groups of 20 patients treated with phenothiaains medication (thorazine and promazine) and ten patients receiving no somatic treatment, matched for age. All subjects were tested prior to treatment, and after four weeks; the convulsive weeks two time a following the third were tested patients A . cessation of treatment. �-15There was a statistically significant increase in mean errors with convulsive therapy, and a significant decrease from the pretreatment scores following treatment. "Control" subjects made significantly fewer errors at each succeeding period. There was a significant difference in EEG low between showing changes as classified errors patients (per cent time delta) when compared with high EEG changes. There were high retest correlations for all groups. There were marked individual differences in response patterns prior to treatment. With brain changes there was a reduction in perseveration, completion and confabulation in some patients, and an increase in others, with no unions Even in those to cerebral dysfunction. attributed patterns EEG with high changes, the "style” of his response patients pattern was maintained. Thus a patient showing completion type errors prior to treatment would continue to make such errors with convulsive therapy, although the threshold at number of which completion was shown might change. (Presented, in part, at the Eastern Psychological Association, Atlantic City, April 1959). b. Rod and Frame Test (Withinz: This task was administered to h? patients consecutively referred for somatic therapy. Marked individual differences in performance were correlated with age, education and score on the California F Scale. Patients whose judgment of the vertical was strongly influenced by the surrounding frame (field dependent) were more frequently �referred for convulsive therapy than drug therapy. No significant change was found with drug or convulsive treatment. For both drug and convulsive groups retest correlations were high (+.86 and +.88). It is considered that individual differences on the Rod and Frame test reflect personality factors that are of importance in psychiatric treatment. �-18B. PSIGHOPHARMACOLOGIC STUDIES; 1. Neurophysiologic Asgects: According to the neurophysiologic~adaptive view of the convulsive therapy process, the clinical efficacy of repeated induced convulsions is dependent upon the induction of a persistent alteration in central nervous function, providing a milieu for changes in the subject's interaction with the examiner and the environment. In these studies the best index of neurophysiologic change has been those aspects of cerebral function reflected by delta activity in the electroencephalogram (Fink and Kahn, 1957). The efficacy of newer psychopharmaceuticals in altering psychotic behavior patterns has led to the suggestion of a similar hypothesis for the mode of action of these agents, and to studies of the relationship and specificity of altered behavioral patterns to neurophysiologic change as reflected in electroencephalography. Of the psychopharmaceuticals tested in acute experiments an increase in synchrony with or without an increase in slow wave activity has been observed for chlorpromazine, promazine and triflupromazine. Behaviorally, these drugs were associated with a) increasing sedation, drowsiness, denial and euphoria; b) decreasing agitation, panic, excitement and delusional and hallucinatory activity; and c) minimization and displacement of symptoms. Barbiturates regularly induced an increase in fast activity with an increase in synchrony, with the associated behavioral changes of sedation, euphoria, denial and minimization. �-19Amphetamine and methamphetamine increased fast activity without increased synchrony and behaviorally were associated with alerting, hypomania, excitement and increased motor activity. Decrease in voltage and per cent time of slow wave activity in subjects with post-convulsive delta activity with LSD-25, benactyzine, Win-2299, JB-318, JB-336 and diethazine. Of these drugs, benaotyzine produced increased alerting, excitement, tension and panic; the other drugs also produced illusory sensations and hallucinatory, delusional and paranoid ideation. was seen electrographic patterns were consistently altered concurrently with behavioral changes both in the acute and chronic administration studies. Tranquilization, euphoria, sedation and minimization of symptoms were associated with increased EEG synchronization and shift of frequencies to the delta range. Agitation, tension, panic, excitement, illusions and hallucinations were associated with desynchronization of frequencies. Similar patterns were demonstrated in subjects with prior delta activity. Agents that tended to synchronize frequencies, as chlorpromazine and barbiturates, augmented the per cent time delta activity and enhanced the clinical patterns; agents that desynchronized frequencies, as diethazine, LSD-25 and benactyzine, minimized the clinical effects typically ascribed to repeated convulsions. The �-20. Various experimental psychopharmaceuticals were tested. In addition to extensive studies of b-b methy].ethylg1utarimide hexaflnarodiethylether (Indoklon) the following agents were studied; phenyltoloxanine(PRN-Bristol), methonalide (ELM-188, Bristol), tropin-h-chlorbenzhydryl ether (WY-21h9, (Megimide) and Wyeth), dimethylaminoethanel and varieties, Riker), its congeners (Deaner and JB-318, 329 and 336 (various piperidyl- benzilates, Lakeside) and imipramine (Tofranil, Geigy). Because significant behavioral and electrographic changes were observed, a more intensive investigation of imipramine (TofrEnil) was undertaken. In 28 acute experiments, consecutive patients referred for physiodynamic therapies were tested in the EEG laboratory at various stages of treatment. TofrEnil solution (10 mg/cc) was administered intravenously at a set rate (1 cc/ho sec) until electrographic or behavioral changes became prominezit, for a total of h0-125 mg (0.5-2.5 Behavioral observation and electrographic recording continued for one to three hours. In patients referred for pharmacotherapy because of manifest depressive, withdrawn or retarded behavior oral TofrEnil of 75-350 mg was administered. In the acute studies there was initial restlessness, associated with dizziness, dry mouth, "faintness," nausea, mg/kg). and on four occasions, vomiting. These symptoms persisted for lassitude, heaviness eventual drowsiness. Heart rate was 10-20 minutes, and were accompanied by of the extremities and unchanged or slowed. Blood pressure dropped by 20-h0% in �-21.. older (age > 60) patients. Subsequently, subjects were relaxed, quiet and disinclined to activity, even when returned to their ward. The electrographoc patterns accompanying these behavioral changes were initiated by a gradual decrease in voltages during the injection. By ten minutes, the per cent time alpha had been halved. In patients with moderate amounts of beta activity, such activity occasionally increased in voltage and per cent time. By twenty minutes, in association with behavioral lassitude, low voltage (to 50 microvolts) random theta frequencies (5-? cps) appeared. In records with post-convulsive delta activity, there was a marked decrease in voltage and per cent time of slow wave activity. These % to two hours. for electrographic patterns persisted There was considerable individual variability in this acute EEG response. In patients who received 100 mg or more of TofrEnil, EEG and behavioral changes were observed in all but three. In six patients, dosage of TofrEnil less than 50 mg were associated neither with EEG nor with behavioral changes. In chronic Tofrénil studies, behavioral changes generally appeared during the second, and were maximal during the third, week of treatment. The most prominent behavioral adaptation was euphoric denial. Patients complained less of somatic displaced their illness became increasingly difficult to discuss symptoms, and denied, minimized or on inquiry. It �-22In six patients them. with significant life relationships and depressive increased and restlessness somatization agitation, restlessness, affect persisted. of cessation the to excitement, insomnia and vomiting, les five patients in noted were symptoms No in change therapy. In three, therapy. showed administration chronic on studies Electrographic Low modulation. record a decrease in voltages with poorer Well 10% appeared. to up cps) activity (5-7 theta voltage few. a in prominent more became defined fast activity after four weeks of NeuroInternationale (Presented at the Collegium the 1958; at September, Psychopharmacologicum, Rome, March, Montreal, Conference on Depression and Allied States, in Published, 1959. EEG Society, June, 1959; and American harmacolo chc Ps of s C.I.N.P.; Proceedin the in gamed. part, Ps Ass. cﬁiat. 1959; 32§~332, N. Kline, ed. 19E8. Frontiers, 682-685, and Neurology __3. _E: 1653117159959; _8_: Relationship Therapist-Patient of the 2. Aspects Affecting Choice of Therapy. than other aspects involves The selection of therapy the In the of patient. the manifest behavioral patterns been have problem this further efforts to clarify past year therapist-patient and frustration that We have hypothesized relationship. and implicit relationship hostility in the therapist-patient have a significant environmental pressures or explicit the in factors emphasizing undertaken, influence in referral for somatic therapy. residents with interviews 76 structured In a pilot study somatofor requests and supervisors were initiated following �-23- therapy. These interviews were designed to elicit the basis of the referral. It was found that in only relatively few cases was there a change in the patient's clinical status which directly led to the referral. In most instances there had been no change or progression in the presenting symptoms. Factors contributing to the timing of the referral included impending discharge, avoiding administrative discharge, and pressure from the patient's family or ward personnel. .It was also noted that patients with similar behavior patterns were treated differently, some given somatotherapy and others none. The reasons for this ranged from "whim" to quantitative differences in symptomatology and individual preferences for type of treatment. It was concluded that factors other than clinical indication played a role in the referral in a significant number of cases. These same extraneous factors also influenced the timing of the referrals. As a result of these findings a "Somatic Treatment Referral Sheet" was developed (see Appendix) to be completed by the therapist whenever somatic therapy is requested. This study is continuing. �-2h. 3. Language Patterns as Measures of Behavioral and Neurophysiologic Change with Drugs. In previous studies of the convulsive therapy process, it was demonstrated that two language measures, a syntactic content analysis (Kahn and Fink, 1958) and dyadic diversifica‘ tion scores of unstructured interviews (Jaffe, Kahn and Fink, 1958) provided objective indices of behavioral change, and were related to the degree of altered brain function. In a further test of these language measures as indices of behavioral and neurophysiologic change, they were applied to interviews on acute administration of various psychopharmacologic agents. Seventy-two interviews with patients at various stages of drug therapy have been analyzed, using the following agents: amobarbital, benactyzine, chlorpromazine, diethazine, lysergic-acid diethylamide, and Win-2299. Following a routine electrographic recording, an unstructured psychiatric interview, with short periods of structured inquiry, was tape recorded. With EEG running, an intravenous injection was then given at a slow rate. When specific electrographic or clinical changes were induced, the interview was repeated. Recording periods of EEG and verbal behavior were alternated for the duration of the observation period. The EEG was measured for changes in synchronization, shifts in dominant frequencies, and per cent time of slow waves (delta) and beta frequencies. �.25tape recordings were transcribed and measured for the diversification of consecutive 25 word samples of speech of The both participants (dyadic) and for syntactic changes. In the dyadic analysis, the pooled verbal behavior of both participants was transcribed, divided into 25 word samples, for each sample the ratio of the number of different words to the total number of words (a diversification score) was calculated. The syntactic language analyses were based on the response to standardized questions using a method previously described (Kahn and Fink, 1958), scoring such changes as syntactic use of person, alteration in tense, evasion, qualification, displacement or verbal denial of symptoms, use of stereotyped expression or cliches, cryptic response, and withdrawal or silence. Consistent changes were observed in both the dyadic diversification and syntactic language measures in subjects classified according to the neurophysiologic and behavioral effects of the drugs applied. Amberbital and chlorpromazine are neurophysiologic synchronizing agents. Amobarbital regularly induces high voltage well synchronized fast activity at 20-2h cps, while chlorpromazine administration is followed by increased synchronization of the EEG record and a shift to slower frequencies including occasional slow wave burst activity. Behaviorally these drugs are associated with sedation and tranquilization. On the language measures there was an increase in stereotypy and �-26~ repetitiveness associated with increasing use of alterations in tense, displacement and evasion. and / cliches, Diethazine, benactyzine, LSD-25 and Win-2299 are neurophysiologic desynchronizing compounds. These drugs are characteristically associated with decreased voltage and per cent time of alpha activity and increased irregular low voltage fast activity. Behaviorally hallucinatory, excitatory or illusory activity are observed. 0n the language measures there was decreasing repetitiveness, wide diversity of words, less variability of diversification scores, and decreased use of cliches and alterations in tense. Further exploration of language measures are suggested as a rational basis for the understanding of the psychologic effects of the new therapies. (Presented at the Conference on Psychodynamic, Psychoanalytic and Sociamgic Aspects of the Neuroleptic Drugs in Psychiatry, Montreal, April, 1958, and at the American Psychiatric Association, Philadelphia, April, 1959). �-27. SUMMARY lgsh - 1959 out-“n” laboratories of the Department of Experimental Psychiatry were established at Hillside Hospital in September, 19Sh. During this five year period neurophysiologic, and and perceptual), linguistic (personality psychologic sociologic aspects of "somatic" psychiatric therapies have been the principal foci. The Convulsive Therapy: The view of the convulsive therapy process as the induction of a non—specific state of altered brain function, similar to craniocerebral trauma was supported and amplified 1. cerebral Within subjects altered milieu, this 21). ll, were seen to respond in various ways (26), of which the most "successful" was explicit verbal denial (7, 31). This latter (10, adaptation was most prominent in characterologically disposed individuals (36). An alteration in brain function was pre-requisite to behavioral change (7, 8, 11, 26). Grand mal seizures were essential to this process (26) but electrical induction was not (B-h2). The alterations in brain function were measured in various ways including electroencephalography (6, ll, 12, 2h, 39), language patterns (b, 7, 1h, 31, h3; B-2h), perceptual tasks (2, 16, 17, 3?, h6; B-26, hl, h2) and tests of Reference numbers are to publications or presentations (Blisted in the appendix. ) �recall (8). It suggested that the neurophysiologic basis of convulsive therapy may lie in an alteration in central synaptic cholinergic - adrenergic relationships, with a predominant shift to increased cholinergic activity as the operationally significant pattern. Such interpretations were based on the was relationship of high voltage EEG slow wave activity to behavioral change (6, ll, 26) and the blocking of post-convulsive electrographic and behavioral changes by central anticholinergic agents (21, 3h, 35, bl, h2) and central sympathomimetic agents (h2). A variety of behavioral changes were seen during convulsive therapy (26; B-l7). Such patterns were viewed as adaptations to altered brain function, and were believed dependent upon characterologic and environmental factors (7, 25, 26, 36, ho). Clinical ratings of improvement were seen as value judgments by the observer of behavioral change in the subject (26). Adaptations characterized by denial mechanisms, both in behavior (B-17) and in language (7, 31) were seen as most favorably rated by the psychiatric staff. Such adaptations were related to habitual modes of conduct (character, personality} (36; B-ll, 32). The persistence of the altered behavioral nodes was noted as dependent upon the degree and duration of altered brain function, the environmental expectations, and the type and �+29- degree of family and medical support (26). Different varying types of behavioral patterns were best supported by psychotherapy (19). Measures of linguistic behavior in structured (7, 31) and unstructured (1h, 29; B-2h) interviews showed characteristic alterations towards increased denial, minimization, displacement, stereotypy and repetitiveness related to the degree of altered brain function (B-Zh). These changes were blocked or reversed by anticholinergic hallucinogens (21,h3). Various perceptual tasks provided indices of behavioral change and were related to the degree of altered brain function. These included the perception of simultaneous tactile stimuli (17), embedded (Gottschaldt) figures (37; 8-16), and tachistoscopically exposed words (37) and embedded color figures (hl). Sociopsychologic aspects of age, years of education, nativity and degree of stereotypy and conventionality (measured by California F Scale) were related to selection of therapy, duration of hospitalization, diagnosis and treatment response in hospitalized patients (15, 36, ho, hS). 2. Neurophysiologic-Adaptive Hypothesis of Somatic Therapy. Based on these studies, a hypothesis concerning the mode of action of other therapies such as insulin coma, leucotomy and psychotropic drugs, was expressed (10, 33, 38). This view holds that the efficacy of these therapies depends upon the induction of states of altered brain function, in which �varying adaptive patterns may become prominent. The adaptive pattern is related to the type, degree and duration of altered brain function, the personality of the subject, and tolerances and expectations of the environment. Examination of drug therapies MY—2092 3. is this hypothesis as applied to psychotropic now in progress, supported by USPHS grants and MY-2715. Insulin Coma Therapy. initial case study showed the significance of denial patterns and of persistent altered brain function for the An behavioral changes in insulin In an insulin coma therapy (3). - chlorpromazine control study, no coma differences in hospital improvement ratings were observed in the two treatment groups (27). Chlorpromazine was safer, easier to administer, permitted continued administration and allowed for greater degrees of concurrent relationship therapy than insulin coma. These observations led to a replacement of insulin some by psychotropic drugs in this institution. h. Pharmacotherapy. The ongoing program in evaluating various psychopharma- ceuticals is derived from these hypotheses. Electrographic and linguistic analyses of effects of acute intravenous administration and chronic clinical administration of various new compounds are in progress. EEG patterns, along such continua as synchronization-desynchronization and frequency shift, and various perceptual, perceptual-motor and personality �-31.. and h2) 3h, (21, behavioral bl, to related being tasks, are linguistic changes (21, h3). The neurophysiologic basis of experimentally induced hallucinogenic states has been interpreted as an alteration in synaptic chemical relations, such that the effective levels of cholinergic activity is decreased (h2). Initial work on this hypothesis (21, h2) is now being expanded. �.132-" PUBLICATIONS AND PRESENTATIONS 195k - 1959 A. Publications. 195h Patterns of Perceptual Organization with Simultaneous Stimuli. Arch. Neurol. & Psychiat., 72: 233- 255. Bender, M.B ., Green, E. andFFinE, M. 2. Standardization of the Face-Hand Test. “”""§z Neurolo , h: 1. 211-217. Fink, M. and Green, 1955. M. ' Delusional Reduplication of Parts of Body after Insulin Coma Therapy. J. Hillside Hos ital h: 13h-1h7. Kahn, R. L., Fin , . an rau er , h. The Amytal Test in Patients with Mental Illness. J. Hillside Hospital, h: 3-13. Kahn, R.L., Fink,'M. and Weinstein, .A. 3. 1956 Denial of Blindness Following Cerebral Angiography. J. Hillside Hos ital, S: 238-2h5. Fink, M. 6. Quantitative Studies of Slow Wave Activity Following Electroshock. EEG Clin. Neurophzsiol. Q: 158 (Abst) Fink, M. and Ka n, R.L. 7. Relation of Amobarbital Test to Clinical Improvement in Electroshock. Arch. Neurol. & Ps chiat. 76: 23- 29. E. A. Kahn, R. L., Fink, M. and Weinstein, 8. Relation of Changes in Memory and Learning to Improvement in Electroshock. Conf. Neurol. 16: 88- 96. Karin, H., Fink, M. and Kwalwasser, §. 5. 9. Evaluation of High-Dose Reserpine Therapy for the Relief of Anxiety. Wachspress, Hillside Hospital killer, . 67- 77. J. S .A. M., Blumberg,'I'WG Fin E, ﬂ. and �~33:. PUBLICATIONS AND PRESENTATIONS 1957 Unified Theory of the Action of Physiodynamic Therapies. J. Hillside Hos ital, 6: 197-206. Fink, M. 11. Relation of EEG Delta Activity to Behavioral Response in Electroshock: Quantitative Serial Studies. A.M.A. Arch. Neurol. & Pszchiat..- 78: 516-525. Fink, M. and 10. A w Itajin, ROE. 12. Significance of Individual Variability in the to Electroshock. J. Hillside Green, M.A. 13. EEG An and Response Hospital, 6: 229-2h0. EEG Clinical Response to Megimide. EEG. Clin. Green, M. and Fink, M. Neurophysiol. 2: 180. Objective Study of Communication in Psychiatric Interviews. J. Hillside Hospital, 6: 207-215. J. Jaffe. Social Factors in Selection of Therapy in a Voluntary Mental Hospital. J. Hillside Hos ital, 6: 216-228. Kahn, R.L., Pollack, M. and Fink, M. 16. Perception of Embedded Figures After Induced Altered Brain Function. Amer. Psychol. 13: 361. Kahn, R.L. and Fink, M. 17. Role of Stimulus Intensity in Perception of Simultaneous Cutaneous Electrical Stimuli. J. Hillside Hospital, 6: 2hl-2SO. Karin, H. and Fink, M. 18. Perception Experiments in a Study of Ambivalence. Arch. Neurol. & Psychiat. lg: 167-176. Karin, H., Tarachow, S. and Friedman, S. 1958 with Electroshock 19. Psychotherapeutic Techniques Patients. " ‘J. Hillside Hospital, 1: 17-25. Esecover, 3., JaTTe, 3. and Kahn, R.L. 20. Lateral the Sedation Clin. Neurophysiol. l2: 162-163. Gaze Nystagmus as an Index of Threshold. Fink, Mo EEG. �PUBLICATIONS AND PRESENTATIONS 1958 21. Effect of Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy. A.M.A. Arch. Neurol. & Psychiat. ﬁg: 380.387. Fink, no 22. Effect of Diethazine on EEG and Significance for Theory of Convulsive Therapy. EEG. Clin. Neurophysiol. l2: 207-208. Fink, M. 23. Effect of Anticholinergic Compounds on Post-Convuhive EEG 776 and Behavior. (abst). Fink, EEG. E. Clin. & Neuroph siol. $2: Electroencephalographic Correlates of the Electroshock Process. Dis. Nerv. Sy . $2: 227. Fink, M. and Green, EXperimental Studies of Convulsive and Drug Therapies in Theoretical Implications. A.M.A. Arch. Psychiatry: Neurol. & Psychiat. ﬁg: 733-73h (abet). Fink, M., a n, . . an reen, M.A. 26. Experimental Studies of the Electroshock Process. Dis. Nerv. Sys. l2: 113-118. Fink, M., Kahn, R.L. and reen’ 0 M. 27. Comparative Study of Chlorpromazine and Insulin Coma in the Therapy of Psychosis. J. Amer. Med. Assoc., 166: 18h6-1850. Fink, M., Shaw, R., Gross, G. and Coleman, F.S. 28. ' Clinical and Electroencephalographic Effects of Megimide in Patients without Cerebral Disease. Neurology, 8: ‘ 682-685. Green, M. and Fink, M. Psychiatry, 3;: 2h9-258. Jaffe, J. 30. Communication Networks in Freud's Interview Technique. 29. Language of the Dyad. Psych. Quart. 2g: hS6-h73. Jaffe, J. 31. Changes in Language During Electroshock Therapy. and Ed. P. of Hoch, Communication, Psychopathology Eratton. Kahn, R.Lo and Fink, u n, ., rune M. �-35PUBLICATIONS AND PRESENTATIONS 1959 32. Effect of an Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy. Biol. Psychiatry ed. Massrnan, J., Grune & Stratton, N.Y. pp. 1 -l9 33. Alteration in Brain Function in Therapy. N. ed. Kline harmacology Frontiers, E Co., Boaton, pp. 325-332. Fink, M. 3h. Significance of EEG . Fink, Psycho- Eittle, M. Brown ‘ Pattern Changes in Psychopharmacology. Clin. Neurophysiol. g: 398 (abst). Fink, M. 35. Electroencephalographic and Behavioral Effects of TofrEnil. Canad. Psych. Assoc. J. A: 1665-1718. Fink, M. 36. Psychological Factors Affecting Individual Differences in Behavioral Response to Convulsive Therapy. JoNoMoDo 128: 2h3‘2h8- Fink, Mo, Kahn, Roll. and EEG. PoIIacE, HT" 37. Effects of Diffuse Altered Brain Function on Perception. Proc. XV . Int. Con . Psychol. Publ. North-Holland, Amsterdam, pp. 238-239. Fink, M., Kahn, R.L. & Karin, H. 38. Therapy of Schizophrenia: Role of Alteration of Brain Function on Behavior. Congress Re orts II Int. Cong. Psychiatry, I}: E9?-E§3 Kahn, R.L. and Korin, H. labstS. Fink, M., 39. Relationship of Threshold and Duration of Seizures to Degree of EEG Delta Activity Induced During Electroshock. EEG Clin. Neurophysiol. —2: 399 (abst). Green, M. ho. Prognostic Application of Psychological Techniques in Convulsive Therapy. Dis. Nerv. Syg. 32: 180-18h. Kahn, R.L. and Pollack, H. In Press bl. Effects of Psychopharmacologic Agents. szchotropic Drugs, 2: Ed. Bradley P. Fink, b2. Effect of Anticholinergic Compounds on Post-Convulsive EEG and Behavior of Psychiatric Patients. EEG Clin. EEG and Behavioral Neurophysiol. Fink, M. M. �PUBLICATIONS AND PRESENTATIONS In Press (contd) Interview Patterns. The D amics of Psvchiatric Drug There , ed.-3T arwer-Foner, C.C. nomas, Springfield, Ill. Fink, M., Jaffe, J. and Kahn, R.L. hh. Formal Language Patterns as Character Defenses: Implications for Psychoanalytic Technique. Pszchologz of Speech and Hearing Disorders, ed. Barbara, D. ., Grune & Stratton. Jeffe, 3. h3- Drug Induced Changes in Sociopsychologic Aspects of Psychiatric Treatment in a Voluntary Mental Hospital: Duration of Hospitalization, Discharge Ratings and Diagnosis. A.M.A. Arch. Gen. Pszchiat. Kahn, R.L., Pollack, H. an h6. n, o Set in the Perception of Simultaneous Tactile Stimuli. Am. Jour. Psychol.Korin, H. and Fink, M. The Role of �3. Presentations. 1. Relationship Between Altered Brain Function and Denial in Electroshock Therapy. American Psychiatric Association, Atlantic City. Delusional Reduplication of Parts of the Body after Insulin Coma Therapy. New York Neurological Society, and the New York Society for Clinical Psychiatry, New York. Relation of Changes in Memory and Learning to Improvement in Electroshock. Electroshock Research Association, Atlantic City. h. Quantitative Study of Slow Wave Activity Following Electroshock. Eastern Association of Electroencephalographers, Bethesda. Newer Drugs in Psychiatry. Nassau Neuropsychiatric Society, Long Island. 3. 1956 Changes in Language During Electroshock Therapy. American Psychopathological Association, New York. Electroencephalographic and Clinical Effects of Megimide. Eastern Association of Electroencephalographers, New York. 1957 8. Perception Experiments in a Study of Ambivalence. Section of Neurology and Psychiatry of the New York Academy of Medicine and the New York Neurological Society, New York. Individual Differences in EEG Responsivity. Metropolitan EEG Society, New York. 10. Criteria in Evaluation of Clinical Behavioral Change. Round Table Discussion, American Psychiatric Association, Chicago. 11. Personality Factors in Behavioral Response to Electroshock Therapy. Electroshock Research.Association, Chicago. �938PRESENTATIONS 1957 12. EXperimental Studies of the Electroshock Process. Society of Biological Psychiatry, Atlantic City. Effects of Diffuse Altered Brain Function on Perception. XV International Congress of Psychology, Brussels. Therapy of Schizophrenia: Role of Alteration in Brain Function in Behavior. International Congress of Psychiatry, Zurich. The Relation of Ambivalence to Aggression and Authority in Psychoneurotic Patients. American Psychological Association, New York. 16. Perception of Embedded Figures After Induced Altered Brain Function. American Psychological Association, New 13. York. 17. Behavioral Patterns in Induced States of Altered Brain Function. New York Divisional Meeting, American Psychiatric Association, New York. Objective Study of Communication in Psychiatric Interviews. New York Divisional Meeting, American Psychiatric Association, New York. Significance of EEG Frequency Shift for Psychiatry. Metropolitan EEG Society, New York. Effect of Diethazine on EEG and Significance for Theory of Process of Convulsive Therapy. Eastern Association of Electroencephalographers, New York. An 1958 Correlates of the Electroshock Process. Eastern Psychiatric Research Association, New York. 22. Significance of Individual Variability in EEG Changes During Electroshock Therapy. Eastern Association of Electroencephalographers, Montreal. 23. Experimental Studies of Convulsive and Drug Therapies in Psychiatry: Theoretical Implications. New York Neurological Society and the New York Society of Clinical Psychiatry, New York. 21. EEG �-39. PRESENTATIONS 1958 Patterns with Altered Brain Function. Eastern Psychological Association, Philadelphia. The Relation of F Score to Behavioral and Psychological Response with Altered Brain Function. Eastern Psychological Association, Philadelphia. 26. Intensity of Stimulation and Perception of Simultaneous Stimuli in Cerebral Dysfunction. Eastern Psychological Association, Philadelphia. Communication 27. 28. 29. 30. 31. 32. 33. 3h. 35. SociOoPsychological Aspects of Diagnosis and Treatment: Theoretical Implications (Symposium). Eastern Psychological Association, Philadelphia. Drug Induced Changes in Interview Patterns. Conference on Psychodynamic, Psychoanalytic, and Sociologic Aspects of the Neuroleptic (Tranquilizing) Drugs in Psychiatry, Montreal. Psychological Factors Affecting Individual Differences in Behavioral Response to Convulsive Therapy. American Psychiatric Association, San Francisco. Social Factors in Selection of Therapy in a Voluntary Mental Hospital. American Psychiatric Association, San Francisco. A Critique of "Pre-Conscious" Perception and the "Poetzl Phenomenon". American Psychiatric Association, San Francisco. Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy. Electroshock Research Association, San Francisco. Effects of Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy. Society of Biological Psychiatry, San Francisco. Role of EEG Frequency Shift in Behavioral Effects of Drugs. Section of Neurology and Psychiatry, Queens County Medical Society, New York. Effect of Anticholinergic Compounds on Post Convulsive EEG and Behavior. American EEG Society, Atlantic City. �shoPRESENTATIONS 1958 Prognostic Application of Psychological Techniques in Convulsive Therapy. Eastern Psychiatric Research Association, New York. 37. EEG and Behavioral Effects of Psychopharmacologic Agents. Collegium Internationale Neuro-Psycho Pharmacologicum, Rome; and Eastern Association of Electroencephalographers, New York. Relationship between Seizure Threshold and Duration of Seizures to EEG Change During Electroshock. Eastern Association of Electroencephalographers, New York. 1959 Effects of Tofranil. International Conference on Depression and Allied States, Montreal. Sociopsychologic Factors Affecting Therapist-Patient Relationships. American Academy of Psychoanalysis, Philadelphia. Effect of Induced Cerebral Dysfunction in Man and on Tachistoscopic Perception of Embedded Color Figures. Eastern Psychological Association, Atlantic City. Behavioral Changes with Different Methods of Induced Cerebral Dysfunction. Eastern Psychological Association, Atlantic City. h3. Sociopsychologic Aspects of Psychiatric Treatment. Eastern Psychological Association, Atlantic City. hh. Language Patterns as Measures of Behavioral and Neurophysiologic Change. American Psychiatric Association, Philadelphia. EEG and Behavioral �C. Reports in preparation: 1. 2. 3. Experimental Studies of Convulsive Therapy - a monographic review. EEG Patterns and Synaptic Events in Experimental Hallucinogenic States. Comparative Study of Indoklon and Electrically Induced Convulsive Therapies. Studies of the Sedation Threshold. Effect of Induced Cerebral Trauma in Man on the Tachistoscopic Perception of Embedded Colored Figures. Individual Differences in the Perception of the Upright in Hospitalized Psychiatric Patients. Social Attitude (California F Scale) and Convulsive Therapy. Sociopsychologic Factors in Drug Therapy. Modification of Psychotherapeutic and Supervisory Relationships by Altered Brain Function. �’os. Relation Between Altered Brain Function and Denial in Electroshock Therapy Robert L. Kahn, Ph. D. Max Fink, M.D. Edwin A. Read , at the Weinstein, M.D. Annual Meeting American Psychiatric Association, May 1955. the Research Service of the Hillside Hospital, and the Department of Neurology of the Mount Sinai Hospital, New York. From This investigation was supported in part by the Medical Research and Development Board, office of the Surgeon General, Department of the Army under Contract No. DA-h9-OO7 MD-3763 and grant M-927 from the National Institute of Mental Health of the National Institutes of Health, Public Health Service. �Although many theories concerning the mode of action of electroshock and psycholphysiological among the relationships been have offered, therapy (3,h,5,6) studies In previous understood (1,2). remain poor v ogical factors certain function, that was suggested of brain it of patients with alterations of effects the to therapeutic related of the observed patterns of behavior were electroshock. dis(3,6), anosognosia of or illness denial included patterns in and language, (8) changes time and (7), reduplication orientation for place that indicated was It (9). paraphasia misnaming or particularly nonaphasic These than rather of illness the stress to these phenomena were fonns of adaptation neural of milieu the In judgment. Specific defects in memonv, perception or motivations his the expresses damage, patient brain reorganization provided by the with modes of interaction changed of in new s,rmbolic patterns indicative of forms insuch denies the delusion patient In anosoynosic the environment. of an the and operation, fact blindness, of a limb, loss capacity as hemiplegia, as well as other problems in livinﬁ. In disorientation for place, the way in the symbolic as serves hospital which the patieit be need to the often traumatic situation, representation of some aspect of the the locates or of familiar place a name the he uses well and go home. Thus, misnames and mislocates the the outside hospital. a confabulates journey his to or close hospital academy" skating "roller a as the to hospital 'When a paraplegic patient refers names Mount the (Mount Cyanide, Sinai) hos the ital or a paranoid patient calls home symbolize the patient's feelings in dramatic fashion. In paraphasia, the ob- a to personal related usually are patient jects the Thus, patient and of hospitalization. illness that problem, particularly and and objects the of places body, selects aspects of the environment, parts which are misnamed by the in of his a feelings the exnression for them language his in uses n interaction. new mode of �.3. could be brought out by the administration of amytal sodium ("positive amytal test"). 'With a return of the complaints of pain these changes in behavior were no longer apparent either clinically or under amytal. This sequence of events were repeated during two Subsequent courses of electroshock. While this report supported the hypothesis regarding the therapeutic action of electro- test" in investigating the probdid not represent the usual condition for shock and showed the usefulness of the "amytal lem, it concerned only one case and is given. The theory is further tested in the present study in which a group of potients receiving electroshock for mental illness were given repeated amytal tests before, during and after the course of treatment. The purpose of the study was to determine the relationship between the clinical response to the which electroshock treatment and changes in behavior produced by the drug. theses tested were that those patients more likely to show: (1) evidence The particular hypo- improved with electroshock would be who of brain dysfunction on the amytal test and (2) behavior patterns indicative of denial. METHGD series of amytal tests. In this test, the patient is asked a standard group of questions pertaining to orientation and the patient Each awareness of was given a illness. The drug ution at a rate of .05 grams (1 is then administered intravenously in a cc) per minute until nystagmus, slurred drowsiness and errors in counting backward are noted. now repeated. The The same 5% sol- speech, questions are following changes, when persistent, are called "positive" and are deemed indicative of cerebral dysfunction. 1. Complete denial of illness. 2. Denial of major aspects of illness, such as attributing entry into hospital to a trivial or past illness. 3. Misnaming the hospital, either euphemism as "rest home." its proper name, or in terms of a �ah. Displacement of the location of the hospital, such as to another city. 5. Confabulated journeyt 6. Reduplication of the hospital, as stating that he is in another hos~ pital of the same or similar name. 7. Disorientation for time of day with confusion of day and night. misidentification of the examiner such as calling or an "entertainer". 8._ Gross him a "lawyer" 9. Disorientation for year. The patient was given his first test prior to treatment, and re-tested at weekly intervals. All patients in the series had negative amytal tests prior to the initiation of therapy. Treatments were administered three times a week, so that the patients were generally tested after every third treatment. A test after a treatment. Testing was continued after the termination of therapy until the result had become negative. of and records standard tests memory and learnElectroencephalographic ing ability were also given, but will not be considered in detail in this paper, was always given two days POPULATION Twentyufour patients at Hillside Hospital receiving electroshock with the Reiter Electrostimulator were studied. There authors. The patients were taken on the was no basis of consecutive referrals, and the determination of the necessity for treatment was Some patients were selection of cases by the made by the clinical necessarily excluded because their treatment staff. was terminated or interrupted before they were adequateLy studied. Another was omitted because he had manifestations of brain disease and a positive amytal to electroconvulsive therapy. thirtyvthree. Patients treatments. Some The number who showed test prior of treatments varied from nine to clinical improvement tended to receive fewer of this variability could also be ascribed to differences in the inclination of the resident psychiatrists to use this form of treatment. �~5One patient decided for himself that he had enough treatment and eloped. gnostically, the patients consisted of 1h with depressive schizophrenia and one manic reaction. There were 15 and the ages ranged from 2h series, to 68 reactions, women and 9 men 9 Dia- with in the with a median of h7. of response to E.S.T. Evaluation.Wa— M~~ All the patients were observed for at least eight weeks after completion of treatment. on Determination of the patient's response to electroshock was made staff opinion, the the basis of the resident psychiatrist‘s impression, nurses' notes and the clinical evaluation of one of us (M.F.) who supervised the treatments but was not aware of the amytaltest results. In this way the pat- ients were classified into three groups. gﬁwwyarkedlv Improved; The 11 cases in this group were regarded as show- ing recovery or marked improvement. These patients no longer showed the ptoms which brought them symp into the hospital; their doctors felt they were better; and the nurses' notes confirmed such aspects as being able to sleep without medication, better appetite, and improved capacity to get along with the other patients and participate in hospital activities. B. Moderatelv Improvegz_ The six patients in this group showed some improvement but continued to manifest indications of mental illness. These patients typically relief, i;§:, acute depressive features showed symptomatic might be gone, but the dramatic change so evident in the apparent. Each patient continued to show some first group was not noticeable disturbance such as obsessional thinking, paranoid ideas, or somatic preoccupation, C. Minimally or Unimnroved. In this group were placed seven patients in whom change was not ient improvement. somewhat improved. clearly noticable or Some showed But who showed only equivocal or trans- fluctuations in behavior, at times appearing the change was not sustained, so that by the end of �9-6- much did before. as they appeared treatment, they are aware of the difficulties in evaluating improvement. Others might In by these any case, of in patients. change estimates the have differed in and the between first the differences using this threefold classification, We third groups will be distincto OBSERVATIONS l. ﬂggjggL Test Results of The number tests given amytal Reactions. of A. Distribution Positive -um-W from to three thirteen, ranged electroshock of the course each during to patient shown the data Table is In maintained. I, depending on how long treatment was . for the number of and number and percent posthe treatment tests given during The improved patients markedly each in the group. patients itive for all moderthe with unimproved the group, showed many more positive reactions than between these groups. Every markedly improved ately improved patients in On other the treatment. reaction during ient had at least one positive amytal cases unimproved of the and five hand, one of the moderately improved patients the of incaach A the results of comparison showed result. a positive never the than better at significant groups, using chi-square, is statistically level of confidence. TABLE I pat—_ 1% WWW DISTRIBUTION OF POSITIVE ANITAL TESTS DURING TREATMENT ” No. of tests given durinc treatment Markedly improved (ll) Moderately improved (6) Unimproved (7) Number positive % Positive 50 38 76% 39 15 38% hS 6 13% the In groups of Fig. treatment. each l stase at B. Positive reactions who had positive each in of group the patients percentage for are compared » �treatment. of each stage at results after reactions had positive Almost half the markedly improved patients nine to seven after reactions had positive and.all treatments, three only treatments. In the unimproved cases, on of number positive the hand, other the of the course during increase consistent no was and there small reactions was other the between to tends fall improved group moderately the Again, treatment. two. Although some than more received patients 15 treatments the data is not small too became each number in group the because presented beyond this point than more received unimproved patients of the Four of comparison. for purposes mode One the of with consistently negative amytal test results. 20 treatments occasionally an with only treatments 30 received over improved patients erately positive reaction. There were variations in the per- reactions. positive a .e-u' two consecleast at Using week. week to from sistence of positive reactions improved, markedly the of nine of persistence, criterion the as utive positives showed perunimproved group the of one and only two of the moderately improved C. Duration_3§ “-5 one but patients treatment all of termination the ,After sistent positives. The reconvulsion.. the last after nine days had negative amytal reactions treatment. week after second the by test negative a developed maining patient improved group markedly the in D. Factor of awe. Since the patients conceivis reactions, it from depressive suffering be older tended to persons to age be scley related might results test able that the difference in amytal assum— the is this Underlying improvement. clinical to coincidentally and only funbrain altered show of signs to more s likely i older the person that ption | shown. each is 2 for group mean the Table age In electroshock. when given ction �-8. TABLE 2 RELATIONSHIP OF CLIEICAL_IMPROVEMENT TO AGE Than Age Markedly Improved (ll) h7.6h 0' Moderately Improved (6) 50.00 Unimproved (7) 35-29 It is apparent that the first patients. two groups were older than the unimproved Yet, while the mean age of the moderately improved cases higher than the markedly improved group, theSe patients still show is slightly significantly fewer positive reactions. In Table 3 the number of positive reactions during treatment is shown of he over to age. limited years patients the analysis is for In this table the relationship of positive reactions in the different groups remains unchanged from that when the groups are considered as a whole. each group when TABLE 3 OVER hO PATIENTS IN AMITAL'TESTS DISTRIBUTION OF.EQ§EE;VE a... No. of tests given durine treatment_ Number positive % fpsitizg Markcdly Improved (1m) h6 35 76 Mederately Improved (5) 3h 15 hS Unimproved (3) 17 O O 2. Other Aspects of Behavior. were there and disorientation of denial illness explicit and the of drug influence the under both occurred changes in behavior that fashion progressive treatment is of significantly the course clinically during Apart from in those patients who improved. These aspects may be divided into verbal and non-verbal communication. A. can: Channes in Verbal Language. These consisted of denial expressed in �-99.. evasion and in the use of a syntactical pattern involving the third and second When person. asked about their symptoms patients gave such answers as "it's hard to say" or “I forgot" or "I don't know; I‘ve been waiting for the doctors tell as "it's to me." The change what they in syntactical person is illustrated by such remarks call a depression," "I‘m afraid answering the question "what trouble." Sometimes In patients patients is talk of a relative would there One to the start of treatment what will get hurt" or your main trouble" with "what who improved in the non-drug interviews. somebody was a who was is 3223 main sick. notable development of such patterns patient, for example, whenzisked prior his main trouble, said "I'm depressed." such was After two treatments he answered the question with "I don't get along well with my mother-in-law." After five treatments he said "I don't get what you he said know." After ten I that‘s "I all sick; get after eight, what 11 "in and said way after don't my see wife," "right now, it‘s that I do you mean" and "I don't know how to explain it." At the termination of given home" an followed by "I to want main get was as trouble his tr atment, mean," and account of how "good" his wife was. of these group, increased the use the other hand, on In the unimproved language patterns did not occur. They were not present in some, minimally or inconsistently noted in others. In some of the unimproved patients there was than the of drug the under effects of these language patterns actually less use there had been in the pre-amytal interview. ..B. clinical in Changes in Non-Verbal Behavior. and drug interviews most frequently the moderately improved and improved. Euphoric reactions occurred both in in the markedly improved, less least in the group which were considered un- In the unimproved patient classed as manic, euphoric behavior was present in his clinical behavior and was not changed by amytal. �-10—‘ of of four interviews the amytal in apneared Changes in sexual behavior other the of each in one in only but patient the markedly improved patients makthe examiner, caress hug to form of or This took the trying categories. ing remarks with sexual content or engaging in masturbatory ient in the unimproved group showed activity. this behavior both during are-drug A pat- inter— views and under the influence of amytal. Withdrawal or "selective inattention" was shown by nine of the eleven the amytal of the phase drug during markedly improved patients particularly about the questions answer to of failure consisted interview. This behavior fashion. and cryptic in dysarthric responding and hospitalization or illness the other each of groups. in once occurred only the drug under This reaction who appeared the category unimproved two in of that patients It was interest withdrawn before the test became more responsive under the influence of the drug. ravage: there is that indicate these in patients tests the of anwial results damage or brain of and the production improvement between clinical a relation method of determined this by particular an altered state of brain function as The examination. In patients who improve, the amytal test becomes consistently treatment. of the course in early positive In moderately improved or unimproved does not increase and frequency their reactions patients there are fewer positive such function brain methods of evaluating with more treatments. With other the in showed abnormalities All not patients present. close correlation was found frequently as was and * learning impaired record electroencephalographic damage The brain of effects who did not. those who improved as in in patients are not unitary and different methods of study show varying results. more analyzed_in being are these data in patients a The electroencephalographic the show that The findings preliminary be reported elsewhere. detail, and.will amytal the to comparable EEG improvement, to related abnormality is Wegree of test findings. �.11 - in to changes function brain of altered In relating the various aspects behavior after electroshock therapy defects in the formation of In the of language. first symbol it has been helpful to distinguish between patterns and defects in the adaptive uses category one may include such clinical phenomena as loss. of memory and certain types acalculia aphasia, apraxia, finger agnosia, cannot select he but wants he "know" to what say In aphasia, the patient may and movements and sounds of the appropriate elements from the entire category of elements excannot select the defects With patient memory integrate them. them temporal pata in and units arrange significant perience, class solving of problem manifested in tests commonly also tern. Such defects are fre— Such are patients scale. and in certain subtests of the Wechsler-Bellevue them into quently concerned with their and of marked anxiety degrees and exhibit defects frustration. Adaptive changes in language, on the other hand, relate to interaction They behavior. of motivational aspects the with the environment and concern The besame and disorientation. denial of are exemplified in the phenomena and other in defect a conditions as havioral element may appear under certain cases as a part of an be may example, for form of adaptation. Left~ri9ht disorientation, impaired and is of right which the left concept aphasic defect in a paralyzed able to identify seem not may Other however, patients, or lost. or and ear left arm their (non-paralyzed) Show right their left arm, but can relate not does and as long as it of right knowledge left similarly indicate a the not in electroshock of prois action therapeutic to their illness. milieu neural the in providing rather but formation duction of defects in symbol The in which altered forms of adaptation may be maintained. outcome of electroshock treatment by the psychiatrists predict the Other point treatments. the initial amount of "confusion" that occurs after The test amytal Leprovement. to not related was "confusion" where to cases Many �-12.. should be useful as a prognostic guide by defining the nature of these changes. In cases "confusion" some patients the amytal test mainly a matter of memory defect and in these may be negative. On the other hand, some patients imp such Clinical In of evidenae few without treatments "confusion." a after prove instances the amytal procedure may show an alteration in brain function. In may be this study almost half of the markedly improved patients had positive reactions In another case, treated privately by one of us (E.A.W.), within three treatments. after only two result prior to treat- marked improvement of a severe depressed condition was noted convulsions. Yet this patient, who had a negative amytal ment, showed a markedly positive reaction one day These results do not than patients brain damage ectly measure brain damage, but rem that mean who do improved not improve. rather after the second treatment. patients have a The amytal one deduces test greater degree of does not dir- the presence of braincianage the nature of the adaptive changes in communication. Thus patients with brain damaje who do not show such changes are considered to show a negative re- im~ methods of behavioral demonstrating other that sult. It is for this reason paired brain function may not distinguish between improved and unimproved patpositive do and not others amytal a Why some develop test, patients ients. despite many more convulsions is unclear, but factors and to the patient's habitual mode may be related to personality of adaptation to stress. It is be so function brain of altered state treated a that nevertheless, necessary, that these forms of adaptation or denial can be maintained. It is for these which electroshock methods of administering believed that reasons that it is be not seizures will generally unilateral as function brain minimally alter efficacious. Also it affords some explanation as to why electroshock often has a beneficial short term effect while evaluation of long ternleffects little difference between treated and untreated cases. show �-13In considering what constitutes "improvement," it is likely that such evaluations are dependent in considerable degree on the types of verbal and patient denies that imp he rated and is and uncomplaining, affable he has any problems, appears he has developed he that has or does mean not acquired insight that It proved. non-verbal adaptation that the patient uses. a more realistic understanding Thus, when a of his interpersonal relations. exemplified by the patient previously cited who said he This is well was "depressed" in third person when asked about his illness. While his behavior is rated as improved, actual analysis of his language shows that he is using different forms of symbolic the pre-treatment interview, but later used evasion and use of the adaptation. Recent mechanisms of studies have supported the findings concerning the development of denial in the improved patients. Carter (12) confirmed Janis’ (13) findings of consistent evidence of circumscribed amnesias in patients lowing electroshock. He that general memory impairment did not occur, "selectivity" in forgetting of unpleasant material concluded but rather, that there was a from the fol- patient's past life. Komgold (11;) likewise reports selective and "mechanisms of observes (15) Teicher similarly, sensitized forgetting. highly repression" for "emotional" stimuli after electroshock. Another aSpect of the difference between the improved and unimproved groups which may bear a relation to the therapeutic proved patients there were more changes in all not only in verbal patterns. Thus, a patient mechanism was that in in, types of symbolic adaptation, who appeared withdrawn both in the pre-drug and drug interviews had a poorer prognosis than the patient became withdrawn only under the who showed who effects of the drug, Similarly, the patient altered sexual behavior under the effects of the drug had exhibited this behavior during the prenamytal questioning as well, and did not improve with treatment, while the four patients manifesting sexual behavior only under �ﬁll!" the effects of the drug, did improve. The importance of the change in symbolic pattern is also illustrated by the fact that the unimproved manic patient showed no changes in this aspect of his behavior during the amytal test. It is thus likely that the facility of changing symbolic patterns in a situation of added stress is an important one in determining response in all somatic therapies. �SUMMARY AND CONCLUSIONS ment treatelectroshock for consecutively referred (l) Twenty-four patients the during intervals and at regular during were given amytal tests before, courSe of treatment. (2) There proved to be a close relationship between the shorteterm tests. of the anwtal results treatment and.the to sponse patients showed early, persistent re- The much improved positive reactions during patients showed no positive reactions or and increasingly the course of treatment. Unimproved intermediate group who showed infrequently and inconsistently. unimproved the than reactions showed more positive moderate clinical improvement of reincidence positive the much in improved the of short group but fell far An showed them actions. (3) Changes in behavior forms of non-verbal and language were most consistent and pronounced related to denial in the improved group, even in interviews not employing drugs. (h) The improvement clinical that the hypothesis support observations function in of altered.brain milieu of a in electroshockzmequires the creation mainbe may of those denial, Which new patterns of adaptation, particularly tained. �mmmmggzg 1.) Gordon, Fifty H. L. : 2.) Kalinowsky, L. Shock Therapy Theories, Mil. Surg. $92: 397, l9h8. B. and Hoch, P. H. Shock Treatment, PBychosurgery and : Other Somatic Treatment in Psychiatry, (2nd ed.) 3.) ’Neinstein E. & 1..) Psggrchiat. A. and Kahn, R. L. _6}_1_: Syndrome : Ybrk, 1952. of Anosocnosia, Arch. Neurol. 772-791, 1950. 'E‘Jcinstein, E. A., Kann, R. L., Sugannan, L. A., and Linn, L. Use of Amobarbital Sodium in Organic Brain Disease, 889-8911., Am. : Diagnostic J. Psych., llg: 1953. S.) weinstein, E. A., Kahn, L., and Malitz, S. R. Its the "Amytal Test" for Brain Disease: A. M. A. Arch of 6) New weinstein, E. Serial Administration of : Diagnostic and Prognostic Value, “enrol. and Psychiatu 11: 217-226, A. and Kahn, R. L. : 1951.. Denial of Illness: Symbolic and Physiol- ogical Aspects, Springfield, 111., Charles C. Thomas, in press. 7.) Weinstein, E. A. and Kahn, R. L. Brain Disease, J. Neuropath. 8.) & : Patterns of Disorientation in Organic Clin. Neurol. l; 21h-226, 1951. and R. A. L. E. L. A.: Kahn, Sugarman, weinstein, , A. M. A. Arch. Neurol. uplication, 9,) 'weinstein, E. 0rg-tanic Brain Psychiat. M. A. Arch. Neurol. 10.) weinstein, E. A., Linn, L. and Kahn, R. L.: Its Relation to the Therapy: {31: 808-8111, 1952. L.: Non-aphasic Misnaming (paraphasia) in A. and Kahn R. Disease, A. & Phenomenon of Red- & Psychiat.,‘éz: 72-79,l952. Psychosis during ﬁlectroshock Theory of Shock Therapy, Am. J. Psych., $925 22-26, 1952. 11.) Mcinstein, E. A. and Kahn, A. M. A. Arch. Neurol. ness, 12.) Carter J. T.: Type convulsive Therapy, 13.) Janis, I. L. : R. & L.: Personality Factors in Denial of Psychiat. Ill- Q2; 355-367, 1953. of Personal Life Hemories Forgotten Following ElectroAm. Psychologist §; 330, 1953. Psychologic Effects of Electric convulsive Treatments Post-treatment Amnesias.) J. Nerv. & Ment. Dis. ill; 359, 1950. (I. �REFERENCESz 1h.) Korngold, M.: An Shock Treatment, 15.) Teicher, A.: Investigation of Am. The continued Psychologist Q; Some Psychological Effects of Electric 381-382, 1953. Effect of Electroconvulsive Therapy actions of Schizophrenic patients, Am. on the Visual Re- Psychologist, g, hhS, 1953. �] ONS I REACT. 90 ._” much Improved (11) '*~ Mod. Improved ‘ 80 ” Unimproved (6) /// (7) / t// ‘\\\\\\_ //////////’ “~. * AMYTAL POSITIVE 3o PERCENTAGE 20 / / / (“” \ " , ,/ . " / x,” I f 10 O ' h-é ,__.._..7..___.-_....-_,_....__.-..;}..-.__ 7-9 10.12 13.15 NUMBER OF TREATMENTS occurring reactions test amytal of positive Fig. I.-—- Percentage treatment. of stages different each at in group �{fw g; ,{1/,m»‘-‘ JUN 26 ”12!. :c. .M Altered Brain Function Following Electroshock H—927 Progress Report - February 1 1958 - September 1 1959 Summary: In the past eighteen months various studies of the convulsive therapy process were completed, a program for the investigation of psychopharnacologic agents consistent with the general hypothesis concerning the node of action of physiodynamic therapies was developed. The physiologic effects of nany interrelationship of the neuro- new compounds with the psychodynanic, perceptual, personality and sociologic aspects of patients' behavior provided the framework for tnse investigations. following areas of study were explained: l) of psychotherapy with physiodynanic therapy; The the interrelation 2) the elucidation of the synaptic chemical events which are the basis of the convulsive therapy process by the acute administration or experimental anticholinergic compounds at various stages of convulsive therapy; and behavioral 3) studies of the acute and clinical effects of a EEG variety of psychopharnacologic agents; h) the use or language indices, such as syntactic and dyadic~ 1959 �-2- diversification analyses, as measures of behavioral neurophysiologic changes with drugs; and 5) a comparative study of indoklon and electrically-induced convulsions in psychiatric therapy; duration of 6) sociopsychologic aspects related to hospitalization, discharge ratings and diagnosis in a voluntary mental hospital; 7) the relation of social attitude to the effects of convulsive therapy; 8) aspects of the therapist- patient relationship affecting aha: choice of therapy; 9) studies of individual differences in the selection of, and behavioral change with, convulsive therapy by perceptual aethods. These studies have supported and expanded the neuro~ physiologic-adapative view or convulsive therapy, and demonstrated that such a hypothesis has applicability to our understanding of the node of action of psychepharnacologic agents. �Progress Report: A; Psychotherapy and Physiodyganic Therapy. Previous observations have shown that two types of patients are referred for electroshock in this hospital. largest number are patients in the older limited education and are foreign born, age groups who have They tend to introspective persons, stereotyped in their thinking language and verbally unconmunicative. symptoms The The be non- and Their predominant are depression, agitation, withdrawal and sonatisaticn. second, and smaller, group of patients are younger, native- born, better educated, and verbally ccnnunicativo with a capacity for intropection. They characteristically exhibit thinking disorders and overactive behavior states, with sonatisation and depression occurring An to a lesser extent. oratory explanatory study was undertaken of four patients, two for each group described above, for the purpose of determining 1) reasons for referral for convulsive therapy, 2) whether the differences in patients required different attitudes in psychotherapeutic nanagenent with electroshock, and 3) the �-1... relation of the psychotherapsutic approach to the patient'e clinical response to electroshock. It was found that all of the patients studied were electroshock because of a failure of connunication referred for in the psychotherapeutic relationship. In a reflection of the limited verbal and cases this was two introspective capacity social factors. In the of the patientdue to educational and other two cases, however,-the inpaired communication primarily due wee to unmanageable acting out. Following treatnent, the older, less educated patients were able to naintain this improvement with a reassuring and to nininication the tendencies denial toohniqne,-supporting during developed electroshock. electroshock eeened to make In the better educated patients, the patients nore’anenable to an psychotherapy. torn of interpretive It or psychotherapy was concluded that the relationship to electroshock varies with the particular_type of communication pattern and adaptation shown by the individual patient. This �-5. the and been Journal written up published in material has or Hillside Hospital, 7: 17-25, 1958. B; Biochemical Aspects of the Convulsive Iherapz Process. The significance or high voltage the convulsive therapy process (Roth and Kahn, 1957) and the EEG 22.;l! delta activity in 1951, 1957; Pink report that this delta activity was 'blocked hy the adninistration of ahtioholinergic'compounds; atropine and scopolanine (Ulett and Johnson, 1957) provided the basis for these studies. As there were attendant unpleasant, 'systenio effects with the administration of these agents, .reports describing diethasine as an anticholinergio'conpound' (Jenknerwith potent neurologic but minimal systemic effects l956) Lechner, studies 19553 to.undertake led Lechner, us and sinilar to those of Ulett (Fink, 1958). and Johnson neing this'conpound These observations with diethasine led to the agents. of other antioholinergic experimental investigation Clinical and electroencephalographic responses to the intravenous administration of various anticholinergic agents �-6in psychiatric patients at various stages of convulsive therapy were studied. These observations were related to hypothesis covering the node of action of convulsive therapy and of hallucinogens. The subjects were ninety psychiatric patients referred for convulsive therapy, ranging in age tron Ivariety of diagnoses. since some The total or 18 to 67, with a 107 observations were made, subjects were studied with more than one compound. A drugs were administered at various stages of the treatment process. The observations were laboratory using a standard electrodes. In each intravenously at a trial, 8 made in the EEG channel instrument and needle the compound under star was adninistered until set rate per minute with clinical behavior or electrographic changes were observed. The compounds studied have been diethasine, Win-2299, benactyaine, JB~318, JB~336, and atropine. Each is a potent anticholinergic agent in vitro. It was observed that diethasine, Win-2299, benactysine, �-7; JB-318 or JB-336 administration therapy were associated with at various stages-of convulsive a) desynchronisatien of rhythms with a blocking of post-convulsive b) EEG delta activity; alerting, excitatory behavioral response with illusory, de- lusional and hallucinhtory ideation, and c)_systenic effects ‘drynessof muscular veakness, degrees of the mouth, dry skin and tachycardia. . The electrographic. behavioral and systemic effects were concurrent. These observations are regarded as consistent with the. suggestion that the physiologic basis of convulsive therapy lies in an increase in central nervous system cholinergic activity. Observations that LSD, amphetamine, nescaline and diphenhydranine- synpathoninetic and antihistaminic agents also induce EEG ~ convulsive of desynchronisation, blocking post delta activity and clinical excitatory activity support the suggestion that both the behavioral and electrographic patterns are based on alteration in synaptic activity. Increased synaptic activity (cholinergio, synpatholytic effects) is �-8. associated with 336 hypersynchronisation, and clinical eedation and euphoria; while decreased synaptic synpathominetxic) is associated with clinical excitatery activity (anticholinergic, EEG and hallucinogenic desynchronisation and states. Discrepant observations with the anticholinergic agents, atropine, are considered to be related to significant differences in dongs and structural chemistry. This material was presented EEG at a meeting of Society in Atlantic City, June 1h, 1958. the American �-90. Acute and Chronic EEG and Behavioral Psychophersscologic Agents. Iffects of According to our neurophysiologic~adaptive view of the clinical the convulsive therapy process, efficacy of repeated induced convulsions is dependent upon the induction of a persistent alteration in central function, providing a nilieu for changes in the subject's interaction with the exaniner. In our studies the best index of neurophysiologic change has been those aspects of cerebral function reflected by delta activity in the electroencephalogram (Pink and Kahn, 1957). The efficacy of newer psychopharnaceuticals in altering psychotic behavior patterns has led to the suggestion of a similar hypothesis for the node of action of these agents, and to studies of the relationship and specificity of altered behavioral patterns to neurophysiologic change as reflected in electroencephalography. Of the psychopharnaceuticals tested in acute experiments an in increase in synchrony with or without activity has an increase in slow been observed for chlorpronazine, pronazine and triflupronasine. Behaviorslly, these drugs were associated wave �-10with a) increasing sedation, drowsiness, denial and eqhoria; b) decreasing agitation, panic, excitement hallucinatory activity; of synptons. and and delusional and c) minimization and displacement Barbituratee regularly induced an increase in fast activity with an increase in synchrony, with the associated behavioral changes of sedation, euphoria, denial and minimization. Amphetamine and methamphetamine increased fast activity without increased synchrony; behaviorally they resulted in behavioral alerting, hypcnania, excitement activity. and increased motor Decrease in voltage and per cent time of slow wave subjects with pcst~convulsive delta activity activity in was seen with Lsnazs, benactysine, Win~2299, JB-BlB, JB-336 and diethasine. Of these drugs, benactysine produced increased alerting, excitenent, tension and panic; the other drugs also produced illusory sensations and hallucinatory, delusional The and paranoid ideation. electrographic patterns were consistenthﬁltered concurrently with behavioral changes both in the acute and chronic administration studies. Tranquilization, euphoria, �.11sedation and minimisation of symptoms were conversely associated with increased EEG the delta range. and hallucinations synchronisation and shift of frequencies to Agitation, tension, panic, excitement, illusions were associated with desynchronisation of frequencies. Similar patterns were demonstrated in subjects with prior delta activity. Agents that tended to synchronize frequencies, as chlorpronasine and delta activity barbiturates, and enhanced augmented the per cent clinical pattern; agents that chronised frequencies, as diethasine, minimised the LSD-25 and tine desyno benactysine, clinical effects typically ascribed to repeated. convulsions. Following these preliminary observations more intensive undertaken. was of an (Totranil), agent, inipranine investigation In 28 can3:§:::: acute experiments, patients referred for physio- dynamic therapies were stages of treatment. tested in the EEG laboratory at various Tofranil solution (10 ng/cc) was adninistered intravenously at a set rate(l'cc/h0 sec) until electroencephalographic �total of or behavioral changes became prominent, for a mg (.05«2.5 ng/kg). hO-125 Behavioral observation and electrographic recording continued for one to three hours. A second group of ve, withdrawn 16 patients nanifesting depressienl or retarded bdnvior and were whp referred for pharmacotherapy, received daily oral Torranil of 75-250 mg for four weeks or longer. In the acute studies there was initial restlessness, associated with dissiness, dry mouth, 'faintness," nausea, and on tour occasions, vomiting. These symptoms 10-20 minutes, and were accompanied by lassitude, heaviness of the extremities and eventual drowsiness. unchanged or slowed. persisted for Heart rate was Subsequently, subjects were relaxed, quiet and disinclined to activity, even when returned to their ward. The electrographic pattern accompanying these behavioral changes were initiated the injection. halved. such In {our By by a gradual decrease in voltages during minutes, the per cent tine alpha had been ten patients with noderateonnouniiof beta activity, activity increased in voltage and per cent time. By twenty �-13minutes, in association with behavioral lassitude, low voltage 6 to 50 nicrovolts) randon theta frequencies (5-7 cps) appeared. In six records with poet-convulsive delta a marked decrease activity. two in voltage and per cent time of slow patterns persisted for These electrographic was wave 5 to hours. variability in the There was considerable individual acute of activity, there EEG response. In patients totranil, but three. who received 100 mg or more angptehavioral changes were observed in all In six patients, dosage of Tofranil less than 50 EEG associatedéwith were either EEG mg or behavioral changes. In the chronic Tofranil studies behavioral changes generally appeared during-the second, and were maximal during the third, week of treatment. The most adaptation was euphoric denial which They conplained or displaced prominent behaioral noted in eight patients. was less of somatic synptois, their illness on inquiry. It and ed ed denial. mininisetien became increasingly difficult to discuss significant lire relationships with then. �' ~1h- in three patients sonatiaation and restlessness increased and depressive affect persisted. In two of these, restlessness, insomnia and vomiting led to cessation of therapy. symptoms were noted change in in five patients after four weeks of therapy. Electrographic studies minimal changes. No on chronic administration shoved Voltages became lower and record modulation poorer. Well defined fast activity became more prominent, and in four subjects, low voltage theta (5-7 cps) activity noted. was Details of these studies were presented at the Collegiun Internationale Neuro«Psychopharmacologicum, at the Conference 1958, and Rone, September 12, on Depression and Allied States, Montreal, March l9~2l, 1959. D. Patterns as Measures of Behavioral and Language Neurophsziolegic Change with Drugs. In previous studies of the convulsive therapy process, was demonstrated analysis ( ) that two language measures, and dyadic syntactic content diversification in interviews ( ) provided objective indices of behavioral change, and were related to the degree of altered brain function. In a further it‘ �-15- test of language measures as indicea of behavioral and neurophysiologic change, they were next applied to recordings or interviews on acute administration of various psychopharnacologic agents. At the present time 72 interviews with patients at various stages of drug therapy have been analysed, using the following agents: anobarbital, benactysine, chibrpronazine, diethasine, lysergic~acid diethylanide, and Vin-2299. Following a routine electrographic recording, an psychiatric unstructured physiologic interview, with slow periods of structured inquiry, was tape recorded. With EEG running, an intaavenous injection was then given at a slow rate. specific electrographic or clinical changes interview was repeated. When were induced, the Recording periods of EEG and verbal behavior were alternated for the duration of the observation period. The EEG was shirts in (delta measureg'tor changes in synchronisation, dominant frequencies, and per cent and beta frequencies. tins of slow waves �-16The rthe tape recordings were transcribed and measured for diversification of consecutive 25 word speech and for syntactical changes.‘ samples of dyadic In the dyadid analysis, participants both of behavior verbal the pooled divided into total i;g., the ratio of the number of different number of words. . . The transcribed, samples, and for each sample a diversification 25 word score was calculated, words to the was syntactic language . analysis were based on response to standardised questions using the nothod previously described ( ), scoring such changes as syntactical use of person, alteration in tense, evasion, qualification, displacement or verbal denial or symptoms, use of stereotyped expression or clichzs, cryptic response, and withdrawal or silence. Consistent changes were observed in both the dyadic diversification and syntactic language measures in subjects classified according to the neurophpiologic and behavioral effects of the drugs applied. Anobarbital and chlorpronasinc are neurophysiologic synchronising agents; anobmrbital regularly induced high voltage �-17. well synchronised administration fast activity, at was followed by 20-2h cps, while chlorpronasine increased synchronisiation of the record and a shirt to ﬂower frequencies including occasional EEG slow wave burst activity. Behaviorally these drugs are associated with sedation and tranquilisetion, there was an On the language measures increase in stereotypy and repetitiveness associated with increasing use or cliches, alterations in tense, displacement and evasion. Diethasine, benactysine, LSD~25 and Win-2299 of the neurophysiologic deaynchronising.compounds. characteristically induce decreased voltage of alpha activity and increased irregular are examples These drugs and per cent low voltage tine fast activity. Behaviorally they are associated with hallucinatory, excitatory or illusory activity. On the language neasures they induced ' decreasing repditiveness, wider diversity o: words, lesevariability of diversification scores, and decreased use or cliches and alterations in tense. neasures Further exploration of language are suggested as a rational basis for the understanding or the psychologic �-13- effects of the new therepies. Details of these studies have been presented at the Conference on Paychodynenic, Psychoanalytic and Sociologic Aspects of the Neuroleptic Drugs in Psychiatry, Montreal, April 11—13, 1958, end Aeeocietion, American the Psychiatric et Philadelphia, April 27, 1959. E. Coupereble study or Indoklon and Electrica11y~ Induced Convaleiona in Pczchietric Therepz. A In our investigation or the-node of action of convulsive therapy we have previouslymnnducted a convulsive-subconvnlsive control study. This study demonstrated that e significant behavioral change occurred almost exclusively in patients receiving grand nel electroconvulsive therapy. The present report in an assessment of the relative neurophysiological behavioral and clinical effects of two different methods of and convulsions current) (alternating electrical inducing inhalent (indcklon). �Twenty—five consecutive patients referred for convulsive therapywere studied. They were randomly divided into two groups, 13 patients receiving grand nal therapy induced by the standard while convulsions were Medcratt alternating current instrument, induced in the renaining 12 by the inhalation of hexafluorodiethyl- ether (indoklon). In both groups treatment time a week for a on the total of 10 to 2h wee administered three applications, determined basis of clinical criteria by the supervising psychiatrist. All patients were tested one to two days prior to the first treatment, following 10-12 treatnents, and following the of lest treainent. The two weeks tests given included intellectual functioning (rive subtests measures ' from the Wechsler- perception (figure—ground Bellevue Intelligence Scale), figures, the perception discrimination using embedded.geonetric of peeuoisochronatic color plates at high speeds of tachistoscopic exposure, and the Street incomplete figures test), and social attitude (the Levincon revision of the California I Scale). An EEG was given during each of the testing periods. �-2066 from continuum slow wave cent a tine activity the per second sanple was used as the index of neurophysiologic change. results failed to The test differences show any between the electroshock and indcklon groups at each of the three test periods. showed significant intergroup Intragroup analysis, however, that during treatment both groups on the intellectual and peripheral on the F scale. By two weeks tests, made increased errors and had high scores after the termination of treatment both groups returned to near pretreatnent levels for most Both groups were comparable slow wave activity in the mean EEG after tests. for the degree of induced 10-12 treatnents. The s user per cent tine delta for the indoklon group was 51%, and for the_electroshock group h7.5%. Within each group individual the of behavioral were to related degree change in differences physiologic change, those with the highest per cent tine delta showing the greatest behavioral change. Bath between change in test activity with treatment and correlation performance and degree of slow wave were positive for all procedures, except the comprehension subtest of the Wechsler-Bellevue)and reached a level of statistical significance for Digit Span (e .61, p <-.Ol), �p( object Assembly (+.h6, .05), tachistoscopic perception (+.67, embedded figures (*.h3, p 4< F scale (+.38, p < p < .05), .01) and perception of .05). This study has denonstrated that two very different convulsant agents may produce similar neurophysiologic behavioral change. and It is concluded that behavioral changes in convulsive therapy are related to the degree of altered brain function, and are non-specific for the type of agent used to induce the convulsion. Details of this study were presented at the Eastern Psychological Association in Atlantic City, April, 1959. Sociopszchological Aspects of Psychiatric Treatment. F. In a previous study of the Hillside Hospital population, it was shown tht the factors or age, education, place of birth and social attitudes as measured by the California I scale, were related to the selection of therapy. ‘Those patients were older, had less education, were foreign-born and with high stereotpy scores on the F scales were more whp likely to receive �-22- convulsive therapy. 'In contrast, patients who were younger, the on low and obtained scores native-born educated, better as psychotherapy received scale, their sole F form of treatment. study the relation determine to was Further undertaken of duration hospitalto factors of eociopsychological 1)_th° 2) the isation, The Hospital 171 16 final diagnosis. 3) the and inspatient of Hillside population adult entire on March 7, 1957 was patients. to 68 57 nan and llh studied. This consisted of from in age ranging wonen, median of 35-years. with a years, It period clinical discharge, of time evaluations at was (1—5 shortest the for hospitalized that patients found the least education, were months) were oldest, had foreign-born, the scores andlad highest been have to most likely on the 1 scale. Iounger,native-born, more educated, lower r '(10 more or the longest score patients were hospitalised months). The sane hospitalisation factors of of length to these rdationship made were when analyses found separate was �-23according to diagnosis and type of treatnent (convulsive therapy or psychotherapy). Discharge evaluations of improvement in the population studied were total related to age, the significantly older patients having the nest favorable ratings. Analysis of the data by type of treatnent, however, demonstrated that the convulsive therapy patients ratings of recovered or among much improved were F given to those patients with the highsst scores, least education and who were foreign-born. Diagnoses of schizophrenia or psychoneurosis were associated with lower and high native birth. F The F scores, younger ages, more education older, less educated, foreign-born, score patients were more frequently classified as involutional or nanic-depressive psychosis. It is postulated that these relationships reflect the ingluence of social background on psychological processes, such as the behavioral patterns of communication, nodes or expression and symbolic values. These not only contribute to the pattern or mental illness, but affect all aspects of �~2h- the patient-therapist interaction. Details of this study have been presented at the Eastern Psychological Association in Atlantic City, Avril, '1959, and at the Academy of Psychoanalysis in Philadelphia, April 26, 1959, and has been accepted for publication in the Archives of General Psychiatry. 0. The Relation of Social Attitude to the Effects of Convuleive Therapz. As F indicated in the previous section, the California scale has been found ueeful in understanding factors related to the referral for convulsive therapy and the evaluation of clinical response following have been undertaken with questions: population? a treatnent. Further studies such this scale in regard to the following 1) What does the F scale neasure in our psychiatric 2) What are the behavioral changes induced with convulsive therapy? 3) How are theee changes related to the degree of altered brain function? �-25answer the To first question, in part, the entire in-patient population of the hospital was given the later One month they were retested with a "reverse" in which each statement original. The was changed "reverse" scale was F scale. F scale, to the opposite of the scuzred in the same manner as the conventional scale, with high scores this procedure reflecting greater to determine agreement. The purpose of whether the to the contents related patients' responses were was of the statements, or were a manifestation of a more general personality aspect, such as acquiescence. It was found that those patients who made low scores originally, indicating predoninant disagreement with the statenents, indicating who made showed a large increase the "reverse" scale, on In contrast, patients a high degree of agreement. high scores initially showed little change on retesting, agreeing with the statements to the sane extent even though the meaning was reversed. low I score patients are while those with high It is more evident that, in our population, critical I scores are more and discriminating persons, undifferentiating and �.26.. and stereotyped in their reactions. is related to the process of selection This observation or patients for convulsive therapy. A high degree of atereotypy or thinking and communication is inconpatable with the establishment of a conventional psychotherapeutic relationship, preventing the psychoanalytically-oriented psychotherapy stressed at Hillside Hospital. It follows that the high sill be F score patients unsuccessful in psychotherapy and nest likely reterred for convulsive therapy. To answer the second end patients were given the treatnent period) and F third questions raised above, 69 scale before, during (at 10-12 after convulsive therapy. Ten of these and the control constituted random, group at selected 'patients, received subconvulsive electrostinulation. nean There was a increase of 05.7 during treatment in the convulsive group, a difrerence significant at the control group (+0.5). The showed an SS level. In contrast, the insignificant change during the cane pertd extent or increase in the convulsive patients was �-27- related to the degree of cerebral dysfunction as found to be determined by delta delta (h0% +8.6. activity on the EEG. Those F patients with high or more of the sanple record) had a nean increase of low with delta indices, however, showed a patients statistically insignificant increase of the The +3.h. Following treatnent scores were comparable to the pretreatnent levels. These findings support and elborate previous observations the effects of convulsive therapy. on the F Greater agreement with seere scale statements during treatment stereotypy and difficulty in discrimination. show conventional The change in I n . P score thus seen part of the same process shown by the z characteristic language changes of increased denial, evasion, qualification, I and use of cliches and stereotyped orpressions It is also comparable to the increased visual tactile perception ( and ( ) difficulty in and figure-ground ( ). complex discninination )- Details of these findings were presented at the Eastern Psychological Association in 1958 and will be elaborated at the �forthcoming Divisional nesting of the American Psychiatric Association in H. ﬂew Zork. Aspects of the TherapistaPatient Relationship Affecting Choice of Therapz. As indicated previously the selection or therapy involves other aspects than the actual behavioral pattern or the patient. In the past year further efforts to been undertaken, emphasizing relationship. clarify this problem have factors in the therapist-patient he have hypotheSised increased tension, frustration and that such factors as hostility in the therapist~ patient relationship, as well as implicit and explicit pressures present in the environment have a significant influence in referral for sonatic therapy. In a and pilot study 76 structured interviews with residents supervisors were initiated following requests ﬁr sonatotherapy. These interviews were designed to referral. It there was found a sudden change elicit the basis of the that in only relatively few cases was in the patient's clinical status which directly led to the referral. most In instances there had been �-29- or progression no change the presenting eynptons. in‘ Factors of impending included the to timing contributing the referral diccherge, avoiding administration discharge, and pressure tron the patient's family or ward personnel. It res also noted were'treatod that ptiients with ainilarhehcvior patterns given senatotherapy and others none. The 4‘ renged reasons for this raged from'"whin" to quantitative difference! differently, some . in synptonetelogy and individual preferences for type of treatment. initial The conclueien wen that in a significant 0; cases, factors other then clinical indication played number a role in the referral. These sane extraneous factors also influenced the timing or the referrals is e results of these findings Referral Sheet" to was completed by the From c ’Scnatic Treatment developed‘(see form at end or report) to therapist whenever somatic therapy is reqneeted. this questionnaire we hope to obtain further information regarding indications for somatic treatment, more specific data �-30. concerning the therapist-patient interaction, and a more definite idee of the therapist's expectations for such treatment. I. Individual Differences in Selection of, to Convnlsive.Theragz. and Response In the elucidation of individual differences related to sonstic therapy, a variety of peripheral-cognitive procedureshave been used. tachistoscopic perception of enbedded colored figures The has been given to 65 of 35 consecutive were 20 patients. experimental group consisted The convulsive referrals for therapy. The controls patients treated with phenothiazine medication (thorazine and pronasine) and ten patients receiving no somatic treatment. All subjects were tested prior to treatment, and after four weeks; the convulairee were tested s third tine two weeks following the cessation of treatment. It was found increase in that there mean number was a statistically significant of errors with convulsive therapy, while following treetnent there was e significant decrease from the pretreatment scores. at Controls made significantly fewer errors �.31- (practice effect). errors between patients classified (per cent time delta) were significant difference in There was a when compared as showing low with high high retest correlations for all groups. EEG changes changes. EEG Marked There individual ditferences in response patterns were noted prior to treatment. With brain changes there was a reduction in perseveration, conpletion patients, and contabulation in some and and increase in others, with no unique patterns attributed to cerebral dysfunction. Even in those patients with high his response pattern was showing completion type to make such EEG 'stjh' changes, the ntein naintained. Thus a errors prior to treatment ore patient would continue errors with convulsive therapy, although the threshold at which completion was shown might change. Details of this study were_presented at the Eastern Psychological Association in Atlantic city, April 1959. The Red and h? Irene Test (after Witkin) was administered to Harked somatic for referred therapy. consecutively patients individual dirierencee in performance were correlated with age, �w _‘“ .v .32-‘ education and score on the Calibrnia vertical Judgment of the frame (field dependent) F scale. Patients whose ﬁes strongly influenced by the sunnunding were more frequently referred for convulsive therapy than drug therapy. No significant change ‘ was found with drug or.convulsive treatment. convulsive groups retest correlations drug For both/and were high (.86 and on differences in the individual considered that is It Frame test reflect personality factors that are in psychiatric treatment. .88). Rod and of importance �5 “J a , :1: 7/16/59 L, wig/r 1 _/ Function Brain Altered Following Electroehcck ‘ 24.927 Progress Report - Febmary 1. 1958 - September 1, 1959 m: L previous In our studies we have demonstrated that an understanﬁng of the convulsive therepy process required a nultifectoriel approach involving neurophysiologic, perceptual, personality, paychodynemic and eocielogic eepecte cf behavior. Thus is essential it wee ehcwn that: The convuleim to the therapeutic process (Fink, Green end Kuhn, 1958); murcmeielegic changes reflective of altered brain function ere e a Heinetein, 1956; Fink & Kenn. 1957) neceeeery prerequisite for behavioral change end ixproveemt‘ the (Kuhn, Fink biochemical beeie of the convulsive therapy preceee lay level of cholinergic activity of the central nervous is an mm increased (Fink, 1958); there are characteristic perceptual chengee with altered brain function induced by convulsive therapy (Fink, Kuhn and Korin, 1957; Kehn and Pink, 1957); retina cf improvement after convulsive therapy are related to personality characteristics defined by Rorschach and {mm (Kahn and Fink, 1958). interviews (Kuhn and Fink. 1957); end that evaluations of �mm (Kuhn 8.: -2. were related to changes in syntactic aspects of language Fink, 1958). In the pest eighteen (18) months these statics wen completed and extended, and an investigation of poychophamcologic agents begun. The {mark View we for these investigation: of convulsive therapy (Veimtedn Fink and Kahn, 1957) extended mandarin patients (Pink, The been the nmxrophyeiologic adoptive Kahn, 1955; Knhn 8c at all, 1956; to other physiodynenic treatmmta or 1957) . tho convulsive therapy process were relieving aspect- of studied: 1. Siﬂficence or the Commune Mologic, A cooperative study of neuro- paychologic and bohemian). effects of electrical and inhalant (Indoklnn) induced convuhicaa. 2. @2326 Basic of NeuroMiologg-c Chang: Further studies of the effects of acute wtmtric 3. “notation agents on both the Mgwogo AoEm of of marinentnl anticholinergic 'noml“ and and pout-convulsive EH}. Comm Thomas 3. Relation of the factors or age, education, nativity and �n3. mmotm (mound w the California max-aw, duration of 1:. Chang“ clung» to EEG hoapiuuuum, of F 1" scale) with selection of diagnosis and diochnrgo ratings. scale with treatmnt, and relation of those indiceo. h. Mother-Lg and Conwlsivo Tim-ram: In aupervioory sessions, alterations in psychotherapy with convulsive thorapy were studied. W: 5- Both patterns or change and individunl diffomnooo on tuohistoocopio figumﬂ ground ﬂicker immoy domination tutu, critical and perception of the upright with induced ‘ emulsions were studied. 5093*ch are «tended to dmg therapies and the following studies undertakom 1. 1010 :1. c: Relation of EEG charge on acute and ohmnic administration of poychophamoouticals to clinical behavioral change. b. EEG as a screening device for psychomrnceuuc potency. �.. h .- c. Elation of 6. EEG EEG clause: to hallucinogenic activity. effects at neginide. 2. Omnicstion Patterns: Relation of induced neurophyeolcgie change to dyadic diversifi- cation and syntactic language maeuree. 3. Aspects of the Therapist .. Patient Relationship affecting choice of somatic therapy. metudiec View have supported and expanded the mumphyaiologxo-adapuu of convulsive therapy, and dancnetrated that. such a applicability to our understanding of the mode munch has of action of psycho- phamacologic agents. PROGRESS A. tar: l. REPORT: Gasman new?! PROCESS ﬁgniricance of the Convaleion: A cmmrable study of Indoklcn and electrically-induced convulsime in psychiatric therapy was control eubccmuleive completed. An mm demonstrated changes occurred almost exclusively electrocomruleive therapy. The earlier convulsive- that. uinIicant behavioral in patients receiving grand mal present report is an assessment at �-5the relative neurophysiologic, behavioral and clinical effects of hm different of. methods inciting convulsions - electrical cuxjreet) and inhalant (indoklon) . (eltemating 'consemtive patients referred for convulsive therapy Thaw-nave classified into were tendonly Won / 3Wt, / . ,:./ patients and by two groups the steward - «isms Model-oft mowed in alternating current in. in twelve by the inhalstion of heMlumdetlvl—ether findeklon). In both groups treatment was ochinistered three times a .5 {f} [f book for a total of IKE/o: x! I! if / 3' 10 to 21; applications, determined on the basis clinical criteris by the supervising psychiatrist. ,f‘. \ A All patients were tested one to two days prior to the treatment, following 10.12 treatments, and first m weeks renewing the lost tacatment. In addition to evaluations of behavioral. change, tests included nouns-es of intellectual function (five aubtests In the Kodachr-Bellme Intelligence Scale), perception (figure-groom! discrimination using wedded geamtric figures, the perception of pewdeochrcnstic color plates at high speeds of toohictoocopic exposure, and the Stmt moguls“ figure: test), and lucid �.- 6 1e etﬂtude (the Lennon revision of the California 1" Scale). An testing of each the periods, obtained during electroencephalogram was on! mom-ed for the per cent. time slow we (6 ope or slower) activity from a continuous 66 second sample. The to failed Insults show any significant inter-group teat differences between the electroshock and indoklon groupe at each of the three test periods. Inbregtoup groupe made onlyale, that during treatment both increased errors on the intellectual and perceptual taste, end had higher _ hmr, showed some on the F scale. By two weeks otter the terminal-g for tion of treatment both groupe returned to near pretreatment. levels ' moat mete. Both groupe were comparable for the degree of indeeeed wave activity after for the 10-12 treatments. indokloa group was 51% and The EEG slow per cent time slow activity for me electroshock group It? 5%. within each group individual differences in behavioral change were the with thoee change of neurophysiologic the degree to reload behavioral change. the greateet sharing delta cent tine highest per �-7mm: order correlations batman changes in test performance and degree of slow wave activity with treatment. were positive fer all proeedwes, except the eomehension subtest of the Wechalar-Bellevm, level of statistical significance for digit. span 1" scale (4* .33, 13 .05). .01), object Assembly (hub, and reached a (+ 1,61, p p .05), ucmnoacopac perception (+.67, p of embedded figures («13, p This study demonstrated .01) and perception .05). that up different eonvulsant. agents produce similar neurophysiologic and behavioral changes. eencluded that. the behavioral change It was is related in convulsive therapy/to the degree of altered brain function, and an non-speciﬁc for the type of agent. used to induce the eohvulsion. (mud, in part, at the Eastern Psychological Assecatien, Atlantic City, April, 1959). 2. modicum ”mate of the Convulsive The significance of high voltage There}?! l’ﬁt‘eceae2 m delta activity in the convulsive therapy process (Ruth 213.1) 1951, 1957; Fink and Wm, 1957) and the report that this delta activity ministration (mate was blocked by the of the antteholinergic agents atropine and scepolamine and Johnson, 1957) provided the basis t‘or mane studies. As �- 8 a. there Here attendant unpleuent systemic etfeote with the comm-tre- tion of these agents, report: describing diethulne as an entioholmcrglc effects (Jenknor compound with potent neurologlc but mm manic and Loohner,19553 Lechner, 1956) 13+. us studies similar to those of Ulett and John-on using (Rink, 1956). These observations with diethacine this to mderteke compound lot to the investiga- tion of other experimental antichollnerglc agents. Clinical and electroencephalographic responses to the intravenou- adninistration of dicthaxine and atropine in plychntrlc patients at therapy were studied. Each The Win. 2299, is bemctyam, JD 318, dB 336 various: etegee of convulsion a potent antiohollnergic agent 121 um. eubjecte were ninety psychiatric patients referred for convulsive therapy, ranging in age from 18 to 67, with Wes. A total of 107 observations were rude, a. since variety of some subjects were studied with more than one compound. The observations were 8 channel made in the EEG laboratory ucing a standard instrument and needle electrodes. In each coupound under study was tual, the mastered intravenously at a set rate �-9 .. per minute until clinical behavioral oz- eleetrogrephic changes were observed. It was was observed that salinistrstion of these sntichonnergic agents associated with e) dosynchmmisstion of bloom of post-convulsive delta activity; EEG 1:) rhythms with s alerting, excitstory behavioral response with illusory, delusional end Mllucinatory mention, and c) systemic effects of muscular weakness, dryness of the south, dry skin and techycerdia. end systemic effects The electromﬂuc, behavioral were concurrent. These observations are regarded as consistent with the suggestion that the physiologic basis in central of, convulsive therapy nervous system cholmergic Observations that LSD, lies in an increase activity. substantive, nasceline sympathemnetic and antihistaminic agents - and diphenhydmmns also induced convulsive d‘ delta desynchronisation, blocking post EEG activity clinical oucitstory scﬁviw support the suggestion that the and mvioral md electrogrsphio patterns of these compounds are also based on alteration in synoptic activity. Increased synaptic activity (cholinergic, synpethclytic effects) is sssocieted with - EEG Immora- synchreniseticn, and clinical sodation and euphoric; while decreased �.. 1o - synapmc activity (anticholimrgic, sympathmimtnc) is mandated with dosynchmniution and clinical excihtory and hallucinogmic EEG states, thus supporting the Wthesia mually described mama by Wilder (19514). algont, atropine, Deacrepant observations with the anticholinergic are considered to be related to significant differences in dosage. (Presumed, in put, San d‘ Biological Paymatry, the Society at first Francisco, 1958 and awarded tbs Award of that Society; and, in part, at City, 1959. Published, in part, 380-387, 19573 and accepted 3. Socio a. A. E. Bennett cal 01 A A 1. A American EEG PsycIﬁItrio Research Somty, Atlantic Arch. Neural. & cMat. g9. for publiaation, ma Olin. Nemﬂmool.) shiatric Treatment ate of Duration at Hoggtaluation. Dawn and .' Madam Evaluation. In an earlier study of the Hillside Hospital populationmahn, Pollack birth :3: and Pink, 1957). it was noted social attitudes that age, causation, place of F California measured the by as were related to the aelecﬁm of therapy. Those pation‘ua older, had less education, scores on the F scale, who were were foreign-born am with high stereotype scales were more likely to waive convulsive therapy. �- 11 In oontmt, petiente I ‘ who were .. younger, better eduoehdmetiveobem end obtained it»: theeoree on the 1’" scale, received peyoheﬂmerepy ee their sole router treatment. nutty Another wee undertaken to determine the relations of theee eodepeyohologioal factore to 1) the duration of hospitalization, 2) the Meal evaluations at time of discharge, and 3) the final diegxoaia. The entire impatient edalt population studied. This oomieted on! maize in age from 16 to 171 68 patients, years, no: on March 7, 1957 was 57 men and 11]; mo, a median of 35 years. Patients hospitalized for the shortcut period (1 - 5 months) were noted to be the oldest, have the least education, were more likely to be foreign-hem, and have the highest scores on the “ scale. Younger, native-bum, more educated, loner months). (10 more the or longest each hoepitelieed ship of: F more patients The same these factors to length of hosmtelizetion was found eepehte Ienelyeee them F relation» when were made according to diagnosis and type of (eomleive thempy or peyohotherepy). �,' 12 u. Discharge evaluations of improvemnt were significantly related _ to age - the older patients having the most favorableratingm Miami! of the date by type of treetnent,hovever, demonstrated that among the oeuvulsive therapy patients rating: of recovered or much inproved were given to those patients with the highest F scores, least education and who were foreign-born. Diagnoses of schizophrenia or peyohomuroeie were undated with lower F eeoree, younger ages, more education and native birth. The older, less educated, femignnborn, high more F score patients were frequently classified as involutionel or mic—depressive psychosis. It was postulated that these relationships reﬂect the influence of nodal background and psychological proceeoee, such as the behavioral patterns of communication and modes of expression. These Thane not only oontﬂbute to the pattern of mental illness, but affect all aspects of the patientoﬂxerapiet interactim. (Pmeented at the Beaten: Psychological Association, Atlantic City g April, 1959, and the Acedm of Psychoanalysis, Philadelphia, April, 1959. Accepted for publication, Archives of General Psychiatg.) �.. 13 .. 13. Treatment. Convuleive with Social Attitude in Gwen: Following the earlier observations that the California is 1“ scale useful in understanding mien-a1 for ccnvuleive therapy and the evaluation of clinical reepcnee following such treatment, ﬁzz-ﬂier studies were undertaken with thieeeale in regard to the {alluring 1) iihet deal the F scale measure in a psychiatric question: a population? 2) Dc 1“ scores change with convulsive therapy? 3) Are these changes related to the degree of altered brain function? entire in-patient population of the heepital was given the The :16 one month scale, in later, was retested with a "reverse“ ﬁnch each statement wee changed The “reverse" scale as to the opposite or! F F scale, the original. scored in the same manner as the ccnventicnal scale, with high ecoree reflecting greater agreement. It was noted that than patient: who made low scores initially, showed an with the statements, disagreement indicating a wedcninant increase on the "reverse" scale, indicating a high degree of agreement. In contrast, patients the mde high scores little change on initially shaved same the to etatexunte the with agreeing reteeting, �.. m .. extent even thong: the nearing was reversed. let: P score patients are more critical and It is evident that diesﬂmimting persons , while those with high F scores are more undifferentietihg and stereotyped in their reactions. This aberration is related to the process or selection of patients for convulsive thmpy. thinking and commutation on! A high degree or sterotwpy of is incomtsble with the a conventional psychotherapeuﬁc rehtionship, psychoanalyticslly—oriented psychotherapy stressed Hospital. It follows that the high F establishment meeting the at Hillside score patients will be unsuccessful in psychotherapy and most likely referred for con- vulsive therapy. In anotlmr study, sixtr-ndne patients were given the F scale berm, during therapy. Ten (st 10-12 treatmnt period) patients, selected at group and received subconvulsive mean increase in group a. F random, and after convulsive constituted a control electrostimlsuon. There was s. score of +5.7 during treatment in convulsive a difference significant at the 5% level. In contrast, the �- 15 In conﬁnes. the control group .. showed an insignificant change during the echo period (+0.5). The extent of increase in me convulsive petieﬁts was related to the degree of cerebral dysfunction es <1er by delta sctiﬂw on the m. The patients with my: d6“? (1:010: 3955 of the mp1” 1‘3“”) had a // l'hebe patientsvith mean ' increase e a ’8’6” f low delta indioes, however, off 43.14,. Following treatment the showed an increase 3 2/ 15’03&8tashv ,f 1/ / ”(7/ -/'4,7,3? ,. V ,2” / / ,. /"5 scores were comparable to the levels. ‘ , ‘ “these ,flndmgs support and eleborste previous observations on the [5%. ,2)" , 7752/ 1" cadets” e’f convulsive therapy. Greater agreement with the ,. scale ‘f std/Wes /} F during treatment show conventional stereotypy and 3" /r (35“:ow I _ 1n discrimineuon. Changes in F score thus parallel the fo’hehoteristio hnguege changes or increased denial, evasion, /// " , ,/,.L‘ ,r l7 //qdeiﬂicetlon, ' / / and use of cliches and stereotyped expressions (Kuhn ‘ j" & 2 Fink, i953) . It 1. .1“ ompmble to the increased difficulty in / / l / / cochlea: visual and tactile perception (Flak, fairs-groom discrimination j’(heseo1{;e§ at. Knhn (Karmic Fink, 1957). /ﬂbyohletrlc Association, at the Divisions]. Meeting of the American 3' ‘81 I ‘- r {'1' 4" Karin, 1957) and the Eastern Psychological Association, 1958; and aeoepced for?" presentation ‘ 8: New York, November 1959.) �~16- h. Psychotherapy and thsicdzgamic Therapy: Previous studies indicated that patients referred for of electroshock in this hospital are/two types. The largest number are patients in the older education and are foreign born. age groups who have They tend to be limited non-introspective persons, stereotyped in their language and thinking and verbally unconnunicative. Their predominant symptoms are depression, agitation, withdrawal and somatisation. The second, and smaller, group of patients are younger, native-born, bettereducated, and verbally communicative with a capacity for introspection. They characteristically exhibit thinking disorders and overactive behavior, with lesser degrees of aonatisation and depression. Four patients, two for each group described above were studied to determine 1) reasons for referral, different attitudes management, and 2) whether were required in psychotherapeutic 3) the relation of the psychotherapeutic �-17. approach to the patient's clinical response to convulsive therapy. It was suggested that these patients were referred for convulsive therapy because of a failure of communication in the psychotherapeutic relationship. a In two cases this was reflection of the patient's limited verbal and introspective capacity related to educational and social factors. instances, however, the impaired communication by unmanageable was In two manifested acting out behavior. Following treatment, is older, less educated patients were able to maintain a behavioral change with a reassuring, supportive technique, amplifying tendencies to minimization and denial developed during electroshock. In the better educated patients, electroshock decreased acting out was associated with increased use of interpretive forms of psychotherapy. It uas concluded that the relationship of psychotherapy to convulsive therapy varies with the communication pattern �~18 - and adaptation shown by the individual patient. (Published in the Journal of Hillside S. Hos ital, 1: 17-25, 1958). Perception: A variety of perceptual-cognitive test procedures have been studied in l. patients receiving somatic therapies. Tachistoscopic Perception of Colored Figures: The Embedded This task was studied in an experimental group consisting of 35 consecutive referrals for convulsive therapy, and "control" groups of 20 patients treated with phenothiazine medication (thorazine and pronasine) and ten patients receiving no somatic treatment, matched for age. All subjects were tested prior to treatment, were and tested akhird time after four two weeks weeks the convulsive patients following the cessation of treatment. There was a number of there statistically significant increase in errors with convulsive therapy, was a significant decrease mean and following treatment, from the pretreatment scores. "Control” subjects made significantly fewer errors (practice �-19- effect). significant difference in errors between There was a patients classified as delta) when compared showing low with high EEG changes (per cent changes. EEG tine There were high retest correlations for all groups. There were marked individual differences in response patterns prior to treatment. With brain changes there was a reduction in perseveration, completion and confabulation in some patients, and an increase in others, with patterns attributed to cerebral dysfunction. patients with high pattern was EEG no unique 3V0“ in thOBO changes, the ”style" of his response maintained. Thus a patient showing completion type errors prior to treatment would continue to make such errors with convulsive therapy, although the threshold at which completion was shown might change. were Details of this study presented at the Eastern Psychological Association in Atlantic City, April 1959. 2. Rod and Frame Test gWitkinzs This task was administered to h? patients consecutively referred for somatic therapy. Marked �- 20 - with correlated age, were in performance individual differences education and score judgment of the frame (field on vertical was dependento were more frequently referred for No significant treatment. found with drug or convulsive convulsive groups It retest cerrelations change For both drug and were high (*.86 and +.88). is considered that individual differences Frame whose influenced by the surrounding strongly therapy. than drug convulsive therapy was Patients the California F.ecale. on the Rod and of importance are that factors test reflect personality in psychiatric treatment. B. PSYCHOPHARHAOOLOGIO STUDIES 1. Neuroghzsiologic Studies: view the of neurophysiologic~adaptive the to Acoprding convulsive therapy process, the clinical efficacy of repeated induced convulsions is dependent upon the induction of a providing function, nervous central in alteration persistent the with interaction the in subject's a milieu for changes examiner and the environment. In these studies the best been of those has aspects change of neurophysiologic index the electnoin by delta activity reflected function cerebral �enoephalogran (Fink and Kahp,1957). The efficacy of newer psychopharnaceuticals in altering psychotic behavior patterns has led to the suggestion of aI/ﬂ ,1 1} similar hypothesis for the node of action of these agents{ and to studies of the relationship and specificity of altﬁred behavioral patterns to neurophysiologic change as reflected in electroencephalography. Of an the psychophsrmaceuticals tested in acute experiments increase in syhchrony with or without an increase in slow wave and activity has been observed for chlorpromasine, pronasine triflupronasine. Behaviorally, these drugs were associated with a) increasing sedation,drowsiness, denial and euphoria; b) decreasing agitation, panic, excitement and delusional and hallucinatory activity; and c) minimisation and displacement or synptons. an Barbiturates regularly induced increase in fast activity with an increase in synchrony, with the associated behavorial changes of sedation, euphoria, denial and minimization. Amphetamine and methamphetamine increased fast activity without increased synchrony and behaviorally were associated with behavorial alerting, hyponania, �- - 22 excitement and increased motor activity. and per cent time of slow wave post-convulsive delta activity Decrease in voltage activity in subjects with was seen with LSD-2S, bcnactyzine, Win-2299, JB~318, JB~336 and diethasine. Of these drugs, benactyzine produced increased alerting, excitement, tension and panic; the other drugs also produced illusory sensations and hallucinatory, delusional and paranoid ideation. The electrographic patterns were consistently altered concurrently with behavioral changes both in the acute and chronic administration studies. Tranquilization, euphoria, sedation and minimization of symptoms were concurrently associated with increased EEG synchronization and shift of frequencies to the delta range. Agitation, tension, panic, excitement, illusions and hallucinations were associated with desynchronisaticn of frequencies. Similar patterns were demonstrated in subjects with prior delta activity. Agents that tended to synchronize frequencies, as chlorprcnazine and barbiturates, augmented the per cent tine delta activity and enhanced the clinical patterns; agents that desynchronized frequencies, as diethasine, LSD-25 �-23and benactyzine, minimized the clinical effects typically ascribed to repeated convulsions. Various experimental psychopharnaceutioala were tested. In addition to extensive studies or 3-3 methylethylgiutarimide (Heginide) and hexetluorodiethylether (Indoklon) the following nhsnyltoloxanine (PHD-Bristol), methenalide agents were studied: (BLH~lﬂl;lhristol), tropin-h-Ghlorhenzhydryl ether (WI-21h9, Wyeth), dinethylaninsethanel and verieties, Riker), JB-3;;, its oongeners (Deaner and 329 and 336 (various piperidyl- Geigy). and (Torrinil, Lakeside) inipranine bensilatss, significant behavioral Because or 31:31 changes, a was and electrogrephic intestigation of imipramine (Torrinil), nere intensive undertaken. In 28 acute experiﬂmenta, consecutive patients referred for physiodynnmie therapies were tested in the EEG TofrEnil solution of treatment. various stages at laboratory (10 ng/oc) was administered intravenously until electrographic or behavioral changes a total of h0-12S mg at a set rate (1 cc/ho sec) became prominent, (0.5-2.5 mg/kg). Behavioral observation for �«Zh- and In electrcgraphic recording continued for one to three hours. patients referred for pharmacotherapy because of manifest depressive, withdrawn or retarded behavior oral Torranil of 75-350 mg administered. was In the acute studies there was initial restlessness, associated with dissiness, dry mouth, “taintness,” nausea, and on tour occasions, voniting. These symptoms persisted for t 10-20 minutes, and were accompanied by lasdtude, heaviness of the extremities and eventual drowsiness. unchanged or slowed. Blood Heart rate was pressure dropped by in older (age>’ 60) patients. 20-ho% Subsequently, subjects were relaxed, quiet and disinclined to activity, even when returned to their ward. The electrcgraphic patterns accompanying these behavioral changes were initiated during the injection. had been halved. activity, such by a gradual By in decrease in voltages ten minutes, the per cent tine alpha In patients with moderate anounts of beta activity occasionally increased in voltage and �-25per cent time. twenty minutes, in association with By behavioral lassitude, low voltage (to theta frequencies (5—? 50 nicrovolts) random In records with post~ cps) appeared. convulsive delta activity, there was a marked decrease in voltage and per cent time of slow graphic patterns persisted for i wave to two There was considerable individual acute EEG of Torrinil, EEG who These electro- hours. variability in this received 100 mg or more all and behavioral changes were observed in In six patients, dosage of TorrEnil less than 50 but three. were In patients response. activity. associated neither with EEG mg nor with behavioral changes. In chronic Torranil studies, behavioral changes generally appeared during the second, and were maximal during the week of was treatnent. The most prominent euphoric denial. behavioral adaptation Patients complained less of somatic symptoms, and denied, minimized or displaced inquiry. It became lite relationships third, their illness on increasingly difficult to discuss significant with then. In six patients sonatisation and �restlessness increased and depressive affect persisted. In three, restlessness, agitation, excitement, insomnia and vomiting, led to the cessation of therapy. No change in sfgntons were noted in five patients after four weeks of therapy. Electrographio studies a decrease on chronic administration showed in voltages with poorer record modulation. voltage theta (S~7 cps) activity up to defined fast activity 10% r‘ became more p~ominent appeared. Low Well in a few. (presented at the Collegian Interantionale Neuro-Psychopharmacologicum, Rome, September, 1958) at the Conference on Depression and Allied States, Montreal, March, 1959] and American EEG Society, June, 1959; Published, in part, in the 3 Proceedings of C;I.N.P. Psychopharnaoology Frontiers, ed. 3. 9 Kline, 325-332, 19593 Canad. J. Neurologz, g} 682~685, 1958. Pe chiat., 1959 (in prose); �-272. Language Patterns as Resource of Behavioral and Nauroghzsielogic Change with Drugs. In previous studies of the convulsive therapy process, it was demonstrated that syntactic two language measures, a content analysis (Kahn and Fink, 1958) and dyadic diversification a scores or instructured interviews (Jaffe, Kahn and Pink, 1958) provided objective indices of behavioral change, and were related to the degree of altered brain function. "In a further test of these language measures as indices of behavioral and neurophysiologic change, they were applied to interview on ’ acute administration of various psychopharnacologic agents. Seventy-two interviews with patients at various stages of drug therapy have been analyzed, using the following agents: emobarbital, benactyzine, ohlorpronazine, diethazine, lysergie— acid diethylanide, and Win-2299. unFollowing a routine electrographic recording, an structured psychiatric interview, with short periods of {\‘\ structured inquiry, g was tape recorded. With EEG running, intravenouq injection was then given at a slow rate. When on �—28- specific electrogrsphic or clinical changes were induced, the interview was repeated. Recording periods of EEG and verbal behavior were alternated for the duration of the observation period. The shifts in (delta) The EEG was measured for changes in synchronization, dominant frequencies, and per cent time of slow waves and beta frequencies. tape recordings were transcribed and measured for the diversification of consecutive participants (dyadic) and for 25 word samples of speech of both syntactical changes. In the dyadic analysis, the pooled verbal behavior of both participants was transcribed, divided into 25 word samples, and for each sample the ratio of the number of different words to the words (a diversification score) was calculated. total The number of syntactic langw ge analyses were based on the response to standardized questions using a method previously described (Kahn and rink, 1958), scoring such changes as syntactical use of person, alteration in tense, evasion, qualification, displacement or verbal denial of symptoms, use of stereotyped expression or cliches, cryptic �-29withdrawal and or response, silence. the both dyadic observed in were changes Consistent diversification classified and syntactic language neasurss in subjects behavioral and according to the neurophysiologic effects of the drugs applied. neurophysiologic are and chlorpronasine Ancbarbital high inducing regularly imobarbital synchronising agents. at activity fast synchronised voltage well chlorpronasine administration synchronisation of the EEG was 20¢2h cps, while increased folloudd by record and a shift to slower occasional slow including frequencies wave burst activity. sedation and with associated Behaviorally these drugs are tranquilisation. in stereotpy and On increase was an there measures the language with increasing associated repetitiveness displacement in and-evasion. cliches, tense, alterations of use Diethasine, benactysine, LSD—25 and Wine2299 areheuro» compounds. desynchronizing physiologic These drugs are and decreased per voltage with associated characteristically �-30- cent tins of alpha activity and increased irregular low voltage fast activity. or Behaviorally hallucinatory, exoitatory illusory activity are observed. there was On the language measures decreasing repetitiveness, wide diversity of words, less variability of diversification scores, and decreased use of cliches and alterations in tense. Further explaation of language neasures are suggested as a rational basis for the understanding of the psychologic effects of the new therapies. (Presented at the Conference on Peychodynanio, Psychoanalytic and Sociologic Aspects of the Neuroleptic Drugs in Psychiatry, Montreal, April, l958, and at the American Psychiatric Association, Philadelphia, April, 1959. 3; To be published). Aspects of the Therapist-Patient Relationship Affed ting ” Choice of Therapy. The selection of therapy involves aspects other than the manifest behavioral patterns of the patient. In the past year further efforts to clarify this problem have been undertaken, emphasising factors in the therapist-patient relationship. We �-31have hypothesized that frustration therapist-patient relationship and and hostility in the implicit or explicit environmental pressures have a significant influence in referral for somatic therapy. In a and pilot study 76 structured interviews with residents supervisors were initiated following requests for sonato~ therapy. these interviews were designed to elicit the basis of the referral. It was there a sudden change in the patient's clinical status which vas found that in only directly led to the referral. In relatively few cases most instances there had been no change or progression in the presenting symptoms. Factors contributing to the timing of the referral included impending discharge, avoiding administrative discharge, and pressure tron the patient's fanily or ward personnel. It was also noted that patients with similar behavior patterns were treated differently, sons given eonatctherapy and others none. The reasons for this ranged from ”thin" to quantitative differences in syntonatology and individual preferences for type of treatment. �-32- It was concluded that factors other than clinical indication played a role in the referral in a significant number of cases. These the timing of the As a extraneous factors also influenced referrals. result of these findings Referral Sheet" was developed be completed by the requested. same From a ”Sonatic Treeteent (see for: at end of report) to therapist ehenever somatic therapy is this questionnaire and continued and ward personnel interviews we hope to obtain therapist further infernation regarding indications for somatic treatment, more specific data concerning the therapist-patient interaction, and a more definite idea of the therapist's expectations for such treatment. �Soptonbor 1, 1959 A an»- « FINAL REPORT H~927* ’ Doportmont of Exporinontnl Psychiatry HILLSIDE HOSPITAL Glen Oaks, L. 1., N. I. Aoknowlodgnont Summury, Five Yours, 195k - 1959 Summary #h, Feb. 1, 1958 - Sept. 1, 1959 Publications, 195h - 1959 Prosontationl, Initial studios 19Sh ~ 1959 a. b. 2S 30 bogun 1:11 1953, supportod by tho Board of Diroctora' nooonroh Fund. Supported by Nationul Institute of Mental Honlth Fund, Soptombor l, 195k - August 31, 1959. Study continuing with support of grant MI-2715, United Statos Public Health Sorvico (Jan. 1, 1959) �Acknowledgment studies reported here would not have been possible without the faith and support or the Founder at Hillaide Hospital, Dr. Iorael Strauss, the Board of Directors and tho Administrator, Hr. Maurice Bachraoh, who auetained this program during its early vicissitudes. Financial Support was also given during this period by the Kaufman Foundation, the Foundatione' Fund for Research in Psychiatry, the Daaian Foundation of New fork; the following pharmaceutical firms: Smith, Kline and French Laboratoriea, Wyeth Laboratories, Geigy Pharmaceuticals, and Bristol Laboratories; and the Mental Health Board of Nassau County. The �SUMMARY 14-927 19Sh - 1959 laboratories of the Departnent of Experimental Psychiatry were established at hillside Hospital in September, 195k. During this five year period neurophysiologic, psychologic (personality and perceptual), lingustic, and socioloéic aspects of "somatic" psychiatric therapies have been the principal foci. The 1. Convulsive Therapy: The view of the convulsive therapy process as the induction or a non-specific state or altered brain functbn, similar to. craniocerebral trauma (10, ll, 21) was supported and amplified with this altered cerebral milieu, subjects were seen to respond in various ways (26) of which the most successful was explicitf verbal denial (7, 31). This latter was most prominent in characterologically disposed individuals (36). in alteration in brain function was pro-requisite to behavioral change (7, 8, 11, 26). Grand mal seizures were this to essential process (26) but electrical induction was not (Boh2). Such alteration in brain function was measured by various ways including electroencephalography (6, ll, 12, 2h, 39, language patterns (h, 7, 1h, 31, h}, B-Zh), perceptual tasks (2, 16, 17, 37, hé, 8-26, h1, h?) and tests of recall. A variety of behavioral changes were seen during convulsive therapy (26, 8—17). Such patterns were lbwed as adaptations to altered brain function,wand were believed dependentlupon Refcrbnce nunEers are to publications or presentations (5- I listed in the appendix. �characterologic and environmental factors (7, 25, 26, 36, ho). Clinical ratings of improvement were seen as value Judgments by the observer of the behavioral changes in the subject (26). Adaptations characterised by denial mechanisms, both in behavior (3—17) and in language a, 31) were assessed with the best rating of improvement. Such adaptations were noted to be related to habitual nodes of conduct (character, personality) (36, Bull, ‘ 32). durability of the altered behavioral nodes was seeh‘. to be dependent upon such factors as the degree and duration of altered brain function, the environnental expectations, and the type and degree of family and medical support. Different behavioral patterns were best supported by varyinc types of The psychotherapy (19). It also suggested that the neurophysiologicgbasis or convulsive therapy nay lie in an alteration in central synaptic cholinergic ~ adrenergic relationships, with a predominant shirt to increased cholinergic activity as the operationally significant pattern. Such interpretations were based on the relationship of high voltage EEG slow wave activity to behavior! change (6, ll, 26) and the blocking of the electrographic and behavioral changes in central anticholinergic agents (21, 3h, 35 hl, ht) and by central synpathonimetics (ha). Heasures of linguistic behavior in structured (7, 31) and unstructured (1h, 29, B-2h) interviews showed characteristic was �- 3 - alterations towards increased denial, minimisation, displacement, stereotypy and repetitiveness, related to the degree of altered brain function (B-Zh). These changes were blocked or reversed by anticholinergic hallucinogens (21, h3). Various perceptual tasks provided indices of behavioral change and were related to the degree of altered brain function. These included the perception of simultaneous tactile stimuli (17), snbedded (Gottschaldt) figures (37, 8-16), and tachistoscopically exposed words (37) and embedded color figures (hl). Sociopsychologic aspects of age, years or education, nativity and degree of stereotypy and sonventionality (measured by California F Scale) were also studied and were related to selection or therapy, duration of hospitalization, diagnosis and treatment response/ in hospitalized patients (15, 36, ho, hS). 2. Neurophysiolegic~Adaptive Hypothesis of Somatic Therapy. Based on these studies, a hypothesis of the node of action of other psychiatric therapies such as insulin coma, leucotony and psychotropic drugs, was expressed (10, 33, 38). This view holds that these therapies are also methods of inducing varying states or altered brain function, in which varying adaptive patterns may become prominent. The adaptive pattern is viewed as dependent upon the type, degree and duration of altered brain function, the personality of the subject, and tolerances and expectations of the environment. Examination of this hypothesis as applied to drug therapies is now in progress, supported by USPRS grants HI-2092 and HI-2715. �Insulin Coma Therapz. in initial case description (3) showed the significance of denial patterns and persistent altered brain function to the behavioral change in this form of therapy. In an insulin cons - chlorpronazine control study (27), no differences in hospital improvement ratings were observed in the two treatment groups. Chlorpronazine was safer, easier to administer, permitted continued adninistration and allowed for greater degrees of concurrent relationship therapy than insulin coma. These observations led to a replacement of insulin come 3. by psychotropic drugs in h. this institution. Pharmacotherapz. Also derived from these hypotheses is the ongoing program in evaluating various psychopharnaceuticals. Electrographic and linguistic analyses of effects of acute intravenous administration and chronic clinical administration of various are in progress. EEG patterns, along such continua as synchronisation~desynchronisstion, and frequency shift are being related to behavioral (21, 3h, bl, ha) and linguistic changes (21, h3); The neurophysiologic basis of experimentally induced hallucinogenic states have also been interpreted as an alteration in synaptic chemical relations, such that the effective levels of cholinergic activity is decreased (h2). Initial work on this hypothesis ( ) is now being expanded. new compounds �.32.. In addition to these phenomena, other patterns of language and non- verbal aspects of behavior have been observed which can also be understood as symbolic forms of adaptation to illness. These include the syntactical use of the second and third person, changes in mood, withdrawal and selective inatten- tion, and alterations in sexual behavior (6). in enduring fashion in patelectroencephalographic records indicated diffuse cere- These types of behavior have been observed ients whose lesions and bral dysfunction; In patients with brain damage who did not Show delusional denial and disorientation on ordinary clinical examination, the phenomena might be elicited in sodium. an interview following the intravenous administration of amytal This observation furnished the basis for the ”amytal test" for brain disease in which the persistence of certain patterns of denial and disorient- ation is considered an indication of cerebral dysfunction (h,5). In considering further the relationship between brain damage and the mechanism of denial it has been demonstrated that the premorbid personality important in determining what type of symbolic adaptation occurred. Thus, was pat- ients with the most striking and enduring manifestations of anosognosia were those who had habitually used verbal denial and rationalization as a means of coping with On their problems (10). the basis of these observations the hypothesis was developed that the of creation the convulsions in induced lay of action electrically therapeutic a milieu of brain function in which the patient might express his problems in symbolic fashion, particularly in the form of explicitly denying them. A case reported in which a patient received electroshock treatment in an attempt to relieve intractable pain associated with a Spinal cord tumor (11). After was a number of treatments, coincident with the appearance of disorientation for state, the patient dennot clinically apparent they a place and time, paraphasic misnaming and a euphoric ied pain. ‘dhen these associated.phenomena were � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Relation Between Altered Brain Function and Denial in Electroshock Therapy (research), 1955-1959 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-2-002 Date A point or period of time associated with an event in the lifecycle of the resource 1955-1959 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence: research with Robert L. Kahn, and Edwin A. Weinstein Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/4e44a5022aa24b8167f7810c1ba666eb.pdf 6c8bb654be03cc6faa66ea6f3e6b84ab PDF Text Text ��mm“mh«f.~«»-MM ��Patients with High Delta Activitv during Second, Third Weeks of ﬁeatmnt. Clinical Katina EEG Delta Both High High One None [ﬁramwr - high Moderatelz Imgroved Unimproved Much ImEroved (18) 12 (67%) h (22%) 2 (11%) (16) h (25%) 8 (50%) h (25%) ('20) 6 (30%) 7 (35%) 7 7mm] - (35¢ ��Clinical Ratings Cogpared to EEG and Amobarbital Test Results much Improved High Delta and Positive Amobarbital (29) Either High Delta or Amobarbital (26) Positive Neither High Delta nor Positive Amobarbital (36) [arm - x7414] Moderately Improved Uhimproved 25 3 1 10 ll 5 5 10 21 �and Ruth. Mt: M (29) man: or mum Mu ('16) mm may am: at num- Etc: man Mm mg: (36) �mm. (29) min: mm: W mu a:- mum - Mus m! “WW“! (3% �EEG Delta - Amobarbital Test Delta Activity; Records Middle Low High EEG Amobarbital Test Positive Negative [ﬁﬂ'ﬁ/ - Ifxg' (15) (346) 29 8 8 10 16 20 �(cast rbi Positive (’35) , (M) negative ,.. ! i ,‘ [I \ . I A ’ H' -,‘ I x ‘\\| x\.‘. \ x K i r ‘ 1 (j. ‘\ ; 1 I z E 10 16 20 ��A.m..‘+l__-.A_MA;.“__ A... < �; a M ��uhL—JCICHXU m I Prepared by “MS WEEK IN CHICAGG {DE—JD C) {SINH “ﬁg“ “UL—:X‘Cl A W «LE .00 N ��MURRAY 11an 8-2077 S. F. KURZER VICE-PRESIDENT IN CHARGE OF SALES GRUNE 8: STRATTON MEDICAL PUBLISHERS 381 FOURTH AVENUE NEW YORK 16. N. Y. ��M Merri/ébﬂ M HOTEL WILLIAM HENNING RUBIN PRESIDENT FAMOUS FOR THE "5"" OZMMMC ' — CHICAGO JOHN B. GRANDE GENERAL MANAGER WHERE FAMOUS PEOPLE EAT ��ESRA No. 37 1957 Program -1- ELECTROSHOCK RESEARCH ASSOCIATION SCIENTIFIC SESSION- Thirteenth Annual Meeting Sunday, May 12, 1957 Hotel Morrison Chicago, Illinois Chairman: Ernest B. Parsons, M.D., Pres. Cotillion Room A.MJﬁ: 9:00 Registration \v 9:30 A.M.' 1. 9:45 10:00 2. 3. rNeurophysiology Studies of EEG change with EST with or without Atropine in Man and Rat. Tetsuo Fukuda, M.D., John A. Stern, Ph.D., George A. Ulett, Ph.D., M.D. Discussion opened by: Bernard L. Pacella, M.D. . A.M. A.M. . 15A X/ MIL u 10: Mm" “2?? 30 W1? A. M. Psychological Aspects Personality Factors affecting Clinical Responses to Electroshock Therapy. Robert L. Kahn, Ph.D., Max Fink, M. D. An Evaluation of the Peculiar Selective Quality of Pos Electrotherapy Amnesia. Aloysius S. Church, M.D., 5}t Psychopathology of Electroshock Therapy. W“ ,,. 10:h5 A.M. Bernard L. Pacella, Discussion of 2, 3, 5. 11:15 A.M. Technigues Current Patterns in Cerebral Electro-Therapy. 6. 11:30 A.M. l1:45 A.M. M.D. & 4 opened by: Leo Alexander, M.D. Gerhard Hirschfeld, M.D. Further Studies on the Analeptic Action of Peripheral Electrical Stimulation in Hypoglycemic Coma. Charles H. Jones, M.D. Discussion of 5 and 6 opened by: William L. Holt, M.D. R. Embassy Room P 12:30 to 2: 30 PM 105/” Annual Luncheon and Business Meeting. �' -1- EJJ .. » .u ..., 111'. .j,. . . 4 . ,.‘... ,, - . v 7. ‘ 6‘ r: . . -. - ....£x~ ~ . .“- . .." ' ‘ . -. ‘ ;-‘ . ' . ,.. ... ' -. : I , .-. ..‘ d.I ’ "x - s 1' .- ., L «i=2» '_ " . . f‘: .1)- 1'! 1 ~ I \ WOV'.J“%£M{1A .. ‘ t 4. '- .' . :- .- .- \‘J.'\ .r. . ‘ :' ..:.'.-.3 .~... .. .. ”-0.“.-. : . ' . n}. I . . -,-.L z .‘ ' . 1‘ ' . ‘ ‘ . 5“ma...— ’ ‘I ‘ - -- ‘ ' " ' . . �ESRA No. 37 Cotillion 1957 Program -2- Room 7. 2:30 P.M. 8. 2:45 P.M. 9. 3:00 P.M. 3:30 P.M. 3:#5 P.M. 10. 4:00 P.M. ll #:15 P.M. #:30 P.M. Clinical Aspects Clinical Applicationscﬁ'Nonconvulsive Electro-Cerebral Stimulation. John D. Moriarty, M.D. Indications for Electroconvulsive Treatment in Office Psychiatric Practice. Paul H. Wilcox, M.D. Discussion of 7 and 8 opened by: David J. Impastato, M.D. The Use of Electra-Cerebral Stimulation in Mentally Defective Patients. Harold H. Berman,M.D., Milton ’ Jacobs, M.D., and Joseph Spielman, M.D. Discussion opened by: Charles Buckman, M.D. Drugs and ECT A Comparative Evaluation of the Safety of the Use of Chlorpromazine and Reserpine in Conjunction with Electroshock Therapy: A Review of the Literature and a Clinical Report. David J. Impastato, M.D., Seymour Berg, M.D., Anthony R. Gabriel, M.D. Electroconvulsive Therapy Combined with Chlorpromazine and Reserpine. Frank J. Ayd, Jr., M.D. Discussion of 10 and 11 opened by: Herman C. B. Denber,M.D. ��___.._——.————~—————-————-—————— _m, —-———~———_.———..——————-————-——-——— �mm“. Wm -_ w— _———~——————————_— ! —-——-————-—————__—____.__.._.— p.4— ““—.— __.._._____.. ————————————___——-——____—._— _____ ‘ . __ __ ~ ___.___ .____ ._..._ _ ...___.__._. .— ��w v«w 1. w VW. . ,_ . . wv ﬂ . 9 «x; M“ a? s. ks \ x\ W”. x ‘ \ tn .\n. as .9: ��l L. . x, 93‘1“” nerT/‘wr'y . ‘ V. t i Mm,» ,‘(Z R �rwﬂ‘mrﬂ~“w~&uwwé_é< Wn:~'5~‘~".m . l _ __-. A—e ,...r‘_;..,1... , �PUBLISHED BY INFORMATION SERVICE VOL. 9, NO. 10 OFFICE OF THE MEDICAL DIRECTOR Available to non-members at 35.00 per year. JUNE-AUGUST 1957 (SUMMER EDITION) Dr. Alan Gregg Dies APA Honorary Fellow Dr. Alan Gregg died at his home in Big Sur, California on June 19 at the age of 67. He served as Vice-President, Division of Medical Sciences, Rockefeller Foundation for two decades and in this position of national leadership made psychiatry one of his major interests. Few men have had so profound an effect on the advancement of medical sciences as he. He will be sorely missed by physicians the world over and by psychiatrists most particularly. NINTH MENTAL HOSPITAL INSTITUTE For the ninth year over 400 staff people from all types of mental hospital installations in Canada and the U. S. will come together at the Hotel Cleveland, Cleveland, Ohio, Sept. 30 Oct. 3 to consider common problems and directions of progress. Major topics at this year’s Institute will deal with the problems of the open hospital, revision of commitment laws, management principles, role of private hospitals, mental deficiency as a psychiatric problem and many others. Prof. James L. Hayes, Department of Business Administration, St. Bonaventure University, will deliver the Academic Lecture. The enrollment fee is $50. See program and registration form in Mail Pouch. - All who plan to present papers at the 1958 Annual Meeting in San Francisco please note Form for submitting proposals to the Program Committee in the Mail Pouch this month. NOTICES 1. THE ANNUAL APA DESK APPOINTMENT BOOK FOR 1958 WILL BE OFF THE PRESS THIS SUMMER. USE ORDER BLANK IN THE MAIL POUCH. DEMAND EXCEEDED SUPPLY LAST YEAR. SUGGEST ORDERING PROMPTLY. ($3.00 PER COPY). 2. WE HAVE A FEW HUNDRED COPIES LEFT OF THE BOOK OF SUMMARIES OF SCIENTIFIC PAPERS OF 1957 ANNUAL MEETING, BUT THEY ARE GOING FAST. ($1.00 PER COPY). THE AMERICAN — GRADUATE TRAINING IN PSYCHIATRIC HOSPITAL ADMINISTRATION Two outstanding courses in psychiatric hospital administration are now available and merit the attention of all psychiatrists concerned with advancing professional standards in this area. One is at Columbia University and the other at the Menninger School in Topeka. The Columbia University Course This course, which leads to a Master of Science Degree, is under the auspices of the School of Public Health and Administrative Medicine and the Department of Psychiatry of the Faculty of Medicine. It encompasses basic courses in administration, specialty courses in the Department of Psychiatry, and supervised field work. Recognizing that mental hospitals are hard put to let a staff doctor leave for prolonged periods, Columbia has made every effort to tailor the course to meet candidates’ needs. It extends over 20 months, but ei ht of these are in academic residence broken into four quarters of 2 months each. The preferred plan is for the candidate to spend four months in academic residence, followed by 12 months in a supervised administrative residency or in a position already occupied by the candidate during which time he may carry out a special project. This is followed by a final four months in residence. For candidates who already occupy key administrative posts and who cannot be away for more than one quarter at a time, special arrangements can be made. As for costs, each candidate’s need is likewise evaluated individually. The total tuition for the 8 months of academic residence is $900.00 and Public Health Service stipends are available which will pay this plus ordinary living costs. Frequently, state funds in the state where the candidate works, are available to pay travel costs. There are some openings for the year starting in Sept. Write for details to: Exec. Officer, School of Public Health, Columbia University, 600 W. 168 St., M PSYCHIATRIC . ASSOCIATION Office of Medical Director, I785 Mass. Ave., N.W., Washington 6, D.C. Canada Office, 2I6 W. St. Clair Ave., Toronto 5, Ontario Office of Executive Assistant, I270 Avenue of the Americas, New York 20, N. Y. PLEASE ADDRESS ALL NEWSLETTER COMMUNICATIONS TO OFFICE OF MEDICAL DIRECTOR �The Menninger School of Psychiatric Hospital Administration This School offers a one-year integrated course, leading to a Certificate, which draws on the resources of the Menninger Foundation, Winter V.A. Hosp., and Topeka State Hosp., supplemented by other Kansas state hosps. and schools, an industrial concern, a general hospital, two universities, and several state government agencies. The curriculum consists of didactic instruction in basic administration while clinical experience is provided by systematic rotation in the departments of participating institutions accompanied by seminars with department heads and special projects. With regard to costs, applicants may apply with state sponsorship. The sponsoring state may pay the stipend with the understanding that the applicant will remain in the employ of the state after he completes training. A limited number of stipends at $625 a month are available to unsponsored applicants. The next course starts in September. For full information write to the School, Menninger Foundation, Topeka, necessary. (work on the new home is expected to start this month. Hope is to have it finished by January 1). . Approved setting up separate fund for receiving miscellaneous gifts (such as royalties from publication of lecture series of North Shore Hospital) with proceeds to . be used to add to APA library. . . . Authorized and appointed Committee to work with planning group for the Jamestown Festival this fall which will celebrate Williamsburg State Hospital, the oldest in US. Drs. Zigmond Lebensohn, David Wilson, David Young, and R. Finley Gayle, Jr. are on the Com. with Robert L. Robinson of this office as advisor. . . . Approved contribution of $50 to the National Society for Medical Research. . . . Continued APA membership in the World Congress of Psy- chiatry. . . . Designated Francis J. Braceland as official delegate to the General Assembly of the International Society for the Organization of World Congresses of Psychiatry. . . . Approved in principle proposed constitutional amendment prepared by the District Branch Assembly regarding election to membership in APA through the Branches; and also another proposed amendment incorporating present practices regarding creation and operation of District Branches. . . . Approved recommendation Kansas. of Medical Director to consolidate all central office APA Position services for mental hospitals and to explore ways to Our Association has always insisted that Supts. and finance increased services in this area. . . . Suggested Med. Dirs. of institutions for the mentally ill should be appointments of APA representatives as follows: Dr. Frank J. Curran to World Federation of Mental Health psychiatrists. In doing so, however, it rec0gnizes the need for special training in administration for those who meeting in Copenhagen; Herman C. B. Denber to Congres de Medecins Alienistes et Neurologistes de France et wish to qualify for these positions. des Pays de Langue Francaise at Lyon, France; Rudolph The courses described above have been established with the encouragement and support of the Committee on C. Novick to Advisory Com. of National Congress of Certification of Mental Hospital Administrators. Only a Parents and Teachers. (These appointments were made handful of psychiatrists have completed them thus far. by President Solomon). . . . Recommended to Council The courses are expensive for the sponsoring agencies to reappointment of Dr. Henry Brosin to the American Board of Psychiatry and Neurology. . . . Directed that problem offer and experienced persons have put great effort into of improving dental care in mental hospitals be explored at curriculum development. Commissioners, superintendents, and others in admin- next Mental Hospital Institute. . . . Received announceistrative positions, as well as those who aspire to these ment of retirement of Dr. Frederick L. McDaniel as CIB positions, would do well to give serious thought to sign- inspector and expressed appreciation for his services over five years. . . . Changed dates for fall Council meeting to ing up for these courses. Available financial support should be an encouraging factor. November 23-24 (Sat.-Sun.) in Boston, Massachusetts. . . . Selected Saturday, October 26, as date for next meeting of NIMH GETS $4 MILLION INCREASE: The US ConngS}. has voted $39,217,000 for the Nat. Inst. of M. H. under/h" Robert Felix’ direction. This is $4 million more than/ last year—remarkable in view of general economy dri e. Testimony of Dr. Braceland for the APA and Mike Go of National Committee Against Mental Illness played i portant part in explaining need for additional monies in these areas to the Senate and House Committees. Senator Lister Hill and Representative John F ogarty, always strong supporters of mental health, spearheaded the effort to get the appropriations through Congress. EXECUTIVE COMMITTEE ACTIONS them \ O A pilot training and research program stressing the interrelations of biological and physical sciences as key to better understanding of the nervous system and human behavior has been set up at Albert Einstein Coll. of Medicine, Yeshiva Univ., (Eastchester Rd. and Morris Park Ave., N.Y.C. 61) with a $1,700,000 grant from the Nat. Inst. of M.H. There is provision for 36 pre- and st-doctoral fellowships. The grant covers a six-year d. Write to Labe Scheinberg, M.D., Dept of Mediher details. ° FALL COMMITTEE MEETINGS: Woodner Hotel, WashThe Exec. Com. met at the APA Central Offices June ington, D. C. The following Committees will meet all 29. (Unusual and pleasant feature was that most of the day on Friday and Saturday, Oct. 25-26: Standing Coms. APA staff members attended to become better acquainted on Technical and Community Aspects and Professional with the Com. members and general affairs of the AssoStandards. Also Standing Coms. on Budget, Ethics, ciation.) Among other things, the Com.: With regard to Program and Nominations. Ad Hoc Coms. will meet only financing remodeling of new home, delayed taking out any on request of the Chairmen and with clearance of the mortgage unless and until expenditures appear to make it Coordinating Com. Chairman to whom they are assigned. . �~\ The Council this year will not meet to receive Committee reports until November 23-24, but the Executive Com. will meet with the other Coms. on Sat., Oct. 26. Canadian Mental Hospital Institute Plans for the first Canadian Institute are shaping up nicely. It will be held at the King Edward-Sheraton Hotel in Toronto, Jan. 20-24, under joint auspices of APA and the Canadian Psychiatric Assn. This Institute will be patterned after the U.S. meetings. Major theme will be “The Mental Hospital and the Changing Community," Dr. Mary Jackson is Chm. of the Program Com. with Drs. C. Buck, W. Boothroyd, J. Griffin, J. Hagan, A. Miller, D. Lewis, and Drs. C. Roberts and J.Gilbert of the M.H. Section, Dept. Nat. Health and Welfare as advisors. Since it will have a clinical orientation, this first Canadian Institute is planned for psychiatrists in senior posts in all types of Canadian mental hospitals and for the administrators of Federal and Provincial mental hospital systems. More details in the fall. New Printing of Glossary With the first printing of 30,000 copies of A Psychi- ASSEMBLY OF D,B, NOTES . . . .Met May 13-14 during Annual Meeting. . . . Installed following officers for 1957-58: David C. Wilson, Speaker; Walter H. Obenauf, Deputy Speaker; John R. Saunders, Recorder; Policy Com., (Area I) Albert M. Biele, Frank P. Pignataro (Alt.); (II) Lester E. Shapiro, Ulysses SchutZer (Alt.); (III) J.G.N. Cushing, Edward H. Williams (Alt.); (IV) James L. Sagebiel, G. Wilse Robinson (Alt.); (V) Alfred Auerback, Edward G. Billings (Alt.). . . . Volunteered to assist Med. Dir. in obtaining accurate information to publish obituary notices in Newsletter. . . . Revised Procedural Code. . . . Suggested Council action to seek extension of MEDICARE program. . . . Commended Dr. Wilson for Assembly exhibit at Annual Mtg. . . . Decided to study inspection of psychiatric facilities and depts. of psychiatry in gen. hosps., and facilities of public mental hosps. . . . Submitted two proposed Constitutional amendments for consideration by Council. . . . Will investigate planning of Divisional Meetings. . . . Scheduled next mtg. for May 12-13, 1958 at St. Francis Hotel, San Francisco. PERSONALS. . . S. Spafford Ackerly was honored by a atric Glossary exhausted, a new printing of 22,000 copies Testimonial Dinner on June 19 in recognition of his 25is now available. A limited number of copies have been year contribution to psychiatric education and community health in Louisville and Kentucky. . . . Paul V. Lemkau made up with a hard-cover library binding for libraries has returned to Johns Hopkins Univ. as Prof. of and others who would like it in more durable format. The Public Health Admin. (mental health) at School of Hyhard-cover copies have no cover design—merely the 8: Public Health following a 2-year leave of giene of title the book. They sell for $2 per copy. The paperbound edition remains at $1 per copy. Order from Mental absence. . . . Baruch Silverman was presented a Canadian Mental Health Award on Apr. 17 in recognition of “his Health Materials Center, 1790 Broadway, N.Y. 19, N.Y. outstanding contribution to the mental health of the CaDid you know that the following Isaac Ray Award nadian people,” . . . Alan D. Miller, Dir. of MH Study Lectures had been published and are available through Center of Nat'l Institute of Mental Health, was transferred to England on June 18 for advanced study and reany bookstore? The Psychiatrist and the Law, byL Overholser, 1953; Psychology of the Criminal Act and search. Stanley F. Yolles has succeeded Dr.Miller as Punishment, G. Zilboorg, 1954; The Guilty Mind: PsyDir. of the Center. . . . Major admin. appointments in N.Y. chiatry and the Law of Homicide, by judge John Biggs State on July 1 were: Arthur G. Rodgers (LF) as Dir. of Syracuse State School; Ulysses SchutZer as Dir. of Jr., 1955 (all these by Harcourt Brace 8: Co.); and The Urge to Punish, H. Weihofen, 1956 by Farrar-Straus and Binghamton 8. Hosp.; Charles Greenberg as Senior Dir. Cudahy. The latter publisher will also publish the of Rome State School; and William C. lohnston as Dir. lectures by Dr. Philip 9. Roche given at the Univ. of of Craig Colony. . . . Franz j. Kallmann received an Michigan this year. honorary medical degree as one of 6 scientists in differfields honored ent Third so Int'l Congress of Medical at The General Practitioner Education Project now operQ Arts, Turin, Italy during 1-9. June program, . . .17; from the Office Central E. ating (Charles Goshen, Projand Gantt Harold Horsley Rosen were Visiting Professors would information about psychi- for ect Director) appreciate 2 weeks this spring at Univ. of Arkansas Dept. of atric courses for GPs now in planning stage. It is sugDon D. Psychiatry. . . . Jackson appointed Asst. Clin. gested that when a course is being planned effort should Prof. of Stanford Univ. Med. School and Psychiatry at be made to have it approved for credit by the Amer. elected of Pres. Mid-Peninsula Psychiatric Soc. . . . of Acad. General Practice (through its local or state William H. Kelly has accepted position of Asst. Dir. of branches) as inducement to attendance. Dr. Goshen of Mental Health and Head of Mental Hygiene Div. Dept. will be glad to assist in publicizing such courses. for State of Michigan. 0 The Smith, Kline and French Foundation Fellowship NEW PRESIDENTS 8: SECRETARIES . . . Ark. D. 8.: Committee awarded 19 new Fellowships in May. 13 of Robert G. Carnahan & Leroy D. Lamm. . . . Cent. Calif. them will enable medical students to participate in reWilliam S. Fife & Arnold Sheuerman, Jr. . . . N_o. D.B.: search and training programs this summer. Among other Calif. P. Soc.: Thomas A. Gonda 8: Maleta Jo Boatman. Fellowships announced, one doctor will study research . . . .Kings County (N.Y.) D.B.: Morton H. Hand 8: organization at Boston Psychopathic Hosp., another will Abbott Lippman. . . . Hawaii P. Soc.: Robert A. Kimtake a Master’s degree in public health, and two lecture- mich 8; Robert S. Spencer. . . . Md. D.B.: Leo Kanner & ship programs will be established. Applications for Charles Ward. . . . No. Pacific D.B.: Herman A. Dickel consideration in October this year should be submitted 8r D.E. Alcom. . . . Quebec D.B.: Graham 8; Taylor 16. and Information forms by September application may Henry Kravitz. . . NP Soc. of Va.: Thomas F. Coates, . be obtained from the Fellowship Committee, Box 7929, & W.D. Buxton. . . . Washington P. Soc.: Seymour Jr. J. Philadelphia, Pa. Rosenberg & Marvin L. Adland. . . . Del. P. Soc.: George I �DeCherney 81 Walter Davis. . . . East Bay P. Assn.: Louis B. Boyer & Marion E. Roudebush. . . . Long Island P. Soc.: Edgar D. Congdon 8: Harry H. Gonda. . Milwaukee NP Soc.: David Cleveland 8: Edward C. Schmidt. . . . No. Pacific Soc. of N&P: D.E. Alcorn & Robert M. Rankin. of P. at the Univ. of Miss. under Floyd Moore and Oscar Hubbard. Also visited State Hosp. at Whitfield where . Wm. L. Jaquith and John Head have built up a fine program since 1949. They have a high patient turnover now and a new building for maximum security patients especially worth seeing. Also renewed acquaintance with Beverly Smith and Willard Waldron in Jackson. . . . On BRIEFS. . . . All who attend the World Congress in Sept. June 21 went to NY to speak to Bd. of Directors of will be glad to hear that Nat’l Committee Against N.A.M.H. APA members present were Hon. Fellow Mrs. Mental Illness, Inc. has (through APA) made funds availHenry Ittleson, Walter Baer, G.S. Stevenson, Jules able for simultaneous translation of papers. . . . Herman Coleman, Marion Kenworthy and Paul Lemkau. Was B. Snow, Supt. of St. Lawrence State Hosp. in NYS, pleased by much support from the floor for closer ties writes that 90% of his patients are in open wards exand strong Support for APA’s programs. . . . On June 28 cept at night. . . . Iago Galdston, Chm. of Com. on Int. joined Ewen Cameron’s Com. in Boston on future planRels., has sent over 100 copies of the Summaries of ning for the CIB in Pres. Solomon’s office. Drs. BarteAnnual Meeting Papers to colleagues abroad. . . . I have meier, Ewalt, Braceland, and Yerbury also there. . . . prepared a little pamphlet about my favorite vacation Flew back to Washington to meet with Joseph Barrett on haunt called ”Day Sailing and Cruising in Mahone Bay, planning for celebration of opening of Williamsburg N.S.” and I’ll send you a copy if you write. . . . Chas. State Hosp. (1773) in conjunction with Jamestown FestiBush and David Gaede are inspecting hosps. in Mich., val this October. . . . After the Exec. Com. mtg. Pres. having just finished up in Mo. Hope to start in NYS in Solomon and I flew to Nashville to participate in dedicaa few weeks. . . . Warren Johnson, my asst., recently tion of magnificent new admission and treatment building conferred with Cyril Ruilmann, F. Williams, and O. S. at Central State Hospital named after the Supt. O. S. Hauk in Nashville on psychology legislation in Tenn. . . Hauk. Wm. S. McCullagh, Pres. of the So. Psychiatric Smith, Kline & French Labs. have just granted $10,000 Assn. and Frank Luton also were among the speakers. to the Nat. Acad. of Relig. and Psychiatry for fellowAsst. Supt. White presided and Cyril Ruilmann introships for clergymen who want to become mental hospital duced the speakers. Gov. Clement gave the main chaplains (there are over 300,000 clergymen in the address. The Tenn. program has improved remarkably in country). . . . Sorry to hear of the death in June of Miss the past two years. . . . Forgot to mention last month that Dorothy Clark who rendered such valuable service as in course of Mental Health Week speaking tour I particiAPA Nursing Consultant from 1949-1951. . . . Write to pated in inspiring award ceremony for employees at St. Dr. Leo Alexander for details about the fifth Annual Louis State Hosp. where over 700 have served for 10-25 Institute of Psychiatric Treatment to be held in Philaof Nurses Dirs. his Kohler, Supt. Congratulated years. delphia Oct. 17-19. . . . A lady reporter at the Ann.Mtg. and Volunteers who organized the program. . . . Mike in Chicago was overheard to say, "Next to the White Gorman and I had stimulating talk with Robert Felix and House crowd this is the nicest group I’ve met.” . . . . Seymour Vestermark recently concerning NIMH programs Chas. Goshen and I attended meeting of APA Liaison in coming year which will be expanded with increased Com. with Amer. Acad. of General Practice in NYC to appropriations. . . . Also attended meeting of Wyoming discuss Gen. Practitioner Educ. Project. (R.Matthews, Valley M.H. Soc. in Scranton, Pa. where I met APA Chm., Frank Luton, Phineas Sparer, and Merritt Foster members Robert C. Murphy and Emlyn T. Davies. . . . were there for APA)....On June 6 spoke at Ann. Mtg. of Received notice this month that NIMH Advisory Council the M.H. Soc. in N.J. and on the 10th at the opening had turned down our application for renewing M. H. session of the M.H. Institute at Lansing, Mich. where Architecture Study grant; but funds are available to V. A. Stehman had brought in representatives of all Mich. continue it to end of and in meantime effort will be year hospitals. It was an outstanding meeting well attended. made to find other ways of keeping it going. . . . Expect . . . Went from Lansing to Battle Creek with E.F. Jones, to be off to Mahone Bay, Nova Scotia by end of month for Mgr. of VA Hosp. there, and showed his staff pictures of a few weeks of sailing and loitering. . . . Happy vacationforeign hospitals. . . . Did same thing for residents at ing to you all. . . . The next Newsletter will be in Sept.... Ray Waggoner’s Institute in Ann Arbor a few days later where also talked with Moses F rohlich who (as Chm. of Com. on Nomenclature) is hard at work on system for recording case data on IBM cards. . . .With Robert L. Robinson met in Toronto with Program Com. for Canadian Mental Hosp. Institute to finalize details on June 21 and was also able to visit Homewood Sanitarium at Director Medical Guelph (A.L. MacKinnon, Dir.) where the Ontario Psychiatric Soc. was meeting on the 22nd. . . . Also recently spent several days in Conn. with Chas. Bush where we consulted with the Governor on the mental health prohas Blasko that reJohn there. to Sorry report gram signed the Conn. Commissionership for another job; but P.S. Don’t forget to order of the Desk 1958 copies your his efforts to have the law changed to give the Commisand Book of Summaries the the (33) Appointment have been successsioner more administrative authority Scientific before the (81) Papers supply runs out. the 19 On Dept. visited expanding rapidly ful. . . . June ��WV-..— -»——————. ———_,—_a—.__.._—_,-__ ._________, __._ —_________.___._. _ __ .__- .__.__._. _____... —*_ ��October, 1956 vs Age EST # 1 & 2 - h Below 115 us yrs. over Changes - Reiter - £9 pts. 6 7 H L M 5 S 8 (id—ﬂ) 7 3 10 (50%) 13 5 10 (35%) 6 h 19 (65%) L yrs 50 over yrs 8: Distribution Age — H M 8 h 16 (57%) 12 3 6 (28%) 5 3 13 (61%) - EST 1 & 2 patients h9 5 3 31 - [10 yrs. 1 3 I41 - SOyI‘S. ll yrs. over - 6 5 10 2 3 Reiter vs Medcraft - .ii:;.L_ Reiter (EST # 2) H 12 (h8%) yrs. yrs M 7 30 & L 6 - 61 H 7-2 20 51 " 60 9 M h-6 Below 50 - L yrs. & EEG 25 Medcraft (EST # 3) 16 ptS. pts. LWC - h all ages 6 _Z_:_2_ L M H L M H 11 5 9 7 3 15 2 5 9 1 6 9 �Beiter vs Medcraft h Reiter (EST # 2) ‘17 Medcraft (EST # 3) CONCLUSION: 9 M pts. 8 3 Pts. 2 1 all ages and at h—é and at 7-9, xrs. from left to right. - over - 7 9 L M H 6 h 2 11 6 1 3 5 H older group only) whereas with Reiter Medcraft produces maximal change early in treatment and in changes & 6 L Both groups ( same - MS % it H records with.Medcraft increases. Therefore later changes consist only ��95 (I M hWé/Mv/ém W W/f 44’me Wm" PHI/M41; be M 52/15 ’4 gal/ﬁe): MM) 686cm; Mwwﬁﬁw ��\. \ Séwrﬁ‘sax «wk? '».,_ *Mﬁw'yr-Ea ”138:3? ‘ ��4‘ .' .ﬂu/W aw ' , . b; Izaak?“ wumad, W ’ 147? Xv 520’? ��Ti? V 1‘ s: I. 7:. V Z 1 - \_ rm . 111374;? : 7'“: _ ‘ " - . > v, ‘ y; ’ * Winn-n35 "W" ______ r - “22:! ‘ - -——~‘——‘ . ‘ ~ ' . ‘ ’ ' ‘ ‘ ( ‘ ‘ . I J ‘ 7 ‘ I v ' - ' V n I l ' ¥ ‘ ‘- ��', ’03. Alll‘llll �. ,7 — v Q ,.. r. ‘ _ T TrK. u _ ,.., . V, 9.. 1 , . ., a ‘ ,_. ‘ w, w . n 5 . . , . . i .A . :i.» ,. ...L. I, ( :4 . , ,. . < 5,: _. . . . . z .,. "“ ; .; 'n’hr ' ‘ 1 V 13—, ., awh'A_ “,1 “1.“..«2 , ‘ n .‘ r r 1 . . .a . _ _ ‘ ._ u... , a, h J _, N ‘ '5 _, ‘ v F :. , 'v h, .7 . ‘ 4‘;- _‘ , . x; x , .31.. , u . . . , .. ,2 .. _ "1 , A . ..a h .u '. A ... . i , , . N m. u . 1 , J 1-: I :. r. , , ‘ r ._ ; . . . . .ﬁ . . , rJ . :., I ‘ V, sv,._______-_._..:_:>..7;_.;_T t.« n—' n a. r r , :J: I. I; » .n .= . . II\ ' ' J any. ‘_.‘ , 2 Mr .7 . _ . .3 ‘l ,_ g» ..‘ I .a‘ . ,~ L, m .H _ J ,V , --.,-_.' r, 7 , n .T» . 1 H . — , . ”37:-.." \.L. \I Z" W“ ‘ K A [“97 '. .1:..." , .u: ._, Nu L x; ' ,- , . .. a w H _ H _ _. .,. . . .> . 7 wm _, . . . ., l , ,.. ., ,. . m "W”. 5,2 , , ' .3 1 ., . j A . g ‘ ., i. .. . ‘ V.,, Hutu” ﬂ A, 1 ��.g.W- an}, , 3 ‘ \——r —- --m I-L I I I I ' Mr n/f r? l' 2, 7 6 1 ‘. é ' / ./ o -’ I ' _» ’ //,,../ ’ ‘ , * Q 3 5* �W INDIVIDUAL PSYCHIATRIC TREATMENT INDICATIONS Paul H. Wilcox, M.D. Revised Nov. 21, 1953 Li PREDOMINANTLY NEUROTIC if and Org., B.P., F, otherwise IF start Nm, Ag, 3, 0-0, G, HqA, with Sequence Ir, Un, Of, or Par, start with Sequence I III PREDOMINANTLY SCHIZOPHRENIC if and D or Ag, otherwise I5 (Psychosomatic symptOms, anxiety or reactive depression) start start with with Sequence Sequence I PREDOMINANTLY ENDOGENOUS DEPRESSION start with Sequence Sequence Sequence I Sequence E.S.nc. II III Sequence IV E.C.T. COznc. 002 II \/, \ \ ___, 4______e 93 MANIC _, COznc. ___, E.C.T. ___, ___, low E.C.T. 1: Eu if Tr ______+ 602 \ifD ._____, II ifC 1:0 if c __, if t _____, if 'r _, ___, (III) (for termination of trance) 002m. (II) \<: (III) high E.C.T. C02 (IV) E.S.nc. (I) E.S.nc. (I) ifT if t plus 0...? terminate D if _____, E.C.T. (II) Note: Appropriate psychotherapy should accompany all phases of treatment wherever indicated. The goal of therapy is for the patient to have a mild 002 reaction (t) and be essentially symptom-free (O) for an observation period of at least two months. £21 - anxiety increasing Ag - agitation B.P. - systolic B.P. over 170 mm. Hg., systolic c - brief confusion (e.g. only 5 min.) C - prolonged confusion (e.g. more than AS min.) Cf - clinical confusion coznc. - non-coma 002 (whiffs) C02 - coma 002 D - persisting or increasing depression E.S.nc. - non—convulsive electrostimulation E.C.T. - electroconvulsive therapy Eu - euphoria F - marked fear and anxiety A H-A G Ir - Nm 0 — - severe guilt feelings - marked hate and aggressive tendencies marked irritability severe nightmares symptompfree - for 2 mos. or more obsessive-compulsive features Org. - organic changes Par. - paranoid trends O-C s - sleepless tT - mild tension - mounting tension Tr - prolonged trance state Un - unreality feelings ��52 m - �MAX F'INK. M. D. 275 MIDDLE NECK ROAD GREAT NECK. N. Y. HUNTER 7-4542 \; . :\ \ \ . w . .\\\ a h {zitgiisézirié \ ,5:11:15rfie1 v, flhhugavwx.§.1 at»; J. 3.11.. , _ if NDD‘ $5.. . J 3.25.1.5 4.51 1. $313 £511:er “V :2 1! ��a M.“ .7 �-7 r. v my .‘__r,\~. ‘_,_ an" .7 ”amt , 0, .7.— ..w . x 7 , ,...r,_ ‘_— v-4 . . ,_ w “K- mﬂ.w~..—-~_‘nr—._;_i , _ 7 _ 7V -_.-N,...~ . 1,-.. ~..~._.V..,.v .,_‘,.r_._h., V . if"? ��mw "">‘- aw ﬁn ’4_l4 I; Ant“ . ��4...»... ”Mu-L" ��Ft: £13 3"! HM (M) ��i 3 i E .1 i ��. _ a-‘v—{WWG’W’W‘tVF‘r‘Fw—ugfva , WNW—“W “WW. _ , . , . , ‘ W. . , _. ,' , ‘ A,.V,.. 3m, .zwu -..m~w~ W «RM-4mm "F v :i‘\ @ﬁ - A» \\\ 'l ‘3“ l." ..,. ‘ “ \.§;‘.§g was. wig-33;; __ ‘ ' _ ‘ A Em ' axis: .3, ��(L ALLA 4 4T ��;; i ��For creative activity, as possibly, for problem solving, the hyperh alert state must be avoided. In the alerted individual, discrimination is more focused, acute, and differences are sharply maintained. Under such conditions, old pathways are clearly maintained and the possibility of new associations is less. For creative work, pathways must be connected ected before. This can only be accomplished were not con; discrimination is diminished. reverie; by fatigue (creativity late at night); by isolation; by alcohol; etc. Perhaps in the EST situation, the cerebral state induced This ? is if that done by is similar to drowsiness (Surely the EEG - perceptual effects are similar) patient is able to use ("create") available before. and thus the new defenses which were not Also, in the tachistoscopic situation, the presentation is a hyperalerting situation - but, the reverie state (or dream) afterwards, permits of greater elaboration of the memories (greater range of imagery - greater creativity,). I/e3ﬂd �January 7, 1957 Role of Altered Cerebral Motion in Behavioral Change Following Induced convulsions m m, 14.9., Babe” In M; 31.3. m Hm Karin, 31.1). role of altered consciousness in the clinical behavior of epileptioe, patients with mental disorders, and in the diagnosis: of dis-orders of the central nervous system is unclear. Recent studies of the electroshook therapy process amonamtcd the crucial nature of persist.ent alteration in brain fxmction for the behavioral changes induced. In the course of theee studies, an appreoietion was obtained of the types of alteration in behevior induced 120' diffuse cerebral dysfunction; the role of the pmoz‘bid personality in the behavioral pattern; and the smith. 1w of various tests on indiooe of altered brain function. To define and measure the effeotc of alteration in consciousness Pmblem """"‘""'"" (manning rm diffuse control dysfunction) on clinical be. havior patter-no. The Kethod: Subjects on a voluntary paychiatric hospital referred for electro— shock therapy were studied concurrently by psychiatric, psychologic and neuroplwciologic techniol. Alteration in brain function (the demo of organic mental I; sycamo- was measured by four indicee: (a) Eleotroenoophalogm, moored for per cent time delta under nesting and activated conditions; (1:) Diaoriontetion, confabulatm-y responses one language changes following intravenous mobarbital. (c) Dininution in perceptual discrimination of simultaneous tactile threshold stimulation touts. (d) Interference with recall of 3 letter words after interpolated looming of nonsense syllables (”retroactive inhibition of recall") . mound by repeated psychiatric intent and reports of therapists and hospital personnel timing 2) Behavioral ohengec were views with subjects; and after the period of therapy. pmorbid percoaolity was eotimted by Cstructured interviews with relatives and by Rorschach tests (scored for H o reopens”). ROM“! 1) Modification of twavior is related to the dogma and persistence of alteration in hrm function, as measured by the electroencephalogram, amobarbital teats and perceptual discrimination teats. 3) The �in! 0' J c‘u pattern at the induced behavioral change, manifested by ahnnges in lmguags, mood, attitudes and symptom, is related to the preamorbid personality structure. Such behavioral patterns as euphoria, donisl, withdrawal, severe wry loss and disorientation, paranoia, WMrzitability and installed musty, have been obsemd. 3) Various indicss or altered cembrsl function have different sensitivities to modification depending upon the extent and activity (recent or old) at the dysfunction, and the personality of the subject. 2) The ’ leusiem 1) Behaviors]. nodii‘icstian in canditims inducing altered brain fanatics is ths adaptive response of tbs argmism under the conditian of an aims-stint: in the state of camcioumss. 2) has type of adaptive response is dependant upon tbs premorbid pemomiity of tbs subject and the milieu in which the behavior occurs. altered brain function mt be interpreted in tons of thsir sensitivity; their time of application in the ongoing process; and the pmrbid persmlity “the subject. This significance of them observations in tha understanding of epilepsy; the treatment. or mental illness; and in medsfinition 5f altered states of consciousness will be dissusssd. 3) Tests 01‘ Iron tbs Heumplwsiolom‘r Laboratory, Department of Fotperimental Psychiatry, Hillside Hospital, Gian Oaks, New Iork, U.8.A. �January 7, 1957 Therapy of Schizophrenia: Effect of Alteration of Brain Function on Behavior In the course of experimental studies of the mechanism of actidn of electroShock therapy in patients with psychiatric disorders, a hypothesis was elaborated regarding the mode of action of other therapies in patients with schizophrenia. 1t has been demonstrated that the essenp a electroshock is in therapy behavioral change to pre-requisite tial EEG defined by function as of brain delta, loss altered sustained degree of discriminatory ability on perceptual tests, and disorientation followThe behavioral response sodium. amobarbital of administration the ing under the conditions of an altered state of nervous system activity is an adaptive response of the subject, dependent on the premorbid person, ality . who and the environment. Similar factors have been demonstrated as operating in patients Show sustained improvement following insulin coma therapy. studies of drug therapies in schizophrenia demonstrate that the therapeutic efficacy of the newer psychopharmacologic agents demonmechanisms which brain are to the degree to related is directly strably altered. Conclusion: The mode of action of the various physiodynamic therapies (ICT, EST, Drug) is directly related to the degree of sustained alteration in brain function induced; such alteration being defined by changes in the resting and activated electroencephalogram, disorientation tests, and perceptual discrimination tests. , Ongoing ��can ﬁrsthand for the pemeption 01‘ words momma anti aubjem were unable to Mantify m wows with increasing degrees at cerebral 3-) Wmotim, We: in percoptim were highly sex-minted with other boo Moral chug”, inﬂiaaﬁve of an alumni interaction with the omirmmt. Minimum 1) Diffuse alter-nuns: in brain mum, as measured by elactrmcaphalomﬁzm 631%: mad emanation tests after mammal, results in altemtiw at pamytm pat-toms by an increase in threshold, impaired Metamucil: of stimuli, of which the ability to diacriminato a rignre from a. comply: backgromxd in a 5min h) ' ma We! ' 2) Alteration in pemepbim mpmanu sweet an m rather than a speciﬁc as? altered behavioral interaction with the envirmnt, Maialogieal defect, This factor sham be considered in peroeptnal 112.20.00.21. brain lemma as will. nudist {51% Ion-k, ”.34: m W; mar”?! �December 17, 1956 Concept of Cerebral Localization vs Mass Action Effects Certain functions ascribed to 1) CNS are "localizable", as vision, motor power, motor aphasia; While others, as memory, judgment, insight, cal- culation, figure—ground, are non-localizable. (more peripheral than central); have marked effects; and EEG damage The is generally first group are cortical permanent; small lesions is usually not pathological. lesions are generally deep or basal; recovery of function is possible; small lesions have no effect (i.e. a mass action law is applicable) and EEG effects are prominent. The non—localizable It results in a non-localizable lesion - with diffuse dysfunction. is the technic par excellence to study such mass action lesions. 2) EST 3) Psychological measure mass tests of "OMS” are positive to the degree that they action effects rather than focal - except if focal dysfunction interferes with performance as in lesions affecting vision, motor power and speech. h) Concept of Active vs Static Lesions: In studies of head injuries, lobotomy and post operative cases of six or more months duration, the studies reflect localizable (cortical) defects mainly: for the deeper activities nd are longer active. Any defects in fun- ction are expressions of specific cortical localizable damage. In contrast, studies of brain tumors, immediate post-traumatic states, post- (early) are studies of active dysfunction - a combination of the focal and the diffuse defects. The degree of dysfunction depends on the mass lobotomy, and EST effect, plus the localized defect. m away. ”cw-u W7»: 6% 2.2 .-W M- ��«M m a» mum at :1“er bum mum the dun» Mariam mum sum and chm a! me: aluminum; m vat-um a! the mmw‘mpu and tho «the submit ammmmm mammmmﬁg mumammnwmmm. Mmumafmw mun Winemwnuwm at them mm“). mm 1»th mm mu with annWtupmhupmrbm uwamwmmwwmm, the Mine of at a act-Latin Wm m by th"W”, WV. the an dwaﬁmt mm mm»: Mum Mow, m W: m that mum and. at my m Mum; torﬁumohanin WWMemlmm meettheu MWMWMWMNW¢ » �(July 2, 1965) Jan. 3, 1958 HOLE OF ACTION OF BIOCHEMICAL AGENTS The CNS is IN BEHAVIOR dependent upon a umber of enzyme systems for cholinestemseand including fmction, mtabolisn proper acetylcholine, gluoose-pkwsphetase, etc. CNS function and, thereby, affect of that agents variety behavior- is large, since processes in equilibrim may be shifted The in either direction by increasing or decreasing the available quantity of a metabolite . A. For drug action, therefore, the following are considerations in potency: (a) Does a drug affect an enzyme system in a reliable it way? to affect the system? (c) What defenses does organism process to block CNS? in action once limit drug's or (b) Can B. Secondly, get to mile (NS an agent may directly affect the metabolism CNS the dependent upon the is extent that to of a specific system, system? Is the defect thw induced simificant for the netsbolism of CNS underlying behavior? that defenses can body cell into play when system is affected to substitute other energy system? Thus, the variation in drug effects in behavior depend upon: (a) Behavior at onset; and predisposition (personality) to response; (b) Drug dosage - availability to has on an enzyme system; CNS and the effect it �(c) Dependence of organism on specific enzyme - and organismic defenses (i.e.,-~ substitution for affected system) . Whether effect was gmdual (allowing for system ((1) defenses, i.-e . , alternate mtabolic system) or acute (not allowing defense). Imividual diffemnma in response may be due, thus, to differences in: (a) Dosage, mtio S mute of Ministmtim (b) dependence on the affected system (c) adaptive ability to biochemical changes. To these clauses, EEG is a gross approximation and indicator, reflecting the homeostatic balmce in various enzym systems of the CNS. ��Personality-O.M.S. Tests of O.M.S. 2-5-57 The All our tests of changes in cerebral function tapas continuum. degree of cerebral dysfunction at the time of examination will determine which tests will The degree of “ show changes in patterns. cerebral dysfunction is dependent on numerous variables including; Rate of develogment of dysfunction Premorbid state of functioning on the tests employed Stress of the examination- needs and motivation of the subject Localization of the cause of the dysfunction (local vs. diffuse) ' factor, the premorbid state of functioning, as characterized the present evaluations of personality organization by the Rorschach One by test and by interviels, graphic fashion; can be pictured as operating in the following ‘ ��V E F E E F E ;‘ ﬁs‘;’*;)¢¢2\ _ a '“ﬁ‘ �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource EEG (notes), 1955-1957 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-3-003 Date A point or period of time associated with an event in the lifecycle of the resource 1955-1957 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence: EEG notes Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/97daec70fcaf9223c3cc93bef9185f48.pdf ea0a277a541fba43d45012096746cae2 PDF Text Text W, ;_ . » _ . ‘g wA .73.- ..g c 7... ._.‘ .v —.—‘.n, we“--- , V ,_ m- V ,7 , v.‘ -,v V. - , — xv- .r f.»--,—- ,.v—.-“.....:v«u..w,amw . .mmng—W (tr/33‘; «waver—u... .Mwm—V w... _ - . Electroshock and in Improvement Charges of Electroencephalographic Relation Therapy * Max Fink, M.D. Robert L. Kahn, Ph. D. This study was undertaken as part of an investigation of the relationship between V ”0.4",“ ., altered brain function to electroshock therapy. Twentyb prior to and at weekly intervals duringanki following the course of treatment. The total of four consecutive patients referred for A. awn-wmw and response 160 records so obtained were age percent time time delta at EST were given EEG'S classified according to five criteria: the aver- delta for three given lead combinations, the highest percent any one lead combination, the slowest delta frequency, the durb ation of the longest bursts and the highest delta amplitude. On the basis of the percentile scores obtained for each factor, the relative position of each record was determined. in the upper third of the distribution were Those considered to have high degree abnormality, while those on the lower third were low degree abnormality. By this method found between improvement and the EEG showed a high degree abnormality after weeks and over 90% after three weeks. of analysis a definite correlation was rating. Of one week of first three had such a record by the fourth week of treatment. for each of the EEG treatment, 80% A factors analyzed separately. week two weeks and only one similar relationship The was findings were con- firmed in a subsequent investigation of 30‘patients in which the tained in the second and third after 25% In the unimproved patients, however, none had a high abnormality record during the found the improved patients, EEG data ob- of treatment were used to prognosticate �nﬁi m\ improvement. It is as determined by concluded that early and persistent altered.brain function, this method, is a necessary prerequisite for improvement after electroshock therapy. * From the Research Service, Hillside HoSpital, Glen Oaks, New York. �sawmm MMW§WM w, VJ'IWWVWMM-ﬂmmﬁmm hula-«ﬁght ﬁwﬁymgmrmwt mm“ Wmmunmwm; W mmummawmmmwwmmm W - ’3 mmmmmmmammmm mummmmmmummm» "$01:me ‘-;:wamaf w*:.mmuumwmm_ m h zwm .»,wmawmmmuwwwm m Eegmuﬂ) , W3¢MW.M: ��WMWWnMﬂmmemW-,' W mmmmwmummwt tmmttnwWmhmhmz-Mnnmhmumtnmw thatmatmm WM” mmmmmt Wanm mummm Mahatma: Wmmmm “ mmmm mum mammmmmm manpmuummmmm,mmmmmm mwmmhm «mmmmmmm mmmwmm ammumthlm mm Wrmmiarmm Wthanntht mmnmm% my were” mmww Mmgmhhu hmwwmm mwmmmmmmwmmmwm WWWmtmrm-rammwww Wag“ mm hm mamwmmmmmmmmmmwm - , - pa. �Relatidn of Electroencephalographic Changes and Improvement in Electroshock Therapy ( 3 M , 7' W41] Fink M .D Robert L: Kahn, Ph.D. Max fir/V v, , .y This' study was undertaken as part of an investigation of the relationship 41/4er between altered brain function and reaponse to I/mt—wju? Twenty-four consecutive ’P—EII‘P patients referred for were given EEG-'5 EST prior to during and following the course of treatment. The .« and at weekly intervals total of . 100 records‘ were classified according to five criteria: the average percent If time delta for 'Mbmﬂavv I three given lead, the highest percent time delta at any one lead; the slowest WM frequency; amplitude, w“ H, mm. W the tame- of the longest On the basis of )‘n. MAJ bursts and the highest 601/9“— percentile scores ob- samba-med ' tained for each factor, the relative position of each record was determineg gose in the upper third of the destribution were considered to have 1 high degree A W MW W“ correlation tau/inc. Ml‘tW/‘au‘ abnormality, By this method of analysis improvement and the FE . after ‘ 1gh’abnorma11ty was found between _ 6f the oniy‘one week of treatment, 80 a er two weeks and over ' g . , A weeks. In the 'mimproved patients, during the A w a marked first c'atrately. The I I was found I I I I loe-ether-kand, g three weeks and only one similar relationship 313 ‘ had. such a each of the $in yw EEG 90% 4’ improved patients after three none had high abnormality record b% the fourth factors as . . 30 ‘ were usedﬁ progn altered bain EEG data obtained in the second and third week of treatment concluded that early and persistent W1 W im«Lu function, as determined by this method, is a necessaryﬂfor provement after electroshock therapy. W MM”- week?” analyzed findings were confined in a subsequent investigation of patients in which the 24’? " � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Relation of Electroencephalographic Changes and Improvement in Electroshock Therapy (research) Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-4-004 Date A point or period of time associated with an event in the lifecycle of the resource 1955 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a>; Kahn, Robert L. Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence: research with Robert L. Kahn Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/d01fea06dd83b521f86d15c567b14a69.pdf 5db07271542a5e11cdde7c401a2c6afa PDF Text Text ��s [.9 227mb, ‘5)04 ..: L M ~17!ou ' m ,1 Z 0 is ,« , 042454 “11“., m «:4 ’ ‘ ,J‘vmw& —!—.‘W_ ��W ﬁfw_“______‘______Wr r M l)CZ¢/vw€u M“ @WLE; $54: W gm . KW C Z’W ‘TN’M 2r 3) am! Vn. Fr‘e—L WW’ Am); Maﬂuﬂ/EW/ �INDEX TO ADVERTISERS _ PAGE AAAS ........................................................ 5, 394, 396, Inside Back Cover American Tobacco Company _____________________________________________________ Back Cover Columbia University Press _____________________________________________________________________ 6 Ford Instrument Company ______________________________________________________________________ 391 International Equipment Company _____________________________________________________ 398 Johnson Research Corporation..--__________--_.____-________________-_.-____; ______________ 5 Macmillan Company _________________________________________________________________________________ 8 Measurements Corporation _____________________________________________________________________ 6 Microcard Foundation _____________________________________________________________________________ 392 Oxford University Press, Inc ________________________________________________________________ 391 Rinehart & Company, Inc ________________________________________________________________________ 394 Ronald Press Company ___________________________________________________________________________ 2 Schwarz Laboratories, Inc ______________________________________________________________________ 4 Ivan Sorvall, Inc ______________________________________________________________________________________ 7 Taconic Farms, Inc __________________________________________________________________________________ 394 University of California Press _______________________________________________________________ 393 University of Chicago Press ___________________________________________________________________ 3 D. Van Nostrand Company, Inc _____________________________________________________________ 395 John Wiley & Sons, Inc .......................................................................... 397 399 ��£32 » . x : ‘ . . . , V ( - 4 ‘ V ‘ ‘ ' . , \ . , - '1' ”:5. .9. ,2; «E a‘ ,7;- 7- \77 ‘- . _ mtg if} m: 34ifv; 5:32;: ;. ‘ , er?” is VF» ‘ﬂh‘flaz: ”r: 91‘;._;.;..,.::_:.»’~~:_V ;‘;,».+~:-.éé ,5». ifp. ,, ..~- .393, - ,_-_».;,-,-« r .- - ' - 2 . . �DEW? 17; 1956 Gamept of Gamma]. Localisaﬁm to Hana Action Effects 1) Certain functionnascribod to CNS are "localiaable", as motor power, motor aphasia; while others, an memory. Judgment, Mm, insight, m1- culation, figure-ground, m nmlocaliuble. The first. greup am aortical (mom pariphemi than antral); damage is generally permanent; will lenient! have maimed exam; and EEG is usually not pathological. lam-vloodiubla lesions are generally deep or basal; mowezy at m:ctim is possible; null lesions have no effect (1w. at mass wtian 1am in The effects are pmﬁnmt. 2) m results in a nonuloealiuble lesion .. with diffuse Mfmcﬁwa is the teahnic gxgalleneo to study such mass whim lesiom‘ applieabla) and It 3) EEG a; Psychological tests ’of ”OW” am positive to the dogma that they measure mass action affect»: ram” than focal - exaept it focal interferes with pexfbmnoe as in lesions meating 75.31011, actor power and mum speech» 1;) Concept of Active vs sum Lesions! In studies of head insulin, lobotom and post. apex-nun me! of an or more mths duration, the atudiaa reflsct 100311111313 (cortical) Meats mainly: for the deeper activities am no lager active“ Any defects in hm» cticm am expresaima of speciﬁc certioal laculinbla W» mtmst, studiee of brain tumors, immediate post-tnmtie statues, post-v 19mm, and EM (early) are stud-m or active dysfunction - a. cambinntim of the focal and the diffuse defeats. m degmo of: dysmnction depends on the ma In offset, plus the localised defect. �J.A.M.A., Dec. 13, 1958 PNEUMOTHORAX—MAURER ET AL. 2014 ination revealed adherence of the fundus and nodules throughout the adnexa. A diagnosis of pelvic endometriosis was made, and on Aug. 18, 1955, total hysterectomy with bilateral salpingo-oophorectomy was performed. The patient’s postoperative recovery was again uneventful. In the four and one-half years after the thoracotomy, the patient has had no recurrent chest symptoms or pneumothorax. Comment Aberrant endometrial islands have been reported in many locations, including the ovaries, uterine ligaments, rectovaginal septum, sigmoid colon, urihernia umbilicus, bladder, laparotomy scars, nary sacs, appendix, vagina, vulva, cervix, lymph glands, and small intestine, and in bizarre locations, such as the upper and lower extremities, lungs, and pleura.l Sampson’s2 original theory of transtubal regurgitation of menstrual blood and endometrial particles, published in his original paper in 1921, could certainly explain the method of implantation of endometrial growths on the pelvic and intraabdominal viscera, as well as on the inferior aspects of either leaf of the diaphragm. The lymphatic and hematogenous dissemination theory of Halban would be necessary to explain distant endometrial implants in the thigh, lung, and pleura.1a Distant spread without passing through the pulmonary capillaries could occur only by way of the vertebral veins or “lung shunts” which have apparently been demonstrated between the pulmonary arteries and veins bypassing the lung capillaries. In view of the concomitant ﬁnding of pelvic endometriosis and the involvement of all layers of the right leaf of the diaphragm, with perforation and supradiaphragmatic seeding demonstrated by thoracotomy, in the present case report, it would seem logical to conclude that the endometrial involvement of the diaphragm must of necessity have occurred as the result of transtubal regurgitation and transperitoneal dissemination. Exact explanation of the method of development of the pneumothorax on the right side is more difficult. However, the clinical observation that all episodes of pneumothorax occurred only during the time of menstruation, and the inability to demonstrate any source of lung leak or primary disorder in the lung which could explain any possible leakage of air into the pleural cavity, would suggest that the recurrent pneumothoraces in the case reported here were the result of erosion and perforation of the right diaphragmatic leaf by endometrial implant and the fa]of the from the of air by uterus way passage lopian tubes into the peritoneal cavity and then by way of the opening in the diaphragm into the pleural cavity, with consequent pneumothorax. Although we are unable to ﬁnd any reports of spontaneous pneumoperitoneum occurring during the menstrual cycle, the practical possibility of this is suggested by the free anatomic communication between the cavity of the uterus with the peritoneal space by way of the fallopian tubes. Practical application of this knowledge is regularly used in the so-called Rubin test for patency of the tubes. During this procedure, carbon dioxide is passed into the uterus and then by way of the tubes into the peritoneal cavity. During the test, patients may experience shoulder pain and present roentgenographic evidence of pneumoperitoneum. Summary Chronic recurring pneumothoraces resulting from erosion of the diaphragm by endometrial implants during periods of menstruation occurred in a young woman. This was surgically corrected by excision of the involved portion of the diaphragm. The un— anticipated ﬁndings encountered at operation in this patient present an additional indication for exploratory thoracotomy in all cases of unexplained, constantly recurring, spontaneous pneumothorax. 827 Union Central Bldg. (Dr. Maurer). References 1. (a) Novak, E., and Novak, E. R.: Textbook of Gyne- cology, ed. 5, Baltimore, Williams & Wilkins Co., 1956, p. 546. (b) Nunn, L. L.: Endometrioma of Thigh, Northwest Med. 48:474—475 (July) 1949. (c) Hartz, P. H.: Occurrence of Decidua-Like Tissue in Lung: Report of Case, Am. J. Clin. Path. 26:48-51 (Jan.) 1956. (d) Hobbs, J. E., and Bortnick, A. H.: Endometriosis of Lungs: Experimental and Clinical Study, Am. J. Obst. & Gynec. 4:832-843 (Nov.) 1940. (e) Nicholson, H.: Endometriosis of Pleura, Thorax 6:75-81 (March) 1951. 2. Sampson, J. A.: Perforating Hemorrhagic (Chocolate) Cysts of Ovary, Arch. Surg. 3:245—323 (Sept) 1921. FUNCTION OF THE BRAIN.-—Any biological view of the function of the brain leads us to an unavoidable conclusion: consciousness is not unique to man, to the primates, or to the mammals: it goes back to the roots of vertebrate history and has been progressively elaborated in content, coloring and complexity roughly in proportion to the evolution of the neuromuscular system. It cannot even be argued that consciousness is a unique vertebrate invention—the crab, the octopus, the butterﬂy, the ant, all possess sensory devices imparting to them the awareness of their world; all demonstrably engage in integrated time-binding, self-serving action, and it must be presumed that all participate in some proportional measures in conscious awareness of themselves and their environment—H. W. Smith, The Philosophic Limitations of Physiology, Perspectives in Physiology, Washington, D. 0, American THE Physiological Society, 1954. �2013 Vol. 168, No. 15 TO DUE PNEUMOTHORAX SPONTANEOUS RECURRING CHRONIC ENDOMETRIOSIS OF THE DIAPHRAGM Elmer R. Maurer, M.D., James A. Schaal, MD. and F. L. Mendez Jr., M.D., Cincinnati Chronic recurring spontaneous pneumothorax is results which disorder usually common relatively a from rupture of subpleural blebs. Endometriosis of the diaphragm, on the other hand, is an exceedingly has be determined, lesion as and, nearly can as rare never been reported in association with, or as a cause of, unilateral recurring pneumothorax. The following case report is presented because of the extreme rarity of the lesion involved and the unusual association of pneumothorax with the menstrual cycle. It is the ﬁrst recorded instance of successful surgical treatment of chronic recurring pneumothorax by excision of a defect in the diaphragm that has resulted from endometriosis. communicated This diameter. in 2 cm. was an aperture freely with the peritoneal cavity. The area of disease in the diaphragm, along with the defect, was widely and completely excised. The consequent diaphragmatic opening was 0. size of cotton, sutures mattress with interrupted repaired Examination of the specimen showed that the disease had involved the complete thickness of the diaphragm. Final inspection of the superior surface of the diaphragm revealed which 1 in diameter, nodule, cm. purplish-red a solitary obviously represented a supradiaphragmatic endometrial implant. This also was completely excised. Following reexpansion of the lung and the placement of an intrapleural catheter for water seal drainage, the chest wall was closed of endometriosis diagnosis was The postoperative in layers. the right leaf of the diaphragm resulting in perforation and Report of a Case A 35-year-old woman was ﬁrst seen in consultation on March 13, 1953, because of pain and dyspnea resulting from a spontaneous pneumothorax on the right side. The patient had had two previous spontaneous pneumothoraces 1952. Nov. 14, occurred ﬁrst on the having the right, on Findings on the general physical examination were negative except for distant breath sounds over the upper right part of the chest and hyperresonance of the percussion note due revealed chest of the Roentgenograms pneumothorax. to a a very minimal pneumothorax (15%) over the extreme apex and the base of the right lung. No emphysematous blebs were apparent in any portion of either lung. Because of the small quantity of air in the chest and the absence of serious thoratube thoracentesis or of air the by removal symptoms, costomy was not thOught to be indicated. The patient was discharged from the hospital for follow-up care by her attending physician. She was again seen in consultation on March 20, 1954, approximately one year after the original examination, because of 12 new episodes of recurrent pneumothorax on the right side. All pneumothoraces were associated with pain and mild dyspnea and had been veriﬁed ﬁrst the chest. For of the examination by roentgenographic 15 all that information the volunteered the patient time, episodes of spontaneous pneumothorax had come during the period of menstruation. The important clinical signiﬁ— time. the at appreciated not observation this of was cance Because of the chronicity of the lesion, open thoracotomy with possible talc poudrage and excision of any blebs that examinaroentgenographic been on have apparent not may tion was recommended. Right thoracotomy on March 31, 1954, revealed a persistent moderate pneumothorax on the right side. Careful examination of all lobes of the right lung revealed no evidence of blebs. Testing of the lung with positive pressure, while saline solution was dripped over the surface, disclosed no points of air-leak. The lung parenchyma grossly presented a normal appearance and consistency. The most re— markable ﬁnding involved the right diaphragm. Near the point of emergence of the inferior vena cava and extending radially and laterally in the central portion of the right leaf of the diaphragm was a circumscribed, oval-shaped area of attenuation which measured 4 by 3 cm. in diameter. Numersurface. this modulations on apparent were purplish-red ous In the central portion of the diseased area in the diaphragm Photomicrograph of excised lesion, showing, endometrial stroma and glands extending through ﬁbromuscular structure of diaphragm. implant of endometrial nodules on the intrathoracic surface of the diaphragm. Microscopic examination of the surgical specimen showed extensive involvement of the ﬁbromuscular stroma of the diaphragm by nests of endometrial stroma and glands (see ﬁgure). The single nodule on the supradiaphragmatic surface was composed of endometrial tissue. The postoperative course of the patient was entirely uneventful, and she was discharged from the hospital on her ninth postoperative day, being afebrile and ambulant, and with her right lung completely expanded. Because of pain in the pelvis and dysmenorrhea, the patient was seen by a gynecologic consultant. Bimanual exam- � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Consciousness studies (notes), 1956-1958 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-5-005 Date A point or period of time associated with an event in the lifecycle of the resource 1956-1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence: notes: consciousness studies Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/866335cd8b6a0e848ec4f05bda1e57d7.pdf 610411ecffe18c07ab2ae5b0c8adcc8c PDF Text Text ZJ’W 4r 9, I; /y’7'.rf [E Wsﬁ%w‘> In a series of investigations of the role of neurophysiologic factors in the changes in behavior induced by convulsive therapy, that an alteration in brain function prerequisite, for behavioral it was concluded necessary, though not a sufficient was a change and "improvement" ( ). Changes in brain function were measured by a variety of indices, of which alteration in the waking was EEG induces a the most satisfactory shift in the EEG ( ). convulsive therapy consistently Spectrum to slower frequencies, with the development of runs and bursts of high voltage delta activity. m frequencyI? per-cent ‘ The degree and rate of development frequ However, there is'uide variability in the I‘ A voltageandr‘degree ,t/ ~e£-~h2rstr time treatment process [lay activity different subjects. With-equal—numbers—and developed ’7 at various stages of delta activity have been related to the age of the subject of treatment 1 Yet, when 1’ ), and mode ), frequency of induction (electrical, chemical, photo-chemical). the degree of delta these factors are held constant, variability in activity is it” ( ( of the still manifest (. ). Previous experience has danonstrated that both the behavioral reSponse Y and ratings of improvement to convulsive therapy a perceptualm processes as may be related to various " . number and type of Rorschach responses ( ), �score on the California F scale ( , ( ), and errors on figure-ground tasks dud. ); and to such sociologic factors as age, education level, place of fail.‘ W‘ M treatment m to explain the degree of the EEG the variability, this W W“? their perceptual-psychologic aﬁﬁability wt mm “a“ pie-treatment ofA W subjects, Ma ‘ ‘ EEG M“ characteristics WWWWMWW» Was“ can—ad. this M. It is the purpose of j study m~--~m to elate pre-treatment. SUBJECTS AND METHOD : W Gonsecutive patients referred for convulsive therapy in a voluntary psychiatric hospital were studied. 22 to so with a median of 149 c and depressive, schizophreniﬁ The patients ranged in age from years; and were diagnosed as suffering from psychotic cyclothymic reactions. While the range of conventionally applied diagnostic categories was ML 5" broad, the population exhibit} the cannon characteristics. MAI. (7414:444aA4;€7 a single ethnic f“ �OBSERVATIONS: l. Quaint. Variability of Induced-Beita—Activityt In the patients receiving convulsive treatment and investigated Mimi Mm , a} 1 M/b/ by the methods outlined, the variability in the Wed-Wotivity is considerable. We have summarized the observations in 1146 patients in Table I0 While the per-cent of records in the high degree category increases with successive treatment given at three tines a week, half the population has Aral“, a; Z:/£ not achieved..:the’ degree of—éelta activit}; in the third week, and in the fourth week. in all subjects. By the fourth week, however, 5% m ‘ y 140%“ is apparent �TABLE I £24 4314/4. Degree of Inducedﬁsihe Activity With Gonvalsive Therapy gPerﬁzem of Groug, Name) Treatment Period W ~lHts-Aetjjri’ox Mao—k ## First Rx High Degree Moderate Degree Low None Degree # Week Second Week ‘l‘hird Week Fourth Week 1-3 h-b 7-9 10-12 ‘ 14% 28% he?! 60% 12% 21% 27% 2275 68% h8% 25% 18% 16% 3% 2% 0% HH 3/58 �-72. BA «MM Relation of Pre-Treatment Rorschach to 3.4.3 *4 Variabili ”“2" In the analyses of parable-meat 21:3... Rorschach 7%). the number of responses andAqualitative aspects *ann—Iimaw.._ .. i’movement Mbﬁuywa/‘iée' related to the degree of induced tel-ta activity. Wm—uummuw z.»_..mM.m.w.w—m:"g:od Me “mum—.9... h re were signiﬁcantly fewer cup-us t W EEG and color were WWW ‘nv mu» magnum-u “a...“ m.» .own-ru‘m-v-u-m: ”4/. ML. m mm.mm wulmw‘w.m mm,,. ‘ that With gh "‘ were observed. WW We activity \ manifesting moderate and low degrees of such activity. degrees of Be W 133121911135 m deem-96") in patients with highNRgrees of -.._-----_---_:.§ w on those activity t , 3* - van.” w rv: .-mm—Nw-w,.bv,W M. In patients who were observed) avid; taéeported signii‘'ican significant differences in Mw‘m.mmq_,m.m-.~=m~ failed to report 44». M ”iv! movement WK ﬂy fewer EEG Low reactivity "égher degrees of 7 ”WW’ / , �... -_’.. .ymrw—W‘w~——-- -w'r“"" ~- v-vwam- / W- --»—',.w erw w �W-num z 19*; III ff ; “¢“-'—-h nqh-II-uylL-" '51? A expressed y‘TAIB'I-E ------ similar relationship is noted for color responses. Patients form-color“ in the Rorschach developed lower degrees of delta activity with treatment than those l or a , greater degrees of human movement who W4. expressed color, coior-forxnll . olor responses. Combining both 1W My who & movement and b color) 4“, Wobserved in patients w who gave nor form-color reSponses, than in those patients who neither expressed either or both these responses. Analyses for number of whole responses (W), per-cent of good form responses (F‘s-$5), significanttx 444% populago) and per-cent oi responses, failed to demonstrate Sawwuﬂ—v M relationships 1; the degree of induced an» activity. �II TABLE Relation of Number of Rorschach ReSponses to Induced wide-«4L EEG 9* Mean Activity $.13. Diff. Number High Degree Moderate, am Low Degree 3m 114.2 7.2 20.8 15.0 High Degree Moderate, b... Law Degree h. of Resgonses 6.6 Number 2.9 3J4 5.0 5.]. ’0 2.8 4L SR2 (.01 of Movement Reagonse 2.1 2.3 wE305 gM+Fm+m2 �TABIE Relation of Movement and To A/ Induced III Rorschach Responses golor EEG M» Activity Ht High Degr_ee .— 9* Moderatesz Degree h Sign; . Human Movement (M) 3? 20 (53%) 18 (147%) Other Movement (FM-m) 2f 20 (71%) 8 (29%) I? 16 (814%) 3 (15%) 33 17 (52%) 16 (h8%) x2== 39 (75%) 13 (25%) P 93 11 (148%) 12 (52%) x2= 7.60 25‘ 15 (60%) 10 (140%) p L .05 37 3o (81%) 7 (19%) No - Movement Form Color (FC) Other Color (C, or None Both mm Either M Neither M or FC nor FC CF 0-0) 52‘- X2= p 6.19 4 .05 3.88 4 .05 �.11.. 3. Relation of Pro-Treatment Errors §g§§gglo"1Variabilit In a previous study ( ) related to changes in the degree of on drug: is scored bveo Smx to q errors on the hidden-figures test were EEG ,1, $.4va eel-be activity and positive reaponses the amobarbital test for cerebral dysfunction physiologic responses into a to on Hidden—Figures Test % ). ( Combining the index, a range of changes from zero (Table Did)- The larger the pre-treatment error score, the greater the degree of physiologic change with treatment. The triserial ILL correlation is +0.3h, significant atA .05 level. TABLE IV In a similar analysis of the pre-treatment errors to /\ the difference just fails of significance Relation of Pre-Treatment 1;. Considering the Spectrum made. An initial some EEG Pattern to amongst EEG ( Variability. ) or these and frequency the subjects, an analysis of the of these characteristics and the study variabilityﬁlm./ (Table Nb). variability in modulation, voltage, in the pro-treatment relation between EEG EEG patients EEG nesponsivity was whose pre—treatment EEG �TABLE IV Relation of Pre-Treatment Errors in Hidden-Figures Test to Physiologic Variabili 132 (a) Combined EEG - Amobarbital Index: Miologic Changes Mean # Errors 6+ (8) 13.3 3+, u+ (19) 11.2 0 (lb) 7.9 5+ ) , 1+, 2+ ~= p +0.31; 4.05 34.» Mark (b) EEG Ma Activity nghﬂai‘ha No Highiﬁ: 5.13. Diff. 3,2, (31) 11.1; 7,7, (13) 8.2 4.? t p M, ms. �.13... manifested slow wave activity had demonstrated that high degrees of delta activity appeared earlier such activity, As was as per-cent M confirming earlier report} of Kennard and W'illner 1" Jawwnw correlated with the degree of induced dean activity, time/)del-ta- activity.* MIX; / in patients without ( ). 13h; pre—treatment per-cent time alpha one approach to the problem, activity h and were sustained longer than measured In 44 subjects, a correlation of +0.35) ‘05‘ week (10-12 treatment). treatment the observed fourth during level/was DISCUSSION : In these studies, the degreeof induced EEG delta activity during convulsive therapy has beer- related to pre-treatment perceptual and dwwations ure, patterns. “i limited and are scope in \\ 2' / concluszwgarding I these\ and d bservati theor data with clini of s th\consistencz \\ explomtiglng; ,2; 1,7 further warrants constructs "”” ‘"‘ ”” "W“ ‘ EEG [While {a 1m.“ reports the behavioral patterns of euphoria, hypcmania and denial were shown to be consistently inter- preted by the psychiatric observer or family as "improvement," While somatization, ).Improvement "unimproved,"( and in excitement rated were as paranoia panic, convulsive therapy has been related to such lire-treatment variables as high * Previously demonstrated as a correlation of +0.81; with degree of delta activity ( ). �scores on denial personality indices anal-eerie the California F scale )t , ( W M ); absence of ( cam-W color, human movement, form-color responses, low number of responses, or high number of whole and tests good form responses on Rorschach and foreign birth ( most highly esteemed, educational ( ) ). Thus, ( ); and low educational attainment in an environment where verbal therapy is patients least like the therapist in social Mattributes W are referred for somatic (or non-verbal) therapy. Under the conditions of induced altered brain WM function, those subjects with least ability Wm hypomania, '\ WW ‘ " , she I; reapond with non-verbal behavioral mode; of euphoria, denial, displacement and minimization, and are rated as M "W ” "“76"“! while Subjects with greater perceptual and linguistic discrimination respond with the more verbal patterns of paranoid, panic, somatization and anxiety, and are I/ rated unimproved. II In the observations reported here, the pre-treatment perceptual also related to the degree of physiologic response. 4 discrimmtion and verbal discrﬁptive ability degree of induced gum» The greater the mode is M“! on the Rorschach, the lower the delta activity; the fewer the Rorschach responses, the less ., �.15discriminating and the less the ability to separate figure from ground, W the greater the physiologic responsivity to induced convulsions. difficult to formulate a causal relationship fer—the—eepeetc—e£ It is clinical behavior,(both pre and post-treatment) perceptual patterns and physiologic response. But M M behaviors it ’L“’Z° is operationally meaningful to interpret these various W of the subject tainteraction with the environment, with each measure of behavior representing an abstract or sample of subjectexaminer relationship. In this framework the problem of the relationdhip between personality and physiologic measures is transformed "whether" to one of "how" and ”under What ccnditions." from one or In these series—aﬂ- subjects, heightened perceptual discrimination appears related to low degrees My» W25 MW Wluf / of alpha activity in routine, suite recording and decreased delta-activity- f06ﬂ””‘$ responssnity to convulsive therapy. In clinical behavior sudn subjects are prone to A tutu: introspection, anxiety and ideastional disturbances; and show poor improvement ratings to convulsive therapy. These observations are and EEG consistent with previous studies relating personality a5pects by Kennard, Ulett and Shagass. Kennard and Schwartzman related resting EEG spectra of low alpha index ( to schizophrenic personality, ) �~16- psychotics , non-mm, while high alpha index to Ulett gt_ a_l_. ( ) psychopaths and young individuals. indicated anxiety prone7ness was ﬂying: correlated with v M poor alpha activity, slow and fast activity in the resting record, and poor response to photic stimulation the sedation threshold amplitude of beta ( ), ), ( activity and with poor in the alpha range. In Shagass' studies of low was responsivity to barbiturate as measured by positively correlated with anxiety clinical response to convulsive therapy ( ' ). and tension Thus, behavioral reaponsivity and interaction, reflected in personalitytheoay ltheenyand psychiatric nosology by EEG may be m related to neurophysiologic reactivity as reflected patterns, within the limits of the sensitivity of our measurements or methods of experimentally altering (activating) both behavior Inherent in neurophysiologic responsivity are all and EG. the aspects of the internal milieu, as reflected in individual differences in biochemistry, and in the pre-treatment continuum as EEG record characteristics; the individual environment reflected in perception, motor patterns, mood’ and verbalization; but also the sociologic aspects of the individual's experience. In the series of patients studied here, an ardysis of educational level with degree of . responsivity demonstrated a I.‘ 24.,q me $45 a: D . 3 EEG V] ( - p< .02) relationvship. Subjects �years of formal education had a lower percentage of high 6&b’tgd7’a" 56w! degree records than subjects with less than eight years or education. \ with nine or m more /CONCLUSI ON: The variability in the degree of induced 5am) mm deb: activity manifest during convulsive therapy has been related to technical factors of the treatment. Yet, when these are held constant, (regs-365%; ' ' y has studies, been patterns. Patients with fewer variability is still manifest. In these related to pretreatment perceptual and EG number of responses, fewer movement responses, and absence of human movement, color and form-color responses on the Rorschach; greater errors on figure-ground discrimination alpha activity 026m) 00'“ ' had higher degrees or induced eel-te- activity. Physiologic reactivity, measured in EEG tasks; and higher per-cent time interpersonabv patterns; behavior, manifest personality measures and d scriptions of clinical or m different verbal behavior aspects of the interaction of subjects If environment. In mks framework, EEG and and personality variables are related within the limits of the sensitivity of the measures used' ��#3:» Mummmammmmtmmmmmmo Mumthanmwmhmwuwuw ). pmmummmtmaﬂommm( mmthCAMomhi‘ﬂmh'f ( . handmmmnwmu )yaaatomahmmctutountm,mumm,m plau.a£b1rth( ). mtmmmmumotuutmtmt imammnmmmummmmmmwamo and thud:in pmptu-luwyuholoﬂo prim, Wow 13mm m WWW. m mam... �swam: 3w m mm mm m cumm- ”that: studio‘s. for W110 3210 than” in a Wham patients runs“! in ago I'm 22 mwumandunorwmsaMnr-dhwumfm psychotic: Wain, mhiaophmic and W110 tho mum mtm‘. from mm minim range of uppnod mm sitcom: m baud, m mm (mum-mm:Maamcm(mhmmm «and common Wmmmum. - m: emu), mugmt and ﬁrst Wm. 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In eerlier reperte the behevierel patterns at euphoria, hype-enie end deniel were eheen he be ceneietently interpreted by the peyehietrie tenily eheerver e! ee 'ieprevenent', while eenetieetion, penis, pereneie end excite-eat were reted ee Inniepreved( ). leprevenent in eenvuleive therepy hee been releted te each pre-treeteent veriehlee ee high eeeree deniel pereeneiitw indicee (e )3 eheence Beele ( ) end an the Geiiternie r or been: eeveeent, color, toreoeolor whole or anther high nether 1e! e! er reeveneee, reepeneee, end seed for: reepeneee on lerecheeh teete )3 end ( lee edecetienel etteineent end tereign birth ( ). Thus, in en environment where verhel therepy ie eeet highly eetee-ed, petiente 1eeet like the therapist in eoeiel end edncetienel ( ) ettrihutee are referred for eeeetie (er nonuverbel) therepy. Under the aenditiene of induced �altered hrein reaction, thoee eanecte with leeet diearieineo ve tiee ehility reepend with non—verbal hehevierel Iedee o: enphorie, hype-enie, deniel, diepleceeent end linieieetien, end ere reted ee 'eueh improved”, while enhjecte with greeter peroepteel end linguietie dieerininetien reepend with the mere verhel petterne or pereneid, penic, eoeetiee~ tiou end enxiety, end ere reted 'uniepreved.“ In the ebeervetione reparted here, the prentheeteent perceptuel node ie elea releted to the degree of physiologic reeponee. the xreeter the perceptnel diecrieinetion end verhel dieeriptive ehility on the Boreahech, the lower the degree of induced elew were activity, the fever the hereeheeh reepeneee, the ieee dieerieiheting end the 1eee the ehiiity to eeperete figure In: ground, the greeter the phyeielosic reepeueivity te induaed aonvuleiene. It ie difficult to rereelete e eeeeel reletiehehip between clinical hehevior (both pre end peetetre%teent) pereeptuel �pottorno and phyoiologic rooponlo. But it in oporotionolly looningtul to intorprot thou. various tasks to rolotod behaviors of tho oubjoot in hit intorootion with tho onvironnont, with ouch nonsuro or bohovior roprouoating on obstruct or Io-plo or oubaootuoxoninor rolotiouohip. In thio tronowork the problon of tho rolotionship botvoon poroonolity and physiologic noosuroo 1| transfornon tron on. or 'whothor' to can of 'hov' and 'ondor what conditions." In than. Jobs-eta, hoizhtouod porooptuol disoriuinotion dogrooo of alpha oppooro rolotod to low activity in routino, waking rooordo and docroosod amount: of inducod slowing in such bohovior In oonvuloivo clinical to thoropy. coupons. ond idootionol to anxiety introopootiou, oro subject: pron. dioturhouooo: and shot poop inprovolont voting: to oonvnloivo thoropy. an... 1/ oboorvotioao oro conoiotont with proviouo studio: toloting personality and EEG oopooto by Konnord, Ulott and �shagaae. Kannard and subvertaaan EEG ( ) related reating apectra of low alpha index to aehinophrenic pereouality, while high alpha index to non-paycbetice, payebopatha and young indiviﬂuale. Ulett g§_5;, anxiety ereneneea and elow and wee ( indicated ) correlated with peer alpha activity, feet aetivity in the reating record, and poor reapenea to phetie atiaulatien in the alpha range. abaxaae' atadiee at the aedatien threshold ( In ), lav reepenaivity to barbiturate aa aaaaurad by amplitude of beta activity teneien wee peaitively correlated with anxiety and ), ( aonvulaire therapy and and with peer clinical reepenee te ). Thee, behavioral reapenaivity ( interaction, retleeted in personality concepta psychiatric neaolexy nay reactivity ae tetlected be by and in related to neurophysiolocio BEG patterna, within the liaita at the aeneitivity at our aeaaureaente er aethoda at experiaentally altering (activating) both behavior and mac. �Ink-rent in nonrophyliologic rcapensivity uro .11 the tnpccta of tho inturuni lilicu, a: rotlnotod in individual prootrostn§nt and 336 ditterouccu in biochonistry, in tho rtcord entrnotorictiolg the individual onvirounont continuum I! rctloetcd in porccption, notor patterns, need lad varbdiiaation; but also tho oeeiologio 33poctn of th- iudividnal'a .xparionec. In the scrioi at pati¢utc otudiud hnro, an anulyuiu of cduentional lovol with dear-o of rooponuivity danonatratud a aiguiricuut ( - p EEG (.02) relationship. Subjects with nine or sore yunra of tarsal cducttion had a lover parcentago at high degree slow unto oleotronruphie rccords than aabjcct- with yuurn or education. lot. thin eight �- 19 . COICLUSIOII The veriebility in the degree of induced aloe eotivity eeniteet during convuleive therepy to technieel feature at the treeteent. held cenetent, etudiee, BEG fit, were hee been when releted theee ee veriehility is still eeniteet. In theee slowing hee been releted to pretreeteent pereeptuel end EEG petterne. Petieute with fewer number of reepeneee, fever reverent reepeneee, end ebeence of hneen eaveeent, color end Rorecheohg greeter errore for-acoler responses on on the figure-ground diecriniwetiou teeke; end higher percent tine elphe edtivity hed higher decreee e: induced elee were eetivity. 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Inc... m mm 1mm. . �February 21, 1957 Individual Differences in EEG Responsivity Fink, MJD. to present observations Nbx 1) Problem tonight is in the laboratory of Ex- made perimental Psychiatry at the Hillside Hospital and then try to discuss their significance. we have no the clarification The problem explanation but wish to present this material for it may bring. is to account for the variability in EEG re3ponse to electroshock. The Observations: 1) Repeated EST induces EEG changes. These are of many kinds includ- ing disorganization of frequency; decrease in beta frequency, amplitude; increase in delta % % time and amplitude; delta bursts; spike charges; increased sensitivity to hyperventilation, amobarbital, There 2) is a direct relation in group data of (a) with degree of induced EEG time and dis- - # of treatments changes (b) frequency of treatment (c) type of ' treatment Note (gm or pm). that our analyses are devoted to one aspect of the EEG response - i.e., delta. quantitative measurements The and myself and included were bursts; slowest frequency 3) % and were described here time delta, highest 1955 by Dr. Kahn time delta, duration of highest amplitude of delta. But analysis of our records, so classified as high, middle and demonstrated a definite relation between the ment" % in EEG response and the "improve- in the behavioral\response. Presented at the Metropolitan EEG low Society, February 21, 1957. �In the first 2h table the was obtained: following patients, % High Abnormality 1-3 h—o 7-9 10-12 25 80 91 88 Moderately improved (6) o 16 so ho Unimproved (7) 0 0 O 20 (ll) Much improved first we were struck by this correlation, and, devoted the subsequent year to demonstrating the significance of this relationship. our conclusion - that, improvement You may know of in electroshock therapy requires the induction of a state of altered brain fUnction, of which the EEG-delta index is a cardinal sign. recently, More notes that 3 we at the part of our table which of 2h patients had high records within 1-3 treatments, and that after 10-12 treatments 5 ord! Why Let took a second look patients still had not achieved a single high rec- this difference? me demonstrate some of our records to show the difference in EEG responsivity to electroshock. It is first series all treatments were given in the in the latest by Medcraft - three important to note here that by Reiter instrument; and times a week. That extraneous ulus was eliminated, all factors as threshold or suprathreshold stim- recent treatments have been given at threshold stimulation, achieved by Dr. Green by repeated PM a seizure resulted. 1) . High EEG 2) Moderate 3) Low EEG response. EEG - Lesnick response. - response. Baum - Silverwater in increasing dosage until �To what can we ascribe the difference in response? immediately come to mind, and I will discuss each one A number of factors briefly: (a) .553: is a factor in this varying responsivity, but not the sigIt is true that some younger patients achieve high EEG abnormal- Age nificant one. ity early; as first two patients over 60; but an analysis of the data of our electroshock studies, for which I am indebted to Dr. Green, indicates do some age to play a small role. Analyzing the records of h9 patients, Dr. Green divided the results in- to those above and below hS; above and below 50 - as significant cut-off points. There was a tendency for the older group to have lower EEG ratings in the h-é period; but by the 7-9 period, the differenCe was gone. ' (b) ‘ §_egc_: Clearly not a factor. (c) Clinical diagnosis: is difficult to assess. As you know, clinical diagnoses have no independent reliability. They are approximate descriptions of experience, clinical states and depend largely‘on the examiner's‘bias, setting This factor [of the examination, purpose,etc; also on the patient's age; and only incident- ally on any operationally defined observable pattern in the patient. For these reasons, this analysis is deferred. However, gross more inspection shows that patients with low reactivity have often been called schizophrenic and paranoid, than involutional depress- ives and manic depressive- and that patients with high reactivity have more often been called involutional depressives and manic depressives than schizophrenia-paranora. -_-——-————————-——— of treatment: �-h- significant factors, and since we are describing the results of individuals treated in groups in whom these factors were constant, we are Both are not going to explain this further than to say that stances, to convert a low a high EEG it is possible, in some in- response to three times per week electroshock to response by going from Reiter to Medcraft; or by going from three EEG times per week to five times per week or twice a day. But these factors only amplify further the variation in response. Egg. DeFede We have assumed abnormality We is have looked appear that the development of cerebral changes, of which delta a prototype, for is the logical outcome of repeated electroshock. an explanation, therefore, of the after adequate courses of It may be may reSpond by failure of delta to shock. that not all patients respond to brain trauma by delta, but other changes (as increased beta voltages and frequency; or increased disorganization; or increased responsivity to hyperventilation). Regardless of the construction, a difference in responsivity exists, and is manifested in our series. we have The factors conceptualized the problem as one of "cerebral reactixdty." we have already outlined are important in such reactivity, as have described, but we believe that more is involved. Out studies are we new in the progress along the following lines: 1) 222 Factor of Personality: In the course of our study of factors which bare on the type of behavioral response euphoria, paranoia, withdrawal define personality -), we to electroshock (i.e., denial, undertook a study of personality. To is extremely difficult. But Dr. Kahn in our laboratory has done so by the use of a variety of indices. The Rorschach; an interview with relatives designed to elicit premorbid behavior, eSpecially denial; figure-ground perception; tachistoscopic recognition of words, 32g. �To our surprise, significant correlations between the degree of delta abnormality and two Rorschach factors I score were achieved. 63 and the patients, EEG have listed the table of in the h-6 score reflects a low or middle The IS as well as the denial interview M & C initial in scores our responsivity. The EEG's were done CHART (M & C) EEG and 7-9 treatment period. The negative response; the plus, a high reSponse. THEN REFERRED TO significance of this chart is in the "apparent" diverse phenomena that it purports to relate. If borne out by future observations, it states, that patients who'have no movement responses and either no color or color-form responses have hh% chance of high EEG delta reSponse in the 2nd and 3rd week of treatment; while patients with Form-color reSponses have only a for such a 16% chance result. it be that one's perception of the world is directly related to one's cerebral respOnsivity? Or, do the conditions which permit delta to appear, that is, those that require an ability to withdraw and assume a passive Could ree Ostow described attitude as by for alpha index, also midify the patient's sponse to the Rorschach? we have become increasingly interested in this problem of passive choose to describe attit- it - in the problem of "vigilance" - "alertness.“ In our laboratory, Drs. Pollack and Kahn are engaged in developing psychophysical ude, or, as we measures of such "vigilanceg" while we have become increasingly aware of the influence of the observer's activity on the ongoing 2) A second factor which EEG. interests us with regard to the problem of in- dividual responsivity is the concept of physiologic reactivity. Electroshock �EEG (17) ResRonsiviﬁz to ECT or R (58) GM 00 2 OM czyc h (33) h (33) 7 M CE/C 3 (30) u (no) M 00 1 (25) 2 (50) OM M m FC 5% level of conf. S (71) 9 (50) h (22) 12 10 �is a way of inducing certain diffuse chemical changes in the nervous system. So is metrazol - barbiturate - activation technics it is show - hyperventilation. significant variation in responsivity. hypoglycemia Each of these For example, that hyperventilation induced delta readily in some patients - eSpecially children - but in others, no such response is noted. Dr. commonly known Green of our laboratory has hypothesized, and is now studying, the possibility that a degree of physiologic responsivity - which is measurable - is an inherent characteristic'of organisms. To this end, he is carrying out pretreatment activation records in all our subjects; as well as measuring their threshold for in EEG depend. electrically induced convulsions. I am confident that there are other "factors" on which responsivity to electroshock - and perhaps to all activation - we the variation may the ones described, namely personality, vigilance, are excited by and physiologic responsivity. tonight, not the common characteristic of the EEG response to activation, but the individual variability and the factors on we have emphasized which this depends. 'We have tried to exemplify our problem by our data of the variation in delta response to electroshock. Further study of each act- ivation technic to relate the role of personality, vigilance and physiologic reactivity to the variation in EEG responsivity. �-3and middle (lower socio-economic upper lower (Jewish)! ' j , ~ first The generation, group. and _ ideation‘ mood , responses. W; in the first hospitalisation, of Psychiatric . psychiatric bellman” «read-tune class), immigrant and were ' patterns we 114' W. They use voluntaﬂeﬁon‘ar predominantly 1, with a short period (few months to few years) illnesjzlectroconvulsive treatment was administered three «W “M'- _ times a week using 1hr % WM mthods. rﬂ L3 r . suprathreshold unidirectional or alternating current A“n*”"t ”WA a Jayne/1nd“! 11’ ﬂat man !0 ti 3.: Wig Ml’" {M-dtun ﬂit/“23‘ Within a week prior to treatment subjects were tested with Rorschach and figure-ground discrimination for presence or absence of j ,x’”‘\_, [I 2 responses and total (H + EM+ tasks. The Rorschach human movement protocol was scored responses (M), total m), type and number of color responses (0, movement CF and F0) In the figure-ground discrimination task, a, () modification of Gottschaldt's hidden figures, the subject number of responses (R). L niacin-mam is presented with and below it a page containing two forms a cmnplex figure in which the - a simple geometric figure, simple figure is embedded. The task is to outline the embedded figure in the complex figure. I' ”A4€ "- ad‘ Electroencephalograms were obtained prior to treatment, andweekly“ on a day following a Mamie, treatment. Patients whose pre-treatment records contained �measurable delta activity were excluded from the study. slow wave activity frequencies of and 7 W MW was measured 04, wave actiﬁty, Based on these activity in the record. of induced by determining the per-cent time of and—less three selected in cps, highest amplitude of slow The amount and leads; the slavest frequency / longest duration of burst indices, records were classified as pan/40M "low," "moderate" or "high" degree delta- W previously described of high degreesdeébba ( activity, according to criteria ). In the observations reported here, the activity in the second and third development weeks of treatment treatment intervals) was used in the tabulation. Patients who M. (We, developed high WWactivity during either or both these periods were classed in 3 of delta degree the high degree group. Those whose records did not demonstrate activity in either ,week were classed in the moderate-low class. 7-9 tt%gree or" �watt—baa WI? “H.“HQ mammmuormmmummmwm "mu alum, that «warm ant m1: of “Mom (W m). In Guide“ the “mummy in mum, vellum, m rmwmmwmmmmmtm mm,“ Wsamunugmmwmmmmmumum mﬂWNudl. MMM3M( )orthmputmtlm mmzmwmnmcmutmwmammwmtw mama in aetiﬁirapmﬁ muormdmmmalmthm such with“ «mum mm mmm< mm an «mu- apart at W )., «mapmwmmmmpmmmm ”mtg-lam muey m “rant-d nth tho W W ma of as pass-mm was at such wuvﬂyw In mum «1' ”3.“, +0.35, " m1: {'“4‘. ..., am “tax”; 44”.. a l1" an activity. tom-rm autism, tho .05, w a WW 2.3.2.1.“ Wmudu‘mumormduummwmu � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Individual Differences in EEG Responsivity Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-6-006 Date A point or period of time associated with an event in the lifecycle of the resource 1957 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence. Drafts, one with Martin A. Green and Robert L. Kahn Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/130db8be85bd0b48cc58aa475a58b045.pdf bc509f8c91b02a75587679edc6e65f4e PDF Text Text J4» M 4‘ \ G: 3/22/57/ s ' Electroencephalogram in Electroshock: Role of Delta Change in Behavioral RBSponse Following the original x observations that electroshock induces changes in the electroencephalogram, clinical studies correlating snob changes with numerous In an exhaustive review of these improvement were undertaken. studies, Chusid and Pacella (1952) conclude their survey with "in our opinion, the slow wave formations after electric shock treatment bear no direct relation- ship to clinical improvement. favorable therapeutic response depends The primarily upon the administration of a certain number of treatments in each particular case,and since patients vary considerably in the degree of abnormality noted with the relationship between changes and EEG it of treatments, same number follows that any clinical recovery is largely coincidentalai. A}; A (. if‘kt" if: I /(/.fr ~”/ his/((9 F ,7 .6- , 221 [ff & \ ('1 F621,!” if , CWA/Ll’ﬁi/I {‘QJ/QJ { (44.1. l '41 [L .6 o ’ f l! if; ,0 a’,,.€"5.,‘ \ 2x )4,er 1. '7 1‘ L-ﬁ ! :13 > I" Bdké’vttfi’ , ”1’ ‘ ‘ ﬂit)"; I , , , .. f, \ Mix/4.x. U ' R.» '4‘) ‘ 1/6, , I. 1| EEG (MA gr,“ I, , p. in 7,1,, V” ‘ 5 .9 4,, (3., "M /QM{ ﬂ’szf/lff’ ,' {.4 L J“ \ (’2‘: / f’ :3 «m 1‘; .- in" O v’ w.» 1 ,2”, 41 ” A £146.11” kg,” (1 r14; 1 Q41 47‘4”! "4 1.0 7’ (nt/Z/ﬂ/f 'I"l.-',v rr c F x9 if; 'A-b- :t {f I , x a ’, A; 5’, ﬂ I”? (11"! ! /‘) "(Wk , /‘ (1.. 1 f) ,- $.44 , a ,c r ., ,7 ‘a K 1 �‘ -' J ’13]? .f‘ 5‘ V In an early report, Hoagland . §§L§;;(l9h6) noted a correlation between changes in the per cent time of more j disturbed behavior tr I /J"‘Z3’fa,t~x V than 13 cps activity and independent clinical ratings became more As -. T} ‘ manifest‘I, the fast activity increased. With treatment induced behavioral improvement, this activity diminished; only to reappear with a ,_‘ if '9‘!“ ‘AlerA ‘ 1“ A 3:419:4{F’ﬁnf reéitumu-ne of symptoms. ~35; ('1 I a! ‘ I .~ ‘ " v I f A“ delta response an activated by intravenous thiopentone, elicited characteristic in the treatment course, there EEG was random changes in every subject. Early irregular slow wave . A... "‘--"'-~—.. tre;;;;;E“‘EQE;eaee3¢%o <§¥¥§:nore a highly rhythmic, amplitude f £41 "I, clinical correlation. Roth (1951), reporting the high I . / Similar observationsﬁwere reported by Kennard and Wilner (l9h8),without a V .v‘ 1/1 4 runs and bursts. These were chiefly activity whicht bilaterally 2 up to 200-350 microvolts and continuous duration of 30 to to synchronous cps, with voltages 3 80 seconds. When the resting record evinced rhythmic delta activity, thiopentone increased voltage and duration, spread its area and decreased its basic its frequency. Ebth believed that these changes were related to the process of recovery, and concluded: "the development of a typical 10 of the 36 patients two weeks. But who transient EEG change does not insure recovery and obtained such change failed to remit for longer than improvement in clinical condition seemed to be related l,‘.' , . , I �to the the EEG EEG change even in these patients. If changes with the therapeutic effect, are correct in connecting we it would seem.since most of the patients developed typical changes, that the physiological basis for improvement is acquired effective in promoting recovery." «amen-«AW... mzu/vx-W it may or may not prove by the majority of cases; ( urn ) y‘a—wnup-H‘QOMﬂh-MIAN-mwﬂmhﬁia m m «WiniWW.iwm~mm , ., 7_ _, W_ni__u..aw»r Iz=tsagillunily agreed'that electroshock induces diffuse slowing and Meade,” (iég increased voltages in the electroencephalogram. There is 1iII some inW dam/a w dication that fast activity’, both in voltage and in per cent timel'aasae dice! dell-Ilia; enlistiées in nlxlxli; patients 2” are intensively treated, -CL¢€- who a slowing of the persistent alpha frequencies. degree, duration and The extent of the delta activity is directly related to the frequency and the number of grand mal convulsions. bInch activity is usually symmetric, and with anterior placed electrodes, appears maximal in anterior electroenceph- alographic leads. In patients received twelve to twenty treatments who have d‘xuet on a twice a week schedule, the electroencephalographic effects usually “WNJw‘A ; “ﬂmwui_w-i «- -‘ disappear in h -8 weeks following the last treatment.§ Studies of the prep it»? p treatment \ EEG 7 characteristics failed to demonstrate any relat’ ship with " _ po;t\seizure the electro cephalogram or clinical \ onse. Similarily, there ,2,. tax: has been n report of \ r C/ﬂu 1 L/{L-"Ligﬂa :14 SM K rum—i If /“ .\ a relation betwe K/ fat 6 Leg/2x,” ﬂu”? K) J M. f.” ( thexpost treatment record x” A v, f a [If ‘ ’ _ .- V: t . �Both of these. reports emphasize a. W relation between the degree of electro- encpphalographic change and current behatioral response. Mﬁﬂferent aSpects are emphasized, namely delta response to barbiturate activation and the beta response .2 m —‘ m-...-‘.......—...7...—....- Had other‘swlstematic studies been done, ha been that n correlation etween elec oencephalographic changes and M f: ”tax-:74“ 5": W” Cu X4,4! .z/f, behavioral response of electroshock exists. / Lack of such if indeed 6W .--, ‘ 5 r \‘p/‘ a relationship arm W Wei “)2” 40 /W does exist, may W # behavioral change, , -.’, ‘K" A_Iff measures of I, — 72:! r.«L.1/€ALI':" elm/7 ”r: ﬂ-the relationship between EEG "’-/ g EEG Chaﬂ geg “(W:tﬂ/f a” kg"; I?! or time or c) methods/of evaluating behavioral response, Whiéfux elucidatgun to reflect ' ' M/E‘C {if (vise/ZZ‘K; response and 44. . "M ‘ ��“NM messwnaithink' human” change was not clearly noticable or who showed only equivocal or transient improvement. Some showed fluctuations in behavior, at times appearing somewhat whom / improved. #1 But the changes were not sustained, so they appeared much that by the end of treatment, as they did before. are aware of the difficulties in evaluating improvement. Others might have differed in the estimates of change in these patients. In any case, by We MW.— using this threefold classification, the differences between the groups will be distinct.“ M‘ﬁe ‘i first . ,, third subjects. these4“me ,w mgﬂﬁﬁwgﬂhuﬁgyé‘wﬂewww“L»?«up,she?w M. and WA“ s...,. 3...... suggestion of Dr. Hans Strauss (Clinical ; cou‘oinﬂtidﬁb three lead or (fnontal. '2’90' 0:" *NWt‘M *0-gis?¢ﬂm av .J,v pgg‘gggja;“1%ngformléqﬁesmefEMMMSMAa‘EE.3.9“‘3' '5" lW-s‘i «#33253 AIWJrrrw-sv‘am . ' ‘ _ ' "‘c~"‘"“M:= 5.»... ,V :4. , �. V .‘4 ,2 C. Minimallzfor Unimproved: In this group were placed seven patients was not cleanLy noticable or who showed only equivocal or change transient improvement. Some showed fluctuations in times appearing in whom behavior, at somewhat improved. But the change was not sustained, so of treatment, they appeared much as they did before. ,\‘\ that by the end are aware of the difficulties in.evaluating improvement Others J» might have differed in the estimates of change in these patients. In any case, by using this threefOld classification, the differences between the we 1 first and third groups will «*K‘EVALUATION OF EEG RECORDS: C ) be A distinct.” 1_”, 1.4 “MW, ”1, total of 160 records were obtained in these subjects. Fbllowing the suggestion ofillluills determined for three lead! and (frontal-parietal, anterior temporal;:vertex, parietal-ear lobe) for 180 seconds of recording for each lead. The delta index is defined as the per-cent time occupied by waves of 7 CpS /°ebdéﬂbb or slew-n. The average delta-index for the three leads, and the highest delta index in any lead were'éég'indices used in the final tabulation. Simultaneously, the record was scanned for the slowest frequency inn identified at least twice in any lead; the highest voltage of any delta wave; and the dhration of the longest burst. Uther aSpects recorded, but not used in the final e/aluation, were the regularity of burst act- ivity, slowing of alpha activity; and.the degree frequencies d'amplitude of fast act1v1t1es. These indices did not lend themselves to s atistical study; and were not identifiable in all the recordsp.’ Fast activit'es were �.u- 7 j. ,2; pézfzn Air. {in //e 4/4; xiv-sea administered by the staff psychiatrists, using electrostimulator. Treatment schedules were three times a 52/ As 9-to showed from number and of 33. varied the treatments week; patients a Reiter h? C greaémae’b clinical fewer tended the to give treatments, psychiatrist , spaced. There were 15 women and 9 men in the series, and and more __,_____.__ 49/ the ages ranged from 2h to 68 with a median of h7. EVALUATION 93 CLINICAL RESPONSE: All the patients were observed for at least eight weeks after termination of ﬁiéemé; the basis therapy. The patient's response to electroshock was of the resident psychiatrist's impression, staff opinion, the nurse's notes and the clinical evaluation of the supervi§gaidxlcharge of electroshock. The patients were<ilvided into three groups - markedly improved, moderately improved and unimprovedJﬂaeduaa3lﬁ§EEEEEEZEEEEJEEEEiBnIhs) response—tejeieetreshock:§ [3 A. Markedly Improved: The 11 cases in this group were regarded as showing recovery or marked improvement. These patients no longer showed the symptoms which brought them into the hospital; their doctors were better; felt they and the nurses' notes confirmed.such aSpects as being able to sleep without medication, better appetite, and improved capacity to get along with the other patients and participate in hOSpital activities. B. some improvement These six patients in this group showed but continued to manifest indications of mental illness. Moderately Improved: patients typically The showed symptomatic relief, 33;, acute depressive features might be gone, but the dramatic change so evident in the group was not apparent. Each patient continued to show some first noticable disturbance such as obsessional thinking, paranoid ideas, or somatic preoccupation. �medication could not be; controlled our evaluations of fast activity follow- 1", ing electroshe’cié are not satisfactory, and the results of Hoagland W’“‘"‘“W .m M ~ v 7,; ,,._,_.,.r..:.:..-.eew.u ttaal, ”Mina-x... .. On the basis of tho the records were placed in a rank order from the greatest abnormality to the lowest. The 160 records were then divided into third = 3 abnomality and lowest third high degree EEG m positive correlation groups = Low - i__e."upper degree abnormal- ity . , ,,,. Wﬂm.wrmnp~4ohm»wz 1..“ cheek? max .. __I . __' and improvement “Wm h. ,.wu...—.mmM ' om muc high een early ahno eA dc of tre tment. Tlie reco ds of the I :psyThese ) Mr"."W“, BydtiliZing these quanfications of slow wave abnormality in\ \ such EEG we be electroshock, abnormalitydnduc d duced conclude that { the in first 3 weeks ,r'response. 2. What M fur“ of treatment is essential for t ﬂea; "3 e short term” clinical k exist between the clinical reaponse»; and then amongeach '1 1. ach of the indices, 0 er? fi\st with ity �//' I, -w _‘ Quantitative Studies of Slow Wave Activity Follgging Electroshock Despite repeated attempts: correlations between slow wave activity induced by electroshock and subsequent therapeutic outcome have been unsuccessful. tain conclusions from previous studies are warrented,.heue¥sih All Cer- patients sub- electroencephalogra‘z;b electroshock the therapy suffer alterations in jected to pliilllﬁ. Three patterns are generally described as 1) the slowing of the alpha frequencies; 2) the appearance of random, symmetric SIOW'wave activity, generally activitygcigiNB) diminution of beta which of high voltage progresses to burst frequencies in rate and amplitude. There is a direct relation between the degree of these changes, and the number and frequency of treatments. saturation point of change is described, which can is not increased. ment, but which, seemingly, changes are reversible. The In many be maintained by subjects a further treat- Also, such electroencephalographic rate of return of the cerebral patterns to the pre- treatment levels is generally 1 to h weeks, depending directly again on the number, frequency and the type of treatment. Another area of agreement among the cited authors ship between degree of manifest roencephalographic abnormality. few treatments and without memory is the lack of direct relation- loss and confusion and the degree of elect- Mamba» cited-of severe Cases are memory changes significant electroencephalographic change; and also of severe changes in cerebral rhythms without manifest clinical confusion or laid memory on such impairment. O Mam! 6f 5. £257 In these reports, emphasis isfrequently organic confusion also correlating poorly with clinical results 0 ,Euﬁada, with �studies, however, Two cited may be 6L0 71t7¥éodf which—noted a correlation between Electroencephalographic changes and clinical improvement. amud, Kaufman and Péagcus Hoagland, Mal- +1924)» in this 19h6 study of involutional in the electroencephalogram and in the excretion of -(changes women ketosteroids 17 accomp panying electroshock therapy of agitated depression, Psychosom. Med. 8' 2h6-251,19h6lg, reported a relation between changes in their clinical me, rating scale and the per cent timeJlB cps activity;AL the bediszirbed havior became more manifest, the 13 cps activity increasedi Sivtreatmeht W induced behavioural improvement, 13 cps activity diminished. of symptoms, there was an increase in the More recently, Roth (6hanges in the % time 13 cps EEG With recurrence activity. under Barbiturate Anesthesia Produced by Electroconvulsive Treatment and Their Significance Theory of action, ECT EEG for the and Clin. Neurophys. 2: 261-280, 1951) described ekseTies-e£.sindies_in_nhieh a relationship between thiopentone induced EEG changes and the recovery process. was—elicited. Roth noted that slow Pod“ $12.94!. wave activity as seen in a routinenrecord was irregular in appearance, and he confirmed the reports that it could not be satisfactorily related to improvement. ; By administering an intravenous solution of‘;fbarbiturate thdoperitone, Beth elicited characteristic changes in the shock in every subject. Early there was random EEG irregular slow after electro- activity, which, with more treatment, increased to a highly rhythmic, bilaterally synchronous, high amplitude delta runs and bursts. These were chiefly wave 2-3 cps, with voltages of 200-350 uv and continuous durations of 30-80 seconds. pentone th: resting record increased its voltage and its basic When W duration, spread activity, thén- its area, and decreased frequency. Roth believed that these changes were related to the process of recovery,‘§i$haagh,;the a typical evinced rhythmic delta EEG ‘4” concluded: “’Enuaner, the development of change does not ensure recovery and 10 of the 36 attained such a change failed to remit for longer than patients two weeks. But who �Similar analyses of the relation of each of the indices and clinical result showed identical curves to the group curve shown before. Slide 2 shows the the relation of the delta index to improvement. to much improved group jumps index in by the 7-9 treatment; while the mod- 52% erately improved and unimproved groups 10-20% by The mean show a gradual, slow increase to the 10-12 treatment. similar set of curves is demonstrated in slide highest percent time delta in one lead. A In the next slide the mean slowest frequency 3 for‘the is recorded, mean and this too shows the same significant relationships. While the much improved patients show delta waves down to 3 cps or less by the second week of treatment, the other two groups barely reach h cps by the fourth week of treatment. Slide the 5 shows correlations for the same The much improved group show mean higher voltages by the second the fourth week the differences are perseatent for Finally, slide 6 shows highest amplitude the mean all three duration of bursts. week and by groups. The records of the much improved patients show longer bursts, averaging more than 7_ seconds by the third week of treatment. Bursts are less frequent in the unimproved and moderately improved groups and are significantly shorter here:€E:::¢::Mthe in duration. Not noted factor oﬁaregulgzgity of bursts. In the lonéﬁbursts, wave forms frequently were more regular in frequency and amplitude, than in the other two groupsl These studies may be measures of slow wave interpreted as demonstrating that each of these activity arise from the same physiological process, and assuﬂe the same significance function induﬁed by electroshock. in relation to the disturbances in cerebral �3. Finally, can these alterations in the aSpects of cerebral function which may EEG have been be correlated with other altered by electroshock? In these studies, three other indices of cerebral function were assayed! the amytal test of Weinstein and Kahn) tests of double simultaneous tactile g?) Si) stimulation/and tests of memory and recall. of these three indices, only “gigpﬁﬁt' V/ the amytal test showed a positive correlation withimprovement and with A); stoma; WW may.4, 41:2th Julia“ We 0’ is this test, the subject is interViewedm uestions o Ahbbld atdkhuus nae: alas/d autbaeaawae cafhﬂa ation of int venou sodium amytal, the stions are repeated errors in thQ/I-vm . e orientation, coniabulation, denial as "POSitive" amytal t:‘t, and illness and reduplicatioh are scored are indicative of cerebral dysfunction. “Ms”r Ab tal test. 9"” ,, .1, #ﬂwwf yyyﬁr” \ In the next,slide, #7, the pe centage positive amytalthSts are if“ if“? compared for edéh of the three groups, «hf weeks of treat- ‘3 - , jge’difference between the much impror -i the other two groups is strfiing. While every patient in the mu_;‘; oved group had a positive gonna al by the third week of treatment, the abno \ity persistedgF ment. M was it W#7 ation with improvement. In this that there are various types of cerebralﬂgyeﬁ function and that”g;:ﬂcannot speak in gross terms of a ”Absfgeeﬂ'thew 0“,.“ n .rvn w..,,«wm.~~m—we rm«Antw-12mm gﬂMéorrelat1on lath and cerebral dysfunction or organighpsychoses. muv maxim» we. \\I ‘\ \ 111; {ZENWWf’IﬂWW showed no can be concl EEG ‘\ ‘15 um! recall? These indices respect, \ \f transient despite continue. treatment. ‘ WW“ Rh “met”. WWW”, ‘ "New“ ewes V4799» “new“.y‘d ”fI M 51““? ﬂag“ ”Why �* Semen, these ethe:ee pemttethe �5M5? Vt m WWM in mamm: Relating at Induced Mu nativity to WMum, Roam Dunno midonblo study and shock mom Wind ahcck 1: menu. the man at Recent tho m enema (9.6mm, at wow-1cm «that. In Mm own... chanson u a, the basin no have: obnexwd n mum at chasm of am. And) hm tor tho 01mm- rolnucn comm chum inmaumdhmmncMmaadthamquRw. hmmmm hum batman clinical Wt 1'ch emanation taunting orientation and olcctmahock nit-h changes in Mam whnrbi’cal ( mummmhngmgcf ).ondmxyandmu1( “My in 1mm: an mluaticn of ”mm mums change: function, and behavioral M, '11: our no mama 1::th mm. 0mm nan and Panama (1952) minim, up direct an an incur W. the observation b y various observers that clontrcmm change: in the olentmencoptulogm, with clinical syn-- ). Thoprcmt in thc thmnnoophalnsx-nm, a» ), slow alumni}: ta Imma- «mung In an exhaustive amm their may W mm c: than nth-tho sum nan fez-mum arm clam-la shod: mm Wmt. such a! Watt tmmt but the favorable therapeutic mmmmmmmommwnmmrﬁ �tmm in tha dame of tone» Wt Maul” each m can, we we abnormality noted with the hem my rahtionuhip patient: vary comidenbly in am number of hmmts, it Em mango: and is War anneal largely wincidental or maul-11y mini-ad to othrrr factors.” Yet, the alwtmcephalognphie chmgu mmnt. and Most new Wen wltagt 611:8.an that fast. tin; and in tho who activity is dimuy mum mnﬂsm ( Bach L» law. ﬂuent: wha have intensively In View electromock, or the it dam, ), The to than {W appears than is a duration and mummy m W ind» in percent slowing at tho meat of delta Mar afar-and m1 and tho and with mtarlor mind in anterior aleetmmeﬁmomphic received twelve to wimpy ramming my be 1:: voltage and W. ( of wires treatments per wok, the diuppear in us new uWhock are con:- The” in considerable nativity in mud]: ”metric, plum mutant. «hatred», In dootrowophﬂm. no Imam. by mart that elactmshock Mm mm» ) ( accrual» ), bath wtivity in paint“ persistent alpha ( Maud mutants dammiognphic a» last mama; ctr tho ( mum: am mu bum max-meme and humeral a. schedub effects usually ). olcotmmephalumphic to an weapons. to that a mktionahip dam changes. Tia swan �.3... do ”human. indicate we}: a Mod a relation human ﬂung» in than :3 spa) and WW MW MW“, behavioral Wm: pentam, elicited characteristic of tmﬁwmt tandem thin xeuuiy EEG Vchanges ungular to m 209—350 m! mum, ”than and. continua-nu m banana that thaw eluded: want-d by 113sz men buﬁenlly m mum its mm changes were (39th of and to 3 which in» Mm, high cps. with voltages up 30 $9 60 seem. when the its thiopsntono increased «creased mum ta typical a. 2 at activity, mu We spread “ﬂy in the ”sunny appomd, slam warm harm. than. mm unravel“ resting more! mm and tmta only to ran in every subject. continued treatment. with to Winnie, cmsgd «puma. Whoa; an. ‘ mapma del‘hn' Wang... A: fem. nativity inerumdu with W” of (3.91:6) w ”want #130 tut activity (mu 9mm, aw; (1951), reporting the cm apart. Renal-ad 33 9; Momdont clinical mung; atbomionl behavior beam man: with 3 m Iﬁ an m its bum tummy... the games: at Waxy, and cam m change does not insure mmzy mmﬂmﬁpmtnmoewmmfailadtaréxd‘bfwlongw h * i’mﬁ and 1mm G (1'9 H u ”I ) won-m “a “mm the behaviaml comﬁtim. ‘ ‘ " :51, 9" L‘lig Yr ' II": .,,i‘3l’ ‘ V �4‘. he than tmiunf. wants; ﬁat ulaudtothcmmnge 1:33 the EEG mm militia“ patient» clung“ with ﬂat therapeutic effect, tin patianta dueloped typical dung”, pmt in 0.1mm audition sound is W by tho lager-1w cf 1.9 b- «mammotof «on, we Ifmara it most» 10111:! that. the physiological hula far in. W311: any or my not pm affective in mixing waver-y." Bow thee» mmmogmphie are Mixed, ”pom «pm-m 1 solution batman the dams of elect“? change Ind cement-mt behavioral suspense. Different aspect: namely delta mm to barbiturate activation and beta. not. ivity. In tho present impetigation, quantitative aerial studio! of the dart: anyone. were undertaken to timer the following quuuonls (1.) What. in tho "lama! of the elomcophalqmphie mama to be- havioral responu 1n electroshock? (2) I: a "hummus: «mm, :1an aubgocta 931; what signification my W’ at prior ta a) In the tmtmt, 8 chums). ﬁnder-It. bipolar, hm tor an under. of tho process of electromoek therapy? 1mm semi, tmnty-four Maw wa- ianta referred for chetmhoek were studied. do!» 11-. mammalogrm an tad at. weekly intervals during and after treatment. wing destromcwphnlognph and noodle and hyperventilation chem. bonding in mmum m mum emu each molding. �' mm Commuting, the at least .6. was scanned for the slowest frequency identified twice in any land; the highest voltage of any delta wave; and. , the dur- atian of the longest period or delta bum activity. mm basis or these five indicate! eleven” nativiwma racom were phoeduinnnkordar,tmthomtmmto£dauwmﬂtytotho lowest. recordanudividod into The 160 3 mu m- m thirdm classiﬁed as “high degree deli: a records"; the middle third, as fmdemto dag-no Fignm delta a records”; I, II, and and than lowest min! as now degree delta III portray pin-mm mama.- and treatment records taken am- inguwlwtmatmntpomodtoemlitythethm rangeaofdel’aamtiuty indwed‘hy electmahock. b) In a second shock some at raw-tour mun, patients, ehctmncopmlogmpluc moon!- lent. ,Mﬂng tin treatment. second and third 531133 records, the wore obtained mks of try-stunt, initial observations were tested in weeks x after «comm W m: mum on A11 of max-aw. after first eerie: of 160 I predictive haw ofthemu patients were The prior to treat-- and two ween the named of analysis developed in the pantie response. mmmxg unselected electro- W m- at 1am «at. patient“ mupomo to the bani: at the resident “psychiatrist’u 15leth m mm, the nut: > �.7... opinion, the man's not» apex-visa in and the 61111130. evaluation of tho charge of elwbroahock. The pntients were dived-d into three groups a mob academia]: uprated and mama, A. WM! mama which «an aim: themaa‘lmtu «coming to the following criteria; :3,an These punts no longer shmd the mm Th. 11 or Inn-had immanent. hmgIt than into mm .. group were mended the 116mm; their doctors folt they warn mum and ﬁleepuithoutmdscant-ad mkupactaasbomgamn to nation, better appetite, an! capmw to gut along with others improved and ‘ participate in B. mm Mimi pmmnt but cmtimed to try'picany shared gm, Each activities. but the The units” mm mun amt!» 01111130 K. idea, or We: m when than; a , m less 111. The a» haunt! teatum night he evident in tho first. group val not apparent . no m noticablo disturbance such an obsession). somatic pmccupauon. raved: mum not clearly noticablo, mo or who beam worse. may showed tons é! loam illness. mane 1.1191, 3&2.” mute dopresiive patinnt conﬂwd to thaw thinking, paranoid lb: patients in thisgmp showed change: were not mmn placed showed equivocal new patient-in or transient changes, ﬂuctuations in bshnvior, at sum, treatment, they appeared Inch as before; however, no that times- appearing by the and of �Mesa the analyses of the mlatian batman the delta activity and clinical ratings, denominated between the proved" early appunnce of high @3290 delta nativity and the classified 861 were in the third week in patients and 88$ who were or third in m who ”lunch won rated 13. u nah high degree 691%! in the second week; 91% mutant. 0: the raced: fourth week of rated as migrated, none wan high degree delta in the weeks at tmtmnt, aim ‘1: The and 20% tare high degree delta 21 the mnsudin mu 1, ma graphical; in ﬂgun h. can fourth week. a induced significant relationship clinical rating» 0! the meow in mucus. mmved, second 1 acme or m a i m 99am Delta mom m Indian W (7) Wed Imam-d 85:113.:- measured Mam: k} (u) 6. ( analyses mm indies: 91‘ of bursts, highest Men M 25 an 91 as o 3.6 50 M o o a an for the rolation hem-n each of mm (avenge S-Mm delta, mm, M. 133 and slowest highest 5mm an... they duration frequmy.) me the clinical rating!- In each instance, the relationship or degree or induced delta index and the clinical rating was sustained. This data will be pramud in detail in a �submmt ”port. taunIndaxotnu- 2. Em mmﬂmtaﬁm, contubulation art! dmial ion: 1' B of. 11111033 in a ”matured latex-via after the: administration or intravenous mobsrbital in patients ﬁrm brain lacuna have ham sum-mm as signs of 13mm arm noted such patterns to ba illness, unless than. was evidence «and probable, themfora, that persistently tum mum or new” cerebral 11' mot subjects, ). ( We had m- m putientl hospitaliud with mm. mum elsutmahock indmed patina nmbarbim tam Wild «ﬁbril be produced. mmmmmu ( ). It dysfunction, This was indeed mp0M< ). 1n ma, mm (58%) and 10-42 fourteen an 7-9 the m period, an am mum that um; report, nu mm cerebral dysfunction (671') at the 2h subjects, had positive period. In than Maw—four subjeotl, than new ninety-one to". sessions during the mac ital tests of therapy for which smear-rem; chumphalogrm and ambush- are availnble. Pro and poet mutant. records are not. mcludod. mmmmnmuummummamdmmmumuw sham a high relationship, both ratings of immt delta wﬁviw a for the tests to each other, during therapy. In Tabla W II, as. and to clinical degree of induced with the results a: the concurrent mbarbihl mu. �W TABLE KEG II 22m .. An___%mm W rat. at Hicidle 313x Low Positive (25) 29 a 8 Negative (us) 10 15 20 Watan relation between the test data and clinical ntings of am also simiﬁmt. In Tabla II, the ma and uobubital tout. results The me'dingtothoevomnl mmmmedgmp 27%,(5 m had n umber of with. gamma test mctm; sad” that tho cluster at with. nomad, high Em delta activity and mummy in» clinical rating. W Vi M proved rating 3.: 3 negative mm Wits). mung a: om. Email: alluifieant in the cluster at test, 19' 1nd Mo me an: activity and clued. Wand. Rat /m m\ rod ma Hunk High Dam and roman Amebazbital (29) Either Positive 33' Dam or obaz‘bital (26) hither High Dalta not Positive Amobarbital (35) Iv Immed r. M W Result! an Moderately Impmvcd 25 3 10 11 s S 1.0 21 3. Thedatain'kbluEmmnhumtommorotabmmtimdum n Simiicant by elm-aqua :t hotter than 2! 1m). of conﬁdence. �the course of therapy in the any are rater} uriy m the It and at We initial twenty-atom petimte. ra’cdsrxzvttl who me): improved tend to develop high degree a: treatmnt, Table 1) similar and sustain ohnmtionl, it throughout mde for the are gnphically portrayed in figure 5. A EEG delta. activity the period. (ﬁgure murbitel test result” Waite of figures it and 5 presented in figme 6, which chm e mmrkable eongmm of the two 3. am to 0n» ‘ » Following the observation: event? is test date. 2 in this group, that the mch :1de patients had developed a high degree delta neurity earl: end had untamed such activity, electroememalogrm were obtained during the week: of treat-ant in undertaken Sh second and lelectmdxock consecutive patients. This study to detenine whether or net the demo «at-delta response in third in pro— dictive of the wort-eta“ thermontic outcome The recent: were sound hand during both, one a to whether h1g1 degree delte activity was who or neither of the h~6 and 7-9 treatment periods, and the data was related to the clinical «elation TABLE I? (Table IV). �Ono "W, um (16) 20 um High (1:) h (25$) a (50%) h (25$) 6 (30%) 7 (35$) 7 (35$) . Total (9‘) "' ' m 31mm 22 at the 2% 19 level of confidence; 13 �«42:» or the 131518!” the Mint 111$ delta ”tawny during tho ”00nd and third mksoftmtnant, éﬂmmuduuwhimmd,mhmly3motp:mu diluent high delta are so mud. The sum inﬂation and dome delta activity in rebut! to the Short ton The arbitrary solution of ma second based upon an 12.15 6100ka trauma. mtotmm Further sax-ion and in which the W delta beauty, persistence of 6113100. mlmtim. third week: of tmmnt was mags tmtaont of this data Wul 1&1“th m course m that the div-lop» 1211le fort. at mm:- of weeks, in round to mum: at of immanent regardlesa of tho tine in the course of thump: II continua: treatment in after 15-20 am trauma, m delta mhngea no first. manifest. subjects resulting in high is associated with 9. MM this later period. Patients given many m dolta activity Won]. msponm at mama n the at. per weak, without the mention of high dogma delta activity, a United behavioral responu an - one that is M mwm mt 5.10 placebo responu ( Diﬁuaaig g of three tines Wm“ significantly different than ). Intansiw uranium. at a. fmqmoy of relultant induction or high dogma dam act- was: per ivity, will damn-cu not. Thu, :1 aignifimnt behavioral name. mesa studies duonstmte a consistent missionship batman the degree and duration or induced uhctrooneephalognphie delta utivity and clinical �‘13- enlmtim at behavioral change. 3ymetr1o 1m been and automated» We at tho evidence of dysfunction (mama; centers and dyerhythuo delta system) mam (own nativity WW Strata»)... and Such indioative of an alteration in the state of consciousness, also activity is new alteration bang unouy related to the aunt-10h, mum with more and frequency and (Strauss slow Bid] wane June, et the :1, of aotivity Brit). and behavioral between Muted one. rolationohip county We m the further electroshock permit: after aspen” on. mmepmm mm no: attendmt pluliologio basis of tho electroshock shock process thus physiologic “mat We conclusion that ohangee in aunties: prom. in consciousness an 1L o No upset: of the electro- elaboration: the mention of the to the behavioral response mm neuro- .. and the eigniﬂoanoe of these observations for a theory of the node, of action of electroshock tangy. (a) Role Won]. cerebral 2mm. change Changes and perception, prone”, whatever cause, ore In this dependent 9%. \mieteot 1: a moo-pennant in mm, Mt extmively mm, I of alteratim in ltti‘budl, judgent,thooght attending changes in cerebral Motion, documented rm liter-store. in the noumlogic electmahook has hem mum to consistently teat emanation, in a {whim Mob we alter two in- have con- to associate with �431). i has biochmm substrate or this mu- away. mm mm has hem placed an tho noctylchonm—ohonmstomso changes a (ﬁnest-in, KeEwhun), tho “Iteration 1n blood-brain burner (Aird), chug» Tower and in ionic prance” has and promnqunbm [9’99 “/fsrué /'(ﬂ’ I‘M? 7 ,r‘ L. j 44“! [Z (3916301 and 31113391 x w A“? 5 1:34: ; I; ' ‘ 3 g a f ff V M v 1 .-‘ - mm), L; z r g» ﬁggéfiten/ �orient-p with extensive In impatience an function. cerebral of altered states am after wherbitel, tests” mama ( Wemauin and his ) ( J ( o be” dmnetmted the pmdictiw mm of this test for arsenic cerebral Winn. Davie workers by ee extensive met-cue experience likewise, Oawendom( )and-ng ).( ), Oatmmdstnnae( ). mum“ ()huefﬂmdthe altered in e hm Matias. W ‘smu signiﬁcancecfdiffuee other tests of unbral mm been applied seriel reunion, it. is anticipated that than, too, mule! dum- mum sponse, within the in cerebral 30.6 delhectivityueninduet chengee W tmtmt salmon to vacuum re- and e units a! the sensitivity of the test. to reflect change! mum. lame mam, elmmwbeuidtcbeenthcdormmge muctﬂundMiantoerMMOmrwachime behevicral respcnae. «diam The mac of belmvioral patterns induced under these is wide. 'Inprcvemnt' being a subjective evaluation On 1e 3 special one at behavionl the part. cf the name, charter that the patient 1: ‘bottor.’ Electrcehcck due not induce “immanent“; diffemt than it indwcs a mum of cmbml activity in men behavicr To the extent that. the induced behavior in deprecaed permeate is perceived as lose whining, depressed, mane 18 or move, before electroshock. or in achnophrenic patients, �.1;- 1m maximal, proved". behavior, Wham complaining, or typo 9! “an. evaluated to. as is patient mm, wmmry or harm, am, 1+. 1.. in pamuivod a: mom, mum, «ammo a; 'milprovld.‘ The paranoid, woman- Warm. pattern induced by electroshock, is «pendent on a m mm, «mammumauyam-mmtt )ummotpmm. lumbar cramp]: o! the relation be to is laﬂw dolt( ) ( Meow m on the of. electroencephalographic mural mom me: to be- of epileptic patients. ban» )deaeribuoymgapﬂspucmm ordinarilypleaant, and cooperative for his clinic visits. consistently dyarhytmc. drnm, and his 1336 0:: on. occasion he 12. than. no: cum}, an ‘1th delta activity. on the that, records m unable and 31th- mbaoqmt visit, tho m was again dynamo-ac and o a behavioral 'zhtpromnt' nu ma. 51:11::- obumtionawm roporwdbyﬂntt( )mdnnnndor( ). (b) Theo Our , of Electron a . 7 _ studies of the electroshock procesn have demonstrated tho ing. ntemtion in brain function in induced only in whom the greatest degrees of behavioral change max deem delta. activity in the taste as indiceu or altered indioea and sustained as noted. Wannalogm and follow— in patimtl is have mailed positive mobarbitll «:0an function, with the knowledge that other at altered brain Motion, applied in the m sex-1&1 fashion, my �‘16-'- alee show We 3mm alteration and a relation to behavioral change. have been mmeeed that the rating: pf impmvemt are value Judg- ment- of the behavioral response. L11 patient-e induced by electroshock in when cerebral wrest changes in behavior. changes are My certain patterns ere evaluated ee immved, believer. while other! are regerded u "unmoved” Immutiaeeenuespeemeeeeefthebehaviorﬂ. mammoftheeuba of the conditions brain altered function. We Jest recent etudiee have netted a relation of the indueed botanical Our Home was to epeeific peremlity aspecteC ).. Patten“ the neat close]: apprm-mte the “explicit verbal denial" personality greater degrees of denial, dieplem, mu ), ( euphoria and Indie beim'ior (tuning electrosheck therapy. and: edeptetime are frequently rated alarmed", and no clinical my mum at! ”m that the reletieaehip between nationality, behavioral response mm is met clear. to the behavioral reepenee The mutton of other upeete of an new ﬁnder investigation. bother new in the nun: of taproment to the induced W103. 1a the environmental w new endeegativill ledificetim Tb of inﬁll, withdmel to excitement, overactivitw and irritebility my be considered e positive movement by may. The the met-cps.“ but a disorganization by the and maiden or goals of the therapist and the family, and their meantime �4.7 bSnoh phyeiologic milieu for an ultomtion the altered cerebral tmotion provides of the organin‘e edeptive interpersmol behavior. Changes are induced in percep- tion, language, mod. recall, and Judaism mick ponit adaptive intonation: new with the omirmmont to unfold. the type of adaptive behavior induced under these conditions which the is dependent upon the pereondity of the subject; the environment in intonation occurs; and the duration or the state or altered cerebral Man. i similar view of the electroshock process m initially expressed by Weinstun, Kuhn ( Linn and chungoe and behavioral ). who mailed the interrelationship or neurOphyeiologic room”. These etudies amplify clude anothar index or oltered broil: function and «e their obeorvotione to in- the eiootrooneuphlograme delte also broaden their initiol empheeie on the denial pmcoeo fol edeptative response, to include no the only cameo. 0. wide variety of indtcod behavioro under the conditions of altered brain faction. The description of the electroshock procese is also comietent with the observations of more 335;( ), Roth ( .) and Lire 59,5 ). This neurophysiologc-edeptive interpretation of electroshock pronides on operational definilan o! the process which has procaine or further elaboration and obeemtiono. Such an hypothesis also hoe application to an understanding of therapeutic process in insulin com. therapy ( ), lobotav and tronquillieing agents ( )e �.3transient in clinical condition improvement seemed to be related to the in these patients. If we are correct in connecting the EEG changes with the therapeutic effect it would seem, since most of the patients develop typical changes, that the physiological basis for imp EEG change even provement is acquired by the it may or majority of cases; may not prove I effective in promotingxrecovery." In the course of studies of‘g§:ered function brain induced by electro- at the Hillside Hospital\in New York, further data on the relationships between EEG changes and clinical effects of electroshock were collected. The general results of previous investigations on the alterations in the shock EEG with electroshock were confirmed, but between EEu effects and the ailgs‘ca,~ clinical result a demonstrated. was \ I are presented today: (l) The definite relationship . Three foci \\ Engpatterns following electroshock and thein\re1ation to K improvement. (2) yThe intercorrelations of different quantifications of delta activity. (3) The relation of these observations to /////X ”WM SUBJECTS aﬁcijLQn.1 "ﬁ-"MW‘ _ i.-..mwm_w~w T /{1 Ionic ﬂ _ merm”wwww‘wmmm,._V.-c.-»...«——v—~~-"'” aim,” Twenty-four consecutive patients U” §§2_MEEHOD:Z§ _ -m “ﬁlm“-..— a theory of electroshock shock were studi d. "“‘m'w-"MW referred for electro- m4 Electroencephalo rams were done "511* few} 1/4?! Lot/W a“: channel Medcraft instrument , needle electrodes, prior to_treatment? “Ki 8 and bipolar recording was used. Hyperventilation wea-the-ealy-activation 6034’ (L. WLALF Q44. a, ‘ technic g treatment, records were taken earths day'aitasrar?;ézﬁé'"v*ﬁ‘ gurum fitter treatment. generally 25 to 31 hours MLWe 0%, 3» 1'9 CL �this point I should like to summarize our findings and express some thoughts as to their significance for a theory of electroshock action. There is little doubt that electroshock induces delta abnormality in the EEG. It is symmetric, chiefly frontal, but with increasingrtreatment, the'gequencies With became treatment leads. to spreads increasing all At slower, the amplitudes higher, the burst activity longer and more regular. While delta abnormality is present in every repord after electroshock, its degree is variable. Roth's experiment's inducing increasing delta abnormality with barbiturate are significant in predﬁting the later changes induced by further electroshock. In mality some subjects however, a high degree delta abnor- is not induced despite extensive treatment. Our correlations of degree of delta abnonuality with improvement are fgggziéam:ch ism of electroshock.therapy. significant An alterationm cerebral“function and also by the ' as measured by the magma as, amytal test,* ,t'necessary pre-requisite for improvement. EEG, zaﬂkﬂ early, sustained Where such 232:::: (and in the amytal test), chan es fail to occur in the a significant clinical improvement will fail to occur in the patient's behavior. not4ﬁghent The fact that the correlations were with memory loss, points to the possibility that this is not a significant factor in improvement. EEG In conclusion, these studies lend lapport tp a theory of EST enumerated action recently by Weinstein and one of us (Kahn). These authors postulated that improvement following electroshock is the result of the creation in the patient of a milieu of altered brain function in patterns of adaptation, particularly those of denial, may be maintained. Theib EEG studies demonstrate that an altered milieu of cerebral which new function as measured by delta abnormality is a pre-requisite for improvement. To supported. this extent the first part of the Heinstein-Kahn hypothesis is 4M.-. .1 �~5During the tram generally 25 be 31 11611113131381an ( the ) was period. words not. noun lam. Emu-mm, We... may“! Wu on a» ﬂy, following a trauma, all Wit”. test 101' at many intervals, berm, during ”mat “him the Wmtnont WI. manly been mported pntieats organic brain and study mm hi" ). ( thaw-ml electromook tharapy m manicured w the mt: manhunt“, tins using a Bauer 0 h? eleabmatdnulator. Treatment schedules. war. three a week; and the number of ,, Won arm- thorapy, reﬁll“ at this The all!!! wore studied by matmnu varied from to 33. 9 As patients show-d a clinical response, the psychiatrist tended to give fiver and more widely spaced treatments. Thorn are 15 women and 9 man in the can“, and the ages authaudiuoth'h mezhto EVALUATIOE 93‘. ject... 33 3'0nt for three lead “natal-ear W: total at 3.60 records were obtained in muse sub- Stmﬁss ( ) the delta index was the suggestion of minnow 10210) A 69%:de (frontal-parietal, anteriar “moral .. vertex, for 180 seconds of recording for each lead. 1: defined as the per-cont tine occupied by waves at 7 0:16 The delta or SWCI'. and 1W The <36;th and load the highsat kit: for, three the combinations, average 1mm in any om lead combination mm the indim used in ma fin-1 inasmuch. �«17end tolermm', are significant factors in the behavioral nepense of the petieet to therapy, am also, in the rating! a! mane effect. sue teeters an signiﬁcant in the The induced changes improvement. duration of the electroshock in cerebral function persist for 24: weeks only following even intensive courses of ti‘xerepy. In respenee ‘ W eases, the behavioral tenatedtemepeﬂodotalmmmmniologyo patterns of behavior we not adaptive in the mum Thackunged of the patient, and the behavior 'regreeees' to pun-treatise“ patterns. In other instance, the induced behavior in adaptive to the envirement. end, we assume, sustained therett‘ter not by the initial change in brain Noam, developedintencﬁenof subjectuithenﬂmmt. is seen by the milieu is may embd. linen in which 13 cheereetm have doctor, have, and peanut. stem a 1:1in or many. led to the conclusion that electroshock a non-specific induction or pernietent discharge mptive (pemnlihy) utilize devices not otherwise available ta - the mm when Altered cerebral fmetion the subaeeb’e different interaction with the envimmenﬁ These matmiswm only to have a mazrrence of disgusted or discharge in prelude: the pbyeiologic preceesea the newly fmeent mememl adaptation of the patient to the hospital after electroshock, planning but. b y of altered cerebral than” mm. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Relation of Electroencephalographic Changes and Improvement in Electroshock Therapy (research) Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-7-007 Date A point or period of time associated with an event in the lifecycle of the resource 1957 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a>; Kahn, Robert L. Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence: research with Robert L. Kahn Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/371617534179d54e66d61621a46020c8.pdf 6e55d00563bbed3481f9a9906c445b08 PDF Text Text therapy, we hue ahead-red at individul wide response. Subjects duomtrete sue to equivalent number: or induced veriebﬂjkgy 1n digress of minim. EEG the EEG delta ee’dvity In the observations observed the to teeters of to be reported, the reletien webologic variability is amend. mam Ed Hethod: referred patients consecutive heapi’oelized malty-dive slammed.“ M with wire tested Subjects studied. therapy were ‘ im’TA‘MVvV «Ov1 M W the tor Bottleneck end ~ ~ within a week prior to treatment. ﬂeetreemphllo— wmdompriortotreemnt,endetweek1yintemledunng treatment. The records were wt! for the degree of induced deeoribed< previously indieee £5} activity using quentitetive Bad; petienh wee or imml’bbq Medea-eff. 5? Gem flaw. Reﬂexeither using week, times a three trotted instruments. I «M—-W-nuzwm: .4- HH' an. -\'. [UK/W Clo.) f‘ru’f a?) �heults: 1. Subjects with 1! and FC human moment (H), fem-color Rorschach responses showed induced delta (PC) signiﬁcantly lesser activity than subjects who had no such or bath amounts of responses. 2. Subjects with fewer Rorschach responses (R) and fewer total moment (Home) teaponses of delta activity. m 3. . The .. higher the malted simificantly greater degmee Wmmt «L test, the greater the «rot-beers on the degree of induced delta activity. gnawing: These studies describe a consistent tram perceptual responses and 041v w relationship between pre— obeemd degree of phtsiologic alteration following repeated induced cerebral trams. While factors of current, skull resistance, inherent responsivity of brain, 239. may affect the manifest physiologic alteration, that the subject's usual test eeores) affect the the EEG nodes of adaptation (reflected in his pemptnal physiologic response to cannot be viewed as it is also probable tram. In this context, in isolated physiologic index but is seen �Conclusion: Individual differences in the ma activity are related to have Insurer as latter the” differences in perceptual petteme. been shown to reflect pereomlity differencee, we would the individual'e node of adaptation ('persomliW') ﬂ“ Wﬁest chengef mtg; Physiologic ‘76 5359:: (me). suggest thet Wed—be We EFFE‘ ’1 \ would conclude that those aspects of experience and edaptetion that effect perceptual trauma. me the to at affect also responsivity tests �It't'f7 7-..“. Psychologic Factors in EEG Reactivity to Induced Cerebral Dysfunction In the course of an investigation of the role of alteration in cerebral function in the changes in behavior induced by convulsive therapy, we have observed a wide individual variability in the wide denonstrate degrees of Subjects response. EEG EEG delta activity to equivalent numbers of induced convu1310ns. In the observations to be reported, the relation of pSychologic factors to the Observed variability is assessed. Subjects and Method: Eightyafive consecutive hospitalized patients referred for electroconvulsive therapy were studied. Subjects wire tested with the Rorschach and the Gottschaldt embedded figure Sinai Modification) within a week test (Battersby — prior to treatment. Electroencephaloat weekly intervals during grams were done prior to treatment, treatment. records were measured for the degree of induced delta The and activity using quantitative indices previously described. Each patient was treated three times a or Medcraft instruments. week, using either Reiter �Results: 1. Subjects with H and FC human movement (M), Rorschach responses showed induced delta form-color (F0) or both significantly lesser activity than subjects who amounts of had no such responses. 2. Subjects with fewer Rorschach responses (R) and fewer total movement (MWFM+m) responses Showed significantly greater degrees of delta activity. 3. The higher the nambeehefepre-treatment error.score on the Gottschaldt test, the greater the degree of induced delta activity. Discussion: These studies describe a consistent relationship between pre- trauma perceptual responses and the observed degree of phisiologic alteration folloWing repeated induced cerebral trauma. While of current, skull resistance, inherent responsivity of brain, may affect the manifest physiologic alteration, that the subject's usual modes EEG etc. also probable of adaptation (reflected in his perceptual test scores) affect the physiologic the it is factors reSponse to trauma. In this context, cannot be viewed as an isolated physiologic index but is seen �activity interpersonal in the setting by influenced as one that is of the test situation. Conclusion: to related are EEezeactivity the Individual differences in have these latter as Insofar differences in perceptual patterns. been shown to reflect personality differences, the individual's mode we would of adaptation ("perSOnality") is related to (EEG). index the physiologic in manifest changes that those aspects of experience and adaptation tests suggest that also affect responsivity of the EEG ‘We would conclude that affect perceptual to trauma. ��_..,,, WWw-w ,, .w ”m.“ "Wm“. ‘WW..‘M_ . ,, ’w m—w"'1"‘mr-' W'sw-m-v-ni w ar— w..,._r..._.c ‘11ij ��EE 4» mm 0%; MW I'quw. ”a Mme-(W “,de '. d2. M + F6. Eneu. MwFt 0“ 2° (FMm) 2o " H. M ‘37) H’ (1.9.) e (:42) 6’40. 3 (I57. ($71 “-— .1 E4“ O'C) H I§ «2.) I2 Suﬁ.) (4°74 lo (“74) ‘— oS' - Esr' 0-4 .154; -3": �W M l4. 2 ,2, mm“ ' ”W 3‘!!- 4.6 ”M -?.I 2-! c. 2. 3 .0! non-I- ”*Fm-Ihs (a: EJfI-‘Il .(«y-h ��// 7%2.4“; M»! é 4,4...» r9 x‘W W. 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II 4+"I II III \' ' u {I � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Psychological Factors in EEG Reactivity to Induced Cerebral Dysfunction (research), 1957 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-9-008 Date A point or period of time associated with an event in the lifecycle of the resource 1957 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence: research with Robert L. Kahn Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/8ad71ef7a3c44154da4264a3d36d2625.pdf d939faed36329ffba731bbff9e10004f PDF Text Text An Objective Study of Communication in Psychiatric Interviews Joseph Jeffe, H.D. From the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, Read at the New York N.Y. Divisional MBeting, A.P.A. November, 1957. Supported by Grant 565561 of the Foundations' Fund for Research in Psychiatry. 14’! 10-1h-S7 �The clinical interview is the psychiatrist's primary tool for the diagnosis of psychopathology, the modification of behavior, and the collection of research data. Only in recent years, however, have the actual transactions which comprise the interview been studied objectively. Investigators of the interview have usually employed systems of content analysis (1), which are based upon various theories of psychodynamics. Currently, there is increasing emphasis upon formal aspects of interaction such as temporal patterns of speech (1h) drastic change of subject (3), PHYSiological relationships of the participants (2), grammatical patterns of language (S, 6, 9), and speech disturbances and silences (10). These aspects, in contrast to content categories, are relatively independent of theoretical preconceptions, and are more readily quantified and studied statistically. In many investigations of these formal variables, however, the total context of the interview. These approaches neglect the fact that the psychiatrist is a participant observer, i.e., a significant variable in the interaction (11). Others have attempted to control this variable by means of structured interviews in.which the doctor's contribution is standardized patient's communications are abstracted from the according to a predetermined experimental design (6, 7, 1h). These structured situations delete the very quality of living relationship that is the ultimate concern of the psychotherapist (7). methods of verbal We are in need of interaction analysis that neither preclude nor prescribe the doctor's clinical responses. The this paper is to present a method of interview a) is objective and quantitative, b) preserves the purpose of analysis which �.2... natural patient-therapist relationship, and c) treats the interview as an integrated system of interpersonal communication. This is accom- plished by including the doctor's usual clinical behavior in the data to be studied. the The raw material is not the patient's speech, but rather total verbal output of the "two person" or "dyadic" group. �Method: tape recorded interview The is precisely transcribed, without regard to the speaker of the words. Careful attention is given to subtle repetitions such as "I - I mean," "well as - as I say," polated expressions such as "you know," The inter"so to speak," "as I said," etc. and to transcript is then arbitrarily divided into consecutive units of 100, 50 or 25 words depending on the discreteness of the phenomena to be investigated. Thus a unit contains contributions of words from either doctor or patient alone, or from both in varying proportions. The measurement applied to these units of dyadic Speech is the typetoken-ratio (TTR). This is an index of the balance between repetition variety of words (12). The TTR is the ratio of the number of different words (types), to the total number of words (tokensL in a sample of language. For example, in a 100 word sample the repetition of the identical word 100 times in succession would produce the lowest and possible ratio of .01 of 1.0 would different result if (l type/100 tokens). The highest possible every one of the 100 successive words were (100 types/100 tokens). These extremes of stereotypy and diversity are rarely encountered, situations (8). The i.e. "word-type," ratio and then only the numerator of the in grossly pathological TTR, is arbitrarily defined. All words are different which are pronounced or spelled differently. Thus, ive, gives, gave, given and gizipgﬂ are considered different types, as are "know" and "no." Vocalizations not clearly " �.u-‘ identifiable as which is words are omitted, with the major exception of "mmhmm" a frequent utterance of the interviewer in our records. Contractions are retained as single words, but vulgarisms such as "I dunno" are edited to read "I don't know." The TTR scores is calculated for is graphically plotted, additional precision, the units may be advanced 25 words the last half at unit each as and the illustrated in Figures may be first half unit. This often smoothes the resultant curve. is illustrated in Figure 3. TTR have in a single person's language (12). 1 and 2. For overlapped, e.g. 50 word units a time, so that each unit of the preceding and the Previous studies of the pattern of consecutive is composed of of the subsequent The overlapping technique dealt with the overall average The sequential pattern in dyadic language. present method studies the �Observations: In the last eighteen months approximately sixty recorded interviews this method. The material includes forty patients in all diagnostic categories. The dyadic have been inveStigated by found to be sensitive to a variety of clinical TTR patterns have been phenomena (8). This report illustrates the changes in language interaction occurring during the course of hospitalization and therapy, as well as changes in rapport in individual interviews. and defensive operations A - andic TTR Pattern in Clinical Change. first Figure 1 shows the pattern of the three separate 1500 words of interviews during the clinical course of one patient. The doctor is the in each. This case same was selected as an unequivocal example of gross clinical change. In the first interview the patient was agitated and depressed. She refused to be seated and paced about the room, reiterating stereotyped self-recriminations, crying hysterically, with marked pressure of speech. At the time of the second interview, following a course of grand mal electroshock, the clinical picture was grossly altered. She was less agitated and complaining of a memory appeared more deficit. cooperative, although withdrawn and On alert, poised, conversational insightful. She had been The TTR of later, discharge two months and, she at times, surprisingly rated clinically as "recovered." consecutive 25 word units of interaction, for each of the three periods described, is graphically represented in Fig. 1. Consecutive points are connected by lines so that the fluctuations in the graph reflect the difference between successive scores. The mean TTR for �~6- the complete interview from which these samples were taken is represented line through each graph. by a horizontal strates The a The fluctuating equilibrium about the pattern of scores mean. interviews of these three successive stages changes. The mean demon- show a sequence of level of the interaction is seen to increase as the clinical status changes from psychosis to "recovery." There is a concomitant restriction in the amplitude of the pattern, i.e. a decrease in variation about the mean. Comment: The sequence of change in the TTR pattern parallels the progressive in interpersonal communication that improvement clinically. was apparent This suggests an approach to the quantification of clinical change, defined as an altered pattern of verbal interaction in the interview. B - in Communication‘within the Interview: Changes Figure shown 2 is an enlargement of the in Figure 1. first of the three interactions Here the sequence of changes within a.single interview are examined rather than comparing the patterns of successive interviews. As described before, the patient was speaking continuously in a disorgan- ized affective outburst. mﬂrich The lower line indicates the the interviewer participated. Following remarks, units 3 - 12 ﬁne 25 word units in doctor's introductory represent the patient's uninterrupted speech. Wide oscillations of the pattern are prominent. From samples 13 onwards the doctor made repeated efforts to communicate with the patient. Two independent judges reviewed the transcribed protocol, and both identified three areas in which there seemed to be an understandable, rational �-7interchange between the participants. These periods are labelled "rapport" in the upper line. tions of the pattern are much During these three periods the constricted. Compare oscilla- other non-rapport periods such as 23-2h and 39-hl, in which the doctor's participation amplified the oscillations. Cmmmnh This illustrates a method of quantifying interpersonal phenomena, such as the degree of "contact" with a severely disturbed patient. The affective pattern in this patient represents the psychotic integration, for this reason, the occasional occurnnces of conventional,rational conversation are described as periods of "rapport." The restriction in and the amplitude which characterizes these periods is similar to the overall pattern at the time of "recovery." 0 - Analysis Figure 3 of a Complete Interview. initial demonstrates the dvadic TTR analysis of a complete interview. This interview is the discharge evaluation of a patient had been hospitalized following a months of hospitalization, she who bizarre suicide attempt. After seven had "improved" clinically. This took the form of a hypomanic mood and a gross denial of her severe emotional conflicts. word The interview units advancing by is scored by the method of successive 50 ZS word steps. The mean TTR for the interview is shown by the horizontal line drawn through the graph. The pattern falls into several natural segments. There are two areas in which ten consecutive points fall below the mean (areas h and 7). These are unusual in this interview. There are also areas of gross deviation �~8from the mean (such as area determine our criteria for 2). Thus we allow the phenomena for persistent changes in the TTR to be studied. In general, we look level, gross trends or sudden shifts. Several of the deviant areas are described to The objective pattern to illustrate the method. interview begins with a hypomanic monologue in which the patient visit describes her successful home, her euphoric outlook and plans for a rosy future. Area 2 has been delineated because of gross deviation from the mean. The beginning of this period coincides with a change of topic to her plans is interrupted by a period of confusion as she tries, with some difficulty, to recall one of the details of the job. The end of the gross fluctuation coincides with the rationalization "I don't think I'll have too much trouble." Area h was delineated as one of the two sections in which 10 consecutive for going back to her job scores fall two days hence. Her optimism Its beginning coincides with below the mean. about her depression on admission to the hOSpital. a statement This area ends with the lowest score of the interview which,precedes by only a few words a spontaneous reference to her suicide attempt. This large deviation at the end of area h embodies the main characteristics of the following area. Area 5 The is characterized by large content of this area attempts to prove at the is how much fluctuations above and below the mean. completely on the theme of suicide. She live. The doctor's queries with increasing resistance. In the begin- she now wants to end of the period meet ning of the next segment (area 6) she stubbornly refuses to discuss the subject of suicide further, at which point she changes the subject abruptly. �-9Area 7 was delineated on precipitous drop in the the basis of TTR, criteria. It begins with ”two a followed by 10 consecutive scores below rise. Its the mean, and ends with an equally abrupt beginning coincides with a change of subject by the doctor in the form of a question about her feelings at that the "you-me" relationship, period ends Area 9 when she in the interview. This content area, 1.6. moment is at a very It The of an extremely low score enclosed by two coincides with a brief mention of a meeting with a young man who told her how well she looked. remark and her statement These examples repetitive level. abruptly changes the subject. is delineated because large deviations. pursued "I decided to get illustrate areas him It ends with an embarrassed off the topic." of disturbance or disequilibrium in the verbal interaction pattern. In contrast, areas I 3, 6,,23 and 10 are areas of relative stability or equilibrium in the record. These stable areas are marked by a different quality of communication. They consist either of a euphoric, hypomanic monologue which avoids all stressful areas. or of evasion of the doctor's probing questions by superficial rational- ization and conventional cliches. Comment: Recent reports of objective interview studies using other techniques (10), have noted that the interaction goes through a series of definable phases, which may and successful defense and the events The stressful disorganization correspond to periods of respectively. The phases demonstrated here, that delineate them, suggest an analogous fonmulation. content areas that disturbed the pattern in this final interview �also did so the initial interview seven months earlier. we anticipate that the discussion of a subject that had resulted in disequilibrium but now no longer does so, may constitute an operational on definition of "resolution of an area of conflict." �Discussion and Conclusions: Diverse and highly personal interpretations of interview data limit the growth of psychiatry as a science. Systematic study of the actual transactions may lead to operational definitions of hitherto subjective it is likely that the patterns of verbal diversification presented here constitute part of the subliminal cues to phenomena. For example, therapists affect, etc. which reSpond when.making clinical judgments of anxiety, Objective investigations of the interview must encompass the behavior of both participants since the events observed are interpersonal processes. Gill, Heuman & Redlich (h) define even the initial interview as "the diagnostic evaluation of an interpersonal relationship." Reusch (13) has recently stated have the that “observations made in social situations characteristics of a scientific procedure in which do not one aSpect is studied in detail while all other variables are held constant." The method presented here is an attempt to convert these concepts into practical research methodology. It permits a quantitative statement of various clinical phenomena occurring either within single interviews or in the course of therapy. Disturbances of verbal interaction are defined operationally in terms of the configuration of the Applications to the definition of clinical change and pattern. transactions TTR within the interview have been presented. The TTR is only one of many quantifiable aspects of dyadic speech. interaction, time reference, and relative amounts of participation doctor and patient may also be measured. Further applications of these Pace of by techniques are under investigation. �REFERENCES 1. Auld, F. and Murray, E.J. (1955): Content-Analysis Studies of Psychotherapy, Pslchol. Bull. 2a: 377-395. 2. Coleman, R., Greenblatt, and Solomon, H.C. (1956): Physiological M. Evidence of Rapport During Psychotherapeutic Interviews, Dis . Nerv. 3. Eldred, S.H., sttem, ll: 2-8. E.R., Salzman, L., Meyersburg, Hamburg, D.A., IHWOOd, (l95h): H.A. and Goodrich, G. A Procedure for the Systematic Analysis of Psychotherapeutic Interviews, §§zchiatry, l1: 337-3h5. h. Gill, M., Néwman, R. and Redlich, F.C. (l95b): The in szchiatric Practice. Press. 5. Goldman-Eisler, F. (195h): A New York: Study of Individual Differences and of Interaction in the Behavior of Interviews, Jour.. Rent. Sci. 6. Initial_1ntervigg International Universities Some Aspects of Language in lQQ: 177-197. Gottschalk, L.A., Gleser, G.C. and Hambidge, Behavior Analysis, Arch. Neur. and G. (1957): Verbal ngchiat., 21; 300-311. 7. Grinker, R.R., Sabshin, M., HaMburg, D.A., Board, F.A., Basowitz, H., Korchin, Use m? S.J., Persky, H. and Chevalier, J.A. (1957): The an Anxiety-Producing Interview and Its Meaning to the Subject, Arch. Neur. and Psvchiat., 11: hO6-hl9. 8. daffe, J.: Language of the Dyad: A Method of Interaction Analysis in PBychiatric Interviews, Psvchiat , (in press). 9. Lorenz, M. and Cobb, S. (195h): Language Patterns in PBychotic and Psychoneurotic Subjects, Arch. Neur. and Pszchiat., 1g: 665-673. �REFEREEIJCES lO. Mahl, G.F., (1956): Disturbances and Silences in the Patient's Speech in Psychotherapy, Jour. Abnorm. Soc. Psxcholu §_3__: 1-15. 11. Handler, G. and Kaplan, :‘J.K. (1956): Subjective Evaluation and Re- enforcing Effect of a Verbal Stimulus, Science, l2. Mowrer, O.H. (1953): Verbal Behavior (Ed.) szchotheragz: T1139 1.2143 in Paychotherapy. In 582-583. Mowrer and Research, New York: Ronald Press. 13. Ruesch, J. (1957): Disturbed Commnication, New York: 11.14". Norton. 1h. Saslow, G., Matarozzo, J.D. and Guze, S.B. (1955): The Stability of Interaction Chronograph Patterns in Psychiatric Interviews, Jour. Consult. P§Xcholu 1.2: 14174430. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. 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Title A name given to the resource Joseph Jaffe: An Object Study of Communication in Psychiatric Interviews, 1957 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-8-009 Date A point or period of time associated with an event in the lifecycle of the resource 1957 Creator An entity primarily responsible for making the resource Jaffe, Joseph Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/c779b264e0ba3e779d39ff5db1a0879e.pdf d5ea2d1f830983dbe61a4c62d8e73b61 PDF Text Text Significance of Individual Variability in EEG Response to Electroshock Martin A. Green, From M. D. the Department of ExPerimental Psychiatry, Hillside Hospital, Glen Oaks, N. 10-11-57 "r .50 �Significance of Individual Variability in EEG The assumption Response to Electroshock is often tacitly made in studies of nervous system function that the capacity for neurophysiological change is similar for animals or humans in the groups under study. Differences in response are ascribed to different parameters of the stimulus or to differences in the location and extent of lesions, either spontaneous or experimentally produced. tion may Such an assump» Perhaps another factor in the not be warranted, however. variability of response under these conditions is an individual variability in neurophysio— logical reactivity or responsiveness. The initial "base-line" may not be similar in all individuals. The possibility of different inherent patterns of reactivity has suggested by the studies of the alterations in the have been impressed by the high degree of EEG been during electroshock. variability in such We alterations both in their quantitative and qualitative aspects. Although this variability has been described by previous investigators, it has not been stressed sufficiently; nor have possible explanations been advanced or systematically investigated. present report concerns a description of the changes in the EEG Hillside Hospital during electroshock in the/' material. The concept of neurophysiological The reactivity is presented and studies that may clarify this problem are suggested. �MATERIAL AND METHODS: Eighty-nine patients were studied. The patients who received electroshock for psychiatric illness Hillside Hospital and were voluntary admissions to the majority had not received electroshock previously. The diagnostic groups and schizophrenia. psychosis manic~depressive included psychotic depression, The largest group was patients with depression. Agesranged from 20 to 68 years, with a median of #7 years. Treatments were given three times weekly, each patient receiving at least 12 treatments. The Medcraft instrument (alternating current) was used 61 for current) for 28 patients and the Reiter instrument (unidirectional patients. Electroencephalograms were taken prior to, and two weeks following the course of treatment. EEG was abnormal were to 36 weekly Patients specifically excluded from study. 2h (from day non-treatment a an at whose intervals during, pre-treatment Tracings were done on hours following the previous treatment) with eight channel Medcraft machine using needle electrodes. Frontal, motor, and earlobe vertex temporal, posterior temporal, anterior parietal, occipital, placements were employed with scalp to scalp and scalp to earlobe combinations. �RESULTS : I. Delta Activity. A. Quantitative Differences: delta activity The to the method described by Fink and (8). Kahn The was analyzed according duration of burst activity, the lowest frequency, the average delta index in several leads, the highest measured. were lead one in time delta and the percent highest amplitude, Re— cords were classified as showing a low, middle or high degree of delta activity (Fig. 1) according to criteria previously described (8). All patients developed delta activity during the course of but differences in the amount of the slow activity and were very apparent (Table I). Some early in treatment whereas other even after serial 12 EEG's. not develop in treatments. As treatments of development patients developed "high delta activity" patients showed only "low" or "middle" changes latter patients were followed further with treatment was continued, a high degree of delta activity did some of these patients until on a daily basis. This individual variability in treatments were given change. These its rate 12 20 or more They were EEG treatments, or until resistant to neurophysiologic response was independent of the type of electroshock current employed, being present both with unidirecticnal current applications. alternating and with �- h TABLE Degree of Delta I Activity in Serial Electroencephalograms during Electroshock (2-n records were taken for each patient) No. Activity EEG No change delta activity Low Middle High B. may be ity. - EST 1 delta activity delta activity of Records in Each Treatment Period u L:..§ 3 l 37 21 7 3 20 22 10 1 28 #5 25 1 16 amount of delta the activity Although total Differences: Qualitative activ~ and of delta voltage to frequency records as differ type, similar, One prominent qualitative difference during a course of 12 treatments. is in the form of bursts which as treatments are continued. is the ratio of irregular delta In some patients the become more The show burst activity initial delta change frequent, slower and of higher voltage irregular delta activity in such records is less prominent and usually occurs at faster frequencies. In other patients the reverse occurs. form. 12 0 5 activity to bursts of slow activity. Nearly all records much - 10 Although burst Delta activity appears chiefly in an irregular and scattered activity is also present, third group of patients the amounts of it is not conspicuous. irregular delta and In a bursts are approx- imately equal (Fig. 2). These differences in the form that the delta activity assumes is usually constant during the course of treatment. At times, however, burst activity will �. become more prominent - 5 than the irregular delta only during the latter part of the course of treatment; or burst activity which appears prominent early in treatment may be overshadowed and obscured in later records by a large amount of continuous irregular delta activity. The slow activity is maximal electrodes and less pronounced at the at the anterior temporal more frontal and posterior electrodes. Often asymmetric, being of higher voltage, slower, and in greater amounts anterior temporal Only and frontal electrodes as asymmetry occurs during treatment both with is at the left to the right (Fig. 2). compared rarely is the reverse true, i.e. accentuation it on the right side. This alternating and with unidirectional currents. Another type of abnormality, though an infrequent one, of rhythmic runs of delta activity which (Fig. 2). The may continue for 10 is the to 20 seconds regularity of the frequency and voltage of the slow these runs is very striking. appearance waves in These runs are usually infrequent, but may be the most prominent alteration in the record. In many records the amount of delta activity fluctuates during the tracing. At times, some in other parts of the This variation II. is portions of a record same may appear nearly normal, while record the delta activity may be quite pronounced. independent of the electrode combinations employed. Spike or Spike-Wave Activity: A large number of records or high voltage. Most show single spike activity of low, moderate often such spikes are slower and not as prominent as �- 6 - those present in patients with seizure disorders. show spikenwave A small number of records activity. This is usually at irregular, mixed frequencies and, again, does not resemble the regular rhythmic bursts commonly seen in patients with seizure disorders (Fig. 2). III. Alpha Activity: The alpha activity shows changes both in amount and frequency. As the amount of delta activity increases the amount of alpha activity usually decreases. Changes in frequency occur but are not pronounced. will be slowed by 1-2 cps but tracing. In a small number at times will remain the same The frequency as in the pre-ECT of patients the amount and voltage of alpha activity increases during treatment. This change persists during the post-treatment period after the slow-wave activity subsides (Fig. 3). IV. Beta Activity: The fact that activity in the EEG many and the induce fast barbiturates, particularly sedatives, of administration the in controlling difficulty these drugs in this population studied makes during the course of treatment. are minimal. activity. The most it difficult to evaluate changes In most instances changes in fast activity frequent change, when present, is a decrease in the �Discussion: is that of the individual variability in the As EEG described, electroshock therapy. and of during alteration degree type and of rate slow-wave amount of its the activity manifested in: l) this is (amount slow-wave the in activity differences 2) development; qualitative The problem being raised of burst activity vs irregular delta activity, symmetry, fluctuating appearof 3) slow activity); of presence rhythmic slow of runs ance activity, Spike or spike-z-rave activity; and LL) changes in alpha and beta Previous investigations (2, h, 5, 10, have ll, activity. 12, 1h, 17, 18, 19, 20, 25) stressed possible correlations with age , sex, frequency of treatment, and clinical change. diagnosis, employed, of current psychiatric type Increasin" the frequency of treatment, for example, will increase the degree of similar sex, age and the with same the frequency treatments at given are psychiatric diagnosis same type of electroshock current, variability in the rate of development of alteration in the EEG. However, when "ratients their type anc‘. degree are still very prominent. One explanation for this variability might be the distribution of the electroshock current in the brain. Perhaps minor differences in the resistance of changes in the EEG and and blooc‘ vessels of the distribution of the skull, in their penneability or taken the pathways in differences create of tracts nerve in the arrangement the of brain portions different such Unler circmnstances, the current. by may receive more or less current in one patient as compared to another. variously these by generated of the electrical activity Differences in type affected areas might account for variability in the EEG. Available studies employing direct intracerebral measurements indicate considerable diffusion of current throughout the brain (6, 9, 16, 21). �However, a concentration of current anteriorly and along: large neuronal pathways, such as the corpus callosmn, has been demonstrated. No further infon'ration is available as to amounts of current received. by more Specific cerebral areas. Due to the high resistance of the skull only a small portion of the applied. current actually reaches the brain. The amount of current entering different portions of the brain is said to be determined by the resistance of the skull overlying these areas; the anterior concentration of current being; the result of the thinness of the temporal bone with its consequent lower resistance as compared to other parts of the skull (9, 21). Several considerations, however, indicate that individual differences in these factors of resistance and amount of areas of the brain are of minor, during-g electroshock. It is if current reaching,- different any, importance in the ELG response the occurrence of the generalized seizure 291'. §_e_, rather than the passage of electricity, which is the primary factor. During a course of grand-mall therapy induced by non-electrical means such as metrazol, EEG changes occur which are similar, with electroshock (13, 1h). Diffuse slow-wave in general, to those seen activity, accentuated of The amount described. are activity anteriorly, slow—wave activity increases during treatment but shows individual variability unrelated; to the n unber of treatments. Another observation is that electroand 81‘.de or spike-wave shock therapy nhich induces petit-mal (7, 18) or focal (3) seizures rather than grand-mal, does not produce the characteristic build-up of slow-wave activity. In addition, there is no increase in the degree of delta activity in our patients in whom grand-mal tae rapy is given with high suprathreshold stimuli as compared to those in whom threaiold stimuli are used. �-9- . Factors of current cannot be entirely dismissed, however. Even with grand mal therapy, the type of current employed may influence the we haVe EEG change. confirmed a previous study (20) showing that the rate of increase of delta activity is slower in therapy with unidirectional current than in that with alternating current. Similarly, brief stimulus therapy is said to produce smaller degrees of alteration in the EEG as compared to alternating current therapy (15). The EEG other theory to be considered in explaining the variability in re5ponsiveness, and the one which is probably more determinant, involves inherent differences in neurophysiological reactivity. By this is meant both the quantitative and qualitative aspects of the inherent capacity of the nervous system to respond to stimuli or injury. Not only the degree of response, but also the type of response, type and degree of EEG may have these determinants. The abnormalities developed during electroshock therapy appear to be the reflection of such inherent individual differences in neurophysiological reactivity. Several types of investigation Methods other than electroshock may known serve to to produce test this hypothesis. EEG alterations could be applied prior to treatment. These might include lowering the blood sugar by parenteral insulin, intravenous administration of convulsants such as metrazol or Hegimide, photic stimulation, or the intravenous administration of drugs such as barbiturate. In addition, perhaps the actual electroshock seizure ﬂzreshold or the pattern 0: severity of the seizures measure of nervous system responsiveness. Data from such could be correlated with the degree an? types of shock. In this manner it might be ELG may be a investigations change during electro- possible to demonstrate different patterns �410- classify individuals accordingly. not only help in understanding the variability in reactivity of neurophysiological Such studies may and alterations during electroshock but would have wider application to other problems in clinical electroencephalography and neurology. For example, tie basis for the development of Spontaneous seizures secondary the EEG to traumatic, vascular, or neoplastic lesions of the nervous system known. Patients with lesions comparable in type, size and location or may not develop seizures. As previously described, spike or Spike-wave activity during electroshock. difference in not may subjects some show This suggests an inherent clinical seizures or he capacity to develop is EEG seizure is reflected in the whether the to injury nervous system, "injury" following activity spontaneous or induced. Differences in this capacity may be varying patterns of neurophysiological reactivity. Differences in neurophysiological reactivity in the pre-troatment abnormal (ll), EEG. Patients in whom "instabile" (22), or axons may also be manifested the pre-treatment record is a predominant alpha rhythm (S) LEG the in during electroshock. the alteration to said develop greatest are Other investigators have not confirmed these observations (2, 23). Actually, such correlations depend on the method of analysis of the pre-treatment criteria used for "abnormality." Further investigation of this relationship is necessary. Suggesting that neurophysiological reactivity is an inherent process does not imply that a physiological basis does not exist or cannot be in- record employed and the vestigated. This may reside in the central nervous system itself, consisting of individual differences in neurochemical systems or in the permeability of cells-or blood vessels; or it may be outside the nervous system. Individual �‘11- differences in hormonal or other humeral substances produced during the stress of electrosho k may serve to "sensitize" or "desensitize" the cerebrum with regard to developing ical activity. That such factors following studies. Trypan red different may be amounts and types of electr- operative is suggested by the injected intraperitoneally in cats before a course of electroshock decreased the permeability of the blood~brain barrier and reduced the degree of EEG changes as compared to control animals (1). Atropine and scopolamine adminstered during a course of electnodiock in man blocked the development of the usual slowawave activity (2h). Electroshock therapy affords an excellent opportunity for the experimental investigation of the problem of an inherent neurophysiological reactivity. animals. The One is able to apply studies directly to man, rather than stimulus to the central nervous system can be standardized and the degree of neurophysiological change changing different parameters. controlled, within limits, by Tests of 336 responsivity can be given before such dianges are induced as well as during and after treahnent. Re-study of patients is often possible then subsequent courses of treatment are necessary. �.12.. marl: l. Indiviéual EEG the in qualitative, changes during a course of electroshock treatment in 89 patients are éifferences, both quantitative and described. 2. These differences are pronounced and are not explainable by age, sex, type of shock current, frequency of treatment, psychiatric diagnosis, or clinical change. 3. An inherent capacity for neurophysiological change that has both quan- titative and qualitative aSpects may be the primary determinant of these differences. h. Variation in skull resistance and in the amount of current reaching the brain aspear to be minor factors. 5. Investigations that might serve to described. Such studies may test the hypothesis presented are lead eventually to a classification of individuals as to different patterns of neurophysiological reactivity and clarify other problems in clinical neurology and electroencephalography. �é 13 - REFERENCES l. Aird, R.B., Strait, (1956): S.C. and Bowditch, M.K., Hrenoff, L.A., Pace, J.w., Current Pathway and Neurophysiological Effects of Electri- J. cally Induced Convulsions. Nerv. Ment. & Dis., igg: Bagchi, B.K., Howell, R.W. and Schmale, H.T. (l9h5): alographic and The J. Pszchiat., lgg: h9-61. Am. R. (1953): and S. Feinstein, Berg, Impastato, D.J., P.S., Bergman, Electroencephalographic Changes Following Focal Seizures, Conf. Neurol.hl§: Electroshock, EEG. Chusid, J.G. and Pacella, B.L. (1952): Electric 271-277. Clin. Neurgghxs., g: Shock Therapies, J. Electrically Induced Slow Wave Phenomena Callaway, E. and Boucher, F. (1950): 157~162. Neuro. Ment. H. Dis., llé‘ (1953): shock on the Cortical and Intracerebral shock Process, M. J. Nerv. and Kahn, B.L.: & Response in Electroshock: Arch. Neurol. Hayes, K.J. (1950): Arch. Neurol. & The & 95—107. Electroactivity of the l3: 287-29h. Experimental Studies of the Electro- Ment. Dis. Relation of in Effects of Electrou Brain in Schizophrenic Patients, Conf. Neurol., M., Kabn, B.L. and Green, MLA.: in Intensive The Electroencephalogram Delgado, J.M.R., Alexander, L. and Hamlin, Fink, Electroenceph- Clinical Effects of Electrically Induced Convulsions in the Treatment of Mental Disorders. Fink, 505-512. EEG (in press). Delta Activity to Behavioral Quantitative Serial Studies, A.M.A., Pszphiat. (in press). Current Path in Electric Convulsion Shock, Psxchiat., §§: 102-109. �-1hREFERENCES 10. LC. and Pincus, Hoagland, IL, Malamud, w., Kaufman, G. (19%): in the Electroencephalogram and in the Excretion of 17 Changes Ketosteroids Accompanying Electroshock Therapy of Agitated Depression, Psychosom. Med. , 8: 11. 216-251. Kennard, M.A. and Willner, MD (1908): Electroencephalogram M. lg: 13. Serial (1955): Results from Shock Therapy, 4AM ho-hs. P83111835” £02: Igtz, Which Significance of Changes in the Changes Due to Electrotherapy, Dis. Nerv. $35., 120-122. Knott, G.R., Gottlieb, J.S., Leet, Hull and Hadley, H.D. Jr., (1943): Changes in Electroencephalograph Following Metrazol Shock Therapy: A 1h. Quantitative Study, Arch. Neurol. 8c Psychiat., 29: 529-53h. Levy, N.A., Serota, mm and Grinker, R.R. (19142): Disturbance in Brain Function Following Convulsive Shock Therapy, Arch.Neurol. PsEhiat., ﬂ: Liberson, wur. (1951): 1009-1027. Current Evaluation of Electric Convulsive Therapy, Mento ASS. Nerv. PUbl. R93. D180, 0... nun-U. Lorimer, F.M., Segal, & M.M. and Stein, S.A. 2: 199-2310 (19149): Path of Current Distribution in Brain During Electroconvulsive Therapy, EEG. 17. Clin. Neurophysiol., 3;: 318-3148. Moriarity, J .D. and Siemens, J .0. (19M): Electroencephalographic Study of Electric Shock Therapy, Arch. Neurol. & Psychiat., 21: 712-718. �- 15 REFERENCES 18. Pacella, B.L., Barrera, S.W. and Kalinowsky, L. (l9h2): Variations in of Shock Therapy with Electric Electrocephalogram.Associated the Patients with Mental Disorders, Arch. Neurol. & Pszchiat., 51: 367—381l- 19. Proctor, J.E. (l9h5): Clinical and Electra-physiological L.D. and Goodwin, Observations Following Electroshock, Amer. J. Pszghiat., 39;: 707-800. 20. Proctor, L.D. and Goodwin, J.E. (l9h3): Comparative Electroencephalographic Observations Following Electroshock Therapy using Alternating and Unidirectional Fluctuating Current, 22: 21. Raw 60 Am. Cycle J. Pszghiat., 525-530. Smith, J.w. and Wegener, C.F. (19hh): On Electric Convulsive Therapy with Control??? Electrodes of Application Parietal to a Particular Regard Neurol., et Acta Measurements, Pszchiat. Voltage Intracerebral by lg: 529-5h9. Sulzbach, W., Tillotson, K.J., Guillemin, (l9h3): A Consideration of Some V. Jr. and Sutherland, G.F. Experience with Electric Shock Various to Regard with Special Mental Diseases, Treatment in Psychosomatic Phenomena and to Certain Electro~technical Factors, 23. Taylor, R.M. and Pacella, B.L. (19h8): The Significance of Abnormal Electroencephalograms Prior to Electroconvulsive Therapy, J. Nerv. & Ment. Dis., 291: 220-227. �. 16 - REFERENCES 2h. Ulett, G.A. and Johnson, M.W. (1957): Upon Electroencephalographic Changes Induced by Electro-convulsive Therapy, 25. W911, A.A. and EEG. Olin. Negggghxsiol.,.2: 217-22h. Brinegar, wgc. (19h7): Following Electric 21: Effect of Atropine and Scopolamine 719-729. Electroencephalographic Studies Shock Therapy, Arch. Naurol. & Pszghiat., � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Martin A. Green: Significance of Individual Variability in EEG Response to Electroshock, 1957 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-10-010 Date A point or period of time associated with an event in the lifecycle of the resource 1957 Creator An entity primarily responsible for making the resource Green, Martin A. Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/547dda87f02e63e10815bbd8bd8b58a3.pdf 2de3623b012b67ce51e9e637220d0b84 PDF Text Text Role of EEG Frequency Shift in Behavioral Effects of Drugs mmmm.* During the past few years we have been interested in the interrelation- ship of changes in various measures of brain function and the behavioral response of psychiatric patients to somatic therapies. were devoted Our initial studies to the changes in tactile perceptual tasks in patients with organic psychoses. This study, carried out at Bellevue Psychiatric Hospital, demonstrated that patients with active organic psychotic reactions made repeated errors in the simple task of reporting two simultaneously applied cutaneous stimuli. The persistence of such‘errors was interpreted as an index to the presence of an "organic mental syndrome." In the initial studies at Hillside Heepital in 1952, the same patterns of errors were observed in patients receiving convulsive therapy. we then became interested in the role of altered brain function in the "improvement" induced by convulsive therapy. we In our first group of patients followed consecutive electroshock referrals with weekly measures of changes in brain function of brain function: and memory clinical interviews. tests, simultaneous we used four indices tactile tests, the amobarbital test for organic brain disease described by Weinstein and Kahn, and the degree of induced delta activity in the EEG. It was soon apparent that neither the memory scales nor the tactile tests were sufficiently sensitive indicators of alteration in brain function to be satisfactory for our purposes. The amobarbital test, however, was a sensitive indicator. In this test, the subject is asked a series of questions regarding his illness the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, Island, N.Y. Read at the Section of Neurology and Psychiatry, Queens County Medical Society, June 3, 1958. Frcm Long ‘ �.2and orientation for place, date, time and person. Following the administration of intravenous amobarbital until the patient has nystagmns, the questions are repeated. Errors of confabulation and disorientation are scored as "positive" tests, and have been found almost exclusively in subjects with active cerebral dysfunction. In the patients in the electroshock series, a significant relationship was observed between changes in this test and impmvement ratings in convulsive therapy. Amobarbitﬂ Test EST - Improvement #1 “----‘--- u..---.--—----—--——-we in the also measured the changes in EEG. ﬁne degree of induced delta activity Examination of a series of preliminary records, as well as the description in the literature, demonstrated the early development and ‘persistence of Slow wave activity in the EEG during convulsive therapy. this preliminary information, we obtained weekly records during and ‘We measured of treatment. a after course specified leads for the per-cent time delta, the slowest frequency, highest voltage of delta and the duration With of burst activity. Using these quantitative indices 180 records activity. in The we ranked the initial patients according to the extent of the induced delta upper third were classed as ”high degree delta records," 2h the middle third as "middle or'moderate degree delta" and the lowest third as "low degree delta activity." High, Middle and Low Delta - EST #1 �.3 When we related the development of high degree delta activity to improvement rating, a signiﬁicant relationship Fig. EEE was again demonstrated. 5 Delta - Improvement - EST #1 ---—-—------ -—------ yo--— --—‘-..- ~- In subsequent months development of high degrees of third to EEG delta activity during the second and ratings. In the next table, these observations in the next Sh patients. weeks of treatment have summarized a predictive study, relating the we embarked on improvement F1 . we 6 Table: Patients High Delta 2nd, 3rd weeks of Treatment EST 2’ 3’ ’4 -_------- ----—----‘u-n-—---------_-----m-‘-----—----By this time we believed that EEG delta activity was related to the behavioral changes in convulsive therapy, and its significance in a control convulsive-subconvulsive study. Of was tested consecutive convulsive therapy referrals, randomly selected patients were subjected to a course of subconvulsive therapy instead of the convulsive therapy. This to the patients or their therapists. 0f the substitution was unknown subjects received convulsive therapy in this series, high degree delta who activity records were observed in of treatment. Of the 27 Subjects 3h during the second who to the fourth h? weeks received subconvulsive therapy, however, none demonstrated either-high or middle degree delta activity �.u. EEG . records during any week of treatment. In concurrent behavioral evaluations, of the h? subjects in the convulsive group h2 behavioral change, while only showed such 3 showed marked of the 27 in the subconvulsive group a change. In clinical improvement ratings, 2h of h? were rated "recovered" and "much improved;" 15 "unimproved or worse." But as "improved" and 8 as of the subconvulsive group,only 3 were "recovered" and "much improved," 5 as "improved" and 19 rated as "unimproved cr'worse." we were now convinced that high degree of EEG delta activity reflected the physiologic changes essential to the behavioral change in convulsive therapy. An alteration in brain function, sufficient induce considerable - and of the kind to activity appeared to be the prerequisite, not sufficient factor - in the convulsive therapy EEG a necessary, ﬂaough slow wave process. Perhaps a similar relationship was observable in other somatic therapies? we next examined insulin activity is induced, hours after gavage. receiving deep or prolonged which Not coma therapy. During each coma, EEG delta usually persists for a few minutes to a few infrequently - in approximately 1/3 of patients insulin therapy in our hospital, seizures, aphasia result. After such events, EEG changes of delta activity coma coma persist for days, The relation ' and in cases of prolonged between prolonged coma, coma, for weeks and months. altered brain function and behavioral response has been discussed by numerous authors. Revitch reported eight cases and concluded that improvement was related to the induction of organic brain damage, similar to lobotomy. Yaeger et a1 �-5. noted a correlation between length of coma, degree of organic confusion, remission of mental symptoms and degree of of prolonged coma. EEG In reviewing our insulin abnormality in 12 cases coma experiences, noted we that our best clinical results have been observed in prolonged coma cases. As a result, it has been the intention of our staff to induce such a state. Persistent coma EEG delta activity has been observed in a small subjects, and only in those with prolonged neurologic signs. Thus, in insulin coma number of our or persistent also, a relation between delta change and behavioral response is indicated. Concurrent with these investigations, We had begun clinical EEG coma investigations with the newer tranquilhers. Initial study of Raudixin in 1953 He were failed to indicate any clinical efficacy. able to administer large doses - up to 10 With mgm. reserpine, however, At these levels, behavioral change become prominent but so also did neurologic complications. Parkinsonism was readily induced, and seizure induction and increased clinical depression became prominent. The EEG changes on chronic administration were small. With our doses, desynchronization was apparent, but at higher dosage hyperSynchrony was also noted. With chlorpromazine, however, we were more fortunate. we had undertaken a control insulin coma-chlorpromazine study, in'which the experimental dosage called for levels sufficient to induce clinical parkinsonism. In three of the thirty patients grand mal seizures were induced. In all patients significant changes were observed in serial EEGs. These consisted of increased modulation, increase in per-cent time alpha, and in twenty patients lOW'voltage theta and delta activity. On hyperventilation, delta �burst activity was observed. In reviewing the experiences of others, noted numerous reports of chlorpremazine inducing seizures; exaggerating seizure activity in epileptics; and activating seizure available for reserpine. EEG we records. Similar reports are review of the electroencephalographic effects of various phreno- A tropics demonstrated that not all newer agents induced Meprobamate, in clinical doses, induces an increase in activity. slow wave EEG fast activity, with increased voltage and Spindling. The records are most similar to barbiturate records. Benactyzine (or suavitil) induced neither slow nor fast activity but desynchronized the record, with flattening of voltages and loss of wave whatever rhythmicity was present. clinical experience we were impressed that chlorprcmazine and reserpine were the most effective modifiers of psychotic behavior, with benactyzine and meprobamate as relatively inefficient agents. It From our seemed appropriate therefore to extend the neurophysiologic adaptive hypothesis of the it was mode of action of convulsive and insulin EEG frequencies to the delta range would active in modifying psychotic behavior; while those that induce a shift to the beta range, or As a corollary it was desynchronize the record would be less effective. suggested that agents that induce no change in brain function or changes so small as not to be reflected in serial have therapies; suggested therefore, that agents that induce a change in brain function reflected by a shift in be most coma little EEGs would behavioral effect. Thus, a classification of newer phrenotropic �-7drugs based on their EEG effects was suggested: (3) Increased slow wave activity with hypersynchrony (b) Desynchronization with voltage and frequency irregularity, .and (0) irregular theta Increased high voltage fast activity In reviewing the available literature reports of promazine and perphenazine would indicate delta range. that these agents induce a shift in the Mepazine has minimal EEG effects, EEG spectrum to the and these are largely desynchronization. Information regarding other newer agents was not available. we EEG have undertaken two studies based on changes to behavior. One is serial EEG this hypothesis relating studies of patients receiving chronic tranquilizer medication at the hospital. a study of the relation acute administration: between the EEG and A now second is the behavioral effects on the data of our chronic administration studies are not yet available, but the acute studies have progressed sufficiently to danonstrate the applicability of the hypothesis. Fbllowing the observations by Denber derivatives, diethazine, elicit some EEG when that one of the phenothiazine administered with chlorpromazine, would activity similar to convulsive therapy, we undertook explorations of this compound. In the EEG laboratory with continuous 31 w wave recording, varying amounts of diethazine from 100 to 250 mg. were administered intravenously over a 10 minute period in psychiatric patients at various stages of the convulsive therapy process. Instead of hyperynchrony, patients who were pretreatment and without EEG delta activity, demonstrated significant desynchronization of the record. �-8Fig. 7, EEG - Diethazine - Pretreatment interesting, however, Most 8 was the effect of diethasine in patients with increased slow wave activity during convulsive therapy. Here, too, desynchronization became manifest, and there was a decrease in the voltage and per-cent time of the induced delta activity. EEG - Diethazine - Delta Activity effects, we observed distinctive behavioral changes. Patients became more irritable and restless; they Concurrent with these complained of sensations of extremities. In some, EEG unreality, visual illusory and of dysesthesias of the phenomena and delusional thoughts their illness, the setting of the test procedures or our identity. There were changes in their language patterns opposite to that previously about described for amobarbital, so that denial, minimization, cliches, third person mode and past tense were less prominent. The duration of these behavioral and language changes was from one to five hours. changes were of similar duration administration and disappearing The EEG - appearing during the period of when drug the behavior had apparently reverted to the pretreatment state. The ability of diethazine to activity led to an evaluation of induce other illusory known and hallucinatory hallucinogens. In checking �-9the literature we noted that that mescaline reversed the Denber and Merlis had previously described EEG changes induced by electroshock, in a fashion identical with diethazine. Pennes had observed hallucinogenic activity for another experimental compound Win 2299. We obtained some of this material, and repeated our diethazine studies. Here, too, Win 2299 induced EEG desynchronization associated with clinical patterns of restlessness, excitement, hallucinatory and illusory activity. Fig. 11, Win 2299 We repeated these studies with was a - 12 EEG LSD, and again the same patterns. There difference in the time constant, but concurrent with the behavioral effects we observed EEG changes. Recalling the ability of benactyzine to desynchronize records, this compound intravenously, and again, we observed the same we EEG administered pattern of desynchronization, associated with restlessness and excitement. While not observe the illusory and hallucinatory patterns, kinds of language changes in these patients that we we did note the we did same observed with diethazine. �Fig. 16, 17 Benactyzine The chemistry of these compounds Thus, from each of these agents, - EEG is noted in the next figure: EEG desynchronization was induced, and hallucinogenic or excitatory activity was observed. we can.now amplify our initial hypothesis to encompass hallucinogens. like to refer first to conclusions described in l9Sh by Wikler in a study of the effects of mescaline, n-allylnormorphine In-this regard, I and morphine in would man, in which he stated: ".... regardless of the drug administered, shifts in the pattern of electroencephalogram in the direction of desynchronization occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronbation.with euphoria, relaxation or drowsiness." ‘We would now generalize our observations of EEG changes and behavior to note shift to the delta behavior. Agents that and that agents that induce EEG synchronization range are potent agents in the control of psychotic induce synchronization in the beta range are relaxant, euphoriant and sedative, while agents that desynohronize the record tend to be hallucinogenic. This hypothesis lends itself to a variety of applications. It provides a bases for the understanding of the mode of action of various organic �-11- therapies in psychiatry. EEG analysis may also provide a basis for the assay of new drugs and therapy procedures. Finally, these observations permit a more rational management of the somatic therapies. to explore each application in summary I would like fashion. application of the neurophysiologic adaptive hypothesis - for that is the rubric under which we subsume the relationship between the The in brain function, reflected by the EEG, and the changes in behavior - to insulin coma therapy has already been described. we have changes applied this concept to our studies of phrenotropic agents, and have been able, both It is predictively and retrospectively, to assess new agents. possible to understand lobotomy therapy, and sleep therapy, within this framework. As is for the assay of drugs, our explorations into hallucinogens that each of the potent hallucinogens a biochemical similarity in a common tertiary amine radical connected one example. have new we have recently noted by an ethyl linkage to a large nucleus. compounds with this linkage. One On this basis, we sought for group are known anti-parkinson agents with anti-cholinergic properties as parsidol, artane, kemadrin, panparnit and benadryl. we have not yet tested these compounds for their EEG or clinical effects. Recently, Pfeiffer reported at the Academy of Neurology that these compounds, in trained subjects, were identified most with LSD. In 1956, Gottlieb reported that benadryl desynchronized the patients, much as we saw this evening. available in the literature. shock EEG of electro- Thus, some confinnation is �.12With regard to the third therapies - this hypothesis ammﬂication may - the management of somatic be of considerable help. In convulsive therapy and in drug therapies, the patient'who responds in a favorable fashion is‘no problem. But what of the patients who responds poorly, or not at all? Could the failure of response be related to inadequate dosage? In electroshock, when a patient manifests paranoid or withdrawal behavior, or no significant change, an If the record we may assume fails to EEG provides a guide to management. demonstrate high voltage slow wave that treatment has been inadequate, activity, then and continue the treatnent course or increase the frequency or alter the convulsant method. If EEG changes are present, then we would assume that other factors - personality, sociologic or interpersonal - are not conducive to "improvement" by electroshock, and other remedies sought. Similar applications are possible for phrenotropic agents. In summary, we believe that somatic therapies in psychiatry exert their effects primarily by altering brain function. Changes in the EEG Spectrum are one reflection of sudatalteration and are useful as a guide to the mode of action, effectiveness and application of somatic therapies. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Role of EEG Frequency Shift in Behavioral Effects of Drugs, 1958 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-12-011 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/10dd96ea03d444a3545ca7a104bdf5fe.pdf a67bc54ff65c228d90099b2591e160d9 PDF Text Text SOCIAL FACTORS AND COMMUNICATION IN PSYCHIATRIC PATIENTS I: 11: III: From Pollack Ph.D. Choice and Results of Therapy - Duration of Hospitalization and Diagnosis - Robert Observations in an Interview Setting - Joseph Jaffe Max L. Kahn Ph.D. . M.D. the Department or Murmantal Psychiatry, Hillside Hospital, Glen Oaks, L.I. , NJ. Presented October 19, 1958, at Hillside Hospital. �III: 9-29-58 Social Factors and Commmication in Psychiatric Patients 1: Choice and Results of Therapy Recent investigations by Hollingshead, Redlich, Frank, Levinson and others have indicated a relation between social class and psychiatric disorder with respect to type and incidence of mental illness, selection be present and maintenance of treatment and therapeutic outcome. report is concerned with the role of social factors in the . selection and efﬁcacy of therapy in Hillside Hospital. me most intensive analysis of the relationship of social class to mental illness has been recently reported by Hollingshead, Redlich and their coworkers. In their studies the population of New Haven was divided into five social classes on the basis of weighted criteria or education, occupation and place of residence. or the residents who were under psychiatric care, those from the upper social classes were more frequently treated with psychotherapy, while organic treatment or custodial care was more comm among the lower classes. Of the psychotherapies, psychoanalysis was entirely restricted to the We upper groups. Social class was the predominant determinant of the type of treatment selected even when the diagnosis was held constant. They summarize their observations as follows: I'.... it is found that and does treatment not depend on psychological medical determinants alone, but on the status position of the patient as well. Psychotherapeuﬁc in disproportionately high degree to the upper social data of this study would seem to indicate that most methods are, applied levels. The �in a setting where the background of the patient is similar to that of the therapist." It is possible, however, to relate the results obtained from these commity studies to such selective factors as the patient's financial psychotherapy takes place resources or the extent and type of treatment more critical test of the facilities available. A importance of social factors affecting choice of treatment would be in a setting where the same therapeutic tecrmiques and services are available to all patients, regardless of their ability to pay. is at Hillside Hospital. the of the main criteria for accepting patients is their “ability to participate profitably in psychotherapy." Individual psychoanalytically oriented psychotherapy is regarded as the primary method of treatment with organic therapies available when needed. Thus a patient is seen in This requirement met regular therapeutic sessions throughout his hospital stay even when undergoing a course of caustic therapy. The average length of hospital stay is six months, with some The purpose patients remaining from of the present report is 12 to 16 months. to smnmarize the relation factors of age, education, place of birth, and social attitude (as measured by the California F scale) to the selection or between the treatment and the ratings of improvement at time of discharge in this environment. muons 1957 was The entire in-patient adult population of studied. This consisted of 171 patients, March 7, 57 men and 111; women , ranging in age from 16 to 68 years, with a mean of 35 years. �Procedure: The patients were tested with a ten-item modification of the California F scale suggested by Levinson. The F scale is a questionnaire which has been related to such factors as authoritarianism, acquiescence, ethnocentrism and rigidity. The patient reads ten statements and indicates whether he agrees or disagrees with each statement and to what extent. from one to seven and the The score given for each item ranges total score range is 10 to 70. The greater the agreement the higher the score obtained. The statements themselves are extreme, uncritical or stereotyped expressions. For example, one of the statements would be is: "If people would talk less and work more, everybody better off." Choice of Therapy: will first take up the relation of these social and psychological factors to selection for treatment. During the period of this study, (Table I) approximately one-third of the patients received convulsive The small with and two-thirds treated psychotherapy were only. therapy group of patients who received insulin coma and drug therapies are not We represented on the slide. When compared to psychotherapy patients, the convulsive group were older, had fewer years of education not completed grade school also had a higher F - - many had and were frequently foreign born. They score, which indicates that these patients tended to agree with social stereotypes. At this time, the psychiatric residents and their supervisors were also tested. Their average F score was 21.8 with a mean age of thus more closely approximating the psychotherapy group than the 33 .9. �electroshock group. This figure has dealt with group averages for each of the factors mentioned. There was however marked at the patients is variability within each of the groups, with patients each end of a wide range. grouping shown group with reSpect to length of convulsive therapy. As One method in the analysis of the electroshock hospitalization prior to receiving illustrated in the next table electroshock patients were divided into three groups: were and (Table II), the 1) those who after admission, 2) between three after six months. There is a definite correlation treated within three six months, and 3) of sub- months prior to convulsive therapy and F score, age, education and birthplace. It is of interest that there is a gradient for each of the social factors. As a group the patients referred for between length of stay convulsive therapy after six months of hospitalization are most similar to the psychotherapy patients with respect to each of the factors. Che set of data not shown in the slide is the ratio of male to female patients referred for somatic therapy during each of these hospitalization periods. Although the ratio of females to males in the hospital population is two to one, hh per cent of the patients in the group treated within three months were male. In the group hospitalized for six months prior to convulsive therapy, however, only 7 per cent are males. Thus, male patients are referred for electroshock earlier in their hospital stay than As patients. expected, a larger proportion of depressed patients female ~ 52 cent - received electroshock than did those with other diagnoses. per To �-5. control for the factor of diagnosis in choice of treatment, the psychotic depression patients were subdivided into those who received electroshock and those who were given psychotherapy alone. The results are the next slide (Table III). While the two groups are comparable age and education, the electroshock mean F shown in for patients had a significantly higher score and a higher percentage were foreign born. Thus, it may that persons classified as having a psychotic depression are not necessarily referred for electroshock because they are older or less educated, but rather that they come from cultural backgrounds that are be more commonly associated with psychologic processes that make successful in the psychoanalytically oriented psychotherapeutic relationship less likely. These findings are consistent with previous studies which have shown that patient-therapist differences in systems communication of values may hamper Redlich note: "We therapeutic relationship. As Hollingshead and are not sure what attributes a good patient must have, but they include sensitivity, intelligence, Social and intellectual standards similar to the psychiatrist‘s, a will to do desire to improve one's personality and status in life, attractiveness and charm. Rarely will such standards one's best, a youth, be admitted by psychiatrists. On the contrary, psychiatrists claim that the selection for treatment is based on purely psychiatric criteria....." Results of Therapy: Social factors are as significantly related to treatment result as they are to treatment selection. hospital treatment on To the 171 patients, analyze the effects of the we selected the discharge �evaluation as the criterion of improvement. At time of discharge a patient is classified in one of four categories: recovered, much improved, improved or unimproved. relation of social factors to the discharge evaluations is presented in the next slide (Table IV). There is a definite, almost The linear relationship, between the improvement rating and these four social factors. The recovered group of patients had the highest F scores, were oldest, least educated and of foreign birth. In contrast, showed the highest incidence the unimproved group had the lowest F scores, were younger and better educated - almost all having gone to college - and were primarily native~born. for patients treated with convulsive therapy the improvement ratings parallel those for the total population. Analyzing the data (Table V) Again, the recovered group had the highest mean F scores, was the oldest, most poorly educated with the highest incidence of foreign birth. The illustrates the relation of these observations next slide (Table VI) to time of referral for treatment. Within the electroshock group 67 per cent of those who were treated early in the course of hoSpitalization were rated as recovered or those treated after six these two groups. were more much improved, whereas months only 30 per cent were As was noted earlier, patients in this latter similar to the psychotherapy group It is classified in WEUh respect to these not surprising, therefore, that they were treated with somatotheragy only after an extensive course of social factors. psychotherapy. group �.7In summary, the observations that social factors are related to type of therapy received as well as therapeutic outcome are consistent with the studies of Hollingshead, Redlich and their coaworkers. their findings in demonstrating that these factors are also significant in a hospital setting where where and selection of not therapeutic criterion to a is pay ability all forms of therapy are equally available to the entire population. Furthermore, the present studies extenii While the relation between social factors and treatment selection are clear, and are consistent with previous findings, the relation of these factors to improvement ratings appears paradoxical. observations that those patients with high and less educated, more F scores, The who were older often received convulsive therapy and were discharged more frequently as recovered are consistent with the results reported in 1956 in a follow-up study of Hillside Hospital patients conducted by Rachlin, Goldman, Lurie, Gurvitz and Rachlin. It is possible that the differences in communication between therapist patient that result in referral for convulsive therapy may also influence the discharge rating. Thus, Kahn and and Fink have previously to denial, evasion, and benefit most receive to and of cliches use are likely stereotypy from electroshock. Such language patterns appear more frequent in shown that verbally uncommunicative persons, prone persons in the lower socioeconomic groups. Because of the differences therapist and patient, the therapist may set different criteria for improvement for the older less educated patients than he does for between the young, sophisticated ones, �class patient The lower may also set goals for himself that are The from class patient's the different patient. upper qualitatively aspirations for himself and the therapist's expectancy for the patient of time of hospital improvement at Ratings an interactive are process. discharge are relative in that they refer to a baseline of premorbid functioning. Thus the rating of recovered is defined as, "the reasonable expectation that the patient will be able to return to his community and function as well, or better, than he did before he became ill." therapist's perception of the patient's premorbid functioning may be influenced by the distance between his value system and that of the patient and both influenced by their social class. ‘The greater the social distance between therapist and patient the less rigorous the requirements for behavioral change. Fer example, for older, lower class patients, ability to resume work may loom as the major criterion The of improvement. For the upper class patient work adjustment only one of a may be host of criteria, including such intangibles as work gratification, ease of sociability, etc.. This presentation has dealt with a few of the relationships between social factors and psychiatric treatment in a voluntary, psychotherapeutically-oriented hospital. The other speakers will deal with many of the questions left unanswered in this report. �THERAPY SELECTION F Score Yrs. of Education Foreign gMeanz Age {Mean} Electroshock (Ii-57) 14306 ’40.3 11-2 26% Psychotherapy 36.1; 32.6 11.8 9% Groggs (Na102) SMean) % Born �.10TABLE II LENGTH OF HOSPITALIZATION PRIOR TO ADMINISTRATION OF ELEBTROSHOCK F Score gMeanz Groygs Less than 3 {N-Bh) 3 mos. to 6 mos. (N-IO) More than 6 mos. (N~13) Age (Mean! Yrs. of Education Ween! % ForeignBorn 148.3 M45 10.1 1:173 he. 7 39.8 11.7 30% 32.9 29.5 13.14 �-11TABLE III SELECTION OF THERAPY IN PATIENTS WITH PSYCHOTIC DEPRESSION Yrs. of Education Foreign— Born F Score SMean! Age SMean) Electroahock (N'Bl) 50.3 h8.6 10.6 1:253 Psychotherapy h1.0 h7.6 10.0 2h% GrouEs (n-29) SMean)___ % �-12TABLE :1 SOCIAL FACTORS AND DISCHARGE EVALUATION F Score SMean) Age gMean) Yrs. of Education gMeanz 1 ForeignBonn h2.9 Mus 10.7 Much Improved 39.0 35.6 11.2 22% Improved 36.1 31.2 11.2 16% 31.2 13.2 11% Recovered h1% (N-17 ) (n-82) (N'63) Uhimproved (n-9) 31.1 �-13TABLE V DISCHARGE EVKLUATION IN CONVULSIVE THERAPY Yrs.‘of F Score sMeanz Age SMeanz Education % Foreign- SMeanz Born 53.1 51.6 9.u 50% (N-26) h2.0 h3.8 10.6 35% Improved and unimproved (Ni23) 39.7 32.3 12.3 12% Recovered (N-B) Much Improved �-m- M TABLE VI LENGTH OF HOSPITALIZATION PRIOR TO ELECTROSHOCK AND DISCHARGE EVALUATION Recovered Much 8: Iﬂroved Improved U raved Groggs Less than 32% 6 mos. 70% 30% than 6 mos. 31% 59% (n-Bh) 3 to ms. 68% 3 (N-lO) More (N-13) & �III: 9-29-58 -15- Social Factors and Communication in Psychiatric Patients II: Duration of Hospitalization and Diagnosis Just heard a presentation of factors associated with the selection and results of treatments. I will next conéider the relation You have of these factors to length of hospitalization and to diagnosis. It is obvious that the length of time a patient stays in a mental hospital is related to the particular function and philosophy of the institution. In an institution such as Hillside Hospital which admits only voluntary patients and emphasizes psychoanalytically oriented psychothe In limited. particular of is the hospitalization length therapy, montthin 16 from complete to one was the studied the population range L months. of six over with an stay slightly average hospital, Several factors can.be postulated which might be related to the duration of hospitalization. Since it commonly takes less time to produce behavioral change with convulsive therapy than with psychotherapy, one would expect to find that the consulsive therapy patients are kept in the hospital for the shortest period while the psychotherapy patients are here longer. The data, as presented in Table VII, shows no significant difference between the two groups. If anything, there is a slight tendency for psychotherapy patients at Hillside to be institutionalized for the shorter period. A second possible factor is the severity of the patient's illness. be who will necessarily more intractable those are that patients It maintained in the hospital further to receive additional treatment. Examination demonstrates shown Table in VIII, the however, as data, of those that while patients hospitalized for the shortest period do have may be �Much and Improved, Recovered of of ratings incidence discharge a higher and chance are not significant. variation within a differences are the In the Hillside followhup study of Rachlin there was no relationship EELEE' it was also found that between discharge evaluation and length of time in the hospital. On the basis of the data and discussion presented by Dr. Pollack, be should a relationship there that hypothesis advance the further can we of and duration hospitalization. the background social patient's we oriented psychotherapy psychoanalytically With Hillside's stress on would expect that those patients who are most like the therapists with regard between a to these factors.would be kept The the period. for longest the in hospital data is presented in Table IX. Patients shortest who were period had the highest F scores, were hospitalized for the oldest, had the fewest Conversely, born. of native and smallest the percentage education of years F the lowest had the scores, the who longest the in hospital were those of and smallest the percentage education of most years youngest ages, the foreign born. These differences are statistically significant. In Table X a similar analysis is shown for only those patients receiving electroshock. Again, each of these factors is related to duration of hospitalization. The same results are obtained psychotherapy only is when the data of those patients receiving While XI. shown Table in as analyzed separately, F low have Pollack Dr. scores, are indicated, as these patients as a group, electroshock the than born and native more education have more younger, patients, there is still a significant difference within the group in the the time in hospital. of the to length according direction predicted �These same relationships of social factors to hospitalization are found even when the patients were subdivided according to diagnosis. In Table XII the data is shown for the in the hospital for each diagnostic group. F their final score and months The diagnoses were subdivided into four major groups and include all but three patients in the population studied. For each group there is a significant difference between those in the hospital for the shortest and the longest periods, with those in the longest having the lowest scores. Similar results are shown when the data is analyzed It is also shown for each diagnostic group with respect to age (Table XIII). for education (Table schizophrenic patients stay. It who were who XIV), with the exception of the had about the same education for each length of should be noted, though, that many of the schizophrenic patients here for ten months or more were quite young - around 16 or 17, and so did not have the opportunity to receive education beyond the middle of high school. Analysis of place of hospitalization is shown is associated with a birth for in Table each diagnostic group and length of XV. marked decrease Increase in length of hospitalization in the with the exception of the schizophrenics, number who of foreign born, again as a group, had very few such persons. The previous tables have indicated that not only is there a significant relation between each of the social factors studied and length of hospitalization, but that there are large differences between the diagnostic groups themselves, even when comparing patients with the same period of hospitalization. in Table XVI. The summary It is data comparing the diagnostic groups is shown clear that patients diagnosed as involutional psychosis �have the highest F scores, the oldest ages, the least years of education, highest incidence of foreign born. In contrast, the schizophrenics have the lowest F scores, were the youngest, had the most education and the and the of foreign born. The manic-depressive and psychoneurotic involutionals the to closer with the manic-depressive between, in patients fell least number like the schizophrenics. relationship between these social factors and the psychoneurotics most This marked and diagnosis is not surprising. Certainly the relationship of age and diagnosis is an established concept in clinical psychiatry. In the involutional disorders and What names themselves have a chronological conndstion. in dementia praecox the is unexpected, however, is that age should also be related to the and that the and disorders, psychoneurotic of manic-depressive diagnosis other social factors of education, place of birth and F score should in this hospital. the diagnostic major groups differentiate all significantly we have postulated two hypotheses to account for these relationships. The first is based on the fact that persons from different social backgrounds acquire different habitual and expression. modes of adaptation and patterns of communication Accordingly, under conditions of stress, damaged brain function, or other etiological conditions associated with the onset of mental illness, a person will show those behavior patterns or symptoms his habitual patterns. Thus, a person from background communicate in nonsverbal, to more lower apt social class is a do so in to more while class people likely are physical terms, upper which are of the same type as ideational and verbal terms. Thus, anger may be shown by lower class people by physical violence, while those from upper classes are more and Redlich Hollingshead exhortation argument. to to or resort likely �-19- have noted that these differences among people of different classes lead to different psychodynamic patterns in psychoanalytic terms. Thus, aggressive and sexual behavior behavior variation is is restricted among more acceptable among to lower class parents, while such the upper classes, lending to considerable the different social classes in superego development. Irish Italian patients who were diagnosed as schizophrenic in a V.A. Hospital, found significant differences in their types of symptoms related to cultural differences in their family backgrounds. Patients coming from Irish families in which active expression of emotions Marvin Opler, studying and were frowned upon and with dominant over-protective mothers, were passive, compliant and withdrawn, and fearful of anything which might separate them from the protection of the hospital. Patients with Italian family backgrounds that encouraged free expression of showed were assaultive and emotion and were ruled by a dominant destructive behavior, were difficult to father, manage and rebellious against authority. In a comparable study Miller and Swanson have also noted that hospitalized schizophrenics exhibit significant social class difference in symptomatology - lower class patients showing "motoric themes," while middle class patients exhibit "conceptual or ruminative themes." According to our hypothesis, then, we would expect lower social levels would show symptoms sensory or motor patterns. Among that persons from that are non-verbal, expressed in such types of symptoms would be psychomotor retardation, anorexia, catatonic stupor, muteness, hysterical blindness or paralysis. In this connection it is noteworthy that hysterical symptoms have been reported as the army far men more frequent among enlisted in than officers. In addition hysteria which was apparently so common in‘world.war I was not nearly so notable in wbrld'war II, and, in fact, has been reported �in the general population. This decrease, in our view, is related to the general increase in educational level of the country as a whole. If one finds a classical case of hysteria in New'York today, I on the wane Rican be immigrant Puerto the in likely it population who have the poorest socio-cultural background. (One cannot, of course, ascribe the decrease in hysteria to a greater freedom in sexual will understand that matters; has it is shown, most most common in more poorly educated people who, as Kinsey are least inhibited sexually). In the laboratories at Hillside Hospital the investigations of persons with depressive psychoses have been more intensive. we have noted a common of lack characterized hy these behavior of in people, premorbid pattern imagination, creativity and introspective capacity, and by conventionality and general rigidity. Similar patterns have been noted in a series of studies of such patients by other authors. background, such as that involving little we or believe that a poor cultural no education, spending early and cultural is environment, meager resources, in a illiterate largely years conducive to the development of such a personality pattern. When mentally disordered, such persons tend to react with a repertoire of behavior patterns consistent with their background which A we second hypothesis concerning the term depression. relation of social factors to and between do the with has interaction patient to diagnosis psychiatrist. this hypothesis a diagnosis may not be based on an actual how of the reflection extent a to but behavior great is a pattern, objective psychiatrist perceives or identifies the patient. It has been noted frequently that patients with similar symptoms will be differently diagnosed and treated depending on their social class. For example, we recently studied three According to patients who were admitted with similar symptoms of depression, anorexia and �insomnia. who was All three were referred for convulsive therapy. One woman, 62, born in Russia, of limited education with an F score of 70, was diagnosed as involutional melancholia. this country, with The second, aged hS, born in an F score of 53 and a high school education, was termed manic-depressive, depressed. The third, aged hh, also born in this country, with an F score of 33 and a college education, was diagnosed as psychoneurosis, reactive depression. In conclusion, in the Hillside Hospital population social factors of age, education, birthplace and F score are significantly related to the selection and results of treatment, length of hospitalization and diagnosis. These findings illustrate the importance of social factors in affecting language and communication patterns and the nature of the interaction patient and therapist. Current data, both from our own laboratory and as reported in the work of others, indicates that psychotherapy is most likely to take place with those persons who most closely resemble the therapists between in terms of cultural background and communication pattern. In Hillside, with its emphasis on psychotherapy, it is clear that patients who best meet this criteria are also keptthe longest. This is true for either patients receiving convulsive or psychotherapies alone, and for all diagnostic groups. In the evaluation of clinical improvement there may well be different expectancies towards patients in terms of these social factors. with may little In a person education and different modes of expression than ourselves, we regard, for example, the manifestation of denial as improvement. But in a patient much like ourselves in cultural background, the denial will be regarded as a defense and the patient is showing of considered unimproved. patient,himself, may have different expectancies not only in terms of the type of psychiatric treatment, but for what constitutes improvement as well. The �believe also that the attitude of the patient's family may be crucial in both the patient's and therapist's conception of what constitutes we improvement. relation between social factors and diagnosis was interpreted in affects background cultural one's that indicated was First ways. it The two the type and and accordingly and communication, of expression symbolic pattern the possible type of symptoms a diagnostic statement behavior pattern. patient and is not Rather, it that will be shown. Secondly, we believe that simply an objective evaluation of a given is a reflection of the interaction of the psychiatrist in relation to their respective cultural backgrounds and modes of communication. It is between mind the while relationship that in to keep important social factors and the psychiatric aspects described is probably applicable as a generalized principle, the specific findings may vary in different For example, in a study using the F score at the settings or institutions. Boston Psychopathic Hospital, the same relationship to type of treatment was noted as in our report, i.e., the electroshock patients had higher scores than those receiving psychotherapy. patients there, however, patients is was higher than Since the average score of the at Hillside, their psychotherapy had the same mean score as our electroshock cases. Another example the finding of Hollingshead and Redlich that schizophrenia common diagnosis proportionately among F was a more lower than upper classes, while at Hillside the schizophrenics had the highest education. This discrepancy two of the in composition the variation be accounted by for can probably middle from drawn the largely being the Hillside patients populations, lower classes. social few from the or with upper relatively groups �-23- In Hillside the diagnosis of schizophrenia may indicate an "interesting" same diagnosis the population while State Hospital in a patient, may represent a "hopeless" patient. It be tested to studies these by raised remains for the hypotheses In involved. the psychological of processes studies and for further interaction. communicative of studies on been working have particular we Some Dr. of the details Jaffe. and findings of this work will next be presented by �DURATION OF HOSPITALIZATION AND TYPE OF TREATMENT in Ho§ita1 Months Treatment Grog-pa 1 - 5 6 - 9 10 or more Electroshock (S?) 26% 30% M453 Psychotherapy (102) 32% he}! 25% " 5.73 df " 2 (3112 p - N.S. �-25TABLE VIII DURATION OF HOSPITALIZATION AND DISCHARGE EVALUATION Discharge Evaluation Months in Hoggital Recovered or Much Iggroved Improved or raved EM 1-5 (h9) 69% 31% 6-9 55% 15% 52% 148% (624) 10 or more (58) Chi2 df p - 3-83 2 N.S. �- 26.. TABLE IX DURATION OF HOSPITALIZATION AND F SCORE, AGE, EDUCATION AND PLACE OF BIRTH in Hogi‘bal Months 91-192 - 9 {bl-6h} 10 or more 133.9 10.5 31.0 Mean Age 145-5 32-5 27 .9 Years Education 10.0 11.9 12.8 W 19% 10% 1 ean F Score M Mean 5 Foreign Born - 5 6 ski-582 �-27TABLE X DURATION OF HDSPITALIZATION AND F SCORE, AGE, EDUCATION AND PLACE OF BIRTH IN PATIENTS RECEIVING ELECTROSHOCK Months in Hogaital -5 pm 52 6 Mean F Score 58.2 h5.6 3h.9 Mean Age 51.7 h2.2 32.1 6.5 12.3 13.2 67% 2h% 16% 1 Mean.Years Education % Foreign Born - 9 551-172 10 or more 531-25 2 �DURATION OF HOSPITALIZATION AND F SCORE, AGE, EDUCATION AND PLACE OF BIRTH IN PATIENTS RECEIVING PSYCHOTHERAPY ONLY in HogEital Months 1 - S 6 - 10 or more gN-262 SN‘BB} 9 SN-hB! Mean F Score h0.2 38.6 27.8 Mean Age [‘3 c 2 29 o 1 2,4 0 8 11.1; 11.7 12.1: Mean Years Education % Foreign Born 30% 16% 8% �W TABLE MEAN F XII OF DURATION TO ACCORDING GROUPS DIAGNOSTIC SCORES FOR HOSPITALIZATION Months Diagnostic in Hoggital 3;; L2; 58.2 50.9 35.0 Manic Depressive h0.02 h6.1 33.1 Psychoneuroses h0.05 36.6 36.1 Schizophrenia 36.3 38.5 27.6 Greg Involutional Depression 10 or more K �-30TABLE MEAN AGES FOR XIII DIAGNOSTIC GROUPS ACCORDING TO DURATION OF HOSPITALIZATION 10 or more Diggggstic Gregg 3L;§L £1;;2_ Involutional Depression 58. 8 5h. 5 52. 3 Manic Depressive h6.8 39.1 35.5 Psychoneuroses 141.0 27 .1 27.1 Schizophrenia 27.8 27.8 214. 1 �.31TABLE XIV W OF DURATION TO ACCORDING GROUPS DIAGNOSTIC FOR EDUCATION MEAN YEARS OF HOSPITALIZATION Months in Hogaital 10 or more 1;;;§ 51:113 7.1 9.6 16.0 11.0 11.7 12.3 Psychoneuroses 8.7 12.5 12.5 Schizophrenia 13.3 12.3 12.9 giggnostic Groggs Involutional Dapression Manic Depressive �-3 2.. TABLE Lv OF DURATION TO ACCORDING GROUPS DIAGNOSTIC BORN FOR FOREIGN PERCENTAGE HOSPITALIZATION in Hogital Months Digestic Grougs _1__-_§ 6 - 9 10 or more 0 Involutional Depression 57$ 113% Manic Depressive 39% 23% 0 Psychoneuroses 50% 19% 13% Schizophrenia 10% 8% 12% �TABLE XVI DIAGNOSIS AND F SCORE. AGE: EDUCATION AND PLACE OF BIRTH Dialysis Involutional Depression Mean F Score ' Mean Age Mean Years Education % Foreign Born {NI-21:2 Manic Depressive (NI-322 Psycho- ' neuroses Schizophrenia (Iv-372 $31-68) 52.3 140.8 36.9 32.8 56.7 1:1.9 29.1; 26.1 8.9 11. 5 11. 9 12. 7 146% 26% 22% 10% �-313- Relationship: Patient-Doctor the on Effects of Social.Factors Setting Interview Observations in an illustrate will I In this report how discussed factors the social hypothesis Our interview. clinical the in ommunication c affect morning this and mmunicate, can co that this is why treatment. results of psychiatric and choice the to relevant they are One way to test would hypothesis such a actual an in events, important psychodynamically that he to demonstrate such as age, factors to related significantly are setting, interview of a study the be might A step first and.F score. education, nativity communication of kind the of representative which is event, defined clearly psychotherapy. to relevant that is The phenomenon pattern. communication such one with deals This report e—recording tap the mentioned explicitly the patient no whether or studied is may bear upon transaction spontaneous This interview. during an experimental and interviews rimental in expe develops which transference situation t the well. as in psychotherapy METHOD: The clinical setting in which the observations we re made was an initial of patients edure proc screening the of interview. This was part interviews All hospital. this in therapies sive convul and referred for drug the during Psychiatry, imental Exper of Department the in were performed was It tests. psychological and physiological of battery week as a to asked was The patient and patient. doctor the of the first meeting was procedure unstructured generally and a about his difficulties, tell �.35followed. The purpose was to get an impression of the patient's communication patterns, and to secure a tape recording of the interaction. Several months ago, that the interview it was noted that some patients mentioned the fact was being tape—recorded, whereas nothing about the procedure. Since that time, recorded this data at the conclusion of I other patients said have each session. systematically In addition, the following experimental structure was purposely introduced. A Tanberg tape-recorder was prominently placed beside the desk which the interview took place. This instrument was turned on Just before the patient entered the room, and was clearly in his line of vision. was about at It the level of the desk, at a distance of about seven feet from the patient's chair. The red neon glow bulb, the revolving reels of tape, and the operating noise of the machine could all be observed. An unconcealed mire ran directly from the instrument, across the desk, to a microphone which - lay in clear view between doctor and patient. However, the interviewer no mention of by the made the recording set-up unless the subject was introduced verbally patient. OBSERV£IION33 Since this experimental structure have been recorded. 17 was introduced, 31 initial interviews The tape-recording was mentioned by 1h patients, while others made no such observation. They will henceforth be referred to as the "Mention" and No Mention" groups respectively. a) Qualitative: The patients variety of attitudes. who mentioned the recording expressed a The most common was curiosity, with inquiry as to the purpose of the interview, and the use to which the recordings might be put. �-36A minority expressed overt suspicion, either refusing to proceed with the interview for several minutes, or voicing their fears of humiliating or incriminating uses which might be did'nt know the room was bugged." made A of the recordings. One patient said, "I physician in this group of patients requested that the recorder be turned off for a moment so that he could ask a question as a colleague, "off the record." After a spontaneous mention of the to explore the attitude underlying the remark. recording, an attempt was made This varied from definite hostility and suspicion, through mild objection and uneasiness, to passive acceptance of the procedure. Only one patient expressed delight, saying, "I'm glad this is being recorded, In addition to these subjects who it's like a confession." explicitly mentioned the recording, patient is included in the "Mention" group. to the microphone, shook her head as if She one mute pointed to the recorder, then to say "no," and covered her mouth with her hand. In the "No Mention" group, non-verbal recognition of the recording was often apparent. Most of the patients looked repeatedly at the recorder and microphone , sometimes up furtively. Several of them actually touched or picked the microphone while speaking. I accompanied one patient back to the ward following the interview, and while chatting in a lighter vein she asked way, was that all recorded?" that the ﬂNo-mention" group was aware of the recording. "By the Thus there was considerable non-verbal evidence Quantitative: Quantitative data for the "Mention" and Table-XVILIt is apparent that the group "No—mention" groups is seen in explicitly remarked about the reabout 20 years. They were also better who cording were younger, on the average, by educated, and with only a single exception were native born. They had a lower score on the F scale and I tended to spend more time with them. All the differences between the groups are statistically significant; �.37- TABLE MENTION XVII NO MENTION 53121:). N=17) 26.7 h5.2 1h.1 p< .002 10.9 P<: ~02 93 53 I><: .05 F SCORE 3h.1 11702 DURATION OF INTERVIEW (minutes) 39.6 2900 AGE (years) EDUCATION % (years) NATIVE BORN p‘<:’ .05 �DISCUSSION: Using a single objective index, 3:2. an overt statement about an unexpected experimental procedure, two patterns emerge from patients. The group of this group of subjects mentioning the recording have the same sociological characteristics as those patients from the total Hillside Hospital population are treated by psychotherapy alone. They are who less younger, have some college education, are native born, and are stereotyped in their attitudes. They mention the experimental procedure in a challenging way. Gill, Newman and Redlich have described the anxiety- producing effects of tape-recording psychiatric interviews. This group of patients meet the stress by verbalization of their subjective reactions. talk about it, ask questions, object, 222. The group who do not mention the recording have the same They sociological wharacteristics as those patients in the total Hillside Hospital population who are typically referred for electroshock (i;g. non-venaal therapy) or are hospitalized for the shortest period. They are older, have at most a high school education, are more likely to be foreign born, and are stereotyped in their attitudes as measured by the F scale. These patients the procedure overtly, although they notice the doctor, whatever you do is justified their compliance and what to say, but I'll be glad to it. Their attitude do not question is "You are and should not be questioned." In vauiescence they resemble surgical patients who submit themselves passively to treatment, neither resisting nor actively participating. When asked to tell about themselves their attitude often is, "I don't know The "Mention" group They do answer any questions you may ask." display a different attitude toward the therapist. not treat the physician's procedures as completely outside their �-39- verbalize their resistance, and express their negative feelings directly to the interviewer. The "mention" reaction indicates jurisdiction. They curiosity and the skepticism that Freud felt was required of the analytic patient. In discussing this point, Fenichel notes, that if the patient "is not skeptical at all, the suspicion is warranted that he is repressing negative transferences." It is not surprising that the interviewer, with a psychoanalytic orientation, spent about 10 minutes longer with the "mention" group. This study demonstrates, then, that these sociological factors may be related to actual differences in the quality of patient-doctor relationship. In this one limited aspect of the communication pattern, the sociological background allows us to predict whether the patient will verbalize his reactions or not. If this single stress situation is representative of the general behavior in psychotherapy, we can get some notion of why these related to choice or length of treatment. 'we factors are expect that patients who decline to mention such an obvious situation as a microphone and tape-recorder, will be equally loathe to express the variety of feelings about the therapist which are crucial for analysis of transference. Further studies of the data are in progress which may increase our understanding of the observations reported. For example, a detailed content analysis of the way in which the recording deviant cases. Two of these have already been described. patient, with high F score, who was mentioned sheds light upon the One was an older in contrast to the usual pattern of such persons, did mention the recording. Hewever, he differed from the other older patients in having a medical education. His way of mentioning the �-h0 - recording was to suggest a change in the interview from that of doctorpatient to that of colleagues speaking "off the record." One is tempted to predict the form of his therapeutic resistances from this event. Another patient mentioned the recording,but in an unusual way. She was delighted with the "confessional" aspects. In her sociological characteristics, she too did not fit a clear pattern, being in her 20's, but with a high F score. It is to be noted that she was an ex-Catholic. Other studies of the psychiatric interview, using experimental stresses more characteristic of psychotherapy, furnish additional evidence of the importance of sociological factors. For example, Saslow and Matarozzo research on psychotherapeutic communication. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Max Pollack, Robert Kahn, and Joseph Jaffe: Social Factors and Communication in Psychiatric Patients (research), 1958 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-11-012 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource Pollack, Max; Kahn, Robert L.; Jaffe, Joseph Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence: research with Joseph Jaffe, Robert L. Kahn, and Max Pollack Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/c8041bb911b27dd176a67a53d9ba080c.pdf 51e8ec2d2ba520c72d5afb41bd417d27 PDF Text Text Prognostic Application of Psychological Techniques in Convulsive Therapy Robert L. Kahn Ph.D. and From Max Pollack Ph.D. the Department of Experimental Psychiatry, Hillside Hospital, L.I., N.Y. Aided, in part, by grants M-927 and MY-2092 of the National Institute of Mental Health, National Institutes of Health, U.S. Glen Oaks, Public Health Service. Read at the Eastern Psychiatric Research Association, October 25, 1958. IV: 10-2h-58 New York, �Prognostic Application of Psychological Techniques in Convulsive Therapy One of the more important clinical applications of psychological testing techniques is the prediction of the has there In treatment. in particular, results psychiatric been a considerable effort to determine valid psychological The to results somatic the for therapies. criteria prognostic date, however, have not found clinical acceptance. Using the Rorschach, for example, Rabin (1) has stated that ”single Rorschach factors cannot serve as indices or as has Piotrowski In contrast of improvement." predictors published a number of papers on the prognostic use of the Rorschach in insulin coma and convulsive therapy (2, 3, h, S, 6). Unfortunately, his criteria, as reported in successive papers, are vague and contradictory. In l9h1 he reported six explicit prognostic signs which were applied in predicting clinical months the termination of several after a over period response of treatment. But Rees and Jones (7), in a study of schizophrenic found somatic that of a therapies, receiving variety patients Piotrowski's signs were related to the results on a chance basis only. The differences in the studns of various investigators can be accounted for by methodological variables. These variables include factors of population, number of patients observed, the method of analyzing data, the kind of somatic therapy utilized, and the criteria for evaluating improvement, �-2made in evaluation is which the clinical time the at including incon— Another for basis treatment. of relation to the course sistent results may be the lack of an adequate theretical framework. in been have we engaged several years past These were studies convulsive of therapy the process. studies mode action of the concerning a to hypothesis test initiated of convulsive therapy which was derived from observations on a hypothesis of the to brain-damaged pepulation. According Weinstein and Kahn (8, 9) the therapeutic effect of convulsive function brain of altered the induction to therapy was related of symbolic a new type for conditions the creating necessary adaptation, mainly denial, in characterologically disposed shown altered that have Our already studies previous persons. change behavioral for condition a function is brain necessary (10, 11) and that the manifestation of denial language patterns with treatment is related to the evaluation of improvement (12). The purpose of the present report is l) to summarize the the and demonstrate 2) to on personality factors, findings application of these findings as prognostic criteria for convulsive therapy. For the �Method: studies were conducted at Hillside Hospital, a non-profit, voluntary, mental hospital, admitting patients who are considered as having early and curable illnesses. Psychotherapy is the principal treatment employed, with somatic therapies available when needed. The material presented was collected in a series of studies during a period of three and a half years. While a total of 180 patients have been investigated, varying numbers were tested with each of the techniques of personality evaluation. The patients ranged in age from 20 to 66, with a median of hS, and included twice as These many women as men. All patients received convulsive therapy administered three times a week, using either a Medcraft alternating current instrument or a Reiter C-h? electrostimulator. A minimum of 12 treatments was given, with the total course determined by the supervising psychiatrist in charge of the convulsive therapy unit. All psychological procedures were adminstered in the week prior to the start of treatment. The determination of the patient's response to treatment was based on the medical director's evaluation at the time of discharge, usually within six to eight weeks following treatment. �Procedures and Results: 1. Family Interviews. According to the original theory, it was considered that persons showing characteristics of the "explicit verbal denial" personality, as described by Weinstein and Kahn (13) would be most likely to show a behavioral change rated as improvement following treatment. This was tested in a standardized interview with members of the patient's family, eliciting information on the patient's attitudes, mode of communication and reactions to stress. Fifteen areas of behavior considered to be related to denial tendencies were scored from the interview material. A score of O, 1 and 2 was given for each item, depending on whether the designated behavior was minimally, moderately or markedly shown. The sum of the scores thus obtained was used as the denial score. The relatives of h? patients were interviewed, and denial personality scores ranged from O to 25, with a median of 11. The patients were divided into two groups: those with scores from 11 to 25 were classed as "high denial," and those from 0 to 10 as the ”low denial" group. results of this analysis were significant, showing that of the patients with high denial scores, 58% were in the much improved group and only one patient was unimproved. Of the patients with low denial scores, on the other hand, only The 30% were much improved and an equal number were unimproved (1h). �-5- results based on family interviews felt that our conceptions of prognostic Although these were promising, we personality factors could be extended and made more amenable to practical application by the use of standardized psycholog- ical procedures. For this purpose the Rorschach test 2. The Rorschach Test: We used. have obtained Rorschach was protocols in 87 patients receiving convulsive therapy. The & of the to records were scored according Klopfer criteria Kelley (15). Only those components were analyzed which were considered related to the personality aspects under study. It was found (16) that the much improved patients had significantly fewer total number of responses, and a significantly greater per cent of whole and form responses than did those The who rated as unimproved. were stereotypy and patients limited imaginative capacity of the much improved patients was also shown by their giving a greater percentage of popular responses, with little diversification of content categories. They were less likely to have any kind of shading response. Those patients who had human movement (M) responses had the poorest clinical responses, while those with no movement of any kind had the best results. With respect to color, an F6 response was associated with a poor clinical result, while those with no color at all did very well. Combining some of these factors tended to sharpen the differentiation in terms of outcome. Thus, of those who had �.6. In much improved. as rated both M much 66% improved FC, were with nor neither those of contrast, and only one patient was unimproved. We have converted these results into prognostic criteria, M and FC, only as shown in Table I. 17% In one column are listed those Rorschach closely related to a favorable In the other column are those factors which are factors which have been prognosis. were most For example, outcome. unfavorable clinical of an prognostic 67% much were of those patients with ten or less responses 16 more with or those of 28%, responses however, Only improved. had a good result. �TABLE I Prognostic Rorschach Indices of ImErovement Favorable Prognosis % Unfavorable Prognosis Much % Ingroved Improved of Responses Number Movement Color F and FC less (67%) 16 or more (28%) present present (28%) None (63%) M No FC (60%) FC - 75 a: Shading M 10 or ~ 100 None Much (21%) (59%) o - 59 (27%) (58%) Present (33%) Neither Present (66%) Both Present(17%) �’8- It should also be noted that comparison of post treatment Rorschach records with those obtained prior to treatment failed to show any significant change. This confirms similar observa- tions by others (6, 17, 18, 19) and indicates that the Rorschach pattern is probably a reflection of the basic personality rather than transient aspects of the disease process. 3. Social Attitudes: The F Scale. While these Rorschach results amply confirm the concept of the relation of personality factors and results of treatment, further data was obtained in application of measures of social attitude such as the California F Scale. This scale, originally developed in studies of ethnOa centrism and authoritarianism (20) has been increasingly used in the study of more central psychological processes. In our laboratory the F Scale has been regarded primarily as a reflection of stereotyped thinking and communication. It has been observed that patients who receive convulsive therapy at Hillside Hospital P scores than those given psychotherapy higher significantly alone (21). In these studﬂs a ten-item modification of the F Scale (22) has been used. The test is rapidly administered, taking no longer than 10 minutes in most cases. The subject reads 10 ambiguous statements and indicates whether he agrees or disagrees with each statement, and to what extent. The score given for each item ranges from one to seven and the range of total scores is 10 to 70. The greater the agreement, the higher the score have �-9- statements themselves are extreme, conventional or stereotyped expressions. For example, one of the statements is: "If people would talk less and work more, everybody would obtained. be The better off." This test patients prior to score of ho as a cut-off point,we has been given to 96 convulsive therapy. Using a found that of those patients with scores of ho or more 71% were rated as recovered or much improved. In contrast, only 36% of those with scores below ho were so rated. In general, the higher the score, the better the clinical result. We have also tested an additional 13 patients, referred for convulsive therapy, but who either refused treatment or terminated it of their own accord prior to completion. Of these, eleven had F scores below ho, an observation consistent with the general expectation that such persons haVB a poor response to convulsive therapy. �-10- Discussion: These observations have shown that in the course of the investigation of theoretical problems of convulsive therapy, certain standard psychological procedures have provided data which is significantly related to the therapeutic outcome. This data can now be applied to the practical problem of clinical prognosis. that favorable improvement rating is given to those patients who develop euphoric, hypomanic or denial modes of adaptation following treatment (23). Such behavioral change is most likely to occur in persons whose premorbid personalities may be characterized as non-empathic, non-introspective, nonverbally communicative and highly conventional and stereotyped with little imaginative or creative capacity (1h). On the Rorschach prior to treatment these patients give few reaponses, fail to show human movement, shading or integrated color responses (F0) and have little variety of content. 0n the F Scale, their scores were apt to be over b0, showing a high degree of stereotypy in their communication. In contrast to such patients, others are either unchanged by convulsive therapy or develop such modes of reaction as panic, paranoid behavior, or increased somatic concern, such as We have found a complaints about their memory. These patients are rated as unimproved. While this latter group of patients showed diverse patterns in their premorbid personality characteristics, they were more apt to be imaginative, introspective and less stereotxnd in their communications. On the Rorschach they gave human �-11movement, integrated color and shading responses, and were more On good than the prognosis patients. diversified in their content the F Scale their scores were most likely to be under ho. finding that meaningful prognostic criteria can be derived on the basis of personality constellation rather than in terms of nosological entities has important implications. For one thing, this conception leads to the use of further psychologSuch application is for prognostic ical techniques purposes. laboratory Secondat Hillside under in Hospital. our way currently mental of increased an understanding derive to is possible ly, it disorders, their management and prevention. Thus, we have previously noted (1h) that the same personality factors which are related to a good prognosis with convulsive therapy, are etiologof of psychiathe certain types development in important ically tric disorder. Studies of patients with psychiatric depression, for example, demonstrated a prominence of premorbid personality patterns characterized by the inability to communicate verbally (2b), and rigidity and lack of imagination (25). Such persons and verbal conventional to techniques are generally refractory require non-verbal therapeutic techniques. It seems that the same personality factors which make a person responsdve to nonverbal forms of therapy are involved in his susceptibility to a depressive reaction. The same stereotypy and conventionality which lead to a catastrophic response in the individual faced by the sudden loss of a job or close relative, permit the develop-. t ment of denial, minimization and displacement under the conditions of altered brain function and are considered "improved" by the family and the therapist. The �-12- that in the course of investigation of theoretical problems of convulsive therapy, certain standard psychological procedures have provided data which is significantly related to the therapeutic outcome. This data can now be applied to the practical problem of clinical We have shown prognosis. On the Rorschach test, those patients without human movement, shading or integrated color (FC) responses, few total responses, and with little originality or variety of content have the best prognosis. On the F Scale, a score of less than no is prognostic of a poor clinical reaponse. The theoretical conception developed in these studies leads to the application of additional psychological techniques for prognostic purposes, and to an increasing understanding of the etiology of psychiatric syndromes with its implications for management and prevention of such disorders. �-13- W REFERENCES 1. Rabin, A.I.: Effects of Electric Shock Treatment Upon Some Aspects of Personality and Intellect, Am. Psychol. 23 28,4, 19b7o 5'1 Rorschach the of Possibilities Z.: Prognostic Piotrowski, Method in Insulin Treatment, Psychiat. Quart. $3: 679, 1938. 3. Piotrowski, Z.: Rorschach Manifestations of Improvement Med. Psychosom. in Insulin Treated Schizophrenics, 508’ 1939. 6. l: A the Device for Experimental Z.: Single Piotrowski, in Prediction of Outcome of Insulin Treatment19h0 Schizophrenia, Psychiat. Quart. lg: 26?, Aid in Method a Prognostic Rorschach as 2.: Piotrowski, the Insulin Shock Treatment of Schizophrenics, 19h1. 807, Quart. lg: Psychiat. Effects N.D.C.: Z. and Lewis, Piotrowski, B.L., Pacella, of Electric Convulsive Therapy on Certain Personality 10h: Am.J. in Psychiat. Traits Psychiatric Patients, 83, 19h7. An Rorschach of the A.M.: Evaluation Jones, Test as aPrognostic Aid in the Treatment of Coma Therapy, Electronarcosia Insulin by Schizophrenics & Leucotomy, J. Ment. Sci. Therapy Electroconvulsive Rees, W.L. and 21:681, 1951. Weinstein, E.A., Linn, L. and Kahn, R.L.: Psychosis During Electroshock Therapy: Its Relation to the Theory of Shock Therapy, Am. J. Psychiat. 109: 22, 1952. Weinstein, E.A. and Kahn, R.L.: Denual of Illness: Symbolic and Physiological Aspects, Springfield, Ill. C.C. Thomas, 1955. 10. 11. 12. of M. E.A.: Relation and Weinstein, Fink, R.L., Amobarbital Test to Clinical Improvement in Electro& 1956. 23, Neurol. Arch. shock, lg: Psychiat. EEG M. of Delta Activity and Relation R.L.: Kahn, Fink, to Behavioral Responses in Electroshock: Quantitative & 1957. 516, Neurol. Arch. Psychiat.1§: Serial Studies, Kahn, Kahn, R.L. and Fink, M.: Changes in Language During Electro- shock Therapy. In Psychopathology of Communication, & New Grune York, Roch, P. and Zubin, J. Eds., Stratton, 1958. �~1h— 13. Factors in Weinstein, E.A. and Kahn, R.L.: Personality & Neurol. Arch. Denial of Illness, Psychiat. Q2: 355, 1953. Personality Factors in Behavioral Response to Electroshock Therapy, Conf. Neurol. (in press). Kahn, R.L. and Fink, M.; New The Rorschach D.: Technique. Kelley, Klopfer, York, World Book Co., 1§E§. Kahn, R.L. and Fink, M.: Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy. Paper read at Electroshock Research Association meeting, San Francisco, 1958. Beck, S.J.: Effects of Shock Therapy on Personality as Shown by the Rorschach Test, Arch. Neurol. & Psychiat. ﬁg: h83, 19h3. Kelley, D., Margolis, H. and Barrera, S.E.: Stability of the Rorschach Method as Demonstrated in Electric Convulsive Therapy Cases, Rorsch.Res.Exch. 5: 35, 19b1. B. and 16. 17. 18. 19. 20. 21. 22. 23. Kisker, G.W.: A Projective Approach to Personality Patterns During InsulinéShock and Metrazol-Convulsive Therapy, & Soc. Psych. 21: 120, 19h2. Abn. J. Adorno, T.W., Frenkel-Brunswick, E., Levinson, D.J. and New The York, Authoritarian R.N.: Personality, Sanford, Harper, 1950. R.L., Pollack, M. and Fink, M.: Social Factors in the Selection of Therapy in a Voluntary Mental HOSpital, J. Hillside Hosp. g: 216, 1957. Levinson, D.: Personal communication. Fink, M. and Kahn, R.L.: Behavioral Patterns in Induced States of Altered Brain Function. Paper read at Divisional meeting, American Psychiatric Association, Kahn, New York, 1957. . A a A. N a__..... ..- Cohen, M.B., Baker, R.G., Cohen, R.A., Fromm-Reichmann, F. and Weigart, E.V.: An Intensive Study of Twelve Cases of Manic-Depressive Psychosis, Ps chiatr , 11: 103, 195h. .A-aL.......;.—..M.u ~.~ , i Hamilton, D.M. and Mann, W.A.: Hospital Treatment of In Depression, Hoch, P. and & Involutional Psychoses. Zubin, J. Eds., New York, Grune pp. 199-209- Stratton, 1952, j 5 E t i 2 1 s � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Robert L. Kahn and Max Pollack: Prognostic Application of Psychological Techniques in Convulsive Therapy, 1958 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-14-013 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource Kahn, Robert L.; Pollack, Max Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/e7dc2fcb5fc19380588fec1c1d7b8cf6.pdf e4bf0125cc9cc7fe7c750dbacfa00dd7 PDF Text Text �SOME EFFECTS OF A NEW PSYCHQTOQEN IN BEFRESSIVE STATES J. Mednna Univereity of Illinoie College of L. G. Ahood A and L. Hedioine group of 3~R~snhetitnted piperidyl beneiletee have been recently denonetreted to poseees peychotceieetic propertiee(l.2). The N-nethyl-snpiperidyl beneilete, in doeegee of 5-10 mg orally, produced distinct auditory and visual hellucinatione in every nor-e1 individual teeted. The hallucinations lasted for many bears, and were accompanied by green distortion of visual perand by e confosionel etete corresponding to delirium. ception A nnnber of subjects exhibited paranoid ideotion and ideee of grandeur, while others suffered a conplete loee of contact with the environ-eat, end frequently reacted to their hallocinetione. When the toxic symptoee disappeared, the experienced ethecte e earked physical eeekneee for 10—24 honre, after which period they regained their pro-experimental statue. It see noticed, however, that some of the normal volunteer subJects developed a change in their heeic mood and drive. This change usually appeared 24 to 48 hours after the phyeicel weakness disappeared. The newly energies modulation of need can be characterized es slightly hypenenic end of increeeed drive. This leet observation indicated that the drug night he naefnl in the treatment of peychietric states in which the ontetending eyepton ie a depressed need. In the course of exonining the structureoaotivity relationships of various congenere of the piperidyl beneiletee (3), it wee found that substitution or e cyclopentyl for one of the phenyl groups in beneilic acid considerably enhanced peychotogenie potency end greatly prolonged the duration of action. The colu pound, deeigneted JB-329', has the following structure: Q *- {’ I “2‘5 0 Ell/Q - g 361 ‘0 N-ethyl-B-piperidyl cyclopentylphenyl glycolate hydrochloride This derivative also eeened to produce considerably more hyperend central etieeletion than did its beneilate congener. ectivity The present comnunicotion concerns the nee of J8~339 on psychi- etric patients. DB, one a 60-year-old eon, e first patient, §5g3_ﬁgt_*: ormer r cklayer, who had been hospitalized for the last ten years. Exeeinetion revealed his caee to be one of eevere depres» eion iith suicidal tendencies, ceoeed apparently by the necrotic The �. 7 .., . t V... ".7“ .........4. ,g-vvwmh . ”a...“ . man. w.- ...,..r.....,....... r.” ..u._,..,,.,.—Y “any,” p,..r.._....~.w.....F—, .»... wwv.-.» an...“ ...~.,v»,., . "ﬁn y”... wr—u-nrl’nu _,., V... ..W;.,..I.:.v...._.._..r*‘ 7.. reaction of his burned~out body to the insoluble probles of his wife’s gsychotio illness. The patient eas given 12 as of 33-329, and sit in an hour showed signs of confusion, drowsiness, ataxia, and hypereflexia. A few hours later he began hallucina~ having tions, saa disoriented, extreaely restless, and beg nning to lose contact with the environaent. Autonosic syaptoas were present throughout, such as aydriasis, tachycardia, dryness of the south, and muscular weakness. At the end of 24 hours, he seeaed con~_ siderahly less depressed, sailed, laughed, and was such sore talkative, although he professed to be Just as depressed as he was before the treat-ant. Psychological re-exaaination with the Eduardo and Rorschach tests indicated a definite iaproveaent in seed and general outlook, and although the depression still existed, it seessd realistically based, and was considerably less overehelding. The patient, hosever,.rofased to go back to his psychotic wife, and was returned to a state hospital. EP, a an 33~year-eld unaarried shite aan, coaplained he, 0%.. o extreee apathy, and a chronic spastic colitis. spression, He had quit his job over a year ago because of an increasing depression, accompanied by feelings of inadequacy and lack of desire to work. Psychological tests revealed his to be iasature, with little or no effect, no signs of anxiety, and no insight into his condition. He reacted to 10 ag of JB~329 in such the seas manner as the previous patient, covering a tine-span of 18 hours. At the and of this period, he appeared very cheerful, and of the depressed, haunted features of his face had disappeared. all He gave the iapression of a nan sell on the way to after recovery a long illness. That ease day he indulged in a rather vigorous gene of baseball, nixed, and talked freely with the other patients. He adsitted feeling sore aggressive and exuberant, and expressed a desire to go back to sort as soon as he was discharged. Psychological re~exaaination showed his to be sore responsive, less inhibited, and his outlook less liaited. The patient was discharged two days after receiving the drug, and two days later be procured a position, which he still retains after three aonths. c a had lea, 47-yearweld'aarried.aan, a history §%;f_§g‘_%l 0 ntera ttent depressions since 1953. He had been unable to work during the past year because of the depression. at the ties of his admission, he showed syaptoas of restlessness and extreae agitation; he ens harassed by self-accusations and feelin of guilt. Pro-therapy tests revealed an inadequate personal ty with en extreaely passive dependence.on other people. The existent anxiety and depressive features sore overlaid upon a longostanding character disorder. The patient's response to 12 ng of JB~329 differed fro: the previous patients only insofar as the halluci» natory episodes sere far aore vivid and of longer duration. After 36 hours, the patient exhibited aarked increase in actor activity and a draaatic iaproveaent in need. Psychological reexasination revealed that he was now able to express hopeful and resolute attitudes toward the future, although he still had little confidence in his ability to achieve the goals he envisioned. �after being discharged, which he spontaneously erote a letter were taken the following statements: free For your infor~ nation, ay progress has been good. I as working about [all tine have gained-about ten pounds. ﬂy appetite is very good not. as extremely grateful to you for what you have done.‘ Two weeks ...I ...I who a 54*yearuold earried sea shite eoaan ap» gagg_§g‘_3z each older, and had been in a very severe depree~ pears very sion for the last ten years. She had phobic paranoid reactions, suicidal ideas, and hysterical attacks accoepenied by screening. excessive crying, and other indications of desire {or attention. Psychological exaninetion indicated an unsound personality strse~ tnre which scene to have been infantile even before the onset of the present illness. The effects produced by 12 a; of JB~329 were to those in the other patients. and lasted for 24 hours. eiailer The following day, she appeared more vivacious and nest of the outward signs of her illness had disappeared. 0n the succeeding day, she socialised for the first time with other patients, and participated in occupational therapy activities. She seeaed‘sur~ prisingly cheerful, enjoyed her food, and appeared outgoing. After three days, when her husband case to take her hose, she reacted violently and relapsed into her previous condition. Her' condition was apparently developing into a full—bloen psychosis. Electroshock therapy was adninistered during the next week, and although the patient showed improvement at first, she again relapsed into the previousaagiteted depressive condition. No 5: KB, a 46—year-old shite-nnaerried resale with Ca paranoia delusions. was depressed and apathetic. She was extra-sly tense and anxious. and her grasp on reality was tenuous. Her reaction to 10 a; of JB~329 see similar to that of the other except that the hallucinations and disorientation lasted patients, up to 36 hours. Two days later, she appeared definitely anieated. cheerful. and coegosed. When questioned about her past condition, she replied, "I feel such more alert and don’t toel.depressed. Strangely enough, this was one of the first things I noticed. I feel new as it before the treat-ant I had been living in a [let tee-dimensional eorld and I had sort of retreated into ayseli. and nee, after this treatment, I feel I as out in the noraal three-dioensional world. I feel such sore alive...I have lore energy and enthusiasm.“ The patient resneed her work on the day following.her discharge. She continued to shoe improve-ant during B the next few weeks, although after one south-she appears to be relapstng into her former state. She reported. however, that a symptoms, which she referred to as a ”catatonic nightnere." a condition during which sheeeeeaed to be conscious but was unable to sore and which had existed for eany years before the treat— aent, had coapletely disappeared and had not yet returned. LCCT ' DISCUSSION Five cases have been presented which serve as pilot experiaents in the application of the piperidyl bensilatee to patients manifesting psychopathology. Of the five cases, the first and �“-vv—l‘vrr‘vr‘n-I—vw—v'wvwbvu' .V ‘1"N"x'-w-*,—- meg-w,v—u—m- . mun—aw wr— . Wmuw‘aw—r _.. wenhvvrv-"v' Wham-1 rap. >mvr-.-.—_—,WVgrnww.-m.n WK‘J'W‘ wm ~ wane—v - .w u-‘nnw -4the fourth can be considered eo experieentel ouccooeee but therepeutic failures. These two particular ceeee have never reepondod‘eell to any other for: of therapy, including electron check and drugs. In three case: (Noe. 2, 3, end 3) the single application of the oxperiaentol dru; proved to he of therepeutic value. Cece: No. 2 and 3, who were unable to work for over e before the oxyear porieent, were able to do oo. Case No. 5, which is the neat interesting of our small oxporieental group, wee working prior to the experiment; but that petiont'e state-onto end our objective observation are both indicative of the therapeutic effectivonoee of the drug. Cece No. 4 proved to be a therapeutic failure with reepect to the drug. but the patient aloe failed to recover after electric convulsive trootnonte., All five canoe treated hed only one synptoa in cannon-~ooee degree of doproeeion. The other most remarkable con-on feature of cases No. 3, 3, 4, and 5 one an extreme infantile personality which could not be expected to change after a eingle treatment of whatever eort. If it were not for the fifth coco, where the loot remarkable ohengee were produced, this drug, 38-329 and ite con¢enere could be earmarked for the treatment of depreoeive otateo only. In the fifth case, however, beneath the light dopreeeion were deeper disturbances of thinking end perception eluding superficial observation. In effect, ehe eee psychotic. lhethor her perticular paranoid state ehoold be diegnoeod ae latent eohieophrenie, effeltivo paychooie, or achieophroniforio beside the point. The ieportance of this case io that it indicates some usefulness of the piperidyl benziletee in e patient eith lurked perceptual and cognitive dieturbenooo. There are a great nu-ber of questions uneneeered by thie proliainary experiment. Both the extent and duration of leproveaent have not been fully aeeoeeod. It reneino to be detereinod 1) whether repelted adainietretion of the drug in hallucinogenic doeeo would have produced a greater degree of improvement in the eueceeefei canoe and total or partial leproveaont in the unseen ooeeful fourth cone; or 2) whether the production of the poychotogonic etete ie necoeeery et oil to produce ieprovenent; or 3) if deily repeated small doses of the drug for an extended time would have produced the care but clover iiproveoent. Both the effect end proper doeege ochedule of e aeintonenco ascent of JB-329 have yet to be determined. Finally, the proper field of application of this drug in peychiatry ie in doubt. do for co the cxporieentol results on nornel and pathologic etheoto permit any conclueion, the drug would be epglicable to depree~ eive etetee. Our fifth case. however, reieee some slight hope that JB-329 or related derivetivee night be useful in treating the grove personality dieordere cocoonly diagnosed an albino. , - a phrenil. L of enticholinergic egonte in the treetaont of eohieophroeie ie not nee. Forror and eo~eorkere (4) odainieterod very large The nee '10.!"me �W “u—wmumw—HWM‘ w , y:- m ;«m« mu, 7-" v mlm“ wﬂwnm—u‘u—w“ Imam. m... .. -. . .r t i . a r n . - _ _ i n. --'—-'-v>-vv_uru'v » 'I‘uﬂv-"vWO4‘m‘ <‘AmevN’--ww z-ew11IUI'm—rl—I- .5doses (up to 200 mg) of atropine intramuscnlerly to schizophrenics seniteetinc eose degree of anxiety. [Such doses of atropine produced core; but nest of tho psychotogonic and stisuleting notions achieved with JB—329 were absent. It remains to be seen whether the besic eeoheniss ot-thooe tvo nodes of therapy is sisiler, although our findings suggest that atropine is devoid of the exceesive stimulating properties of JB~329. LSD—38,_enother hellnoinogen, has been used therapeutically in treating psychotics, lsrsely es en edJunct to psychotherapy or electroshock convul— sions (5, 6). With regard to the code of sction hardly more can be said than that the substance has definite enticholinorgic properties, but evidence thet the central ettect itself involved cholisergic blocksde is locking (1, 3). The piperidyl bensiletes in smaller doses produce facilitation of sotor neurons (Renshee cells) in the lesbsr region of the cat‘s spinal cord, while larger doses produced couplete inhibition (7). Acetylcholine is presumed to be a mediator in Renshew cells which are believed to exercise a generalized sup reesion in motor neurons innervating okeletel soocle.v Kiseich ‘8) hes demonstrated en inhibition of electricel activity in the reticular bulber forention of the rabbit with 2.5 eg/kg of JB~329. in contradictincticn to LSD, which in exci~ tetory. Such neurophysiologicel studies are merely prelisinsry end. although they say oxplsin certain effects of the drug, such es hyporrcrlexie. considerably more work of this sort releins to be done. clinical results with the drug are even more obscure, perticnlerly since the therepentic effects become apparent long after the hellucinatione and autonomic sysgtoss have disappeared. Furthersoro, otudieo on animals indicate that the drug is rcedilg hydrolyzed in the body, and is completely elisineted in 24-48 ours.. One can only conclude, therefore, that therapeutic effects are related to the drug in a secondary manner. The piperidyl beneilntos probably serve es a trigger necheniss for e long series of neuroohysiologicol effects resulting in the inprevelent in the pstient s psychopathslogicel etstns. Sub~ sequent clinioel work ie oiled at working out proper dosage schedules, on well no the indications for the use of this and other related drugs. The SUMMARY entioholinergic psychotonimetic agent, Noethyl-3~piperidyl cyclopentylphenyl glycolote (JR-329), has been used in the treat~ sent of e snail author of depreeeed patients. The drug induces e drive of eotivity eccosponied by sons sood elevation. This sceningly desirable effect tron s therapist's viewpoint occurs after e period in which there are psychopathologicel effects or s definitely psychotic nature. The post~psychotic effects which sees desirable are of a prolonged duretion (days to reeks possibly). There is st least all ht evidence in two casee or e continuing stete of isprovenent n inte3retion of the mental functioning and A new behavior. ' �. ,w... E. n‘vw-“m-w~'mwwm‘w‘m‘—Iw — ,., -—- --——- q"r.xr)r.«,"l‘w wine—uw.w m_m , .v . w-..-....w w. m—u—wnm .c up... (“mu—r . .- "le- REFERENCES l. 6., Oetfeld, N., and Biol, J. A new group of peychotceieetic egente. Proc. Soc. Exp. Biol. end ﬂed., Ahead, L. A. 97: 433, 1958. 2. Oetteld. A. l., Ahead, L. 6., end Hercne, D. A. Studies with cerulopleeein end e nee hellucinogea. A.M.A. Arch. Neurol. and Peychiet.. 79: 317, 1958. Abuod. L. 6., 03:5.1a. A. u., and 31.1, a. Structure~ activity roletionehipe of Supiperidyl heneiletee with peychotcgenic propertiee. Arch. Int. Phereecody. ct Thor. (in prose, 1958). Forrer, G. R. AtrOplne toxicity there_y in the treatment of aental dieeese. AI. J. Paychiet., 08: 107, 1951. Just, F., and Penal, ﬂ. Proepective peychietry. Inch. Mod. ﬁche-chr.. 99: 889, 1957. Sandlson, R. A., end Whitelae, J. D. A. Further etudiee in the therapeutic velue of LSD in eentel(illnees. J. » 3. 4. 5. 6. 7. 8. Heat. Sci., 103: 332, 1957. Ueki, 8., hiehi, 8., end chcteu, K. Hieeich. K. Persoael coneunicetion. Personal communication. Foorxowas ‘ Syntheeieed bf Dr. John Biel, Lekeeide Leboretoriee, Hilveukee, Wieceeein. authors ere deeply lndebteﬂ to Dr. F. J. Gerty for hie eeny invaluable suggeetione, end to Dr. Alec K. Roeeneeld for the plydhalogicel teete. Aiéed by greute free the Mental Health Fund, Stete at Illincie. end the Teegle Foundation. The �Institute of Human Nutrition, Praha, (J. Mast-k) A PSYCHOSIS CAUSED BY BENACTYZIN INTOXICATION Minis VoJ'i‘cmuovsm" The dimethylaminoethyl ester of benzylic acid is known in the literature by the following names: Benaetyzin, Suavitil, Parasan. It was synthesized in 1936 in the CIBA Laboratories in Switzerland as a spasmolytic agent, but it was not until 1955 that it first came to be used in psychiatry by Munkuad & Jacobsen, where it proved to be a useful tool for decreasing anxiety and psychic tension, without having any hypnotic side effect. During the following two years it was roughly investigated for both its clinical and pharmacological qualities and was applied to many patients in various institutions. The specific action of this drug upon the central nervous system placed it, together with the tranquilizers, on the level of the leading modern psychopharmacological agents. For its composition and central nervous action it was called an “antiphobic” agent, while its chemical structure ranged it among the diphcnylmethanes having a central nervous effect (together with e.g. Meratran. Frenquel, or Atarax). 'I‘herapeutically it is used more commonly in cases of neurosis than in psychotic cases. Its pharmacological and clinical attributes have been described thoroughly in other publications. This substance was also synthesized in Czechoslovakia, in the Laboratories of the Institute for Research in Pharmacology and Biochemistry and has been tested since May 1956 in several clinical institutions (Dr. Hanzlic‘ek, Dr. Vina‘r’, Dr. Vojté’chovsk‘y). The results of these tests have been published elsewhere. At the clinical department of the Institute of Human Nutrition we administer Benactyzin in the therapy of some gastrointestinal diseases. Thus we had an opportunity to observe the course of an acute intoxication, which we refer to in the following case history. It was the enormous size of the dose used, fifteen times greater than described in the literature (Jacobsen (1955)— 90 mg). as well as the fact that to our knowledge it is the only case where psychotic symptoms appeared, which stimulated the communication. .43, . i �A PSYCHOSIS CAUSED BY BENACTYZIN INTOXICATION MILos \’o.1'r1'«:1;11ovs1\'\" The dimethylaminocthyl ester of benzylic acid is known in the literature by the following names: Benactyzin, Suavitil, Parasan. It was synthesized in 1936 in the CIBA Laboratories in Switzerland as a spasmolytic agent, but it was not until 1955 that it first came to be used in psychiatry by Munkvad & Jacobsen, where it proved to be a useful tool for decreasing anxiety and psychic tension, without having any hypnotic side effect. During the following two years it was roughly investigated for both its clinical and pharmacological qualities and was applied to many patients in various institutions. The specific action of this drug upon the central nervous system placed it, together with the tranquilizers, on the level of the leading modern psychopharmacological agents. For its composition and central nervous action it was called an “antiphobic” agent, while its chemical structure ranged it among the diphenylmcthanes having a central nervous effect (together with e.g. Meratran, Frenquel, or Atarax). Therapeutically it is used more commonlyin cases of neurosis than1n psychotic cases. Its pharmacological and clinical attributes have been described thoroughly in other publications. This substance was also synthesized in Czechoslovakia, in the Laboratories of the Institute for Research in Pharmacology and Biochemistry and has been tested since May 1956 in several clinical institutions (Dr. Hanzlié’ek, Dr. Vina‘r’, Dr. Vojféchovsk'y). The results of these tests have been published elsewhere. At the clinical department of the Institute of Human Nutrition we administer Benactyzin in the therapy of some gastrointestinal diseases. Thus we had an opportunity to observe the course of an acute intoxication, which we refer to in the following case history. It was the enormous size of the dose used. fifteen times greater than described in the literature (Jacobsen (1955)— 90 mg), as well as the fact that to our knowledge it is the only case where psychotic symptoms appeared, which stimulated the communication. �515 CASE HISTORY L.B., a 29 year old married female, a physician by profession, with a sensitivepersonality, but without previous psychiatric symptoms, during a short period of emotional excitement following some misunderstanding with her husband, consumed almost a teaspoonful of pure Benactyzin. (During the reconstruction of the case it was ascertained by weighing approximately the same amount of the drug, that the patient had consumed about 1300—1400 mg of Benactyzin). It was used solely for its soothing effect without any intention of committing suicide. The course taken by the intoxication, as described by the patient herself and corroborated by her husband and the physician summoned to the case, was as follows: About ten to fifteen minutes after taking the drug the patient became confused, she felt as if she were looking at herself and her surroundings from a distance is; as if everything was running away from her. She expected to faint, but remained seated quietly on the sofa. After about twenty minutes she became agitated and leaving her seat walked in a very unstable manner to the bathroom to take a shower. There she noticed in the semi-darkness a pile of laundry lying on the floor, and on top of it she suddenly saw her six months old son. Let us continue in the patient’s own words. “I was unable to realize at the time that this could not be true since the baby was actually at home with his grandmother. As I kept looking the baby suddenly turned pale, then yellow, his eye-balls deviated to one side and he appeared to be on the verge of dying. Finally, before my very eyes, he started fading away and disappeared. In a wild attempt to find him I searched among the laundry and then, feeling completely desperate, I ran out to seek an injection for him. My husband prevented me from going out. I accused him of being the cause of our baby's possible death.” According to the husband there followed a short struggle and the patient was compelled to remain in the room. What occurred in the next period is covered by amnesia (that is between the twentieth and the fiftieth minute), and it is the husband alone who continues the description of the case as follows. “She showed signs of anxiety and her face held a terrified expression. Her orientation in space was altered, when she tried to seize an object she would miss it by about 20 cm, she would also miss the chair when trying to sit down. She became more.and more agitated and repeatedly tried to run into the corridor, even though she was only partly dressed, with the persistent idea of obtaining the injection for saving her child. A short time later, having managed to escape, she was found on another floor, in vain seeking an opening into a wardrobe and talking confusedly about the death of her baby. She was brought back into the room, where she became slightly calmer." The patient is able to continue the description of the events which followed (that is about an hour after the consumption of the drug), as the amnesia was lifted for this period. “I tried to understand that I could not really have seen the baby, since he was not there, but whenever I thought about him the whole situation appeared again very clearly before my eyes and I felt a terrible anxiety. At this time I partly realized that I had only suffered from a hallucination. I tried to focus my mind on my surroundings and the conversation, but my thinking was disrupted and l was unable to integrate individual notions into a logical whole, even though I did partly realize the inadequacy and incoordination of the words I used. I believe I even repeated certain phrases stereotypically.” At this time, that is between the first and second hour of 'the intoxication, the physician, who had been summoned, noted considerable psychomotor excitation, agitation, inadequate behaviour and inadequate answers to questions and diagnosed 33 ac-ra rarcu. rr NIUIOL. scan, 33, 4 �516 psychotic state. The patient confessed having taken a large dose of Benactyzin, but resolutely denied any suicidal intention. Her face was flushed and showed signs of crying, her pupils were dilated and she looked terrified, her pulse was 921 min., her blood pressure was not recorded. Caffeine and coramine Were applied hypodermically. The patient violently protested against taking the injection saying, “Do not give it to me, but to my son, who is dying.” Two hours later, when the physician saw the patient once more, there were still slight signs of psychomotor agitation and emotional instability, but the patient had just experienced a critical attitude towards the hallucination and psychotic state. In her story the patient describes her feelings during the period between the second and fourth hour after consumption as follows: “After the injection I felt roughly normal. I realized the impossibility of what I had seen, but I still remembered it with a feeling of terror.” Her husband observed that she became calmer after the injection, but her speech was still inadequate. Four hours after taking the drug she became normal, but was very tired and sleeply. An hour later, that is five hours after taking Benactyzin, she was able to ride home on the bus. Then she spent a quiet night, and the following day she was without symptoms. a EPICRISIS Ten to twenty minutes after consumption of 1300—1400 mg of pure Benactyzin a 29 year old married and mentally healthy female, a physician by profession, showed signs of indisposition, ataxia and derealisation, later there appeared psychomotor excitation and a temporary true optical hallucination showing the horrible image of the death of the patient’s baby. This experience led to great anxiety and psychomotor excitation and the whole behaviour was centered on saving the baby. In the period between the twentieth and fiftieth minute of the intoxication the patient passed into a delirious state, wih confused consciousness and followed by amnesia. This stage was characterized by the appearance of a secondary delusion about the death of the child and accompanied by aggressive behaviour motivated by the wish to save him. Thinking was incoherent, there was a feeling of blocking of the thoughts with a strong accentuation on anxiety, agitation and ataxia. The physician who examined the patient some time between the first and second hour after the intoxication, noted a psychotic state with signs of agitation, inadequate answers to questions, and the delusion about the death of her baby. Upon physical examination a flushed face, dilated pupils, and tachycardia were observed. The psychomotor agitation decreased after the application of coramine and coffeine and there arose a critical attitude towards the hallucination and delusion experienced, but the emotional bond to their memory remained. Disorders in thinking stood out foremost (blocking of the thoughts). These were apparent in the form of incoherence and perseveration. Three or four hours later the psychotic state had definitely ceased and was re9 �517 placed by tiredness and sleepiness. After this phase there were no further complications. DISCUSSION The toxic dose of Benactyzin has not been ascertained for man. Experiments on the human subject were made impossible by the marked effect of even small doses of the drug upon the central nervous system, as may be observed both clinically and on the electroencephalogram (Coady & Jewesbury 1956). After a dose of four to six mg of Benactyzin, the following unfavourable side effects were described: dizziness, apathy, relaxation of the muscles, a dull feeling of the extremities, as if they were not connected with the body, sluggish thinking and lowered attention, decreased reactivity to external stimuli, blocking of the thoughts, derealisation, ataxia. Among the symptoms of disturbance of the vegetative nervous system, it was especially dryness of the mouth and palpations which stood out. The side effects described above occur in about 40 per cent. of the patients treated, causing a marked decrease in the therapeutic value of Benactyzin. The dose used to date never surpassed 90 mg (per single dose) and were never accompanied by qualitative disturbances in thinking or hallucinations or. confusion (Jacobsen 1955). The Benactyzin intoxication described above (about 1300 mg) was characterized by a delirious psychotic episode with a brief optical hallucination, followed by a secondary delusion, confusion, and psychotic behaviour. Before and after the delirious state in our case, there were the other side effects commonly described in the literature, namely ataxia, derealisation, and blocking of the thoughts. The atropine-like visceral effects which could be expected after such a large dose of the drug were not felt by the patient herself even though they could be observed to a small extent (tachycardia, flushed face, dilated pupils). The psychotic course of the intoxication could be explained by the specific and quantitative action of Benactyzin upon the central nervous system. While the theme of the psychotic episode might well be understood psychodynamically: a sensitive mother whose main problem of life is the health of her six months old child, the optical hallucination may be the realisation of her fears. The relatively benign course and short duration of this intoxication and the negligible visceral symptoms which accompanied it, even though the dose taken surpassed therapeutic dosages more than a thousandfold, denote a relatively low toxicity of Benactyzin. On the other hand this case only accentuates the predominative action of this drug on the central nervous system. 33‘ �518 SUMMARY The clinical course of an intoxication by about 1300 mg of Benactyzin characterized by a short benign delirious psychotic state is described. REFERENCES GeseIIscha/l f. chem. Iniluslrie, Basel, Schw. Pat. No. 183065, 187825, 1936. (.‘oady, A., & E. C. 0.1ewesbury (1956): A clinical trial of benactyzine hydrochloride (“Suavitil”) as a physical relaxant. Brit. med. J. 1, 485—87. Davies, If. B. (1956): A new drug to relieve anxiety. Brit. Med. J. 1, 480—84. Jaeobsen, E. (1955): A new drug efective on the central nervous system. Dan. Med. Bull. 2, 159-160. Jacobsen, E., A. Kehler, V. Larsen, I. Munkvad & K. Skinhaj (1955): Investigations into autonomic responses during emotion. Acta psychiat. (Kbh.) 30, 607—25. Jensen, 0. ”slergaard (1955): Suavitil in the treatment of psychoneuroses. Dan. Med. Bull. 2, 14043. Munkvad, I. (1955): Treatment of psychoses and psychoneuroses with a new sedative (Suavitil). Acta psychiat. (Kbh.) 30, 729—39. Vinar, D., M. Vojté'chovskﬁ & Vinarova’ (1958) : Cas. lik. Ees. (Prague), in press. , Received April 4, 1958. Milo} Vojtéchovsk)", M.D., Praha XIV, Budéjovika 800, Czechoslovakia. �Reprinted from Psychotropic Drugs THE COMPARISON OF THE PSYCHOTIC EFFECT OF TRYPTAMINE DERIVATIVES WITH THE EFFECTS OF MESCALINE AND LSD-25 IN SELF—EXPERIMENTS S. SZARA Central State Institute for Nervous and Mental Diseases, Budapest (Hungary); Forsehungsabteilung, Psychiatrisehe und Nervenklinik der Freien Universitat, Berlin (Germany) INTRODUCTION \ Indolealkylamines have been considered for a long time as a group of active substances of rather slight pharmacological and almost no psychiatric interest. Renewed attention has been focused on them since the discovery of the presence of 5-hydroxytryptamine in blood, in the enterochromafﬁn cell system, spleen, kidney, and the central and peripheral nervous tissue. An excellent review on the pharmacology of indolealkylamines by ERSPAMER appeared in 1954, and many other reviews have appeared on 5-hydroxytryptamine or serotonin (AMIN et al.1; FREYBERGER et al.11; GADDUM et al.12; HIMWICH13; LANGEMANN17 ; PAGE2"; ROTHLIN). The tryptamine derivatives have been of interest only in connection with their effect on blood pressure. Data on their effect on the central nervous system can be found only sporadically (NIEUWENHUIZENlS; SPEETER AND ANTHONY“). Our attention towards their possible psychotic action was attracted by the works of FISH, JOHNSON, AND HORNING9 on Ptptaa’enta alkaloids among which they found bufotenine, N,N-dimethyltryptamine, and their N -oxides. In experiments on animal they found these drugs to have psychotic effects, but experiments on humans were made only with bufotenin by FABING. We therefore decided to make self-experiments and experiments on normal volunteers with N,Ndimethyltryptamine and with the N,N-diethyl compound also (Fig. I). Bufotenine HG I /\ANH/ l I l CH2CH2 N(CH3)2 C (WCHZCHz-N(CH3)2 DMT “ T—g l \ANH /\j—j— \NH CH 2 CH 2 -NCH (2 5)2 Fig. I. The chemical constitution of bufotenine. DMT and T—9. References 1). 466. �PSYCHOTIC EFFECTS or DMT, r-g, 461 MESCALINE, AND LSD-25 METHODS AND MATERIALS The N,N—dimethyltryptamine (DMT) and the N,N-diethyltryptamine (T-g) were obtained synthetically by the method of SPEETER AND ANTHONY. For the purpose of puriﬁcation the amines were distilled in high vacuum. For the experiments, sterile aqueous solutions of the hydrochloric salts were prepared and used in a concentration of 30 mg per ml. The lethal doses estimated in white mice by the usual method were 135 mg/kg in the case of DMT, and I20 mg/kg in the case of T-9. ' Although the substances have been not very toxic in mice, we were very cautious in the self-experiments. In the peroral experiments, starting from 14 mg and increasing the dose up to 150 mg no observable psychic or vegetative effects were found. After the unsuccessful peroral experiments, intramuscular experiments were made. In this titration series other physicians of the Institute of Budapest took part. The doses administered were IO mg, increasing to 150 mg (zle. 2 mg/kg body weight). Psychotic effects were observed from 30 mg, Le. 0.2 mg/kg body weight; they reached their optimum in doses about 0.7—1.0 mg/kg body weight. On further increasing the doses the psychotic symptoms were suppressed by the vegetative and organic symptoms. Therefore the further experiments on normal volunteers were made with the above-mentioned optimal dose. A detailed paper on the results obtained with normal volunteers, is to appear in Psychiatria at N eurologica (SAI—HALASZ et al.22). THE SELF-EXPERIMENTS The purpose of this report is to compare the psychotic effect of tryptamine derivatives with the well-known effect of mescaline and lysergic acid diethylamide in self— experiments. I believe that this method of experimentation is one of the best ways of obtaining direct information on subtle psychopathological phenomena, which are of great importance in understanding the schizophrenic syndrome. TABLE I THE DATA OF SELF-EXPERIMENTS Dose Substance I. Mescaline II. LSD-25 III. DMT DMT DMT DMT IV. T-9 0.35 g IOO lug 0.25 mg—I 50 mg 75 mg 75 mg 60 .mg 60 mg A dmin. Date per 05 per 05 per os i.m. Dec. 1955 Dec. 1956 i.m. i.m. i.m. March—April 19 56 April 1956 June 1956 March 1957 Nov. 1956 Place Budapest Vienna Budapest Budapest Debrecen Berlin Budapest The experiments were carried out over a period of 16 months. I took mescaline at Christmas—time 1955, and the LSD—25 was tested in Vienna at the Psychiatric Clinic of the University, by courtesy of Prof. Dr. HOFF and Docent Dr. ARNOLD, in De— cember 1956. The ﬁrst intramuscular administration of DMT occurred at the end of April 1956, and was followed by the experiments on normal volunteers. We reported References 1). 466. ' �s. szARA 462 the results at the Annual Meeting of the Hungarian Physiological Society in Debrecen. During this meeting I made the second intramuscular experiment in order to get an electroencephalographic recording. A third DMT—experiment and some biochemical investigations were made in Berlin at the Research Department of the Psychiatric and Neurologic Clinic of the Free University, by the courtesy of Prof. Dr. SELBACH. The T—g—experiment was made intramuscularly in November 1956 in Budapest. I shall not go into details about the effects of mescaline and LSD-25 becauseI am not able to add any new aspects to that well—known picture. Nevertheless, the chief features of these experiments will be mentioned later. At present I shall only describe in more detail the symptoms of DMT and T—g model psychoses, in View of the lack of such reports in the literature up to now. (a) The BAIT—experiments As mentioned above, DMT ingested per as has no observable effect. But an intramuscular injection of 30 mg could already produce some mydriasis and subjectively some perceptiOn disturbances. The larger the dose, the more striking are the symptoms. About the self—experiment made with 1.0 mg/kg, Le. 75 mg DMT in total, I can report the following: In the third or fourth minute after the injection vegetative symptoms appeared, such as tingling sensation, trembling, slight nausea, mydriasis, elevation of the blood pressure and increase of the pulse rate. At the same time eidetic phenomena, optical illusions, pseudo—hallucinations, and later real hallucinations, appeared. The halluci— nations consisted of moving, brilliantly coloured oriental motifs, and later I saw wonderful scenes altering very rapidly. The faces of the people seemed to be masks. My emotional state was elevated sometimes up to euphoria. At the highest point I had compulsive athetoid movements in my left hand. My consciousness was completely ﬁlled by hallucinations, and my attention was ﬁrmly bound to them; therefore I could not give an account of the events happening around me. After %—I hour the symptoms disappeared, and I was able to describe What had happened. In the second intramuscular DMT-experiment, the duration in time and the symptoms were mamiy the same. At the third DMT-experiment, the dose was somewhat smaller (60 mg); the symptoms were thus milder, but qualitatively the same. (b) The T—g—exyberimem The symptoms of the T-g—experiment are brieﬂy as follows. About 15 minutes after the injection of 60 mg of T-g came the same vegetative symptoms as described for DMT. The illusions, hallucinations, and the athetoid compulsive movements in the left hand were the same as for DMT. But the alteration of the surrounding world and the emotional reaction to them were strong and impressive. The mask-like faces of the' persons, the dream-like mysteriousness of the objects and the room gave me the feelnig that I had arrived in another world, entirely different and queer and full of secrecy and mystery. This wonderful but strange world attracted me at one moment, but the next moment I did not want to accept it. I became perplexed; I did not know what I ought to do. I began to walk anxiously up and down, and said: ”I ought to do something, I must!” There was a peculiar double orientation in space References p. 466. �463 PSYCHOTIC EFFECTS OF DMT, T-9, MESCALINE, AND LSD-25 and time: I knew where I was, but I was inclined to accept this strange world as a reality, too. The dusk of the room was lightened for some minutes, and again the light was switched off, and that seemed to me as if this period might be an entire epoch, ﬁlled with events and happenings, but at same time I knew that only several minutes had passed. (6) The comparison of the results I should like to compare the effects of the two tryptamine derivatives outlined above with the effect of mescaline and LSD-25. The most outstanding differences can be established in their time of duration. Intensity of symptoms T-9 DMT LSD-25 Mescalin Flg. 2. Schematic course of the self-experiments. _ In Fig. 2 it can be seen that the duration of the DMT-induced model psychosis is about one hour, that of T—g is about three hours, while the LSD— and mescaline symptoms lasted for 8—10 hours. The onset of the symptoms in the case of tryptamine derivatives is wsentially quicker than the onset of the others. The elevation of the dose of DMT did not produce a longer state of intoxication, but the symptoms were more organic. It is remarkable that in all the four model psychoses the symptoms developed and passed away in wave form. The specialsymptoms are demonstrated in Table II. TABLE II THE MAIN SYMPTOMS OBSERVED IN SELF-EXPERIMENTS Symptoms I. Vegetative symptoms 2. Athetoid movements 3- IIIUSiODS 4. Hallucinations 5. Disturbances of a. spatial perception b. time perception 6. Bodily sensations 7. Depersonalisation Emotional reaction a. euphory b. anxiety 9. Autism 10. Language changes 8. References 1). 466. Mescaline DM T LSD-2 5 T- 9 Preceded the other symptoms Coincided with the other symptoms — + + ++ ++ — _ I +++ + + ++ +++ + ++ + ++ + —_ — -— ~—— +++ ++ —|— ++ _+ ' , +++ + +++ + + + +++ ++ + + +++ ++ +++ + +++ ___ +++ _+ �464 s. SZA'RA As can be seen, the different symptoms were not equally apparent in every case. (I) The vegetative symptoms in mescaline and LSD-25 preceded the other symptoms, while in the case of the tryptamine derivatives the disturbances sensory appeared as early as the vegetative symptoms began. (2) An interesting phenomenon observed only in the tryptamine derivatives was the appearance Of athetoid, choreiform compulsive movements. As far as I know, these symptoms have not yet been described in the case of other hallucinogenic substancesf (3) The perceptional disturbances are qualitatively the same for all the substances; only quantitative differences could be observed. (4) The emotional reactions, however, were qualitatively different, viz. my reaction to mescaline and DMT was euphoric, to the LSD—25 anxious, but in the case of T-9 euphoria and anxiety alternated. These phenomena, together with the severe autism and the above-mentioned ambivalency were observed only in T-g. However, it is well—known from the literature that it can occur in the case of mescalnie and ‘ LSD-25 also (HUXLEY14, SOLM523). The comparison shows that the structure of a model psychosis, which can be considered as a form of the acute exogen reaction type (BONHOEFFER), depends on the chemical structure of the causative agent, apart from the fact that absorption, metabolic and excretion processes may determine the course in time. BIOCHEMICAL INVESTIGATIONS v ‘ The rapid onset and the short duration of the symptoms in the DMT—induced state is very interesting from a biochemical point of View, and it is probably connected with the rapid metabolism of DMT (FISH ct LIL). We know from the investigation of ERSPAMER6 that in rats the main breakdown product of DMT is 3—indolylacetic acid (3-IAA) which is excreted in the urine partly in free form, but largely bound to glycocol as indolaceturic acid. We investigated the excreted indole derivatives in the human volunteers chromatographically and photo— metrically, and obtained the same results as ERSPAMER (SZARA25). In addition, an interesting phenomenon was observed (Table III). We found in the urine after a larger dose of DMT more 5-hydroxyindolylacetic acid (5-HIAA) excreted than was normally present. Unchanged DMT was not estimated in the urine extracts. These data suggested TABLE III TOTAL 5-HIAA EXCRETED THE APPROXIMATE AMOUNT OF AND AFTER THE N 0. I 2M 3‘” 4 * Dose of DM T 150 mg I50 mg 75 mg 60 mg IN A 6 DMT EXPERIMENT h PERIOD BEFORE Amount of 5-HIAA* alter expt. 1.0 mg 1.2 mg 1.5 mg 2.0 mg before expt. 3.0 mg 3.0 mg 1.2 mg L5 mg Estimated by two-dimensional chromatography, developed with p-dimethylaminO-benzalde‘and the hyde, eluted spots measured colorimetrically. ** Self-experiments. References p. 466. �PSYCHOTIC EFFECTS OF DMT, T-g, MESCALINE, AND LSD-25 465 that the DMT is very rapidly metabolized, and perhaps displays its effects by means of serotonin. In order to obtain more information about the relationship in the blood, I made an experiment with 60 mg DMT. The extracts of I5 ml blood taken before, and IO, 30 and 90 minutes after the experiment, were chromatographically investigated, and I found qualitatively only two indol derivatives, namely tryptophan and 3—IAA, but no serotonin 5—HIAA or unchanged DMT could be demonstrated. The 3—IAA level of the blood was elevated in the 10th and 30th minute (Fig. 3). 3- 1AA lug p.c. 100 50 10 _ 30 ._+.> 90 minutes Time in after injection of DMT _ . Fig. 3. The 3-IAA level of blood during the DMT experiment. This ﬁnding did not support the presumption that serotonin plays a role in the psychotic effect of tryptamine derivatives. The evidence, however, is not sufﬁcient to allow one to draw deﬁnite conclusions in this respect. DISCUSSION In discussing the mechanism of action of tryptamine derivatives, it must be admitted that at present there is no deﬁnite knowledge about the biochemical mechanism of action. The clinical picture, however, taking the other experiments on normal volunteers also into consideration, enables us to give some information concerning this mechanism. The rapid onset of the psychotic symptoms makes it seem probable that DMT affects directly those brain structures that are affected indirectly by LSD and mescaline (BLOCKZ). The appearance of choreiform athetoid movements is possibly due to an effect on structures other than those affected by LSD or mescaline. The tryp— tamine derivatives seem to be the ﬁrst hallucinogenic substances to cause athetoid movements, and should therefore provide a new tool for investigating experimentally the exact mechanism of this phenomenon. Unfortunately, I have not enough time to develop in detail the very interesting psychopathological symptoms of T—g, which reminded me of the conception of the “schizophrene Grundstimmung”, described by WYRSCH27. It is, however, very remarkable that tryptamine derivatives without the OHgroup in the 5-position are able to produce mental phenomena. As UDENFRIEND at al. demonstrated in animal tissues, there is no enzyme that could decarboxylate trypto— phan to produce tryptamine; it is assumed therefore that only the enteral bacteria can produce this substance. ‘ References p. 466. �s. szARA 466 There is a possibility that from this tryptamine the schizophrenic organism may is It noteworthy in the enzymically. substances way hallucinogenic wrong produce in of disturbance evidence team4 a his BUSCAINO presented and recently Prof. that be desirable. would ﬁeld in this work Further in schizophrenia. metabolism indole the SUMMARY The psychotic effects of N,N-dimethyltryptamine (DMT) and N,N-diethy1tryptamine (T—9) have been compared with the effects of mescaline and LSD-2 5. The most outstanding features of DMT model psychosis are the rapid onset and the short duration Of the symptoms. This may indicate a different mechanism of action from that of LSD and mescaline. New symptoms appearing with both tryptamine derivatives are the choreiform athetoid movements. This phenomon could be a new tool for investigating experimentally the mechanism of the extrapyramidal compulsive movements. of indole and aminotoxic the theory Of derivatives supports effects tryptamine The psychotic schizophrenia. REFERENCES ]. Physiol. (London), 126, (1954) 596. A. H. AMIN, T. B. B. CRAWFORD AND I. H. GADDUM, 2 W. BLOCK, Z. physiol. Chem., 294 (1953) 1; lbid., 294 (1953) 49; ibid., 296 (1954) 1; ibid., 296 (I954) 1083 V. M. BUSCAINO, Quaderni aeta neural, (1953). 4 V. M. BUSCAINO, D. KEMALI, R. BAGNULO, Aeta Neural. (Naples), 10 (1955) 547. 5 V. ERSPAMER, Pharmacol. Rev., 6 (1954) 425. 6 V. ERSPAMER, 118. (1955) (London), 127 Physiol. ]. 7 H. D. FABING, Am. ]. Psychiat, 113 (1956) 409. 8 H. D. FABING AND J. R. HAWKINS, Science, 123 (1956) 886. 9 M. S. FISH, N. M. JOHNSON AND E. C. HORNING, ]. Am. Chem. 500., 77 (1955) 5892. 10 M. S. FISH, N. M. JOHNSON, E. P. LAWRENCE, E. C. HORNING, Blaehim. Biophys. Aeta., 18 (1955) 56411 W. A. FREYBURGER, B. E. GRAHAM, M. M. RAPPORT, P. H. SEAY, W. M. GOVIER,O. F. SWOAP AND M. J. VANDER BROOK, ]. Pharmacol. Exptl. Therap., 105 (1952) 80. 12 I. H. GADDUM AND A. HAMEED KHAN, Brit. ]. Pharmacol., 9 (1954) 240. 13 H. E. HIMWICH, Nervous Mental Disease, 127 (1955) 413. ]. 14 A. HUXLEY, The Doors of Perception, London, 1954. 15 D. KEMALI, V. M. BUSCAINO AND R. BALBI, Aeta Neural. (Naples), 11 (1956) 209. 16 D. KEMALI AND G. ROMANO, Aeta Neural. (Naples), 11 (1956) 959. 17 H. LANGEMANN, Sehwelz. med. Waehsehr., 85 (1957) 957. (9). (1936) 18 F. Amsterdam, Akad. Koninkl. Wetensehap, 39 Proc. NIEUWENHUYZEN, J. 19 I. H. PAGE, Pharmaeal. Exptl. Therap., 105 (1952) 58. ]. 20 I. H. PAGE, Physlal. Revs, 34 (1954) 563. 21 E. ROTHLIN, A. CERLETTI, A. KONZETT, W. R. SCHALCH AND M. TAESCHLER, Experientia, 12 (1956) 15422 A. SAI-HALASZ, GY. BRUNECKER AND S. SzARA, Psychiat. et Neurol., (in press). 23 H. SOLMs, Praxis, 45 (1956) 746. 24 M. E. SPEETER AND W. C. ANTHONY, Am. Chem. 500., 76 (1954) 6208. 25 S. SzARA, Experientia, 12 (1956) 441. 23 S. UDENFRIEND, C. T. CLARK AND E. TITUS, ]. Am. Chem. 500., 75 (1953) 501. Daseinwer’se. Paul 27 Psychologie. Klinlk, Studlen des zur Die Person Sehlzophrenen. WYRSCH, J. Haupt, Bern, 1949. 1 j. ' DISCUSSION A. SAI—HALAsz, I stltuto Centrale per le malattie Nervose e M entali, Budapest (Ungheria) Il collega SzARA ha avutO occasione stamane di parlare in dettaglio sugli esperimenti fatti con me Or—a vorrei richiamare l’attenzione soltanto su un normali. in soggetti la dimetiltriptamina con fenomeno, che mi sembra assai interessante dal punto di vista clinico. Su 30 persone esaminate 22, schema dello i disturbi 1e le allucinazioni, illusioni e semilateralizzati: i1 sintomi cioé 73% avevano i segni di lesioni piramidali prevalevano a anche ed atetosici i movimenti dello spaziO, e corporeo �PSYCHOTIC EFFECTS OF DMT, T-9, MESCALINE, AND LSD-25 467 sinistra. Questa differenza era netta. Per esempio un soggetto sperimentale guardando la mano sinistra diceva che essa non gli apparteneva pil‘l, aveva cambiato forma ed era divenuta luminosa e bellissima; guardando invece la mano destra, diceva. che non presentava nulla di straordinario. Abbiamo sperimentato su tre persone mancine, e in questa i fenorneni prevalevano alla parte destra. Si dovrebbe concludere che 1a dimetiltriptamina produce una Iesione semilateralizzata dell’emisfero non dominante del cervello. Questo fenomeno ﬁnora. non segnalato dalla letteratura. per gli altri farmaci psicotropi ci propone due questioni: (1) La prima sarebbe la seguente: come si pub immaginare, che una sostanza chimica abbia un effetto nocivo molto pi1‘1 forte sull'emisfero cerebrale non dominante? Sappiamo a1 contrario, che é appunto l’emisfero dominante i1 ph‘l sensibile, specialmente se danneggiato nel sistema vascolare. (2) La. seconda domanda é di carattere psicopat'ologico. Si tratta cioé di sapere se questa semilateralizzazione ci pub dire qualcosa sugli aspetti delle psicosi sperimentali. HOFF e PéTZL hanno gia‘L/dimostrato collo “Zeitrafferphéinomen”, che lesioni organiche dell'emisfero non dominante possono produrre fenomeni psicopatologici molto strani. Lo “Zeitrafferphéinomen” é stato descritto gié da BERINGER nel corso di psicosi sperimentali mescaliniche. Secondo 1a nostra. opi— nione sarebbe di grande interesse studiare ancora. 1e psicosi sperimentali gié conosciute, a1 ﬁne di evidenziare se ci sono diﬂerenze fra. 1e due parti del corpo. Ci pare probabile, che questo fenomeno non sia un eﬂetto solo della dimetiltriptamina. Ad ogni modo, conoscendo i fatti suddetti, noi possediamo ora una. nuova. sostanza per aiutarci a conoscere meglio i problemi dell’emisfero cerebrale non dominante. ‘ �Reprinted from Psychotropic Drugs SHORT COMMUNICATIONS 283 Effects of psychomimetic drugs on cerebral synapses The psychomimetic drugs allow us to elicit at will a limited, reversible, mental derangement in man and a related distorted behavioral pattern in animals. They can therefore be highly potent tools equally for the physiologist, the behaviorist, and the experimental psychiatrist. The tremendous versatility of the brain is nonetheless the manifestation of activity in a ﬁnite number of structures and of mechanisms relating them. It follows, therefore, that the multiple patterns that add up to biological behavior must share in part the available mechanisms. It is by virtue of this probability, rather than because of any exact or fancied resemblance to the clinical conditions, that the study of chemical or so-called model psychoses and the agents producing them can be expected to be fruitful. To the physiologist this suggests the need for identiﬁcation of the underlying unitary processes involved; to the behaviorist, the identiﬁcation of the combinations constituting known behavior patterns; and to the experimental psychiatrist, the comparison of natural and induced psychoses. All can proﬁtably use drugs as tools for analysis. The clinician, furthermore, can convert these ﬁndings into tools for diagnosis and the means for therapy. The high vulnerability of synapses to chemical inﬂuences makes them a natural focus of inquiry. We have utilized the synapses of the optic cortex of the cat (lightly anesthetized with sodium pentobarbital) activated by transcallosal impulses initiated in one cortex and evoking post-synaptic impulses recorded at the symmetrical point in the opposite cortex. This has proved a very convenient preparation and the data are representative of a variety of cerebral synapses, including cortical, subcortical and medullary synapsesl. By intracarotid injection we achieve an active concentration of the drug or chemical in the ipsilateral hemisphere with sufﬁcient dilution on entry into the systemic blood stream to obviate peripheral effects. The ipsilateral recording elec— trode simultaneously monitors the input and output of the terminal synapses in the system, which is submaximally activated every two seconds. In this way we have established that synaptic transmission is under the control of a delicate chemical equilibrium between cholinergic excitation reciprocating with adrenergic inhibition. It is then evident that a disturbance of this equilibrium would lead to abnormal synaptic transmission, resulting in disturbed cerebral and mental function. Among the synaptic inhibitors naturally found in the mammalian brain are adrenaline, nor— adrenaline, and serotonin. The last is by far the most powerfu13. Substances with a chemical similarity to these become candidates for the role of psychomimetic drugs. Such is indeed the case with mescaline, adrenochrome, adrenolutin, lysergic acid diethylamide (LSD-2 5) and bufotenine. Mescaline is closely related chemically to adrenaline, which on oxidation is converted initially to the indole, adrenochrome. Adrenolutin is a minor modiﬁcation of adrenochrome. Serotonin and dimethyl-serotonin, or bufotenine, are indoles, and LSD-2 5 can be regarded as built on an indole nucleus. It strengthens the argument, therefore, that we ﬁnd all of these to be synaptic inhibitors3 4. Furthermore, their ranking as synaptic inhibitors parallels the ranking as to psychomimetic potency in man. The agreement between data from the anesthetized cat and the human encouraged us to believe and test that tranquilizers, reported to be clinically effective in partially offsetting mental disturbance, would have a predictable action on synaptic inhibition by psychomimetic agents. If the synaptic inhibition so produced were truly instrumental in bringing about psychotic behavior, then the improvement of such behavior that is observed clinically might be due to antagonizing of an endogenous chemical corresponding to the exogenous psychomimetic drugs. This, indeed, turns out to be the case. The prophylactic administration of chlorpromazine, promazine, reserpine, and azacyclonol, in doses having no effect per 33 on synaptic transmission, prevents or reduces the synaptic inhibitory action of the psychomimetic drugsz. Overdoses of tranquilizers clinically produce toxic phenomena, some of them taking the form of depression, and even psychosis. Likewise, large doses of the tranquilizers produce a depression of synaptic transmission indistinguishable from synaptic inhibition. Characteristically, the tranquilizers exercise their clinical effect without a corresponding degree of depression. This is reﬂected in the ratio of depressant to prophylactic dose, or “synaptic safety margin”. This safety margin is nonexistent for phenobarbital, equals 2 for reserpine, IO for promazine and 20 for chlorpromazine and DEPARTMENT OF EXPERIMENTAL PSYCH'IIRY ‘ s “ APR wetHyTAL 30 40.59 �284 SHORT COMMUNICATIONS azacyclonol. The above data suggest the hypothesis that synaptic inhibition is one of the mechanisms responsible for some forms of mental disturbance. A perversion of metabolism resulting either in an excess of endogenous inhibitory substance or an excess susceptibility of the neurons upon which it acts, would result in abnormal patterns of activity whose variety would be determin— ed by varying thresholds and, in particular, by abnormal inhibition interrupting normal control, and thereby releasing more primitive and less adaptive —perhaps subcortical—t—patterns of activity. Such conceptions emphasize the role of naturally occurring inhibitory indoles in mammalian brain. Of these, serotonin is highly active, dimethyl—serotonin or bufotenine is twice as active as serotonin, while adrenaline and adrenolutin are relatively weak inhibitors. Psychotic manifestations have been clearly described for all but serotonin, whose powerful peripheral disturbing actions seriously obscure the picture when it is introduced by the usual routes. For this reason we are testing the effects of intracarotid serotonin injections in man. The importance of serotonin has caused us to extend our original observations of its cerebral synaptic inhibitory action with experiments designed to record the action of “in situ serotonin”. This is accomplished by the use of iproniazid, the inhibitor of monoamine oxidase (MAO), the enzyme responsible for the destruction of serotonin. With intracarotid injections of iproniazid we can reproduce the cortical action of serotonin and show that, at the height of the synaptic inhibi— tion, the MAO titer on the inhibited side is, in fact, lower than on the control side; as would be expected if iproniazid is exercising its action by inhibiting MAO and, consequently, accumulating natural serotonin at the synapses. Following the reasoning already outlined, we again assessed the pertinence of the data to possible clinical signiﬁcance by testing the action of tranquilizers against serotonin. We ﬁnd that the tranquilizers exercise a prophylactic or preventive action against the inhibitory effects of serotonin in the same way that they antagonize psychomimetic drugs. A comparison of the cerebral synaptic action of psychomimetic drugs with that of naturally occurring cerebral synaptic inhibitors and their modiﬁcation by tranquilizers produces data consistent with the hypothesis that a disturbance of synaptic equilibrium—in this case, by a preponderance of inhibitory effectiveness—is a potential mechanism for some kinds of mental disturbance, and that therapeutic results could be anticipated by various means of preventing or annulling this eﬂect. The opposite kind of disturbance or a preponderance of excitatory effectiveness seems also plausible. The prevention or annulling of this deviation in synaptic equilibrium would require different measures. The effectiveness of different tranquilizers and varying therapeutic measures might be expected to become diagnostic criteria. Veterans Administration Research Laboratories in Neuropsychiatry, V. A. Hospital, Pittsburgh, Pa. U SA. 1 2 3 4 A. A. A. A. AMEDEO S. MARRAZZI S. MARRAZZI, Science, 118 (1953) 367. S. MARRAZZI, Ann. N. Y. Acad. Sci, 66 (1957) 496. S. MARRAZZI AND E. R. HART, Science, 12I (1955) 365. S. MARRAZZI AND E. R. HART, ]. Nervous Mental Diseases, 122 (1955) 354. APR ,7 3 ‘0"!!! DEPARTMENT OF EXPERIMENTAL PEVOH‘AIRY HILLSIDE HOSPITAL GLEN OAKS, N. Y. �a hemical aspects of Psilocgpin p39 0......” “-4 cum -c£—¢h—-g-M- by A;Hofmannj Eagle psychotropic act1ve principle of Psilocybe mexic! Helm has been isolated in crystalline form. This fungus 6ne is of the so- called magic or s.a¢red Mexican mushrooms used since orecolumbian times by the indians of Mexico- dur1ng religeous ceremonies and also by soothsayers to acquire clairvoyence. The inawater, but practically unsoluble organicmost in solvents._r Analysis, Spectra and colour react10ns indicated that 1t 13 a \\ tryptamine. The spec1al structural features of psilocybin are dis~. . �to central autonomic stimulation, the study of Psilocybin on 1solated variety of organsshows Only on peripheral structures ¢ littleactivity ofshe ‘ adrug 5 ‘ ��8 MARCH 1958 . ‘ PSYCHOSIS AND TREMDR DUE TO ' \L MECAMYLAMINE . _ M. HARINGTON M.B. Cantab., M.R.C.P. SENIOR REGISTRAR AND MEDICAL TUTOR PRISCILLA KINCAID—SMITH M.B. W’srand, M.R.C.P., D.C.P. REGISTRAR DEPARTMENT OF MEDICINE, POSTGRADUATE MEDICAL SCHOOL OF LONDON ganglion-blocking agent for treat— ing hypertension was introduced two years ago (Freis 1955, Ford et a1. 1955), and since then it has been widely used in clinical practice, its chief advantage being that it is fully and regularly absorbed when given by mouth. It produces the same side-effects, due to blockade of the parasympathetic system, as do other ganglion-blocking drugs, but in addition reports have been published in America indicating that mecamylamine may also have a toxic action on the central nervous system (Schneckloth et al, 1956, Deming et al. 1957). We describe here four patients in whom tremor and mental disturbance, with confusion and hallucinations, developed while they were receiving mecamylamine, and we suggest that this may be a not uncommon complica— tion of treatment with mecamylamine given in large dosage. MECAMYLAMINE as a \ Case-reports Case l.—A man, aged 55, was ﬁrst seen in July, 1955, com— plaining of headaches. He had two years’ history of high blood-pressure and ﬁfteen years’ history of gout. Although intelligent, he was unstable and did not follow any regular occupation. On examination his blood~pressure was 230/140 mm. Hg; he had numerous retinal haemorrhages and exudates; his urine contained a trace of albumin and could be concentrated to 1.020; and his blood-urea level was 30 mg. per 100 ml. Treatment.—-—Benign essential hypertension having been diagnosed, he was treated with subcutaneous pentolinium, to which reserpine 0-1 mg. thrice daily was later added. This regime reduced his blood—pressure, and his fundi considerably improved. Mecamylamine therapy—In July, 1956, mecamylamine was substituted for the pentolinium, 20 mg. thrice daily being necessary to keep the blood—pressure down to 140/80 mm. Hg, with the patient in the erect position, for the greater part of the day. This dosage, however, caused troublesome side-effects, at ﬁrst principally constipation, but later difﬁculty in micturition associated with frequency. DR . HOBSLEY BaraEtlaésCZIS 499 ORIGINAL ARTICLES REFERENCES M. (1952) Rev. Sanid. Polie., Lima, 12, 198, cited by Ferris et al. 2 Bernstein, C., Klotz, S. D. (1952) Ann. Allergy, 10, 479. Dameshek, W., Neber, J. (1950) Blood, 5, 129. Dobson, A. M., Ikin, E. W7. (1946) 3'. Path. Bact. 58, 221. Ferris, H. B., Alpert, S., Coakley, C. S. (1952) Amer. Praetit. 3, 177. Frankel, D. B., Weidner, N. (1953) Ann. Allergy, 11, 204. Hoffmann, C. R. (1957) Surgery, 41, 491. Loew, E. R. (1950) Med. Clin. N. Amer. 34, 351. Maunsell, K. (1944) Brit. med. _7. ii, 236. Mollison, P. L. (1951) Blood Transfusion in Clinical .Medieine, p. 317. Oxford. F. M., Margolin, S., Jackson, D. (1953) 3‘. med. Soc. N. i. 50, Offegkgantz, 3 . Simon, S. W., Eckman, W. G., Jr. (1954) Ann. Allergy, 12, 182. Stephen, C. R., Martin, R. C., Bourgeois—Gavardin, M. (1955) 7. Amer. med. Ass. 158, 525. Wilhelm, R. B., Nutting, H. M., Devlin, H. B., Jennings, E. R., 0. A. (1955) ibi‘d. p.’ 529. W’inter, C. C., Taplin, G. V. (1954) Ann. Allergy, 12, 717. Wright, W. A. (1950) .Med. Times, N.Y. 78, 466. Brines, Readmission.—In February, 1957, retention of urine developed and the patient was readmitted to hospital. His bloodurea level was now 60 mg. per 100 ml., rising after ten days to 72 mg. per 100 ml., he had a urinary infection, which was treated with tetracycline. Soon after admission his requirement for mecamylamine fell: the dosage was reduced from 60 to 30 mg. daily, and his blood-pressure was maintained at 110/70 mm. Hg with the patient in the upright position. Mental and nervous symptoms.——On Feb. 19, 1957, he had a tremor of the hands. All hypotensive treatment was stopped, but next day the .tremor had increased and he became mentally confused. Two days later his condition had deteriorated further: he had a coarse generalised shaking affecting his whole body, present at rest, and accentuated on attempting any voluntary movement. His speech was slurred and jerky. There was a general increase in muscular tone and in the deep reﬂexes; the plantar responses remained ﬂexor. He was completely disoriented in both space and time and had vivid frightening hallucinations. His extreme restlessness and picking at the bedclothes suggested alcoholic delirium tremens. From time to time he had lucid intervals during which he had considerable insight into his condition. Repeated large oral doses (10-15 m1.) of paraldehyde subdued the tremor and relieved the hallucinatibns for three to four hours at a time. This striking clinical picture persisted for a week and then gradually subsided. By March, twelve days after the mecamylamine treatment had been stopped, the hallucinations had disappeared and the patient’s mental state had returned to normal. He could now remember in detail what had happened during his delirium. Slight tremor persisted for a further two days before ﬁnally clearing. During this period he had been treated with subcutaneous pentolinium because his blood— pressure had risen after the cessation of hypotensive therapy; but it was difﬁcult to keep his blood-pressure down, because he was conﬁned to bed. He was discharged from hospital on March 14, 1957, taking two injections of pentolinium daily; his blood-urea level had fallen to 38 mg. per 100 ml. Readmission.——Four months later he was readmitted with uraamia and left ventricular failure and died in ﬁve days. Necropsy There was atheroma of the blood-vessels at the base of the brain, the gyri were ﬂattened, but no localised abnormality was found on section of the brain. The kidneys showed lesions of malignant nephrosclerosis. Case 2.—A woman, aged 65, was admitted to hospital in July, 1956, with left ventricular failure. She had eight weeks’ history of exertional dyspnoea. Her blood-pressure was 300/160 mm. Hg, and she had hmmorrhages and soft exudates in her fundi. Her blood-urea level was 30 mg. per 100 ml. She was treated with digitalis, mersalyl, and hypotensives— at ﬁrst subcutaneous pentolinium and later oral mecamylamine. When ﬁrst seen at Hammersmith Hospital in September, 1956, she was very much improved symptomatically, but her bloodpressure was 200/130 mm. Hg, and the dosage of mecamyla— mine was increased from 12-5 to 20 mg. twice daily. In October the dosage was further increased to 45 mg. daily; but, although this dosage did not control the hypertension, urinary retention developed and she was admitted to hospital on Oct. 29, 1956. On admission she was cooperative and well oriented but somewhat apprehensive and overexcitable. Her blood-pressure was 290/140 mm. Hg, and soft exudates but no papilloedema were noted in her fundi. There was no sign of heart-failure. Her urine contained albumin, and her blood—urea level was 66 mg. per 100 ml. Mecamylamine therapy was continued, the dosage being slowly increased until on Nov. 6, 1956, she was having 65 mg. daily. Her systolic blood-pressure remained about 200 mm. Hg. .Mental and nervous symptoms.—ln the early hours of NOV. 11, 1956, she became agitated and confused, having hallucinations of voices and complaining of noises in the head. Her bloodpressure was 170/90 mm. Hg. She had general hyperreﬂexia. K2 �M 500 ORIGINAL ARTICLES During the succeeding days her confusion increased, and she was disoriented for most of the time but had intervals of insight and cooperation. Mecamylamine therapy was stopped on Nov. 13. On Nov. 17 she was grossly confused and hallucinated, with paranoid delusions. She also had a coarse tremor of arms and legs. Her blood-urea level had risen to 97 mg. per 100 m1. on Nov. 17 and to 140 mg. per 100 ml. on Nov. 20. She became more agitated and violent and was completely inaccessible. On Nov. 21 her condition made it necessary to transfer her to a mental observation ward. She went progressively downhill, her blood-urea level rose to 296 mg. per 100 ml., and she died on Nov. 30, 1956, without any improvement in her mental state. mid-poms. The kidneys were typical of malignant nephrosclerosis. Case 4.—An electrician’s mate, aged 46, presented in January, 1956, with four months’ history of blurring of vision and dyspnoea. His blood-pressure was 250/150 mm. Hg and he had bilateral papilltedema with scattered retinal haemorrhages. His urine contained albumin, granular casts, and occasional leuco— cytes; his blood—urea level was 155 mg. per 100 ml. There was no history to suggest previous renal disease. In view of his visual symptoms hypotensive therapy was considered advisable, in spite of the severe renal failure, and treatment was started with subcutaneous pentolinium. At the end of February his blood-urea level was 222 mg. per 100 m1. Mecamylamine therapy—At this stage he was given oral mecamylamine. He was not very sensitive to it, 60 mg. in divided doses daily being needed to keep his blood—pressure down to 160/100 mm. Hg. On April 14, 1956, six weeks after mecamylamine therapy had been started, he was readmitted to hospital with increasing trembling of his arms and legs for the previous three days. On admission his blood—pressure was 160/90 mm. Hg. He still had bilateral papilloedema. He was dyspnmic, and his jugular venous pressure was raised. Mental and nervous symptoms.—He was drowsy and mentally! confused. He had occasional spontaneous quivering of his lips and a coarse irregular tremor of his limbs. His muscular tone was increased; his lower limbs showed almost cogwheel Necropsy The left kidney was small (55 g.) with generalised ischazmic atrophy suggesting occlusion of the renal artery. The right kidney weighed 110 g., and its histology was that of ﬂorid malignant nephrosclerosis. The brain showed a small area of softening in the right internal capsule, and the cerebral arteries were considerably affected by atheroma. Case 3.—An electrical engineer, aged 53, was found in January, 1956, to have a blood—pressure of 240/140 mm. Hg, bilateral papilltedema, heavy albuminuria, and a blood—urea level of 40 mg. per 100 ml. Malignant essential hypertension was diagnosed, and he was treated with subcutaneous pentolinium and with rauwolﬁa alkaloids; but his“ blood—pressure was difﬁcult to control, and during the next six months further deterioration in the fundi and increasing cardiac enlargement were noted. On admission to Hammersmith Hospital in July, 1956, he had heart-failure, blood—pressure 260/140 mm. Hg, bilateral papilloedema, haemorrhages and exudates in his fundi, and albuminuria. His blood-urea level was 139 mg. per 100 m1. Treatment with subcutaneous pentolinium was continued, a dosage of 30—40 mg. twice daily being necessary to control his blood-pressure. Rauwolﬁa was not given. Chlorpromazine 50 mg. thrice daily was given because of vomiting. After a month the heart-failure had cleared and the blood-urea level fallen to 60 mg. per 100 ml. Mecamylamine therapy—On Sept. 10, 1956, mecamylamine therapy was started, and pentolinium was withdrawn gradually during the next few days. The blood—pressure was not satisfactorily controlled during the period of transfer, but by Sept. 17 it was down to 140/80 mm. Hg, with the patient in the erect position, for most of the day. This was achieved with a dosage of 20 mg. mecamylamine thrice daily. By now the blood-urea level had risen again to 100 mg. per 100 ml. The fundi still showed papilloedema, but there were no fresh exudates or haemorrhages. Mental and nervous symptoms.—On Sept. 24, 1956, shaking of the limbs and trunk was ﬁrst noted. This tremor also affected the face and tongue; it was coarse and present at rest but exaggerated on voluntary movement. The speech was jerky and difﬁcult to understand. There was a general increase in muscular tone; the tendon—reﬂexes were exaggerated, and knee and ankle clonus could be elicited; the plantar responses were ﬂexor. Mecamylamine was withheld after it had been taken for fourteen days, and pentolinium therapy was restarted; but the tremor increased, and four days later the patient became drowsy and confused. He was now disoriented and hallucinated, speaking to imaginary people and seeing snakes and insects crawling across his bedclothes. His body shook so violently as to rock the whole bed. Paraldehyde reduced the tremor somewhat, but he remained confused and steadily deteriorated. His blood-urea level rose to 170 mg. per 100 ml. , his urinary output fell, and he died, after repeated attacks of left ventricular failure, on Oct. 7, 1956. Necropsy The brain was overweight (1490 g.) and oedematous, with a small area of recent softening at the posterior end of the putamen on each side and a recent small haemorrhage in the THE LANCET rigidity. His tendon-reﬂexes were uniformly increased, and he had bilateral ankle clonus. His plantar responses were ﬂexor. Hypotensive therapy was stopped, and he was treated only with digoxin, but the confusion and tremor persisted, and he died on April 16, 1956. Necropsy ' The kidneys showed the changes of malignant nephrosclerosis. The brain showed cerebral oedema, but no localised lesion or other abnormality. Discussion The clinical picture was similar in each of these four patients. In three the ﬁrst neurological abnormality to be noted was a coarse tremor which affected the trunk and head as well as the limbs and caused difﬁculty with speech. It was variable in the early stages, perhaps hardly noticeable when a limb was at rest, but brought out when voluntary movement was attempted. The shaking of the trunk made it look as if the patient was shivering. The tremor was equally present on both sides of the body. At its height it was so violent in two patients as to shake the whole bed. Mental symptoms were observed before the tremor in one patient, but in the others a few days after the tremor. They consisted of a clouding of consciousness with confusion and disorientation, together, in three cases, with hallucinations which were usually visual but sometimes also of hearing or of touch. The mental state ﬂuctuated, and there were lucid intervals, with some insight, between periods of extreme delirium. Both tremor and mental symptoms were alleviated temporarily by administration of paraldehyde, in case 1 strikingly so. In this patient, who recovered from the episode, the mental abnormalities disappeared ﬁrst, the tremor persisting for a few days before ﬁnally clearing. Examination of the nervous system in these patients revealed a general increase in muscle tone, symmetrically exaggerated tendon-reﬂexes with clonus, and ﬂexor plantar responses. In no case were any lateralising signs found. Electroencephalography in three cases gave records which were difﬁcult to interpret because of arte— fact due to muscle tremor; there was complete absence of alpha rhythm, but in no case was positive evidence found �8 MARCH 1958 501 ORIGINAL ARTICLES either of a general metabolic disturbance or of a localised lesion. The patients all had severe hypertension. In two this was frankly malignant, with papillaedema; in the other two the presence of active retinitis and progressive renal failure indicated that the hypertension was in a premal— ignant phase, and at necropsy lesions of malignant nephro— sclerosis were found in the kidneys. Renal function was impaired in all. In three there was gross renal failure with a raised blood-urea level which continued to rise until death in case 1, who already had some renal impairment, shown by a failure of concentrating power, but who had a normal blood-urea level, there was a further deterioration in renal function and a temporary rise in the bloodurea level coincident with a urinary infection. This patient’s blood-urea level had returned to normal by the time that his neurological symptoms had cleared, but it rose again later, and uraemia was present at his death four months afterwards. All four patients were receiving large dosages of meca5 mylamine (60—65 mg. daily) because smaller amounts had not reduced the blood—pressure. The duration of admin— istration of mecamylamine before neurological symptoms developed varied from seven months in case 1 to fourteen days in case 3. Case 1 had the least impairment of renal function. Since cerebral arterial disease is common in hypertensive patients, the question arises whether organic brain damage due to haemorrhage or to infarction could have caused the symptoms observed. Evidence of local cerebral lesions was found at necropsy in two cases: in the right internal capsule in one case; and in both basal ganglia and the pons in the other. The whole clinical picture, however, was more like a toxic confusional reaction, bearing in its fully developed state a striking resemblance to alcoholic delirium tremens. The symmetry of the tremor, the absence of any lateralising signs in the central nervous system, and particularly the complete disappearance of symptoms in case 1 after mecamylamine had been withheld suggest strongly that this drug was to blame. In the patients who did not recover, uraemia and death supervened probably before sufﬁcient time had elapsed to allow the mecamylamine to be cleared from the body. Mecamylamine is a secondary amine and freely diffusible across cell membranes. There is evidence that this drug is concentrated within the cell (Milne et al. 1957). It is therefore likely that its mode of action differs from that of ganglion-blocking agents such as hexamethonium and pentolinium, which are quaternary ammonium compounds and are distributed only in the extracellu— lar ﬂuid. That mecamylamine has a different, and previously unrecognised, mode of action at the neuromuscular junction has been shown by Bennett et al. (1957). From this it might also be expected that mecamylamine, apart from producing the same side—effects due to parasympathetic blockade as other ganglion—blocking drugs, might also have toxic actions from which methon— ium compounds are strikingly free. There is some experimental evidence of a direct toxic action on the central nervous system. Rats given mecamylamine in large doses develop a tremor and have generalised convulsions before death (Milne et al. 1957). The frequency of this complication of treatment is not certain. Doyle et al. (1956), Smirk and McQueen (1957) and Kitchin et al. (1957), in their accounts of clinical experience with mecamylamine, do not mention any neurological symptoms related to its administration. The four cases described here occurred among ninety patients treated with mecamylamine at this hospital (twenty of them with malignant hypertension). The average daily dosage of mecamylamine in the whole series, however, was only 35 mg. , and only sixteen patients received more than 50 mg. daily. Moreover, this is a selected group of patients, including some with severe hypertension who were speciallyreferred. In addition to the cases described in detail above, three other patients treated with mecamylamine developed a tremor without mental symptoms: a woman, aged 31, with malignant hypertension and systemic lupus erythematosus and a woman, aged 51, with malignant hypertension and renal-vein thrombosis, both with moderate impairment of renal function (blood-urea level 40—70 mg. per 100 ml); and a man, aged 51, with malignant essen— tial hypertension and urxmia (blood-urea level 114 mg. per 100 ml.). The daily dosage of mecamylamine in these patients was 25, 50, and 30 mg. respectively. In the two women the tremor disappeared when the dosage of mecamylamine was reduced and pentolinium was partly or wholly substituted. It certainly seems that patients with severely impaired renal function are much more likely to develop symptoms of neurotoxicity while taking mecamylamine: of ﬁve patients in whom the blood—urea level was 100 mg. per 100 ml. or higher at the start of treatment four developed tremor and three of these mental symptoms. This complication is presumably related to the retention of mecamylamine in the body, its urinary excretion being reduced in renal failure (Milne et al. 1957). Summary Four cases are described in which a syndrome of tremor, mental confusion, and delirium developed under treatment with mecamylamine. Tremor developed in three other patients. This complication of mecamylamine treatment occurred in patients receiving large dosages thereof (60—65 mg. daily); all these patients had or subsequently developed malignant hypertension and in all renal func— tion was impaired. We thank Prof. J. McMichael and Dr. M. D. Milne for their help and advice; and Dr. I. F. Goodwin for permission to report a patient under his care. REFERENCES Bennett, G., Tyler, C., Zaimis, E. (1957) Lancet, ii, 218. Deming, . B., Hodes,M . E., Edreira, J. G., Baltazar, A. (1957) New Eng]. E.Med. 256, 739. Doyle,A ,y,Murph E A. Neilson, G. H. (1956) Brit. med. ff. ii, 1209. Mo yer,]. H. (1955)]. Lab. clm. Med. 46, 815 Ford, R. Dennis,E., Freis, E. D. (1955) Lancet, ii, 977. Kitchin, A. Lowther, C. P. Turner, R. W D. (1957) 1'b1'd. p. 605. Milne,M. D., Rowe, G. G., Somers,K., Muehrcke,R. C., Crawford,M. A. (1957) Clin. SE1. 16, 599. Schneckloth, R.E ,Corcoran, A. C. Dustan, H. P., Page, I. 3'. Amer. med. Ass. 162, 868. Smirk, F. H., McQueen,E G. (1957) Brit. med. 3‘.1, 422. H (1956) “ How then does a good physician help a patient to face death and, accepting the ways of nature, to meet it? It is not done by all the busy paraphernalia of scientiﬁc medicine, keeping a vague shadow of life ﬂickering when all hope is gone. . . . If man lives as a stranger in a lonely crowd, he dies utterly alone. Whereas his entry into the world is the ﬁrst stage of the dissolution of an intimate partnership with his mother, his ﬁnal departure is the ultimate in solitary procedures.”——WILLIAM B. BEAN, Arch. intern. Med. 1958, 101, 201. �W 502 ORIGINAL ARTICLES ESSENTIAL FATTY ACIDS AND IDIOPATHIC HYPERCALCIEMIA OF INFANCY A. T. JAMES J. WEBB Ph.D. Lond. and then after roller drying of this concentrated milk. No loss of these two acids was found, although the same experiment was repeated several times. Table I also shows the linoleic-acid + linolenic-acid contents of the same sample of milk after storage under various conditions. After three months at room temperature or at 37°C the “ essential ” fatty-acid content had fallen to two-thirds of the original value 5 after six months’ storage under similar conditions the “ essential” fatty acids had dropped to less than half their previous B.Sc. Lond. THE NATIONAL INSTITUTE FOR MEDICAL RESEARCH, MILL HILL, LONDON T. STAPLETON W. B. MACDONALD D.M. Oxon., M.R.C.P. M.D. Melb., M.R.A.C.P. ASSISTANT DIRECTOR LECTURER PEDIATRIC UNIT, ST. MARY’S HOSPITAL MEDICAL SCHOOL, LONDON ATTENTION has been‘drawn deﬁciency Of “ essential ” fatty to the possible role of a acids (linoleic and arachi— donic acids) in the genesis of idiopathic hypercalcaemia Of infancy (Lancet 1957). It has been suggested (Sinclair 1956a) that in the preparation of evaporated milks there is some loss of essential fatty acids and an even greater loss in the production of National Dried Milk made by passage over hot rollers; thus infants fed on dried milk preparations might receive a diet deﬁcient in essential fatty acids. This suggestion could have provided an additional explanation of the frequency with' which hypercalcaemia of infancy has been recognised in the United Kingdom, where dried milks are widely used, although one established factor to explain this frequency has been the extent of fortiﬁcation of infant foods with vitamin D (British Medical journal 1956). We have studied the fatty-acid composition of samples of human milk, cows’ milk before and after drying by a variety of commercial techniques, stored dried milk, and evaporated milk. Similar analytical studies of whole blood from three healthy infants have been made, as well as from three infants with idiopathic hypercalcaemia; the latter were studied both before and after treatment with cotton-seed oil (a rich source of linoleic acid). The fattyacid analyses were made with the gas-liquid Chromatogram (James and Martin 1956). value. Comparative Analyses of Various Milk Preparations used in ' Infant Feeding Table II shows comparisons of the fatty-acid composition (major components only) of two samples of human milk, fresh cows’ milk, roller-dried milk, National Dried Nlilk, and ‘ Carnation ’ evaporated cows’-milk. The difference in the levels of linoleic + linolenic acids in TABLE I—LINOLEIC-ACID CONTENT OF cows’ MILK DURING PROCESSING AND STORAGE (As PERCENTAGE OF ACIDS IN THE RANGE C3-C20) Milk Under the conditions used for the fatty-acid analyses the gas chromatogram does not differentiate between the cis-cis, cis-trans, and trans—trans forms of linoleic acid. In addition linoleic and linolenic acids (the C18 di- and tri-unsaturated acids) are not separated; so‘ the ﬁgures reported refer to the sum of these two acids. However, the linolenic-acid content of all the fats studied is likely to be low. Studies in collaboration with other laboratories have shown excellent agreement between the gas chromatographic and spectrophotometric techniques for determining (1) a combined value for linoleic and linolenic acids and (2) arachidonic acid. The linoleic acid isolated from cows’ milk by the gas chromato— gram has been shown to be 9 : lZ-octadecadienoic acid by the micro degradation procedure described by James and Webb (1957). Results Changes in Fat-composition of Milk on Processing to Dried Milk and on Storage In Table I are listed the linoleic-acid + linolenic-acid contents of fresh milk, the same milk after concentration, Powder Powder stored stored Powder 3 mos. 6 mos. stored at room at room 3 mos. 8 temp- temp- at 37° erature erature Fresh concen-. milk trated After before roller 120/ t ota(l drym dryin _ solids (21% Kincaid) so Linoleic acid + linolenic acid 3-2 s 1 3-0 3-4 2-3 1-4 2-4 Powder stored 6 mos. at 37° 1-1 human milk and cows’ milk was less than has sometimes been supposed; but the effect of diet on these levels has yet to be determined. “ Essential Fatty-acid ” Levels in Blood of Infants with Methods Each sample Of milk was extracted exhaustively with ether-ethanol overnight to remove the lipids. Samples of whole blood were similarly extracted. The lipid extracts were saponiﬁed with methanolic potassium hydroxide, and the non-saponiﬁable material was extracted with petroleum ether. The alkaline solution was acidiﬁed with 5N sulphuric acid, and the fatty acids were extracted with petroleum ether. The extract was dried over anhydrous sodium sulphate, and the acids were converted to methyl esters by reﬂuxing with anhydrous methanolic hydrochloric acid. Samples were stored in high dilution in petroleum-ether solution at +2°C, and the solvent was removed by evaporation before applying the sample to the gas-liquid chromatogram. THE LANCET . Hypercalcaemia Case 1.—A male infant, born on Feb. 21, 1956, who had well-established hypercalcaemia, was studied at the age of 9 months. He was fed cotton-seed oil containing 500/0 w/w of linoleic acid for twenty days. During the ﬁrst ﬁve days he received about 5 ml. of cotton-seed Oil a day; during the next twelve days about 8 ml. a day; and during the last three days about 20 ml. a day. The serum—calcium (table III and ﬁg. 1) had been high for so long that it seemed improbable that the fall from 15-8 mg. per 100 ml. to 9-9 mg. per 100 ml. in ten days was due to a chance variation in its level, although such variations are known to occur. Analyses were made of the fatty acids of whole blood taken from this child before, while, and after he was given cotton-seed Oil. NO signiﬁcant change TABLE II—MAJOR COMPONENTS OF MILK FATS FROM VARIOUS SOURCES EXPRESSED AS PERCENTAGE OF FATTY ACIDS IN RANGE C3-C20 Human milk Sample 1, ten days after start of lactation Acid Myristic . . Branched C15. . nC15 .. Palmitoleic .. Palmitic Branched unsat. C17 nC17 . . . Linoleic Oleic . . . . Isomers of oleig acx Stearic . . Poly-unsat. C20 (not arachidonic) Cows’ milk Sample 2, three mos. Fresh after start of lactation 5-7 0-5 0-8 3-9 26-5 1-5 9-0 0-2 0-4 2-6 20-0 0-7 5-1 38-6 Trace 4-4 46-0 0-7 3-2 23-3 12-1 1-8 7-7 10-6 1-6 1-2 2-0 16-6 2-0 1-1 36 3-5 26-1 3-1 0-6 4-1 30-4 10-0 0-8 4-4 26-0 5-1 10-3 12-0 10-5 1-0 13-8 2-0 . 0-8 1-0 2-2 26-4 1-5 Not measured Not measured National ‘ Cama— OsterDried ’ milk Milk tion ’ roller- bought tinned dried from a milk clinic 10-7 1-3 1-3 2-2 29-7 1-5 . 0- ‘ Dill"; . . . i . . . EXPERIMEI‘EIAI. r. .5 .....;-.‘a' {II HILLSIDE HOSPITAL “24.53 GLEN OAKS, N. Y. 9-4 1-8 1-4 2-4 21-8 1-5 �Effects of Pitressin Hydration on the Electroencephalogram Paroxysmal Slow Activity in Nonepileptic Patients with Previous Drug Addiction ABRAHAM WIKLER, M.D. Surgeon (R), United States Public Health Service LEXINGTON, KY. 0. s. MPMTWHT or HEALTH, tenement... MD rustic mum: sum! ﬁEPRiN‘lED WITH PERMISSION FROM “in"!!! A. M. A. ARCHIVES OF NEUROLOGY ANi} P‘S‘IQHIATRY VOL. 57-JAN. 194')" HEV-J-L’EI" KV'. �EFFECTS PITRESSIN HYDRATION ELECTROENCEPHALOGRAM OF ON THE Paroxysmal Slow Activity in Nonepileptic Patients with Previous Drug Addiction ABRAHAM WIKLER, M.D. Surgeon (R), United States Public Health Service LEXINGTON, KY. LTHOUGH hydration by forcing of ﬂuids and the use of pitressin has long been employed to precipitate epileptic seizures for diagnostic purposes in persons suspected of having idiopathic epilepsy,1 no study has been made of the electroencephalographic changes produced by this procedure, either in normal or in epileptic subjects. 'A single injection of pitressin has been reported to have no effect on the electroencephalogram,” but no data have been found on the effects of water intoxication except for the statement by Allen 3 that some experiments of this type on dogs had been attempted. The present study was undertaken in an attempt to solve a clinical problem. A patient at the United States Public Health Service Hospital was referred for electroencephalographic study because he exhibited periodic episodes of antisocial behavior. A diagnosis of psychopathic personality had been made, but it was desired to rule out epilepsy. A routine electroencephalogram was essentially normal. A pitressin hydration test was then made with a view to provoking a ﬁt, antisocial behavior or “epileptiform” changes in the electroencephalogram. Neither a ﬁt nor antisocial behavior occurred during this procedure, but paroxysmal slow activity did appear in the electroencephalogram. This was difﬁcult to interpret because of the lack of control data in the literature, and therefore further investigations were made. MATERIALS AND METHODS The subjects for these experiments were 14 male patients at the United States Public Health Service Hospital who were undergoing trearment for addiction From the United States Public Health Service Hospital. 1. McQuarrie, I., and Peeler, D. B.: The Effects of Sustained Pituitary antidiuresis and Forced Water Drinking in Epileptic Children: A Diagnostic and Etiologic Study, J. Clin. Investigation 10:915. 1931. Hilger, D. W.; Mueller, A. R., and Freed, A. E.: The Pitressin Hydration Test in the Diagnosis of Idiopathic Epilepsy, Mil. Surgeon 91:309, 1942. 2. Gibbs, F. A.; Gibbs, E. L., and Lennox, W. G.: Effect on the Electroencephalogram of Certain Drugs Which Inﬂuence Nervous .Xctivity, Arch. Int. Med. 60:154 (July) 1937. 3. Allen, F. F.: Spontaneous and induced Epilegtifo: 1n Attacks in Dogs, in "tr-rel iat. 102:67, 1945. Relation to Fluid Balance and Kidney Function, f= m. 5 �to opiates while serving sentences for violation of the Harrison Narcotic Act and who volunteered for this test. All these subjects had been in the institution six months or more and had not used opiates habitually for at least that length of time. Their ages varied from 32 to 46, with an average of 37.1. None gave a history of epilepsy, and in no case had a seizure been recorded since the patient’s admission to the institution. All were in good health. For 7 patients a diagnosis of psychopathic personality was made on admission. Electroencephalograms were made before and after pitressin hydration. Silversilver chloride cup electrodes were applied to the scalp, and bipolar recordings were made from the frontal, precentral, parietal and occipital regions. The electroencephalograph was a four channel, capacity—coupled, ampliﬁer and oscillographic apparatus with photographic recording on bromide paper. During the recording the patient lay quietly on a comfortable bed in an electrically shielded, sound— proofed, air-cooled room. An observer was always present to note movement and to make sure the patient was not asleep. Records were taken before, during and after hyperventilation. Each record was analyzed as follows: A representative thirty second sample was selected, and all waves over 5 microvolts in amplitude were measured and counted. Paroxysmal activity was not included in the strip. The mean alpha frequency was calculated by averaging all frequencies from 8 to 13 per second, and the percentage of alpha activity was determined by calculating the time occupied by such frequencies during a thirty second recording. A frequency spectrum was then plotted. The limits of individual variation from day to day were determined on several records, and, with this method of analysis, the variation in alpha frequency was found to be not more than 0.5 cycle per second, and that in percentage of alpha activity, 12 per cent. The method of hydration varied to a considerable extent because of differences in the ability of the. subjects to tolerate this procedure. In the ﬁrst few experiments, pitressin was injected hypodermically every hour for seven hours (in doses of 0.3, 0.4, 0.5, 0.5, 0.5, 0.5, 0.5 cc.), and the patient drank 500 cc. of water every hour for eleven hours. Some patients were able to tolerate this, but others suffered from vomiting and abdominal cramps. The procedure was then altered by giving smaller doses of pitressin hourly for eight hours (0.2, 0.3, 0.3, 0.3, 0.3, 0.3, 0.3, 0.3 cc.) and administering 1,000 cc. of 5 per cent dextrose in distilled water intravenously every two hours until a total of 5,000 cc. had been given during the eight hour test period. Some minor modiﬁcations were made in the dosage in individual cases. The patients were admitted to the research ward in the morning, and preliminary physical examinations and records of pulse, temperature, blood pressure, respiration and weight were made. An electroencephalogram was made in the afternoon. Pitressin hydration was begun early the next morning, and the patient was weighed at frequent intervals. Another electroencephalogram was; made the same afternoon, after maximum ’hydration had been achieved. The patients were closely observed, and records of blood pressure, pulse, respiration and temperature were made every four hours during the period of hydration. A regular' diet was prescribed, but coffee, tea and soup were excluded. RESULTS Clinical Observations—Some of the patients were fairly comfortable during these procedures, but most of them had some degree of discomfort, chieﬂy nausea, abdominal cramps and occasional vomiting. �Considerable puﬂiness of the face appeared in a few patients. In none did alarming reactions of circulatory nature appear, and there were no signiﬁcant changes in pulse rate 'or blood pressure. No epileptic seizures of any kind were precipitated. It was found that the smaller doses of pitressin (0.3 cc.) were just as effective in inhibiting diuresis as larger amounts and produced less discomfort. On the morning fol— lowing pitressin hydration voluminous diuresis took place, and the patient’s weight returned rapidly to or slightly below the control level. Electroencephalographic Observatiom.—The data are summarized in the table. The average gain in weight at the end of hydration was Eﬂects of Pitressin Hydration on the; Electroencephalogram r—A—‘M—q Total Per Cent Alpha Frequency Alpha Percentage Snb- Pitres- Gain in ject sin. Body Differ No. Cc. Weight Before After ence Before After Difference 1 3.4 5.3 9.9 10.1 +0.2 71.0 73.7 + 2 3.4 3.2 3.2 5.0 4.5 2.7 10.2 11.1 10.7 9.8 10.6 —0.4 10.5 ——0.2 83.5 47.3 42.3 82.1 40.0 63.3 — 1.4 — 7.3 2.6 5.1 11.5 11.6 10.9 11.4 ~0.6 42.7 57.4 42.2 67.8 — 0.5 3 4 5 6 3.0 3.0 4 —-0.5 —0.2 8 3.2 2.6 1.8 3.2 9.9 10.3 10.0 10.0 +0.1 —-0.3 87.1 76.2 90.8 67.7 9 2.5 7.3 10.3 9.7 —0.6 74.3 58.9 10 1.3 4.3 11.5 11.5 0.0 22.6 22.9 11 1.3 5.3 11.1 10.5 —0.6 42.9 63.9 12 1.3 4.4 10.9 10.7 —o.2 63.3 41.2 13 14 1.7 1.0 5.3 3.9 10.4 11.1 10.4 10.6 0.0 67.0 60.8 61.2 46.9 7 ——0.5 2.7 Comment Shift to slow side and paroxysmal delta activity after hydration 721.0 Shift to slow side after hydration +10.4 Shift to slow side and parox~ ysmal delta activity after + 3.7 — 8.5 hydration " Shift to slow lid-e after hydration —15.4 Shift to slow side and paroxysmal delta activity after hydration + 0.3 Paroxysmal delta activity after hydration +21.0 Shift to slow side and paroxysmal delta activity after hydration -—-92.1 Paroxysmal delta activity after hydration 5.8 —13.9 —- Shift to slow side and paroxysmal delta activity after hydration ’_—“__——-—-——————— 3 4.1 or per cent of body weight. In 3 of the subjects the mean alpha frequency was lowered 0.6 cycle per second, but in the remainder the changes in alpha frequency, although mostly in the direction of slowing, were within the range of daily variation. In half the patients the frequency spectrum showed a deﬁnite shift toward the slow side (ﬁg. 1). In the remainder no deﬁnite shift could be observed. In no case was there an unequivocal shift toward the fast side of the spectrum. The most striking change, however, was the appearance of bursts of slow activity (6 cycles per second) of moderately high amplitude in 7 of the 14 records after hydration (ﬁg. 2). All but 1 of the control recoyds were essentially normal and contained no paroxysmal slow activity, either before or after hyperventilation. In the one record Kg.,. �a scant amount; of paroxysmal 6 per second rhythm was present, and this activity was greatly increased after hydration. In those records which showed paroxysmal :3 per second rhythms, such activity appeared in short bursts of 8 to 15 waves two to six times during the entire run, which was usually about three or four minutes. The incidence of paroxysmal slow activity was not entirely the same as that of shift in the frequency spectrum to the slow side. In 2 records there was a shift but no paroxysmal slow activity. and in 2 the latter was present but there was no shift in the spectrum. There was no correlation between the incidence of paroxysmal slow activity and the degree of hydration or the total amount of pitressin injected. Nor was there a correlation between the admission diagnosis of psychopathic personality and shift in frequency spectrum or incidence of slow activity. Such changes in the electroencephalogram after pitressin hydration were present in 50 per cent of patients with diagnoses of psychopathic personality and in 50 per cent of the others. Consciousness was not grossly disturbed 5 6-7 89 IOII l2!) l4 '5'l6 I? 2| M27 30 Fig. 1 (case 1).-——Eﬂ'ects of pitressin hydration on the frequency spectrum of the electroencephalogram. The solid bars indicate values before, and the outline bars values after, pitressin hydration. On the abscissa are plotted frequencies in terms of cycles per second; on the Ordinate, the number of such frequencies in a thirty second record. Note the shift to the slow side after hydration. IS during the electroencephalographic recording so far as could be determined by the observer in. the electroencephalographic chamber. COMMENT Although none of the patients gave a history or showed clinical evidence of epilepsy, the electroencephalograms obtained on‘ half the subjects after pitressin hydration could be termed “epileptoid” because of the presence of paroxysmal slow activity. Furthermore, it is noted that this change occurred in only half the subjects and was independent of’the degree of hydration. This suggests that the appearance of “epileptoid” changes in the electroencephalogram depends on individual susceptibility. It should be emphasized here that the persons subjected to this test were not truly representative of a “normal” group, since all �had previously been drug addicts and recent studies at this institution have shown that the great majority of the drug addicts fall into either the psychopathic or the psychoneurotic group.‘ The ﬁndings provide a partial answer to the clinical problem which gave rise to this study. It is evident that the appearance of paroxysmal slow activity in the electroencephalogram after pitressin hydration cannot be considered indicative of epilepsy in the clinical sense of the W. wwmwww.WWwwmwwwwMaW A l 2 3 4 . ”NM.“.V“Mm”,rwyﬂ-MMMW‘MWﬁ«MV"V’AM'W‘W(VM/MVW‘v’w..”’V"'V’”‘tM/“ﬁ'“MP“v . WW WW",MM:A 2 3 A' ﬂ ,1 , 35‘3“” 'W ”Ki—mﬁmmwmwwm IVWWWWWM mm . A “A I .5. 1 v n________r_______,____ vwmsxwlMMWWmswwm . 4 .— . g. .l W.NWMNWJWW¢MW{MINWMMMWW N‘MMWEMWMWMMMWWwmwwwvwﬂwawwWW - 2 3 ii “WW MW M;WWWMWIW{V\I‘JNWW ”Wm-WWW h___________n_________n B I ' ‘JWMWN MMWWi‘Wlw 5‘ WWW“V““M/“V’WMWMWWW-wWWW" t 5- H 2 3 4 “W . hW‘Wmm» ‘ , n n ,- [-1 4 M'._M"‘wfw”.“f{‘wﬂgﬂ/ﬁfﬁAewMﬂWWNVI‘ﬁM'JWI/l {\VWK‘WAWMV l W“ W.’x{AMA}.A!W‘My/WWJfNUWWWW'WIl/V”NWAAfv’KVM/MM'y‘M‘fMﬁWV’V/‘N‘ F“ ' WVNVWMmtwAvW‘fPMdWWM . , M B - - '1 2-. a a I r‘v‘wAMN/WwwwwwwwMMNMWx/vvwvvwv .WW“.[it~ww’hwtwmwmmwniM”"¢"MWWWW‘MW n P Wﬁ__u—rh———nn-_ of pitressin hydration the “W- Fig. 2 (case 6_‘i.«—~-Effects on electroencephalograg: (bipolar recording from the frontal (1), pretentral (2), parietal (3) and occipital (4) leads; calibration 50 microvnlts; time in seconds). A and B are control records made before and after hyperventilation, respectively; A' and 8’, records obtained before and after hyperventilation after pitresszin hydration. Note the paroxysmal 6 per second activity gr hydration. 4. Aldrich, C. K., and Ruble, D. Addicts, to be publishsd. x." : Studizs w“ the Pe sonalities of Drug �term. However, it does suggest the possibility that the physiologic mechanism which underlies the production of clinical seizures by this method is also operant in certain susceptible nonepileptic persons and that, essentially, quantitative threshold differences determine whether or not, in any given case, clinical seizures will be precipitated. It would be illuminating, in this connection, to compare the group observed in this investigation with “normal” subjects and with persons known to have epilepsy with special reference to the incidence of paroxysmal slow activity. in the electroencephalogram after pitressin hydration. However, such studies have not yet been made. SUMMARY AND CONCLUSIONS The electroencephalograms of 14 nonepileptic men with previous drug addiction were studied before and after pitressin hydration. No clinical seizures were induced by this procedure. The alpha frequency showed a tendency to slowing after hydration, but in only 3 instances was the degree of change greater than that which could be expected from day to day variation. There was no signiﬁcant change in the percentage of alpha activity. In half the records there was shift to the slow side of the frequency spectrum. In half the records paroxysmal slow activity of moderately high amplitude appeared after hydration. There was some correlation between the appearance of paroxysmal slow activity and the shift of the frequency spectrum to the slow side, but no correlation with the degree of hydration or the amount of pitressin ' administered. The possible signiﬁcance of these observations in their relation to idiopathic epilepsy is discussed. United States Public Health Service Hospital. �Reprinted from THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 98, No. 4, April, 1950 EFFECTS OF METHADONE AND MORPHINE ON THE ELECTROENCEPHALOGRAM OF THE DOG ABRAHAM WIKLER AND SOL ALTSCHUL‘ U. S. Public Health Service Hospital, Lexington, Kentucky Received for publication January 26, 1950 | J-. .4. ‘v... The present study was made as part of a comprehensive investigation of the comparative actions of methadone and morphine on the central nervous system (1, 2). The dog has been utilized in these studies because the effects of small doses of methadone and morphine on this species are analogous to those in man (3—5). In particular, however, we wished to compare the effects of large doses of methadone and morphine on the electroencephalogram since such studies cannot be made with safety in man. Some of the observations made in the course of these investigations are also of interest with reference to the pharmaco—physiologic aspects of convulsive seizures. Electroencephalographic studies were made on eleven dogs. In eight of these animals the effects of methadone and morphine were observed without previous anaesthesia or curare. This was accomplished by the insertion of wire or “mercury cup” electrodes which made contact with the dura over the desired cortical area. The mercury cup electrode (ﬁgure 1) was inserted under aseptic conditions and permitted the recording of electroencephalograms without muscle artifacts in the same dog as often as desired over a period of several months. In one experiment a bipolar wire electrode insulated except for the tip (interelectrode distance about 1.0 mm.) waslinserted into the left anterior lateral hypothalamic area and ﬁxed in place by cementing its upper end to a metal cylinder which was screwed into the calvarium along with other screw leads which served as cortical electrodes. In these eight dogs the electrodes were inserted under sodium pentobarbital (Nembutal) anaesthesia but experiments were not made until one or more days later after full recovery from the anaesthetic. In the three remaining dogs screw electrodes were inserted into the calvarium and in the midline plane of the sphenoid bone (Via the oropharynx to a depth of 1.0 to 2.0 mm. below the ﬂoor of the sella turcica). This was done under ether anaesthesia and the animal was then curarized (“Intocostrin” 1.5 cc. I.V. initially and 0.5 cc. I.V. at about 40-minute intervals thereafter) and artiﬁcial respiration was maintained through a tracheal cannula. Experiments were not begun until the ether effects had worn off as indicated by a return of the electroencephalogram to a normal pattern. In all dogs, silver disc electrodes were also ﬁxed on the ears to serve as reference leads. In most experi— ments, a 3-channel Grass resistance-capacity coupled inkwriting electroencephalograph was used; in some, a four channel resistance-capacity coupled ampliﬁer-oscillograph was used with photographic recording. Shielding of the animal was accomplished by a wire screen grounded cage. The motor patterns of convulsive seizures produced by large doses of methadone or morphine were studied in six other dogs. After one or more seizures they were terminated by intravenous injection of Nembutal. Moving picture records were made for subsequent analysis of the convulsive patterns. The dose range for methadone was 2.0 to 75.0 mgm./kgm. and that for morphine, 5.0 to METHODS. 1 Now Resident Psychiatrist, Illinois Neuropsychiatric Institute, Chicago, 437 9 (as. is ‘ it 111. �438 ABRAHAM WIKLER AND son ALTSCHUL initial doses were given subcutaneously while subsequent doses were given subcutaneously or intravenously. 350.0 mgm./kgm. In all experiments The pre-medication resting electroencephalograms of the dogs varied considerably from dog to dog and on different days in the same dog (ﬁgure 2, control records). However, the changes produced by methadone or morphine were quite different from spontaneous variations in electroencephalographic pattern. After small doses of methadone (2.0 mgm./kgm.) or morphine (5.0 to 10.0 mgm./kgm.) irregular high voltage random slow waves appeared in cortical tracings although fast activity present in the control records persisted (ﬁgure 2). After larger doses of methadone (about 75.0 mgm./kgm.) or morphine (about RESULTS. LUGITE CUP RUBBER DAM MERCURY ,4 SILVER m: _%/ WIRE \ mLT‘T" \ ,//ﬂ\\\\\\\m&\‘ //// Hm ' . . ,l y } 2 -' ,, , J ‘ ._ _— SCALP ———MUSCLE SKULL DURA —r---CORTEX FIG. 1. Mercury cup electrode for recording E.E.G. from dura in unanesthetized and uncurarized animals. Under Nembutal anesthesia, the scalp and muscles are incised and a threaded trephine opening is made in the skull. The mercury cup is screwed in place and the scalp sutured over it. After recovery from anesthesia and healing of scalp wound, recording of EEG. is made by inserting a sharp-pointed, ﬁne but rigid needle, insulated exis The latter conthe into dam rubber and the mercury. scalp for cap the through tip, cept nected by the stout silver wire to the underlying dura. After completion of record, the needle is removed. Mercury is rescaled in cup by rubber darn. Procedure may be repeated indeﬁnitely over a period of several months. 200.0 mgm./kgm.) the earliest change (about one to three minutes after sub— cutaneous injection) was the appearance of bursts of high voltage moderately fast activity (ﬁgures 3B and 4B) in the cortical tracings. Later, high voltage slow waves appeared in the cortical tracings (ﬁgures 30 and 4C). In several exof of bursts high voltage the another change was striking appearance periments less and (ﬁgure 4D) after dome morphine mal”—like and spike sequences “petit frequently and less typically after methadone (ﬁgure 3D). These complexes apassociated not but both were from hemispheres in cortical or one tracings peared with any signiﬁcant change in tracings from sphenoid leads (ﬁgures 3D, 4D, and 4F). In some experiments bilaterally synchronous spike and dome activity in the cortical tracings could be induced by sudden loud noises (clapping hands—ﬁgure 4D). Relatively early (twenty to thirty minutes) after methadone seizure discharges spike voltage after high four morphine to hours) later (two or appeared synchronously in the cortical tracings (ﬁgures 3E and 4G). In one of .-. f? n r �438 ABRAHAM WIKLER AND SOL ALTSCHUL In all experiments initial doses were given subcutaneously while subsequent doses were given subcutaneously or intravenously. 350.0 mgm./kgm. The pre-medication resting electroencephalograms of the dogs varied considerably from dog to dog and on different days in the same dog (ﬁgure 2, control records). However, the changes produced by methadone or morphine were quite diﬁerent from spontaneous variations in electroencephalographic pattern. After small doses of methadone (2.0 mgm./kgm.) or morphine (5.0 to 10.0 mgm./kgm.) irregular high voltage random slow waves appeared in cortical tracings although fast activity present in the control records persisted (ﬁgure 2). After larger doses of methadone (about 75.0 mgm./kgm.) or morphine (about RESULTS. W /// ' LUCITE CUP RUBBER DAM / MERCURY SILVER wnRE \m+.—' \ //ﬂ\\\\\\\\\\\‘ 3W ,1 . ..,\//l 0/” V x//// W, , .. 5 ‘.,- '_' 23932,, "ww/ , .. y i . ' “‘8-//////////%m,m . J \N 1 1 2 _ SKULL DURA -————coarsx FIG. 1. Mercury cup electrode for recording E.E.G. from dura in unanesthetized and uncurarized animals. Under Nembutal anesthesia, the scalp and muscles are incised and a threaded trephine opening is made in the skull. The mercury cup is screwed in place and the scalp sutured over it. After recovery from anesthesia and healing of scalp wound, recording of EEG. is made by inserting a sharp-pointed, ﬁne but rigid needle, insulated exis con— The latter the into dam rubber and the mercury. scalp for the cap through tip, cept nected by the stout silver wire to the underlying dura. After completion of record, the needle is removed. Mercury is rescaled in cup by rubber dam. Procedure may be repeated indeﬁnitely over a period of several months. 200.0 mgm./kgm.) the earliest change (about one to three minutes after sub— cutaneous injection) was the appearance of bursts of high voltage moderately fast activity (ﬁgures 3B and 4B) in the cortical tracings. Later, high voltage slow waves appeared in the cortical tracings (ﬁgures 30 and 4C). In several exof of bursts high voltage the another change was striking appearance periments “petit mal”-like spike and dome sequences after morphine (ﬁgure 4D) and less frequently and less typically after methadone (ﬁgure 3D). These complexes apassociated not but both were from hemispheres cortical in or one tracings peared with any Signiﬁcant change in tracings from sphenoid leads (figures 3D, 4D, and 4F). In some experiments bilaterally synchronous spike and dome activity in the cortical tracings could be induced by sudden loud noises (clapping hands— methadone after minutes) to thirty (twenty early Relatively 4D). ﬁgure seizure discharges spike voltage after four high morphine hours) later to (two or appeared synchronously in the cortical tracings (ﬁgures 3E and 4G).-Irr gnepf W-." : "em 4" , ‘ .1] — *Since the publication of“ 95. paper we -nvo substitutged fdi'ﬁi's an the since Wire latter for *"z’rplatinum Silva. a Fer-i 0d of time and permits amalgam with mercury a mercury to leak throughw rel ~. _ ‘ .4 , . ‘ ‘ ‘5: 3.: �439 METHADONE AND MORPHINE ON EEG three experiments with sphenoid leads, such spike seizure discharges appeared in the basal lead as well (ﬁgure 3E) and were followed by a steady 25 per second rhythm in the latter while the cortical tracings were isoelectric or showed only l N~VAVE K..~u,,V‘.~ -. v I". fl ,' .w.”w“: ‘w‘ﬂxﬁﬂl‘ﬁ,'\" I} c V ——.—-—_—.~. .’ 1 \ .-*.*' - 9' N\W’WW§;""MJ a? u :~' .I. $15” A ,5 '—- _ FIG. 2. Dog #70. Mercury cup electrodes in left fronto-parietal and right parieto-occipital regions. No anesthesia or curare. All tracings bipolar transcortical. Time in seconds. Gain same throughout. A—control. Note predominantly fast activity. B—two and onehalf hours after methadone 2.0 mgm./kgm. subcutaneously. Note general increase in voltage and admixture of irregular slow waves. C—control, two days later. Note irregular rhythms, varying from 10—30 per second (large “spikes” are probably EKG artifacts). D—two and one-half hours after morphine 10 mgm./kgm. subcutaneously. Note changes similar to those in B. slow activity (ﬁgures 3G and 3H). In another experiment the spike seizure discharge from the cortex followed immediately after a typical spike and dome paroxysm (ﬁgure 3G). In the single experiment with hypothalamic bipolar leads, typical spike and dome discharges after morphine 20.0 mgm./kgm. (subcutane- �440 ABRAHAM WIKLER AND SOL ALTSCHUL WWW WWWW WWW/«WAN EFFECTS OF METHADON 75 MG/KG. ON E.E.G. OF DOG ”AI—um... axe SMMA’“ A ”“1 smVI WWW WWWMMW WWW . .. l \ FIG. 3. Dog #102. Curarized. Artificial respiration. Screw electrodes in left anterior- parietal, right posterior-occipital and basi-sphenoid regions. In all records, upper tracing is right occipital to right ear, middle tracing is left parietal to left ear and lower tracing is sphenoid to left ear. Calibrations on “A” apply to all records except “F” where gain was reduced as indicated. A—control. Note mixture of fast and slow frequencies of moderate voltage in cortical tracings and periodic 4 per sec. waves of moderate voltage on a back‘ ground of low voltage fast activity in basal tracing. EKG is shown to point out slow activity in basal tracing is of approximately the same frequency as heart rate. B—three minutes after methadone 75 mgm./kgm. subcutaneously. Note bursts of high voltage spikes in cortical tracings and little change in basal tracing. C—ﬁfteen minutes after methadone. Note admixture of high voltage slow waves in cortical tracing; occasional random spike in basal tracing. D—nineteen minutes after methadone. Note burst of 2 per sec. dome ously) appeared in the cortical tracing from one hemisphere; later the spike components increased progressively in voltage and the pattern assumed �441 METHADONE AND MORPHINE ON EEG EFFECTS OF METHADON 75 MG/KG. ON E.E.G. OF (CONTINUED) 006 WMWMMWWWWh MUM/MtllttﬂtttttttttttltWWW MNWWWMMWMWWW WWWMWWMWMWWWWWWWMWWW WWWWWWWWWWWMIWW [WV wwwwmwwmwwtwwmwwwwmwm I “0}N FIG. 3 (Continued) and spike discharges from left- parietal region alone. E—twenty-two minutes after metha-I done. Note very high voltage seizure discharges synchronous1n all tracings, consisting of repetitive spikes of about 8 pe1 sec. frequency, gradually becoming faster. F—twenty-eight minutes after methadone during a second seizure discharge, shown at 1educed gain. Frequency 15 per sec. G—end of seizure Note steady low voltage 25 per sec. terminal discharge in basal tracing while cortical tracings are practically isoelectric at ﬁrst, then show only irregular slow activity. H~thirty- seven minutes after methadone. EKG and basal tracings showing cardiac slowing and abrupt end of another seizure discharge followed by steady 25 per sec. low voltage activity. that of a sustained high voltage spike discharge. The tracings from the contra- lateral cortex and from the hypothalamus showed no signiﬁcant changes during this period. In all instances, after subsidence of the seizure discharges the cor- �442 ABRAHAM WIKLER AND SOL ALTSCHUL EFFECTS OF MORPHINE 238 MG/KG. ON EEG. OF 006 M'L’NMWNWNWWW WWWWW 7 lhll I fl wwMMJ‘tWJlsl .«qulllllll 'uln kW] \liiWW”"AMMWMAN'"MW,“AA . : :4 ii D respiration. Screw leads in right parieto-occipital, left fronto-parietal and basi-sphenoid regions. In all records, upper tracing is right parietois lower and tracing left to is fronto—parietal left ear middle tracing to right occipital ear, record middle Note records. all on gain refer “A” to Calibrations left on to ear. sphenoid is almost twice that on the others. A—control. Note mixture of moderately high voltage slow and low voltage fast activity. B—one minute after morphine 200 mgm./kgm. subcutaneously. Note increase in moderately high voltage fast activity in cortical tracings; there is little change in basal tracing. C—twenty-seven minutes after morphine. Note admixture of high voltage slow waves in all tracings. D—one-half hour after total of 238 mgm./kgm. FIG. 4. Dog 7% 93. Curarized. Artiﬁcial tical tracings were isoelectric for a few seconds and then high voltage slow activity appeared. In most experiments this sequence of events was repeated several times after the last injection of either methadone or morphine. The motor patterns of the seizures were similar after either drug except that �443 METHADONE AND MORPHINE ON EEG EFFECTS OF MORPHINE 238 MG/KG. ON E.E.G. OF (CONTINUED) 006 mll‘léllllijlW-“meww WSMI , FIG. 4 (Continued) of morphine (24 mgm./kgm. I.V. 3% hours, and 14 mgm./kgrn. I.V. 4 hours after ﬁrst dose). Note burst of high voltage spike and dome complexes from right parieto—occipital region alone; irregular high voltage slow activity in basal tracing. E—seven minutes after D. Burst of spike and dome complexes from right parieto-occipital region with synchronous activity in left fronto-parietal tracing, elicited by clapping hands loudly. F—eight minutes after E. Similar synchronous cortical discharges occurring spontaneously. G—continued from F. Note burst of spike and dome complexes from cortical leads followed immediately by seizure discharge of very high voltage spikes. No change in basal tracing. H—end of seizure. No change in basal tracing. they appeared sooner after large doses of methadone (ten to thirty minutes) than after large doses of morphine (two to four hours). Clonic movements were more prominent in the seizures produced by methadone. The morphine seizures were predominantly tonic. �444 ABRAHAM WIKLER AND SOL ALTSCHUL between the effects of methadone and morphine on the electroencephalogram have been reported in the cat (6). In this species small doses of methadone produced diphasic spikes with admixture of slow waves while larger doses produced seizure—like sustained spike activity. Small doses of morphine caused an increase in frequency while larger doses produced slow waves and subsequent disappearance of electrical activity. These differences appear to be peculiar to the cat for in our experiments with dogs, small doses of either drug produced admixtures of slow waves while larger doses produced seizure-like discharges. The bursts of moderately high voltage spike discharges seen early after methadone or morphine were very similar to the changes produced ab~ in of this the species cortical in the electroencephalogram rat; morphine by olition of cortical electrical activity seemed to be due to anoxia since brain waves reappeared after tracheal insuﬂiation of oxygen (7). In man also, the effects of single and repeated doses of methadone and morphine on the electroencephalogram are comparable (5, 8). Likewise in chronic spinal and in chronic decorticated dogs single and repeated doses of methadone and mor— phine produce similar effects (1, 2). However, in our present studies, some quantitative differences between the effects of these drugs were noted. Convulsions appeared much sooner after subcutaneous injection of methadone than after morphine. Also “petit mal”-like spike and dome activity in the electroencephalogram were much more prominent after large doses of morphine than after methadone. Electrical seizure discharges from subcortical basal structures of the in of in but dose methadone none experiment one after large a were seen experiments with morphine. However, this difference may not be a consistent one since a sphenoid lead was used in only three experiments. Nevertheless, some differences in the actions of methadone and morphine may be expected since these drugs appear to exert different actions on enzyme systems concerned in brain metabolism (9). Our observations are also of interest with reference to the origin of the electrical signs of convulsive activity, particularly the spike and dome pattern. Hursch (10) found that section of the corpus callosum did not alter the pattern of bilaterally synchronous “petit-mal” discharges in the cortex. Jasper and Drooglever-Fortuyn (11) and Hunter and Jasper (12) were able to produce spike and dome and sustained spike activity in both cortex and thalamus by electrical stimulation of medial thalamic structures. These observations suggest a subcor— tical origin of “petit-ma ” complexes. On the other hand, Hayne, Belinson and Gibbs (13) as a result of studies in man, concluded that “. . . The present ﬁndings do not suggest a subcortical but a cortical origin for the three per second wave and spike of petit mal, because (a) the spike registers on the cortex as neg— ative when referred to a relatively inactive area, (b) it can appear as an isolated and purely focal discharge in one cortical area and (0) no evidence was found that it is causatively related to thalamic or other subcortical activity.” Our ﬁndings are strikingly analogous to those of the latter group since after large doses of morphine electrical seizure patterns could, and most often did appear in cortical tracings without concomitant signiﬁcant changes in tracDISCUSSION. Differences �METHADONE AND MORPHINE 0N EEG 445 ings from sphenoid or hypothalamic leads, and spike and dome discharges were frequently observed in cortical tracings from one hemisphere only. However, while suggestive, our evidence is not conclusive with regard to the origin of spike and dome activity since in our experiments the two cortical electrodes were not in strictly homologous areas and our basal electrodes (sphenoid lead and bipolar hypothalamic leads) could not be relied on to pick up electrical activity in the dorsal thalamus. Our records also indicate that the spike and dome discharge and sustained spike activity are closely related since in several instances after large doses of morphine a spike and dome pattern was followed by prolonged sustained spike activity without interruption. Except for the question of the thalamic origin of these seizure discharges, these observations are analagous to those of Hunter and Jasper (12). It is also of interest to note that when a seizure discharge was recorded from the sphenoid lead, this was followed by a sustained low amplitude 25 per second discharge apparently originating in subcortical basal structures. This resembled strongly the “after seizure” discharge seen in chronic decorticated cats following electroshock (14). In the latter study, morphine appeared to alter the electroshock seizure pattern so that fast and slow sequences resembling “petit mal” discharges were seen in some records. In our present investigation, this 25 per second discharge appeared in the sphenoid lead tracings while cortical activity was absent or of a different character. Such independent activity of subcortical structures and cerebral cortex has also been noted after ﬂuoroacetate (15). SUMMARY The effects of small and large doses of methadone and morphine on the electroencephalogram were studied in unanesthetized and uncurarized dogs and in curarized dogs. The motor pattern of the convulsive seizures induced by large doses of these drugs was also observed in different dogs. 2. A “mercury cup” electrode is described which facilitates the repeated recording of electroencephalograms from the dura over the cerebral cortex in unanesthetized and uncurarized animals, without interference due to artifacts from the scalp and temporal muscles. 3. Small doses of methadone or morphine produce an admixture of fast and high voltage slow activity in cortical tracings. Large doses of either drug produce seizure discharges which may appear synchronously in cortical and basal tracings or in cortical tracings alone. The seizure discharges from cortical tracings were both of the spike and dome and sustained spike patterns. At times the former passed over into the latter Without interruption. An “after-seizure” 25 per second low voltage discharge in the tracings from the sphenoid lead was not associated with activity in the cortical leads. 4. The motor pattern of seizures induced in dogs by large doses of methadone or morphine were essentially the same, although clonic movements were more prominent in the methadone convulsions. These seizures appeared much sooner after subcutaneous injection of methadone than after morphine. 1. �446 ' ABRAHAM WIKLER AND SOL ALTSCHUL REFERENCES 99°F!" S" WIKLER, A.: Am. J. Psychiat., 105: 329, 1948. WIKLER, A., AND FRANK, K.: THIS JOURNAL, 94: 382, 1948. SCOTT, C. C., AND CHEN, K. K.: THIS JOURNAL, 87: 63, 1946. SCOTT, C. C., CHEN, K. K., KOHLSTAEDT, K. G., ROBBINS, E. B., AND ISRAEL, F. W.: THIS JOURNAL, 91: 147, 1947. ISBELL, H., WIKLER, A., EISENMAN, A. J ., DAINGERFIELD, M. A., AND FRANK, K.: Arch. Int. Med., 82: 362, 1948. LEIMDORFER, A.: Arch. Internat. Pharmacodyn. et de Therap., 76: 153, 1948. CAHEN, R. L., AND WIKLER, A.: Yale J. Biol. Med., 16: 239, 1944. ANDREWS, H. L.: Psychosom. Med., 6: 143, 1943. GREIG, M. E., AND HOWELL, R. 8.: Arch. Biochem., 19: 441, 1948. HURSH, J. B.: Arch. Neurol. Psychiat., 63: 272, 1945. JASPER, H. H., AND DROOGLEVER-FORTUYN, J .: Res. Publ. Assn. Nerv. Ment. Dis., 26: 272, 1947. HUNTER, M. B., AND JASPER, H. H.: J. Electroencephalog. Clin. Neurophysiol., 1: 305, 1949. HAYNE, R. A., BELINSON, L., AND GIBBS, F. A.: J. Electroencephalog. Clin. Neurophysiol., 1: 437, 1949. WIKLER, A., AND FRANK, K.: Proc. Soc. Exper. Biol. and Med., 67: 464, 1948. WARD, A. A.: J. Neurophysiol., 10: 105, 1947. » E‘PSDSDF'?’ Hg... 12. ~ 13. 14. 15. �EXPERIMENTAL SCHIZOPHRENIA—LIKE SYMPTOMS MAX RINKEL, M. D., H. JACKSON DESHON, M. D., ROBERT W. HYDE, M. D., AND HARRY C. SOLOMON, M. D. Boston, Mass. Reprinted from AMERICAN JOURNAL OF PSYCHIATRY Vol. 108, No. 8, February, 1952 Printed in U. S. A. �[Reprinted from THE AMERICAN JOURNAL OF PSYCHIATRY, Vol. 108, No. 8, February, 1952] EXPERIMENTAL SCHIZOPHRENIA—LIKE SYMPTOMS MAX RINKEL, M. D., H. JACKSON DESHON, M.D., ROBERT W. HYDE, M.D., AND HARRY C. SOLOMON, M. D. Boston, Mass. Printed in U. S. A. �EXPERIMENTAL SCHIZOPHRENIA-LIKE SYMPTOMS ‘ MAX RINKEL, M. D., H. JACKSON DESHON, M.D., ROBERT W. HYDE, M. D., AND HARRY C. SOLOMON, M. D. Boston, Mass. - The nature and cause of the major psychoses are still unknown. Repeated attempts have been made to reproduce experimentally psychotic symptoms in the hope to uncover their psycho—physiological relationship. In 1886, Schmiedeberg succeeded in producing cataleptic phenomena in rabbits by the use of ethyl-urethan. In 1904, Peters(II) discovered the cataleptic action of bulbocapnine; Baruk and de Jong(1, 9, Io) investi— gated this, as well as many related chemicals, more extensively and demonstrated the catatonic elfect upon man and animals. With the discovery of new chemicals and chemical compounds, new tools are made available to the psychiatrist to investigate psychoses experimentally, and a new branch, experimental psychiatry, is emerging. The experimental psychiatrist has the advantage of knowing the one factor, in the causation of psychotic symptoms, the chemical that was administered to the patient and started the chain of reactions. The psychopathological genesis, however, of the psychotic phenomena will best be investigated by methods of the inter— Read at the 107th annual meeting of The Ameri— can Psychiatric Association, Cincinnati, Ohio, May 1 7-11, 1951. From the Department of Psychiatry, Harvard Medical School, and the Boston Psychopathic Hos— pital; Dr. Harry C. Solomon, Director. Aided by a grant from the McCurdy Company, Rochester, New York. H C /8 HC \‘/ CH. \C/ /\{twin/ \/ \/ C‘ CH 572 H / */\ C _, CH. 8 > CH. \f”? /\if”?!/ \/ \/ HC N~CH;; CH_ NH \r/ HOOC .. GET—CE 5 HC Chemistry and Plu'zrmacology L.S.D., which stands for the German Ly— .vergsdure Didthylamid, is the abbreviation used for the diethylamid tartrate of lysergic acid which, according to A. Stoll, A. Hofmann, and F. Troxler(I7), is diastereomer but not structurally isomeric with isolysergic acid as seen in the accompanying formula. coon \*/ Hi pretative analytical branch of psychiatry. Of the chemicals used experimentally at present 2 are outstanding: mescaline, an alkaloid known in its crude form as peyote for hundreds of years, though only in the past few years chemically synthetized, and d—lysergic acid diethylamide tartrate (L.S.D.), a member of the ergot group. Although these chem— icals are quite different in their chemical structure, in their effect upon normal subjects and psychotic patients they show great simi— larities with regard to the production of psychotic symptoms. The schizogenic effect of mescaline has been reported in a number of articles, most recently in a brilliant experimental and psychopathological publication by Paul H. Hoch(8). Our paper is concerned essentially with the description of the effect of d-lysergic acid diethylamide tartrate (L.S.D.) upon male and female individuals who, subsequent to the administration of this chemical, responded with the production of psychotic-schizophrenic-like phenomena. +— C Hi HC CH C CH NH N—CH. CH. �- I952] M. RINKEL, H. J. DESHON, R. W. HYDE AND H. C. SOLOMON It is water soluble and administered orally. Pharmacologically L.S.D. belongs in the group of the ergonovine substances. It has a deﬁnite“ effect upon the in situ uterus of the rabbit, and causes peculiar states of motor rigidity similar to the catatonic phenomena in the dog and cat as' seen with bulbocapnine (19). In our own experiments we noted an especially strong physiological reaction in a 29-year-old very sensitive white girl who was menstruating at the time. She complained of most violent abdominal constrictions, which may have been caused by vehement uterine contractions. The peculiar psychological effect, seen as excitation in experimental ani— mals, was ﬁrst observed and described by the chemist, A. Hofmann. In his laboratory notes of April 4, 1943, he remarked that, while working with L.S.D., he noticed in himself a peculiar restlessness associated with slight dizziness. He had to interrupt his work and went home to rest. While at home, he felt as if intoxicated, a condition characterized by an extremely stimulated phantasy. After darkening his room, for the daylight bothered him very much, he had a most wonderful experience. Phantastic images of most extraordinary plasticity and intensive kaleidoscopic coloring passed before him. This state of intoxication lasted about 2 hours. Literature Following this discovery a number of au— thors investigated the effect of L.S.D. in self-experiments, on normal subjects, and on psychotics. W. A. Stoll(18), who ﬁrst systematically investigated the psychological phenomena of LSD, conﬁrmed Hofmann’s experiences and reported as the most striking psychological ﬁndings disturbances in perception that led to hallucinations, acceleration of thinking, slight dimming of consciousness, but maintenance of judgment. He regarded the psychotic condition as an acute exogenous reaction type and pathologically as diencephalosis. Condreau(4) conﬁrmed most of Stoll’s ﬁndings, but reported that in his experiments the subjects’ consciousness was not disturbed aside from the feeling of intoxication. He added that the subjects maintained their capacity of self-criticism, but showed increased distractibility andiwere less able 573 to concentrate. The basic theme of thought remained unchanged, and the changes in feeling tone he felt to be merely an intensiﬁca— tion of the previous underlying mood. He added as a new observation forced laughing and one instance of athetoid movements as suggestive of involvement of the diencepha— lon, thus contributing to W. A. Stoll’s origi— nal conception. A. M. Becker(2) essentially conﬁrmed the observations of Stoll and Hofmann and emphasized the astounding production of psychosis—like syndromes following the administration of mere “traces” of a chemical substance. He believes the psycho— logical manifestations are the result of two different basic disturbances: affectivity and impulsivity on the one hand, and intention— ality on the other. The most striking contrasts among his observations were manic— hyperkinetic and inhibited depersonalized manifestations. In contrast to Stoll, who termed L.S.D. a “Phantasticum,” Becker suggested the designation of “Psychoticum” for L.S.D. Umberto de Giacomo(6, 7), of Italy, in his experiments with rather large amounts of LSD. (300 to 500 gamma) ob— served in his patients catatonic-like phenomena, which were similar to those produced by bulbocapnine. M. Rinkel(12) and Victor H. Vogel(18) reported their experiences with diethylamide of lysergic acid, adding as new observations paranoic trends and, in contrast to previous publications, slowing of thinking and poverty of thought. Bush and Johnson( 3) used L.S.D. as an aid in psy— chotherapy, and reported that their psychotic patients responded with an increase in activity and greater verbalization of psychopathology. They noted occasional short periods of confusion and disorientation, and occasional transitory visual hallucinations. Most of their patients showed some degree of eu- phoria. Method and Procedure In our own experiments, L.S.D. was given I 7 times to 15 normal adult volunteers, students, nurses, and doctors, in the 19—48 age range, and, as freshly prepared solution, to some psychotics: dementia praecox and manic-depressive, depressive type. The observations on the psychotic patients are still in progress and will be published later. The �574 EXPERIMENTAL SCHIZOPHRENIA-LIKE SYMPTOMS normal subjects, who were kept without breakfast, received LSD. in doses ranging from 20 to 90 gamma p. 0., in most cases one gamma per kilogram body weight, while the psychotics were given 3 gamma per kilogram body weight. This increased dosage for psychotics was chosen on the basis of the unanimous reports in the literature that psychotic patients were particularly resistant to the effect of LSD. The subjects were kept under continuous observation by at least one of the authors for the ﬁrst 5 hours and, on occasions, tape recordings of the subject’s productions were made. The subjects remained under observation the same day at the hospital, and were seen again the following day. The main emphasis in our observations was on the clinical psychiatric picture. Routine neurological and circulatory system examinations were not done, but signs occurring in these areas were noted, if observed. In 9 of the experiments, electroencephalograms at or near 2 hours after L.S.D. were taken, and Rorschach tests were given to 5 normal subjects and concrete-abstract thinking tests to 2 subjects during the height of the L.S.D. reaction. Controls of EEGS and psychological tests were done while the subjects were in their normal mental state. Results I. Disturbances of Thought and Speech.— The most prominent psychological changes observed were those in thinking and speech. They were present in all our experiments. There was no cloudiness of consciousness, no intellectual weakness, but most frequently we observed difﬁculty in the power of expression. The subjects became more and more slowed down, poverty of thought became apparent, and the ﬂow of speech became increasingly diminished and blocked. One subject, a middle-aged depressed pa— tient, went into a complete stupor. In another instance occurred unwillingness to speak, a symptom similar to the negativism of the schizophrenic. Hesitancy, indecision, and impairment of abstract thinking were frequently present; also looseness of thought and actual disconnection with increased dis— tractibility were common observations. As in schizophrenic patients, some of the sub— [Feb jects exhibited such phenomena as lack of spontaneity, irrelevance, pedantic imitation, and subjectively automatic speech. In one instance, we had the impression of the formation of a neologism. Acceleration of thought with ﬂight of ideas associated with rhyming and punning; garrulity and loquacity of the hypomanic type were seen in a cyclothymic medical student within 45 minutes after the administration of LSD. In general, the effects appeared within 30-45 minutes after the oral administration of L.S.D., and disappeared gradually after 3-4 hours. II. Affect and M ood.—-Clear-cut blunting of affect and suspiciousness, as often seen in schizophrenic patients, were outstanding. These symptoms frequently led to feelings of indifference and unreality with disturb— ances in body image. The subjects experienced hostility and resentment, and on rare occasions ambivalence. The phenomena occurred about 15' minutes after the administration of LSD; feelings of indifference and blunting tended to be protracted; suspiciousness, hostility, and resentment were always more transient. Changes in mood were twofold: euphoria and depression, which occurred in about equal number. Euphoria was either of the shallow elation type with silliness, as seen in the hebephrenic, or, in a cyclothymic subject, of the jovial and infectious type, as found in hypomanic and manic states. Depression was combined with dependency, indecision, insecurity, passivity, and feelings of being “lost.” In no instance did we observe the happy and dreamy feeling of ecstasy as it has been described by other authors who experimented with L.S.D., mescaline, and other similar chemicals. III. Perceptiou.—Usually within 40 minutes after the intake of LSD. disturbances of perception were observed. Those of visual perception were most common and mainly of the illusional type. The subjects would see rippling or wavy lines on the wall that might evolve into geometrical pattern, or be associated with color such as yellow, orange, or pink. In some instances, subjects saw a thermostat on the wall as a cruciﬁx but fully realized that the experience was an illusion. None of the subjects, however, had the feeling of seeing something of extraor— dinary beauty, as it was stated in early re- �I952] M. RINKEL, H. J. DESHON, R. W. HYDE AND H. C. SOLOMON ports on L.S.D., or as it may occur under the inﬂuence of mescaline. Gustatory disturbances occurred frequently; the subjects experiencing a metallic or “funny” taste or heavy tongue. Auditory perception was changed only in a few instances. The subject would hear a sound that was either near or distant, and in one instance of a depressed patient, the noise of a typewriter in an adjoining room was perceived as music, seemingly beautiful music. The sense of time was disturbed in II out of 17 experiments. It was characterized by the feeling of time accelerated or retarded. IV. Hallucinations and Delusions—Disturbances in perception, in a complex way, often lead to hallucinations and delusions. A vivid phantasy, a pseudohallucination or illusion, in the process of mental dissociation, may ultimately appear as a real object outside the subject and thus constitute a real hallucination. By a similar process, changes in auditory perception, combined with exist— ing suspiciousness, may lead to ideas of reference and delusions of persecution. It may be stated that hallucinations, predominant under the inﬂuence of most phantastica, sub— sequent to the injection of LSD. were rather meager and never showed the quality of an extraordinarily beautiful or threatening experience. The occasional visual hallucinations consisted mainly of formed images, which occasionally were preceded by crude ﬂashes of light. Perhaps the above—men— tioned disturbances of taste perception should be mentioned here as gustatory hallucina— tions. In only one instance we noticed an auditory hallucination, which consisted in hearing bells, although there were none anywhere around. Haptic hallucinations were experienced by two subjects. One male sub~ ject had the rather vivid feeling of his trousers being wet from urine, and one female schizoid patient was convinced that she lost urine and wet her slacks and the bed. She actually, later on, did wet the bed, and it may be possible that her hallucination was stimulated by autonomic excitation of the bladder mechanism. Morbid ideas were common; they included ideas of reference and ideas of inﬂuence. One female volunteer became quite paranoic and was Still disturbed the following day. Major delusions, ideas of gran— 575 deur or persecution, as seen in the delusional states of the paranoic or paraphrenic, were not observed. That may be due, perhaps, to the fact that in our experiments on normal volunteers we used only relatively small amounts of L.S.D. V. Depersonalization.—Alteration of personality occurred rather frequently. Those changes consisted mainly in the subject’s feeling that his legs were either extraordinarily long or heavy; in one psychotic patient the feeling was that the leg between ankle and hip had disappeared entirely. Most common was the feeling of unreality as regard to the subject, himself, and the outer world. Though these phenomena were of minor magnitude, they, too, indicate symptoms particularly ob— served in the schizophrenic patient. In no instance were we able to elicit experiences, of synaesthesias, as frequently seen in mescaline intoxications. VI. Behavior.—The most and striking change consisted in underactivity, associated with lack of spontaneity and initiative. One schizoid-depressed patient went into a state of catatonia; another one became stuporous. A female schizophrenic patient, who had received 3 gamma/kg. body weight of L.S.D., became agitated; after an initial state of inertia, she suddenly stood up and went through many and various motions. She knelt down, kissing the wall, the ﬂoor, the examining table, and progressively became more and more excited. She tore off her clothes and became noisy to such an extent that the ex— periment had to be terminated by the intravenous injection of 0.5 g. of sodium amytal. In our normal subjects, overactivity or in— appropriate behavior was rarely noted, but psychomotor manifestations, such as smiling, giggling, and laughing, more often appropriate than inappropriate, were frequently observed. This was particularly so in a student of cyclothymic personality make-up. VII. Intellect—In our normal subjects, intellectual functions were never disturbed. The subjects were aware of what they were doing at every moment of the experiment. Their memory also never became disturbed; each one was able to give, in a written report, a description of all the experiences he went through. Also, the psychotic patients did not show any particular memory defect. . �576 EXPERIMENTAL SCHIZOPHRENIA-LIKE SYMPTOM S Patients Whose verbal expression became slowed down and ﬁnally completely ceased, as in the case of stupor or catatonia, were able the following morning, under sodium amytal or d—desoxy-ephedrine, to recall their thoughts or personal experiences of the day before under the inﬂuence of L.S.D. VIII. Autonomic Nervous System.—All normal subjects and also the psychotic patients had numerous subjective complaints and symptoms. Since they mostly belong in the group of disturbances of the autonomic nervous system, they are best described here. The most common symptom was change in appetite, which more often was decreased, and associated with nausea, than increased. Complaints of headiness, giddiness, faintfre— and tremulousness, shaking were ness, The subjects complained , quently expressed. of chilliness and coolness of whole or part of the body, lump and “funny” feelings in ab— domen, constriction with oppression in chest and precordial discomfort, violent cramps and constriction in the abdomen in a pa— tient who just happened to menstruate. Objectively observed were ﬂushing, sweating, shivering, and shivering with goosepimples. Tachypnoea, salivation, pallor, sighing, and obscattered micturation of were urgency servations. Changes in pulse rate and blood pressure were of minor magnitude and observed only occasiOnally. Involuntary smiling, giggling, or laughing were considered in the nature of “risus sardonicus” where the subject described these phenomena as occurring Without or against his will. One subject stated that in a smile he felt as if his facial muscles were like plastic wax being moved by some inexorable force. Pupils were often maximally dilated. Gross disturbances of the cerebrospinal nervous system were not observed, except in some instances “dysarthria,” which consisted of a transient stumbling over words and was never marked. IX. Electroencephalogram.—EEGS were taken in 9 experiments at about the height of L.S.D. reaction, and compared with the EEG of the same subject in his normal state. In general, the EEG changes were only slight. Principal changes occurred in the alpha rhythm, which was characteristically increased in rate from 1-3 cycles per second. [Feb. In one case, an individual who was very relaxed, a slowing of about 2 cycles per second was observed. Hyperventilation showed a diminished responsiveness and may be due to the subject’s reduced cooperation. X. Psychological Tests. A. Rorschach—Controlled Rorschach tests were given to 5' subjects at the height ofL.S.D. reaction. All tests given during L.S.D. reaction showed abnormalities principally of the schizophrenic or paranoic type. There was noticed autistic thinking with decreased organization, contamination responses, and lack of logical thinking, also negativism and diminished emotional inhibition indicating anxiety, depression, and aggression. One Rorschach test revealed a moderately schizophrenic picture with autistic thinking and withdrawal. B. C oncrete-Abstract Thinking—The tests consisted in employing proverbs and aphorisms and recording the subject’s reaction. On the whole, the results, especially the wide range of responses in abstraction and overgeneralized and tangential thinking, were similar to those obtained in schizophrenic patients. DISCUSSION The common denominator in all our experiments with L.S.D. on normal subjects is a profound transformation and alteration of the psychic state of the individual, as it is a common factor in all psychotic states. The various mental phenomena that we have reported were brought about by mere traces (I:I,000,000g/kg. weight) of a chemical, d—lysergic acid diethylamide tartrate. The mental phenomena show similarities to symptoms that occur in actual psychoses. We noticed, predominantly, changes similar to those seen in schizophrenic patients. The subjects exhibited preeminently difﬁculties in thinking, which became retarded, blocked, autistic, and disconnected. The affect was shallow or there was clear-cut blunting. Feelings of indifference and unreality with suspiciousness, hostility, and resentment also approximated schizophrenic phenomena. Hallucinations and delusional disturbances though present were much less prominent or striking, but together with the manifestation ' �‘ 3952] M. RINKEL, H. J. DESI-ION, R. W. HYDE AND H. C. SOLOMON of depersonalization were most reminiscent of schizophrenic dissociation. To a much lesser degree were there similarities to the confusional states. Gross clouding of consciousness was absent in our experiments, but illusional misinterpretations were not infrequently observed. A few cases showed similarities to the manic-depressive states, with changes in mood of euphoria or depression. However, only in one cyclothymic-pyknic subject the intensity was of a hypomanic or manic state. Delusions of grandiose or persecutory nature, familiar in the paranoic psychoses, were not seen. We mention the similarities of the experimental phenomena to actual psychotic states in order to caution against fallacies that may occur in the interpretation of experimental psychotic disturbances. The same caution that is warranted in the application of an animal experiment to a pathological condition in man is needed in the application of the psychiatric experiment to natural psychosis. Our experiments have brought to light the fact that, in a short space of time, under the inﬂuence of a mere trace of a chemical agent in normal subjects, a variety of mental symptoms occur that are similar to natural psychoses, and that in psychotic patients an accentuation of existing, or elicitation of latent, schizophrenic phenomena takes place. It may be possible to assume that fundamentally the mechanism of origin of natural and experimental psychotic phenomena is a similar one: a chemical agent that pathologically stimulates selectively various higher, especially perceptive, brain centers with the result of hallucinatory and delusional experiences. H. J. DeShon, M. Rinkel, and H. C. Solomon( 5) have already pointed out that the clinical effects of LSD. imply such an involvement of the higher and highest centers of the central nervous system, and perhaps of lower levels of the nervous system as well. Many authors assume that chemical endogenous substances are the cause of schizophrenic psychosis. We must bear in mind that, in addition to d—lysergic acid, a great variety of seemingly unrelated chemical substances are capable of producing transi- 577 tory psychotic-like symptoms. Although observations are still too few to allow the for— mulation of a well-founded scientiﬁc theory as to the chemical origination of psychotic symptoms, we strongly believe that this branch of experimental psychiatry is progressing in the right direction, and may some day provide an answer to the most perplexing problems in psychiatry. SUMMARY The effects of minute amounts of dlysergic acid diethylamide tartrate (L.S.D.) on normal subjects, with an age range of 19—48 years, and some psychotic patients of the schizophrenic, depressive, and paranoic type are reported. 2. Psychotic phenomena and alterations of the autonomic nervous system were observed. The psychotic phenomena were pre— dominantly schizophrenia-like symptoms that were manifested in disturbances of thought and speech; changes in affect and mood; perception; production of hallucinations and delusions; depersonalization and changes in behavior. The basic intelligence was not reduced. 3. Electroencephalographic examinations at the height of the L.S.D. reaction revealed only slight changes, principally increased alpha rhythm, except in one case where there occurred a slowing of about 2 cycles per ' second. 4. Rorschach tests showed abnormalities principally of the schizophrenic or paranoic type. Concrete—abstract thinking tests also, on the whole, showed responses similar to those obtained in schizophrenic patients. 5. N 0 scientiﬁc theory for the origination of the natural psychotic phenomena or psychoses is being advanced, but the belief is expressed that experimental psychiatry progresses in the right direction. 1. Credits Our preparation of LSD. was supplied, in ampules containing I mg. substance, by courtesy of Professor E. Rothlin, Director of the Pharmacological Laboratories of Sandoz Chemical Company, Inc., Basel, Switzerland. �EXPERIMENTAL SCHIZOPHRENIA-LIKE SYMPTOMS 578 BIBLIOGRAPHY I. Baruk, H. Psychiatric. Medicale, Physiologique et Experimental. Masson et Cie. Paris (VI), 1938. 2. Becker, A. M. Zﬁr Psychopathologie der Lysergsaure-Diathylamid-wirkung (On the psychopathology of the effect of lysergic acid diethyla— mide). Wien. Ztschr. Nervenh. 2:402, 1949. 3. Bush, Anthony K., and Johnson, Warren C. L.S.D. 25 as an aid in psychotherapy. Dis. Nerv. Syst. 11 : 241, Aug. 1950. 4. Condrau, Gion. Klinishche Erfahrungen an Geisteskranken mit Lysergsaure-Diiithylamid (Clinical experiences in mental patients with lysergic acid-diethylamide). Ejnar Munksgaard, Copenhagen, 24: 9, 1949. 5. DeShon, H. J., et 31. Mental changes experimentally produced by L.S.D. Unpublished article. 6. Giacomo de, U. Données biologiques sur l’ac— tion psychopharmacologique de la diéthylamide de l’acide lysergique (Biological data on the psycho— pathological action of Lysergic acid diethylamide). Paper read at the Symposium on “Chimie cerebrale” of the International Congress of Psychiatry, Paris, Sept. 18-27, 1950. 7. Giacomo de, U. La catatonia sperimentale. Schizofrenie, 4: 195, 1934-1935. 8. Hoch, Paul H. Experimentally produced psy— choses. Am. J. Psychiat., 107:607, Feb. 1951. 9. Jong de, H. Die experimentelle Katatonie als vielfach vorkommende Reaktionsform des Zentralnervensystems (Experimental catatonia, as a frequent reaction type of the central nervous system). Ztschr, ges, Neur. Psychiat., 139 : 468, 1932. 10. Jong dc, H., et Baruk, H. La catonie experimentale par la Bulbocapnine. Paris: Masson et Cie, 1930. Pharmacologische Untersuchungen iiber Corydalisalkaloide (Pharmacological in- II. Peters, F. [Feb. vestigation of Corydalisalkaloids). Arch f. Experi— ment, PathoLogie, 51:130, May 1904. 12. Rinkel, M. (I) Discussional remark on L.S.D.—Clinic of the American Psychiatric Asso— ciation, held at the Annual Meeting of the A.P.A. May 1, 1950, in Detroit. J. Clin. Experiment. Psy— chopathol., Jan. 1951 (Van Ophuijsen Memorial Issue). (2) Discussion at symposium on “Chimie cere— brale” of Ist World Congress of Psychiatry, Paris, Sept. 18-27, 1950. Printed in “Les comptes-rendus du Congrés.” 13. Schmiedeberg, O. Uber die pharmacologischen Wirkungen und die therapeutische Anwendung einiger Carbamin Séiure-Ester. (On the pharmacological effect and therapeutic application of some of the esters of the Carbamin acid). Arch. f. Experiment. Pathologie und Pharmakologie, 20: 203, 1886. J. E. Psychopathologie der 14. Staehelin, Zwischen-und Mittelhirnerkrankungen (Psychopathology of the diseases of the diencephalon). Schweiz. Arch. Neurol. und Psychiat. 53 : 374, 1944. 15. Stoll, A. Les Alcaloidés de L’Ergot (The alkaloids of ergot). Experientia 1:250, 1945. I6. Stoll, A., and Hofmann, A. Partialsynthese von Alkaloiden vom Typus des Ergobasins (Partial synthesis of alkaloids of the type of the ergo— basins). Helv. Chim. Acta, 26:944, 1943. 17. Stoll, A., et a1. Ueber die Isomerie von Ly— sergsaure und Isolysergsaure (On the isomery of lysergic acid and isolysergic acid). Helv. Chim. Acta, 32 (No. 2) : 506, 1949. I8. Stoll, W. A. Lysergsaure-diithylamid, ein Phantasticum aus der Mutter-korngruppe. (Lysergic acid diethylamide, a phantasticon of the ergot group). Schweizer Arch. Neurol. und Psychiat., 60: I, 1947. 19. Vogel, H. Victor. Discussional remark to Hoch’s paper (ref. 8). ‘ ��ILQMH ‘_ .1”. '_ ., z::y1;,;m.ynom 32/ [7 _ kHLLQJ-» '2 2rd, GLEN QAKS N. L CLINICAL EFFECTS OF A “STIMULANT” BARBITURATE (Sodium I :3—dimethylbutyl ethyl barbiturate) in Schizophrenics BY HARRY [Reprinted from H. PENNES, MD. T8: JounNAL or Nnnvous AND MENTAL DISEASE, Vol. 119, No. 3, Mar. 1954] �[Reprinted from THE JOURNAL OF NERVOUS AND MENTAL DISEASE, Vol. 119, No. 3, Mar. 1954] CLINICAL EFFECTS OF A “STIMULANT” BARBITURATE (Sodium 1:3-dimethylbutyl ethyl barbiturate) in Schizophrenics HARRY H. PENNES, M.D.‘x‘ central the nervous than rather depress stimulate barbiturates Many of these drugs evaluation clinical but animals in experimental system barbitu— of central—depressant Administration a limited been has (15). of amelioration transient often sodium produces such amytal as rate different symptoms' in schizophrenics (6, Io, 3). These symptom changes are usually attended by a variable degree of hynotic (sleep— producing) eﬂect which may proceed to actual sleep as the dosage is increased. In the drug therapy of schizophrenics the excessive narcosis produced by the central-depressant action of the barbiturates in common administered. be which conveniently total the limits dosage may usage It was considered possible that a central—stimulant barbiturate might of the desirable ordinary depressant the activity therapeutic possess barbiturates without the disadvantage of excessive narcosis. The stimulant barbiturate utilized to test this hypothesis was 1,3— dimethylbutyl ethyl barbiturate, sodium salt (15), (hereafter designated as DMBEB) which is similar structurally to sodium amytal (14). A small number of observations has also been included on another stimu— lant barbiturate, namely, 3,3—dimethyl allyl ethyl barbiturate, sodium salt, (supplied for research purposes by Eli Lilly and Company, Indianapolis) (16). According to reports, DMBEB produces a period of increased alertness and restlessnes in unanesthetized dogs, followed by convulsions; the seizures, which occur only in warm-blooded animals, are Violently tonic in type and the locus is probably the spinal cord; no hypnotic or anesthetic effects are noted in sublethal doses (13, 14,). The reﬂex contraction of m. tibialis anticus is augmented in spinal and barbital—anesthetized dogs; in this regard it is I/250th as active as strychnine, one—fourth as active as picrotoxin, and more active than caf— feine, cocaine, or ephedrine (9). The crossed—extension reﬂex in m. gas— trocnemicus and respiration are also augmented (8). The convulsant activity of DMBEB may be antagonized by administration of sodium amytal (14). The sodium salt of 3,3—dimethyl allyl ethyl barbiturate produces a restless, frightened, or boldly vicious animal in which con— ‘From the Department of Experimental Psychiatry (Paul H. Hoch, M.D.), New York State Psychiatric Institute. [25I] �252 Harry H. Penna: vulsions ﬁnally ensue; blood pressure and body temperature rise while respiration is stimulated (I6). Gottlieb has previously observed that DMBEB produces a euphoric effect in depressed patients after oral administration in subconvulsant doses (4). The drug was likewise maintained at a subconvulsant level in the present study in order to rule out the possible therapeutic effect of a generalized seizure. PROCEDURE schizo— administered hospitalized 20 to Patient5.—DMBEB was duraMean mean females. 8 males and was 32.5 12 years; age phrenics, tion of illness, 13.4 years; mean duration of hospitalization, 2.2 years. The diagnostic categories were as follows: pseudoneurotic, 6; catatonic, The pseudo— unclassiﬁed schizophrenic, mixed 1 II. ; or hebephrenic, 2; neurotics presented diffusely neurotic symptomatology in a basically of criteria the and to according diagnosed were schizophrenic setting schizo— unclassiﬁed and mixed of The Polatin Hoch and (7). group phrenics presented admixtures of catatonic, hebephrenic, and paranoid cata— Gross disease. of the features the well as primary as components tonic stupors or excitements and diagnostic categories other than schizo— phrenia were not included. Most of the patients were quite well pre— served. Sixteen of the 20 cases had either no or slight deterioration (6 pseudoneurotics, 2 catatonics, I hebephrenic, and 7 mixed or un— classiﬁed schizophrenics); these patients were chieﬂy short-term, volun— tary hospital admissions. The remaining 4 subjects displayed an advanced degree of schizophrenic deterioration and were long—term, state hospital patients. All but 2 patients had received at least one course of electric convulsive and/ or insulin coma therapy at some time during the course of the illness. Dru gun—DMBEB was dry—sterilized in an electric oven at I50—I60° C. for one to two hours. Immediately prior to intravenous injection the drug was dissolved in 20.0 cc. of sterile distilled water at a concentration of 5.0 mg. per cc. A colorless solution was quickly formed. The the in administered 20 of that dose 63.5 DMBEB was was mg. average subjects. An injection rate of about 5.0 mg. per minute was used in all subjects. The same procedure was followed in the administration of 3,3—dimethyl allyl ethyl barbiturate, sodium salt, to 2 patients both of whom also received DMBEB on another occasion. Each patient also independently received intravenous injection of sodium amytal (Amobarbital sodium, Eli Lilly and Company, Indianapolis), 250-500 mg. dis— solved in 10.0 cc. of sterile distilled water at a rate of about 50 mg. per minute, as well as 20.0 or 40.0 mg. of pervitin hydrochloride (Smith, �Eﬁect: of a "Stimulant” Barbiturate 253 Kline and French Company, Philadelphia) in 2.0—4.0 cc. of solution in one minute. Six patients also received intravenous sodium amytal in the same dosage and rate of administration as that of DMBEB. The drugs were administered in random orders to the various subjects. Injections were performed between 8:00 A.M. and 4:00 P.M. without limitation of food or the subject’s usual ward activities. Changes in the patient’s baseline clinical status were recorded in protocol form for a period of at least 48 hours following injection. RESULTS I. Mental Reactions.——DMBEB reduced clinical symptoms in II (55.0 per cent) of the series. Three patients (15.0 per cent) showed only increase of symptomatology and 6 (30.0 per cent) had no reactions except for side-effects to be described in section II. A. Symptom-reducing reﬂect—The therapeutic action was most pro— nounced in the pseudoneurotic group. Four out of 6 patients in this group experienced complete or almost complete relief of anxiety and tension, phobic concerns, irritability and hostility, and depressive manifestations. All 3 obsessive—compulsive patients in this group experi— enced amelioration of the disabling symptomatology, slight in I and quite complete in 2. The usual duration of relief was two to eight hours, but in 2 subjects the improvement lasted 16 to 24 hours. The symptomatic improvement began during the injection, usually concurrently with cephalic sensations described variously as “light—headed” or a “subtle feeling of relaxation.” In the 14 overt schizophrenics (hebephrenics, catatonic, mixed, and unclassiﬁed), 7 patients showed slight to mod— erate therapeutic responses which were in general less complete than those of the pseudoneurotics. The effects in the overt schoziphrenic group consisted principally of signs of personality reintegration with more normal emotional feeling and display, less self—concern and self— preoccupation, an increased tendency to contact the environment, and a somewhat higher verbal productivity. The most deteriorated cases responded least to the drug in a therapeutic sense; these patients also responded least to sodium amytal and pervitin. These therapeutic responses to DMBEB were qualitatively identical with those often produced by central—depressant barbiturates. How— ever, the therapeutic response to DMBEB was more complete than to sodium amytal administered in the same low dosage to 6 patients (30, 50, 65, 89, 100, and 100 mg.); this was particularly true in the pseudoneurotic group. Moreover, clinical signs of hypnosis with DMBEB occurred in only 4 patients in the series and consisted of transient drowsi- �254 Harry H. Pennes excessive slurred speech, and nystagmus, a sleepy expression; ness euphoria, and other signs of acute barbiturate intoxication were not feel— relieved reported no subjects present. Some of the most completely after such of signs and objective of drowsiness displayed no ings DMBEB. In addition, DMBEB produced none of the signs of psychic “stimulation” that usually occurred after pervitin, a cephalotropic sym— pathomimetic amine. Administration of pervitin was almost invariably attended by a positive “stimulation” aspect consisting of increased alert— ness and energy, feelings of optimism, and heightened psychomotor acaction the DMBEB, to therapeutically In responding patients tivity. elimina— neutralization or summarized be therefore a as symptom may tion without concomitant “stimulation” and, as described above, with occasionally a minor degree of sedation. B. Symptom—increasing eﬂects.—Symptom intensiﬁcation occurred in him— for felt copiously, follows: sorry one subject wept 3 patients as self, and complained bitterly of mistreatment by doctors; a second identi— of seizure origin hysterical subject had a brief, opisthotonic cal with the type occurring in the drug—free state; the third subject felt more perplexed, confused, and depressed. These reactions were all exacerbations of pre—existent manifestations which had also previously increased spontaneously or in response to amytal and/or pervitin. These excessive reactions appeared to be precipitated “psychologically” as a secondary reaction to the unusual side effects produced by DMBEB barbituof showed acute of these signs None subjects Section 11). (see resemble did the reactions entirely not In subnarcosis. addition, rate the exaggerated emotional discharges so often produced after pervitin, since none of the primary “stimulation” effects of pervitin on psycho— motor processes was present. C. Absent mental reactions.—Six patients (30.0 per cent) had no reac— tions to the drug in terms of pre—existent symptomatology. In 3 of these, the side-reactions to the drug were so intense that the patients were preoccupied with little else. In the 3 other subjects, there were no mental side-effects. considerable of absence the of despite signiﬁcance changes II. Side Reactions.—Practically all (18 out of 20) patients experi— enced side—reactions. The toxic effects appeared during the injection and the sequence of events was approximately the same in the majority of subjects. Tingling sensations or other paresthesias began in any part of the body, and rapidly became pruritic in nature; this was followed by or associated with hot and cold sensations and a mottled erythema in face, chest, and trunk. Pilomotor reactions often appeared on arms �Eﬁect: of a "Stimulant” Barbiturate 255 and back; less frequently there were feelings of vague abdominal dis— comfort or slight nausea; repeated, forceful sneezing; and occasionally burning of the eyes. Cephalic sensations previously referred to (Section IA) usually began early in the injection in a small minority of sub— jects; on assuming the erect position some patients complained of a vague vertigo of nonspeciﬁc nature and minimal degrees of ataxia were observed. The maximum dosage of DMBEB that could be comfortably tol— erated by the subjects was limited by the pruritis, which was the most frequent side-reaction (18 out of 20 patients). The itching usually began in scalp, face, eyes, soles of feet, or genital areas. Spread was rapid and in some cases the pruritis became generalized; some subjects rubbed and scratched vigorously and became extremely distressed, tending to disregard the other actions. All the side-reactions enumerated above were of relatively short duration, usually subsiding in IO to 30 minutes. In some cases, the pruritis persisted for several hours, although distress was always minimal after the ﬁrst 10 to 30 minutes. In 17 cases, the injection was discontinued when the above reaction deﬁnitely appeared, particularly the pruritis. The average dosage administered to these subjects was 64.4 mg. total or 1.01 mg. per Kg. of body weight. The threshold dosage for the appearance of any effect, mental or toxic, was in the neighborhood of 30.0 mg. The range of effective therapeutic dosage without toxicity was therefore quite narrow. Two patients received full dosage of 97.0 and 101.0 mg. total without side— effects and a marked symptomatic improvement in one. Two subjects displayed seizures at dosages of 59.0 mg. (0.65 mg. per Kg.) and 68.0 mg. (1.04 mg. per Kg.), although other subjects receiv— ing equal or larger dosages did not display seizures. The involuntary movements were of a jerky, nonrhythmic myoclonic type; in one subject the movements were more or less generalized and in the other limited to the right arm. The movements occurred in cycles of about 15-20 seconds duration for a period of about 10 minutes. Consciousness was not impaired during the seizures; deep reflexes were normal in the inter— seizure phases; there were no facial weakness, pupillary changes, nys— tagmus, Hoffman or Babinski reﬂexes. The seizures appeared in these two subjects after the itching had become severe and generalized. Continued experience with the drug showed that no patient developed a seizure if the injection was discontinued at or shortly after the appear— ance of the pruritis. None of the side—effects of DMBEB occurred after sodium amytal with the exception of its quite minor hypnotic action. Pervitin sideeffects were totally distinct, consisting usually of mouth and throat �256 Harry H. Penna: dryness, peripheral numbness and lightness, chest pressure, and cephalic tightness or aching. Sodium 1,3-Dimet/zyl Allyl Ethyl Barbituratc.—This stimulant bar— biturate was administered in doses of 1.26 and 1.37 mg. per Kg. to 2 subjects. The same side-effects were produced as with DMBEB and with the same apparent intensity. One subject experienced generalized myoclonic—like twitchings. No therapeutic effect on mental symptoma— tology was observed. DISCUSSION DMBEB has been classiﬁed as a “stimulant” barbiturate in animals in the experimental pharmacologic literature because of its convulsion— producing property and augmentation of spinal reﬂexes (13, I4, 8). The epileptogenic action was conﬁrmed in this clinical assay of the drug inasmuch as 2 subjects had seizures under the drug, the dosage being maintained at the subconvulsant level in the other patients. The seizures occurring in these 2 subjects were of myoclonic type, whereas Swanson and Chen reported that the drug produced severe convulsions of tonic convul— of difference This animals to as in (14). type laboratory type sion may be a species difference or reﬂect the limitation of dosage in man. The median convulsant dosage after intravenous administration to guinea pigs, rabbits, cats, dogs, and monkeys ranged from 2.0—3.0 mg. with brief the whereas episodes myoclonic (14), weight body Kg. per DMBEB in this series occurred with dosages of 0.65 and 1.04 mg. per Kg. The numerous side—reactions observed in man have not been reported in animals; some of these side—reactions are purely subjective and there— fore not observable in animals. Knoefel found that DMBEB produced a stage of increased alertness and restlessness prior to the seizures (8); dogs under sodium 1,3—dimethyl allyl ethyl barbiturate became restless and also appeared frightened or boldly vicious prior to the onset of convulsions (16). These apparent changes in emotion and behavior in animals could have been secondary to a highly distressing action such as occurred in man, mainly the severe paresthetic and pruritic response. Either a peripheral or central locus of action might underlie the typical constellation of tingling, burning or cold, pruritis, pilomotor contrac— tions, erythema and sneezing. The sneezing in man may be analogous to the respiratory augmentation observed in animals (16). Gottlieb noted that the toxic reactions to DMBEB in man were not signiﬁcantly affected by administration of antihistaminic drugs (4). Despite the motor Stimulation caused by DMBEB in man and reported in animals, there was little or no evidence that the drug acted �Eﬁects of a “Stimulant" Barbiturate 257 in stimulation” The “psychic in stimulant” term patients. as a “psychic behavioral and emotional the is exaggerated to applied generally man the to sodium amytal, or with intravenous of subnarcosis as phenomena with as mood of psychomotor processes, or “primary” heightening of these of Neither amines. types the cephalotropic sympathomimetic be the this drug In may DMBEB. after respect reactions occurred which and are potent metrazol strychnine such with as grouped agents of absence The stimulants.” weak “psychic convulsants but relatively be in DMBEB with man stimulation” may of obvious signs “psychic associated with the fact that the seizure locus in animals is apparently the spinal cord (14). have been no hypnotic or has to reported DMBEB Although observed effect weak was hypnotic animals effects a in (14), anesthetic difference This series. of the may of the present in the minority patients reﬂect species variation or technical limitations in animal experimenta— tion inasmuch as a slight degree of narcosis is often purely subjective. From the therapeutic point of view, DMBEB produced symptom effects the of the series; of cent 20 or 55.0 per amelioration in II out ob— Gottlieb were most complete in pseudoneurotic schizophrenics. 60.0 i.e., material, different in results patient the tained almost same of series IO in administration a oral after per cent improvement, schizo— of a whom as diagnosed was only one severely depressed patients, establish advisable deemed therapeutic been to has It not (4). phrenic value on more than the present preliminary tentative basis because of the high toxicity of the drug which would preclude therapeutic appli— cation. The same conclusion was reached by Gottlieb (4). The observed therapeutic activity of DMBEB cannot be explained allevia— because action weak symptom hypnotic—narcotic in terms of its tion (particularly in pseudoneurotic schizophrenics) occurred without obvious of absence and the fact this of view In action. such appreciable the of action the that is therapeutic it stimulation,” apparent “psychic drug requires another explanation. Two hypothetical explanations are the following: and stimulation” properties does “psychic DMBEB really possess I. in addition the hypnotic action of the ordinary barbiturates; the balance between these two actions is such that a net weak hypnosis is occasionally the resultant in man. In this case it would have to be assumed that the complete almost the theoretically retained is despite action therapeutic of level far effects in stimulant as and so narcotic of cancelling-out consciousness is concerned. In support of such a possibility is the clinical observation that in simultaneous administration of amytal and benzedrine to mental patients, considerable therapeutic activity may ensue �258 . Harry H. Penna: despite a fairly complete mutual neutralization of the narcotic and stimulant actions of the two drugs (11). In this connection it may be observed that Gottlieb interpreted the euphorizing action of DMBEB in mental depression as a consequence of its “stimulant” properties and from this concluded that amytal may exert its euphorizing action in the same condition by a stimulant rather than a narcotic action (4). Gottlieb did not report any hypnotic action of DMBEB in his series such as was observed in the present study; the difference may possibly be a function of the oral route of administration in his study as compared with the intravenous route in this report. His data could also be inter— preted in terms of a narcotic rather than a stimulant action of DMBEB and the beneﬁcial effect of amytal in depression still explained in terms of a narcotic action rather than a stimulant one. 2. The second hypothetical mechanism for the therapeutic action of DMBEB would be that the drug exerts this effect by a mechanism other than central depression or stimulation. Direct evidence for this interpretation is lacking. However, there are several sets of data which suggest that the ordinary central-depressant barbiturates exert their therapeutic action on mental symptomatology independently of their hypnotic-narcotic actions. These data are the following: (a) a few subjects display almost complete relief of symptomatology after intra— venous injection of small amounts of sodium amytal before any or much intoxication is apparent in the form of drowsiness, slurred speech, or nystagmus. Conversely, a few subjects show little change in the mental status even though the central-depressant action may be carried to the point of sleep (10, 5). (b) The ﬁrst effect of the barbiturates on the human electroencephalogram is the appearance of relatively rapid (20-25 sec.), medium—high voltage activity, particularly in the frontal leads (II, I, 12). The appearance of this activity coincides temporally with reduction of anxiety and tension in some patients and the appearance of a more or less euphoric state (11, 12). The physiologic signiﬁcance of this rapid activity has not been fully determined as yet but in any event it is distinct from the EEG charges which are usually accepted as manifestations of depressed consciousness, i.e., high voltage, slow activity (2). In view of these considerations, it is possible that both DMBEB and the ordinary barbiturates owe their therapeutic effect on mental symptomatology to some hitherto undisclosed feature of their action. The pharmacologic literature contains reference to a large number of motor stimulant barbiturates which have never received clinical assay. These compounds show no underlying uniformity of chemical structure and many are in the thiobarbiturate series. The possibility exists that �Eﬁ‘ects of a “Stimulant” Barbiturate 259 without these of drugs with obtainable some therapeutic action may be the excessive toxicity of DMBEB. SUMMARY bar— ethyl The “stimulant” barbiturate, sodium 1,3—dimethylbutyl various with 20 patients biturate, was administered intravenously to value. of its therapeutic forms of schizophrenia in a preliminary assay effect therapeutic occurring I. The drug exerted an irregularly in pseudoneurotic degree of complete which most was (55.0 per cent) further establish advisable to deemed been schizophrenics. It has not which toxicity the high of relatively because the therapeutic efficacy would preclude therapeutic application. in convulsant is the a that drug literature the 2. In accord with remainthe in seizures; had series myoclonic this animals, 2 patients in level. A subconvulsant maintained a at ing subjects the dosage was small minority of subjects showed weak signs of central nervous system central—depressant the drowsiness; of form the slight in depression action has not been reported in animals. occurred independently the of usually effect drug The therapeutic 3. evidence was No action. central—depressant and of its weak infrequent of the in sense stimulant” acted “psychic as a obtained that the drug heightening of mood and psycho-motor processes. action the of therapeutic mechanism the of 4. Several explanations of the stimufurther of investigation the desirability and offered were lant barbiturate series indicated. BIBLIOGRAPHY the Cerebral CorBarbiturates of Action on E.: and I. Finesinger, A. M. B., (1) Brazier, tex. Arch. Neural. 6r Frye/liar” 53: 51-58, 1945. Brain. the of Activity Electrical the Underlying Mechanisms : Physiological (2) I. Neural, Neurosurg, 6* Psych, 11: 118-133, 1948. Sodium Amytal of Intravenous Value M.: Prognostic and I. Hope, S., (3) Gottlieb, I. in Cases of Schizophrenia. Arc/z. Neural. 6' Prychiat., 46: 86-100, 1941. Acid. Arch. Barbituric 5-(1,3-Dirnethylbuty1)-5—Ethyl of Action Antidepressive (4) Neurol. 6r P5yc/ziat., 66: 318—328, 1951. and Sodium Amytal of Administration of Effect S. B: (5) Harris, M. H., and Katz, Sodium Rhodonate on Mental Patients. Am. I. P:yc/ziwt., 12: 1065-1083, 1933. NERVOUS & JOURNAL and Therapy. of Narcodiagnosis Status Present (6) Hoch, P. H.: MENTAL DISEASE, 103: 248-259, 1946. Psychiat. of Schizophrenia. Form Pseudoneurotic P.: Polatin, and (7) Hoch, P. H., Quart., 23: 248—276, 1949. by Nervous Central System the of and Depression Stimulation K.: (8) Knoefel, P. Therap., 6' Pharm. Exper. Acids. I. Thiobarbituric and Barbituric of Derivatives 84: 26-33. I945<9 Exper. Therap., 57: Pharm. Barbiturate. I. Convulsant of Action a : The (9) 130, 1936 (Proc.). Sodium Amytal, Pervitin to of Schizophrenics Reactions Clinical H.: H. (10) Pennes, ' —: �260 (11) (12) (I3) (I4) (15) (16) Harry H. Penna: Hydrochloride, Mescaline Sulfate and D-lysergic Acid Diethylamide (LSD25). (To be published.) : Personal Observation. Rubin, M. A., Malamud, W., and Hope, 1.: EEG and Psychopathological Manirestations in Schizophrenia as Inﬂuenced by Drugs. Psychosom. Med., 4: 355-361, 1942. Shonle, H. A., et 31.: Relation of the Structure of Dialkyl Barbituric Acids to the Length of Their Action. I. Am. Chem. Soc., 58: 585—587, 1936. Swanson, E. E., and Chen, K. K.: The Aberrant Action of Sodium I :3—dimethylbutyl Ethyl Barbiturate. Quart. I. Pharm. é‘r Pharmacol., 12: 657-660, 1939. Tatum, A. L.: Present Status of the Barbituratc Problem. Physiol. Rem, 19: 472502, 1939Taylor, N. B. G., and Noble, R. L.: Some Pharmacological Properties of Sodium Ethyl, 3:3 Dimethylallyl Barbiturate. Nature, 163: 447, 1949. ��W Ruth. t , mm mm.bail. Ion-r “I!“ i mammcsmmcm mmmnuﬂ.‘ iv P.hmulJ.I.lIOou ,_ «2:! "WWW“ 'thﬁ-WMW-lmw mun-nuns; MM,” mug-v.4 pawn 1...,” .»,t Proof. to: Dr.J.D.lcCou it. nonu- Ltd. but lo: 959 “on“, “a m �gnu-gotta or ﬂu «unnoand at up nun-um at»), mum». Ann; tho mm, (mm, mauuorummwgpu'wubom attache-amid. ”haul-Watt!” muunuu,nwu,mumwwu1uu vlllult. m,ud¢mlduquuonofﬁom¢nub Mr uticomamnleutboc-W mummwu,muuaoomump mm,1umovd1h-u(cmsuand,19533 Inn-r, M1955, mam, 1955. 1957; 1956; -.‘-a.-1-- ran 195‘). mmmuxtuwmtmsmtzu “mummmwmumm Min-lull. Itmmuthttumotm «rutnammuummwwmd Wan-«An m .u-.. 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MI. 1. and lb :.n. sun, Wall, In 1957, and pro“. 3001.1, 1.3., aura, 9., ll», IJ. 3.3. 1955. 1949, 99 n. we n. 3&6 ��‘ .........,., 4 8n» AU 8. _ Ian-av. 8m. o8 08 so an» 8. on. a... 8. a. a. : an»? u n ,5 9.5. .3.an . “at. LED- ..,..y �CV A3 ot'oﬂg gwgong p.» aw.a.p.uv pro Acto.9.wv . a.» Au.~.w..v u.w or» Aarqnarov a o ~u...u.nv �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Files and reprints: hallucinogens and EEG, 1958 (folder title 1/2). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-002-13-014 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource Various authors Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/c577bc7f069484c31c474ab088079b96.pdf ecc528f0eb233cc9aa9e8503f0092d28 PDF Text Text OF' THE EFFECTS CERTAIN DRUGS ON CEREBRAL SYNAPSES By Amedeo S. Marrazzi Reprinted from ANNALS OF THE NEW YORK ACADEMY OF SCIENCES APR 3 0 1qt§9 ‘ ‘ Volume 66, Article 3, Pages 496—507 March 14, 1957 DEPARTMENTOF . EXPERIMENT” PSYBH‘HRY SIDE HOSPlTN- Hug-LEN OAKS. N- Y- �THE EFFECTS OF CERTAIN DRUGS ON CEREBRAL SYNAPSES By Amedeo S. Marrazzi Velerans Administration Research Laboratories in Neuropsye/ziatry, Veterans Administration II ospital, Pittsburgh, Pa. As Edward Evarts has so clearly indicated in his contribution to this volume, we are all interested in determining the neurophysiological correlates of mental disturbance in the hope of thereby gaining an inkling of its underlying mech— anisms and developing a rational therapy for it. Humphry Osmond has drawn a dramatic picture of the opportunity presented by the situation made possible by the psychotomimetic drugs, which afford us the means of inducing at will a reversible model psychosis. This model psychosis, even though it bears only a fragmentary resemblance to schizophrenia, nevertheless simulates certain aspects of mental disturbance by perhaps similar mechanisms. Furthermore, the so-called model psychosis also can be shortened and terminated is in effectiveness clinical which for schizophrenia will the tranquilizers at by claimed. The use of drugs as tools thus creates favorable conditions for studies of mental illness. Our efforts, as investigators, are directed more toward an intelligent applica— tion of the hypotheses of mechanism rather than toward simple clinical evaluation. The conditions that we wish to interpret are fully and truly exhibited in man but, before we can take full advantage of controlled conditions induced in humans, it is necessary to perform some prototype experiments in animals since, in such experiments, more procedures are permissible and in them those experiments intended for man can be constructed and rehearsed. This pur— is be humans with work before done, needed can the my groundwork pose, justiﬁcation for presenting some data on animals and making comparisons with clinical conditions and experimentally induced conditions in man. FIGURE 1 summarizes the data that led my co—workers and me to a hypothesis that served as the point of departure for studies in this ﬁeld.1 It shows that in our survey of a variety of sites in the nervous system we ﬁnd, as far as we have gone, that a consistent reciprocal relationship exists between excitation or enhancement by acetylcholine and acetylcholinelike substances, including anticholinesterases, on synaptic-transmission phenomena and inhibition by epinephrine, norepinephrine, all sympathomimetic amines in varying degrees, and related substances.2 It seemed plausible that any perversion of metabolism that would distort the balance of endogenous chemical or neurohumoral control of synaptic-transmission processes could lead to abnormal cerebral performance or mental disturbance, and that chemicals or drugs could alter the equilibrium of transmission and thereby alter cerebral and mental function in the direction of health or disease. The limitations of communication with animals make it exceedingly difﬁcult, though not impossible, to relate the behavioral disturbances that can be produced in them with mental disturbance in man. Since our basic premise, however, is that all cerebral function, including both behavior and mental proc— in series and in accumulated parallel of units is functional made esses, up 496 �Marrazzi: Effects of Certain Drugs on (‘erebrztl Synapses 497 SIMILARITY OF CHOLINERGIC EXCITATION AND ADRENERGIC INHIBITION AT VARIOUS SYNAPSES ACETYLCHOLINE ATROPINE 0R CURAFIE ANTICHOLINESTERASE TEA EPINEPHRIQJE mnzpmepuamz AMPNETAMINE Epnsonms (-) CORTEX ‘MIDBRAIN (—) ~n£spmnoav (_) CENTER PARASYMPATNETIC GANGLIA (-) svunmznc GANGLIA (_) ”c/ (-I 6.23536: * ----------- 553%? ( - 4 ENHANCEMENT 3' BLOCK ‘I HONOLOGUE OF SVMPATHETIC mcounzn OF ** GANGLION FIGURE an. , _______ (-) INHIBITION CNOLINERGIC EXPERIMENTS 2‘ DEPRESSION EFFECTS IN PROGRESS 1 combinations to form patterns, I believe it of value to study such units, that is, the synapses. The transparent model of the brain of the cat (FIGURE 2) illustrates a relatively simple synaptic* preparation that we have found convenient for study. I must emphasize, at the outset, that we consider the experiment pertinent to the extent that it deals with visual pathways, since the powerful psychotomi— metic drugs exhibit an important Visual component in the hallucinations, dramatically so with mescaline. More important than that, our ﬁndings im— press us with the similarities rather than the differences between synaptic per— formance and susceptibility to chemicals, either endogenous or exogenous (drugs). Therefore, we are really using the transcallosally activated cerebral synapses in the visual area of the cat merely as representative of cerebral synapses in general, all of these synapses having qualitative similarities and varying principally by differences of threshold. We do not intend to suggest that an alteration in this speciﬁc pathway is necessarily responsible for mental disturbanceT A little later I shall outline a general working hypothesis based ‘ “Synapse” is used throughout in the sense of designating the total complex involved the functional arat ticulation of 2 neurons, that is, presynaptic nerve ends, transmission process, postsynaptic dendrites, and soma. ’r Chronic interruption in a system such as the transcallosal. as mentioned by Edward Evarts, should not necessarily be expected to produce the same changes as an acute interruption by drugs unaccompanied by surgical trauma and subsequent degenerative processes. �498 Annals New York Academy of Sciences 93 .5“ .Qaﬁda 05 mm 399% @003 .3235 029533 33. Saginaw Qumozaumqnbv 18:38.35 gobs—Tm wagon? £35 2: we 1:58 “223359 .12.— . .N 35c 5:... ~ A 688.: . �Marrazzi: Effects of Certain Drugs on Cerebral Synapses 499 patterns that results from alteration in amounts of synaptic regulators or in the thresholds of the neurons upon which they act. Since Edward Evarts has already outlined our technique I can be very brief in pointing out certain features. Because the brain is a communication system it seems most appropriate to measure function by recording the handling of a test message. The test message is supplied in the form of a submaximal elec— trical stimulus applied to 1 optic cortex in a cat that has received a. light dosage of pentobarbital sodium. This stimulus initiates a conducted response in the association or transcallosal tract that connects the stimulated point to a sym— metrical point in the contralateral cortex where, after synaptic. transmission, the stimulation evokes a cortical potential, as first described by Curtis and Bard.3 To help distinguish between peripheral effects that would contribute to the afferent drive constituting the background against which the impulses are elicited and the strictly central effects, we take advantage of the fact. that an intracarotid injection will achieve a transient, higher concentration of drug on the ipsilateral or recording side but, when diluted by the blood in the general circulation, the concentration of the drug is brought down to levels that are below the threshold for the peripheral effects. Under the conditions of our experiment, the amounts of the drug passing through the circle of Willis to the other cortex are unimportant. In this way it becomes possible to demonstrate (FIGURE 3) that epinephrine, a chemical natural to the body, one known to produce anxiety when accumu— lated in sufﬁcient amounts, either endogenously or exogenously, also produces cerebral synaptic inhibition, as indicated by the reduction in the signal (surface on a disruption of normal negative wave) corresponding to outflow, while the inﬂow (surface positive wave) is essentially unaltered. The same type of synaptic inhibition is shown for another cerebral neurohumor, norepinephrine, in the next line of the same IOO LIV. IOO ”\4 The cerebral synaptic action of epinephrine and norepinephrine in a 2-neuron intercortical (transcallosal) system. Potentials are evoked in the optic cortex by the electrical stimulation of a symmetrical point m the contralateral cortex. Epinephrine (10 lag/kg.) was injected into the i silateral carotid artery after A. and norepmephrine (150 lug/kg.) was injected after D. A and D are centre 5, B and E represent inhibition, and C and F show recovery. FIGURE 3. �500 Annals New York Academy of Sciences 0-9-? H I HO H0 H I OH H I H -N\ CH3 EPINEPHRINE (dihydroxy-phenyl—ethonol methyl amine) h‘h‘,“ ”'9?" HCH3H AMPHETAMINE (phmyl-isopropyl amine) _*.+ H __'.+ H CHSO MESCALINE (trimethoxy-phenyl-ethyl om'ne) FIGURE 4. Types of phenyLethyl amines producing mental effects. ﬁgure, but this action is evidently weaker than the other, requiring a larger dose to produce approximately the same degree of inhibition. In FIGURES 4 and 5 are shown some structural chemical similarities of compounds with which other contributors to this volume have already dealt. Attention is called to the close structural similarity (FIGURE 4) of epinephrine to amphetamine, which is also capable of producing anxiety, and mescaline, which does so regularly and with dramatic intensity, producing a full-blown “model psychosis.” These drugs in turn are related to the group shown in FIGURE 5, in which epinephrine15 once more presented alongside a ﬁrst— oxida— tion product, adrenochrome, which is an indole. Below these are pictured d- lysergic acid diethylamide (LSD- 25), the very highly potent psychotogen which can be considered to be built on an indole nucleus, and 5- hydroxy— tryptamine, or serotonin The epinephrinelike psychotogens thus can be chemically related to the indolelike ones, including established drugs such as LSD— 25, reputed drugs such as adrenochrome, described at the beginning of this monograph by Humphry Osmond, and by myself elsewhere,2 and the b which is 4“ in the postulated by Woolbrain, naturally occurring indole found ley and Shaw5 to be sufﬁciently related to LSD- 25 possibly either to compete with or to add to its action. We now looked to see whether there was any functional parallelism or neurophysiological correlate of this relationship by using the objective test of cerebral performance afforded by the evoked- potential ac— IS FIGUR126 the that data there an showing the c.at presents in technique tual correspondence111 structure, and that all the compounds produce synaptic �Marrazzi: Effects of ("ertain Drugs on Cerebral Synapses - EH-c-("6"3 no no on 0 ——> 0 501 N has EPINEPHRINE H CON ADRENOCHROME /\ Cat's C2H5 N-CH3 -c-c-NH2 HO N N SEROTONIN D-LYSERGIC ACID DIETHYLAMIDE (LSD-25) FIGURE. 5. inhibition identical in kind to that produced by epinephrine, but vary in degree of effectiveness, so that for the approximately equivalent effects shown it re— quired milligram amounts of mescaline, but only microgram quantities of LSD-25, which duplicates the relative potency of these compounds as found in clinical experience. The dosages used throughout our experiments are inten— tionally of a size selected to produce incomplete actions, so that recovery back‘ to the control level can be secured more readily. Very interesting is the ﬁnding with serotonin, which turns out to be the most effective cerebral synaptic inhibitor of all, being effective in as little as l—ug. doses. Accordingly, rather than being an antagonist, this indole, or something like it, may represent the type of endogenous substance that is instrumental in bringing about some forms of spontaneously occurring mental disturbance. b and is brain48h is in the serotonin since so naturally present Furthermore, highly potent (about 20 to 25 times as potent as epinephrine in the same experiment), serotonin becomes, as we pointed out over a year ago,2 an even better candidate than either epinephrine or norepinephrine, which are also found 6 1" for the role of inhibitory neurohumor.* This ﬁnding would in the brainﬁ‘“ must penetrate the blood-brain barrier at least in the small amounts required to exercise the cerebral action described. ’ Serotonin �Annals New York Academy of Sciences 502 IOO MESCALlNE IOO UV. IOO ’D 100‘: UV. / 4" A A A A '°°” A A SEROTONIN CONTROL MAXIMUM EFFECT RECOVERY FIGURE 6. point even more closely to a derangement of neurohumoral balance at synapses as a potential mechanism of cerebral or mental derangement. Unfortunately, except for the intraventricular injections described by Sherwood,7 there have been, thus far, no documented reports of serotonin—induced mental disturbance* in man that are clearly separable from the natural anxiety initiated by the profound peripheral effects such as circulatory disturbance, other autonomic effects, and emesis. There are, however, such reports for a close analogue of serotonin, dimethyl-serotonin, or bufotenin, which is used for its mental eﬁects by some primitive peoples and has been observed by Fabing8 to produce such disturbances in man experimentally. These 2 subof metabolite epinephrine that well presumed adrenochrome, a as as stances, ‘ The fact that patients with carcinoid have large amounts of circulating serotonin without showing marked has develsym toms of mental derangement could represent an adaptation to very high levels of serotoninofthat such patients ope and accumulated gradually. This suggestion would account for the relative immunity to the possible central effects of high doses of serotonin injected intravenously. �Marrazzi: Effects of Certain Drugs on Cerebral Synapses 503 CONTROL MAXIMUM EFFECT SEROTONIN IO pg RECOVERY nomcwcnmn, N H0 /hCH- /kg. CH 3 CHEN'CH’ ./\N H BUFOTENIN 0= 0: 5 pg /kg MON / N H ADRENOCHROME 2000 pg/kg. FIGURE 7. (‘erebral synaptic inhibition by indoles in a _2-neuron intercortical (transcallosal) system. The potentials evoked in‘the cerebral cortex of the cat by electrical stimulation of the contralateral cortex every 2 seconds. The injections were given in the 1psxlateral common carotid artery. Hoffer, Osmond, and Smythies9 report as reproducing some aspects of the clini— cal syndrome of schizophrenia when injected intravenously in man, are com— pared in the cat in FIGURE 7. Again, all these compounds have the identical qualitative effect, namely, synaptic inhibition, but bufotenin, tested in the same animal, exhibits twice as much effectiveness as does serotonin, which required 10 pg. for its effect on this occasion. Adrenochrome, though it does induce synaptic inhibition, requires so large a dose, 2 mg, that it seems an unlikely candidate for the role of endogenous psychotogen responsible for a form of mental illness, although a substance somewhat like it might be responsible. The great effectiveness of serotonin not only suggests that this is the type of chemical structure implicated, with the reservations already noted, but that it constitutes 1 link, another being its natural occurrence in the brain, in the chain of evidence identifying it as a cerebral neurohumor. A required piece of information to round out this evidence would be the measurement of the actual liberation of serotonin during, or prior to, the recorded synaptic activity. This is a tedious and difficult type of experiment, and it is attended by special handicaps in work on the brain. Another approach leading to a similar conclusion, however, is quite readily followed. This approach is the accumulation of what must be naturally occurring serotonin, strategically located at the synapses, by the poisoning of the enzymes that normally lead to the destruction of serotonin and account for the ready reversibility and short duration of the action of serotonin. This is the technique that has been used so successfully in the study of the function of acetylcholine in the brain, and it is in this manner, by the use of a powerful anticholinesterase, that we demonstrated the presence and operation of acetylcholine at cerebral synapses.1 Serotonin is known to be very susceptible to destruction by monoamine oxidase, which is abundantly �504 Annals New York Academy of Sciences CONTROL EFFECT RECOVERY FIQURE 8. The cerebralsynaptic action of iproniazidin a 2-ncuron intercortical ttranscallosal) system. potentials evoked in the optic cortex of the cat by electrical stimulation of the contralatcral cortex every onds. The iproniazid (S mg./lu;.) was injected into the ipsilateral carotid artery. MAXIMUM The 2 sec- present in the brain.10 We therefore attempted to inhibit. this enzyme by iproniazid (Marsilid). FIGURE 8 shows the result of a preliminary experiment in which we injected iproniazid into the common carotid artery of the cat. in the same way that we had done previously with serotonin. The effect produced duplicated the serotonin effect as if, indeed, the serotonin at the synapse had been preserved by the inhibition of monoamine oxidase by the iproniazid. I believe this ﬁnding offers another piece of important evidence that serotonin is present naturally, not only in the brain, but at strategic sites where it is capable of inﬂuencing synaptic transmission. We have not as yet measured, as we need to do, how much this dose of iproniazid, given in this way, inhibits cerebral monoamine oxidase in the cat. We believe that the somewhat discouraging attitude of some investigators toward basing clinical prediction on animal experimentation is not, entirely justiﬁed, since this procedure is a natural result of the comparison of objective criteria such as we have just described with clinical evaluation based upon questionnaires and much undoubtedly shrewd clinical observation, both of these types of data being very difficult, indeed impossible, to quantitate. Ac— cordingly, we are more impressed by the degree of correspondence obtainable rather than by the discrepancies that are to be found. Thus our evoked-potential experiments in the cat rank the psychotogens and psychotomimetic substances studied so far, in general, in the order of clinical effectiveness, and they suggest that at least part of the mechanism responsible for mental disturbance is to be found in an imbalance in the regulation of synaptic transmission. One such imbalance we have already described. If this hypothesis is truly useful, and if the animal preparation used bears other than a merely empirical relation to the clinical data, we should expect that. the various tranquilizers for which varying degrees of clinical success have been claimed would have some action here also. “'e proceeded to test this extension of our thinking, and we found that all of the several types of tranquilizers are capable, when administered prophylactically to cats, of partially preventing, in the doses used, the cerebral synaptic inhibition of a test dose of mescaline. this reaction, using chlorpromazine ('l‘horazine). 'l‘he figures now read from top to bottom instead of from left to right, as in the previous FIGURE 9 shows �Marrazzi: Effects of Certain Drugs on Cerebral Synapses 505 MESCALNE 2.5mg/kg MESCALINE AFTER CHLORPROMAZINE CHLORPROMAZNE 0.05mg./kq. CONTROL MAﬂMUM EFFECT RECOVERY 60’\. 200 UV. The_prevention of the mescaline effect by chlorpromazine in a 2-neuron_intercortical (transcallosal) system. The potentials evoked in the cerebral cortex ofthe cat by electrlcal stimulation of the contralateral cortex every 2 seconds. The injections were made in the 1psrlateral common carotid artery. FIGURE 9. The ﬁrst column shows the control, the mescaline inhibition at B, and the recovery at C. After this, chlorpromazine is given in doses which, per se, have no apparent effect on synaptic transmission, as shown by the new control D in the second column, but now when mescaline is given again, the synaptic inhibition E is much reduced when compared to B. Without the tranquilizers, the same degree of inhibition of mescaline can be repeated several times in succession, provided that complete recovery is allowed between in— jections. Records G and II show again that this dose of chlorpromazine did not impede synaptic transmission despite the ability of the drug to protect against mescaline. If the dose is increased twentyfold it does have a depressant ﬁgures. MESCALINE A 2.5 mg./kq. MESCALINE AFTER RESERPINE D CONTROL B MAXIMUM EFFECT C RECOVERY n E RESERPINE 0.lmg./kg. G m I The prevention of the mescaline effect by reserpine in a 2-neuron intercortical (transcallosal) system. The potentials evoked in.tlie cerebral cortex of the cat by electrical stimulation of the contralateral cortex every 2 seconds. The anCCtlonS were given in the ipsilateral common carotid artery. FIGURE 10. �506 Annals New York .‘Xcademy of Sciences MESCALINE CONTROL MAXIMUM 2.5m/llq. MESCALINE AFTER FRENOUEL FRENOUEL tqu/kq. m The prevention-of the mescaline effect by It‘renquel in a Z-rieuron intercortical (transcallosal) system. The potentials evoked In the cerebral cortex of the cat by the electrical stimulation of the contralateral cortex every 2 seconds. The unections were given in the ipsilateral common carotid artery. FIGURE 11. action on synaptic transmission. The same prophylactic action is obtained with reserpine (Serpasil), as shown in FIGURE 10, and with azacyclonol (\lt‘renquel), as shown in FIGURE 11. Another point of correspondence with clinical findings is that the margin of safety, in this case the range between the prophy— lactic and the synaptic-depressant, dose, is large, the depressant dose being 15 to 20 times the prophylactic. dose with both chlorpromazine and azacyclonol, but the factor is only 2 with reserpine. The latter drug approximates the action of the barbiturates, which can reduce the degree of demonstrable inhibition from mescaline by reducing synaptic transmission in the ﬁrst place. I feel justiﬁed in saying, then, that the preparation described is pertinent to the clinical situation in that it ranks the psychotomimetic substances in the order of their clinical eli'ectiveness, and that the action of mescaline, the only drug that we have tried so far, is prevented by the tranquilizers. By use of the evoked—potential technique, we have demonstrated that: (1) There exists an equilibrium of neurohumoral control of transmission at cerebral synapses and throughout the nervous system, as far as I have surveyed it, that is susceptible to distortion and imbalance by disturbance in the amounts of chemical regulator or the susceptibility of neurons. (2*) The psychotogens and psychotomimetic substances discussed. structurally and functionally resemble the actions of the fairly well-established inhibitory synaptic neurohumors, epinephrine and norepinephrine, and of sero— tonin, the new one that we have described. (.3) Serotonin or its dimethyl derivative, bufotenin, comes close, even closer than does LSD-25, to representing the type of endogenous psychotogen that might be a natural cause of some forms of mental disturbance. We speculate that such disturbance can be produced by direct perversion of normal patterns of neuronal activity by the undue inﬂuence of synaptic inhibitors or, indirectly, by such inhibitors impeding the ﬂow of impulses from higher controlling centers and releasing the more 1,)rimitive, simpler, and less well—adapted patterns of activity that we call abnormal. �Marrazzi: Effects of Certain Drugs on Cerebral Synapses 507 References 1. MARRAzzr, 118: 367. A. S. 1953. Some indications of cerebral humoral mechanisms. Science. E. R. HART. 1955. Relationship of hallucinogens to adrenergic cerebral neurohumors. Science. 121: 365. 3. CURTIS, H. J. & P. HARD. 1939. lntercortical connection of the corpus callosum. 126: 2. MARRAZZI, A. S. & 473. B. B. CRA\\'F()RD & J. H. GADDUM. 1954. The distribution of substance P and 5—hydroxytryptamine in the central nervous system of the dog. J. Physiol. 126: 596. 4}). PAGE, I. H. 1954. Serotonin (5—hydroxytryptamine). Physiol. Revs. 34: 563. 5. WOOLLEY, D. W. & E. SHAW. 1954. A biochemical and pharmacological suggestion about certain mental disorders. Science. 119: 587. 6. VOGT, M. 1954. The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J. Physiol. 123: 451. 7. SHERWOOD, S. L. 1955. The responses of psychotic patients to intraventricular injections. Proc. Roy. Soc. Med. 48: 855. FABING, H. D. 1955. Personal communication. 99° HOFFER, A., H. OSMOND & J. SMYTHIES. 1954. Schizophrenia: a new approach. II. Result of a year’s research. J. Mental Sci. 100: 29. 10. KOELLE, G. B. & A. DE T. VALK, JR. 1954. Physiological implications of the histochemical localization of monoamine oxidase. J. Physiol. 126: 434. 4a. AMIN, A. H. T., '1‘. �APR 23 ‘959 DEPARTMENT OF EXPERIMENTAL PSYBHMIRY HILLSIDE HOSPITAL GLEN OAKS, N. Y. �PSYCHOTOMIMETICS, CLINICAL AND THEORETICAL CONSIDERATIONS: HARMINE, WIN-2299 AND NALLINE 17%;»4” M :9 HARRY H. PENNES, M. D., PHILADELPHIA, PA., AND PAUL H. HOCH, M. D., NEW Reprinted from AMERICAN JOURNAL OF PSYCHIATRY Vol. 113, No. 10, April, 1957 YORK CITY �PSYCHOTOMIMETICS, CLINICAL AND THEORETICAL 1 WIN-2299 AND CONSIDERATIONS: HARMINE, NALLINE HARRY H. PENNES, M.D.,2 PHILADELPHIA, PA., AND This report describes the clinical effects of 3 psychotomimetics in mental patients. The results will be related to nosological and certain biological aspects of the “model psychoses” in general. The agents are (I) harmine, an alkaloid present in plant prepara— tions ingested by some South American tribes(1) ; (2) Win-2299, a synthetic cholinolytic(2) and (3) N-allylnormorphine (Nalline), a synthetic morphine antagonist (3, 4, 5). MATERIAL AND METHODS Single dosages of the drugs were given to 32 voluntary, physically normal mental patients, at the New York State Psychiatric Institute; 29 were in the 18-35 year age range; 19 were males and I 3 females. Twenty-two were schizophrenics of the pseudoneurotic and other nondeteriorated types, with only the primary symptoms of the disorder. Five additional schizophrenics had auditory hallucinations or delusions be— fore the drugs. The remaining 5 subjects had severe psychoneuroses or recurrent depressions. No patient had clouding of consciousness. Each drug was given about 9: 00 and breakfast after a 48-hour light a am, medication-free period. Examination by the authors and nurses were made for the remainder of the day in a shaded private room and also in the succeeding 72 hours. No patients were informed of the probable effects of the procedures. Most subjects showed excellent cooperation in reporting drug effects. In most cases, each patient received one drug of the 3 tested, but some received different doses of harmine on differRead at the 112th annual meeting of The American Psychiatric Association, Chicago, Ill., April 30May 4, 1956. 2 Director of Clinical Research, Eastern Pennsylvania Psychiatric Institute, Philadelphia, Pa. 3 Commissioner of Mental Hygiene, New York State. The actual study was performed at the New York Psychiatric Institute, New York, Department of Experimental Psychiatry. 1 PAUL H. HOCH, M. D.,3 NEW YORK CITY ent days. Each drug was given in salt form but for brevity will be referred to as the base. RESULTS GENERAL Since the new manifestations under the drugs were not present in the pre-administration period, they were clearly distinguishable from the patients’ baseline symptoms. At low dosage, each drug produced slight drowsiness, either with or without other symptoms. With medium or high dosage, the reactions qualitatively resembled those in a former series of similar subjects who received mescaline or LSD(6, 7, 8). Thus, diffuse alterations usually occurred in many realms—autonomic, motor, perceptual, emotional, intellectual, and be— havioral. Unlike mescaline or LSD (cf. Discussion for dosages), the present drugs regularly elicited some degree of clouding of consciousness in addition to the preceding changes. The characteristic reaction at medium or high dosage was a semidelirioid or confusional state with intermittent drowsiness or sleep. The confusional periods were cyclic. Their intensity and time of occurrence correlated only partly with drowsiness or sleep. Major symptoms were impairment of contact, attention, grasp, responsiveness, and concentration, with general “dreamy” or twilight quality. Full delirioid reactions occurred in 2 subjects at the highest dosages of 2 drugs (Win-2299, Nalline). Most subjects had intermittent amnesia during the reaction itself but were able to provide adequate descriptions of the major events. A spotty defect in recall was usually present in the 72-hour follow-up period. Visual hallucinations (cf. Discussion for alternative terminology) occurred at medium or high dosage with all 3 drugs. Subjects were easily roused after the onset of drowsiness or sleep and reported some of the hallucinations that had occurred in the “dream887 �888 CONSIDERATIONS OF PSYCHOTOMIMETICS ing” state. In all cases, the hallucinations occurred only with eyes closed and disappeared promptly when the eyes were opened. Hallucinations other than visual were infre— quent. Perceptual distortions of body and environment were moderately frequent. Neurological changes included varying degrees of subjective vertigo, light—headedness, subjective and objective ataxia, and sluggish speech. Like mescaline and LSD, these drugs produce a variable degree of intensiﬁcation of different types of baseline symptoms. Harmine also occasionally produced a shallow euphoria. Nalline often produced relaxation of rather marked degree. After a few initial hours of peak intensity, reac— tions usually subsided gradually between the fourth to eighth hours, often with ﬂuctuations in degree before complete remission. No subject reported effects after 24 hours except for minor, nonspeciﬁc “hangover” feelings. INDIVIDUAL DRUGS Harmine.——Turner, Merlis, and Carl have recently pointed out that the alleged hallucinogenic activity of pure harmine is a complicated issue on the basis of the previous literature on crude plant extracts(9). The threshold hallucinogenic dose of the pure drug in the present study ranged from I 50.0— 200.0 mgm. intravenously. With this route, 5 of 11 subjects reported visual hallucinations of varying degrees of complexity and organization. Bradycardia and hypotension occurred with all doses of intravenous harmine despite a 20- to 30-minute injection time, thereby limiting maximum dosage to 300.0 mgm. Average maximum changes were a pulse rate of 18 beats per minute and systolic blood pressure fall of 16 mm. mertermi— in was one subject Injection cury. nated at 210.0 mgm. because pulse rate dropped from 82 to 48 per minute and blood pressure from 118/78 to 88/60. Recovery occurred in about 30 minutes. The drug was not hallucinogenic by the oral or subcuta— neous routes. However, ingestion of crude plant extracts by natives does produce visual hallucinations according to ﬁeld observations(10, 11, 12). In an experimental study by Cardenas(13), normal subjects also reported visual hallucinations and other effects [Apr. noted here, after ingestion of an aqueous solution of yahé (Banisteria caapi, a source of harmine). Visual hallucinations might have occurred in the present study with higher oral (loses, the maximum oral amount (960.0 mgm.) being 4.8-6.4 times greater than the intravenous threshold hallucinogenic amount (150.0-200.o mgm.). The amounts of harmine taken orally under ﬁeld conditions and in Cardenas’ study are unknown, precluding comparison with the present study. Further analysis of the hallucinogenic activity of harmine is complicated by nu— merous botanical and chemical considerations(1, 10, 11, 14). Additional reactions to harmine which occurred frequently were: nausea and vomit— ing; slow, coarse, spontaneous tremor of the extremities of an “extrapyramidal” appear— ance; humming and buzzing noises (no voices); “waviness” of the environment; “sinking” sensations of the body; subjective sense of body vibration; and subject numb— ness, accompanied by objective evidence of reduced sensitivity to light touch and pinprick. These reactions, plus all the preceding, occurred in almost every patient with the intravenous route; and (except for hallucinations) some occurred with oral dosages higher than the threshold of 3000-4000 mgm. The reactions were generally more intense by the former route. Win-2299.—The mental effects of Win2299 in man have apparently not been described previously. The 2 subjects receiving 2.0 mgm. had the sedative effect. One of these subjects in addition became “hypersensitive” to light and sound, and spots on the wall moved and changed form. At the 6.0 mgm. level, all 4 subjects had severe mescaline- or LSD-like reactions plus a confusional state of moderate degree. These mescaline-like effects included bizarre perceptual distortions of soma and environment, unreality feelings, and synesthesias in one case. The single subject at 10.0 mgm. had a full delirioid episode with complete loss of contact, disorientation for time, place, and person, and responses to complex, organized visual and auditory hallucinations. This reaction occurred in brief but cyclic episodes; partial contact and lucidity were restored after persistent comments and questions. �I957] HARRY H. PENNES AND PAUL H. HOCH Most subjects had a moderate degree of mydriasis; blood pressure and pulse rate changes were insigniﬁcant. Nall-ine.—The results with Nalline in the main conﬁrmed previous observations of others in different types of subjects, includ— ing normals( 3, 4, 5). Past and present ﬁndings included varying degrees of relaxation or euphoria, anxiety and dysphoria, miosis, nausea, drowsiness and sleep, thought disturbances, feelings of heaviness or lightness of limbs, and visual hallucinations. In the present series, visual hallucinations occurred in the single subject receiving 10.0 mgm., in 7 of 8 at 20.0 mgm., and in 2 of 3 at 30.0 mgm. In 4 cases (and in 2 with harmine) the hallucinations were Lilliputian in type, a not infrequent feature of acute toxic psychoses in general. So far as can be judged from the literature, a possible major difference from previous observations consisted in the occurrence of frank mescaline-like or delirioid reactions. At 20.0 mgm, 3 subjects had typical diffuse, bizarre per— ceptual disturbances, severe unreality feelings, and other signs of psychic disorganization. At 30.0 mgm., a similar reaction occurred including auditory hallucinations and synesthesias. In another subject at this dose the effect was overtly delirioid, with a strong resemblance to the Win—2299 toxic psychosis previously described. The intravenous route probably accounts in part for the appearance of these reactions, since previous reporters of the mental effects of Nalline have used the subcutaneous route, usually at dosages of 10.0-15.0 mgm. and sometimes higher( 3, 4, 5). DISCUSSION Relatively high doses of harmine by the intravenous route were required to produce the full psychotomimetic effect with visual hallucinations. The same was probably true of Nalline. It is conventionally stated that acute toxic psychoses occur in apparently normal individuals after high dosages of various other drugs, for example, atropine and cocaine(I5). There is a dearth of precise data on the number of such drugs, dosages required, and regularity of effects. However, not all drugs in relatively high dosage produce the diffusely abnormal men- 889 tal changes which are the criteria of psychotomimetic action. For example, clinical differentiation may be made between a confusional-hallucinatory state and a simple, progressive depression of level of consciousness elicited by narcotics and other agents. High dosage alone would therefore not preclude the classiﬁcation of the present or other drugs as psychotomimetic in a selective or speciﬁc sense. Transient cerebral anoxia could have resulted from the hypo— tension and bradycardia with intravenous harmine or a respiratory depressant action of Nalline, which has been reported at dosages used in this study(3, 5). The ﬂorid and diffuse reactions elicited by these 2 drugs would certainly not appear to be characteristic of those in cerebral anoxia. In addition, the circulatory effects of harmine usually disappeared about 20 minutes after termination of injection, whereas the mental re— actions lasted at least several hours at peak intensity. Harmine, Win—2299, and Nalline fundamentally produced an acute organic reaction type, because of the basic mental clouding and confusional effects. Harmine and Nal— line each produced mental clouding together with systemic toxicity (cf. above) ; on the other hand LSD and mescaline elicit neither clouding or toxicity in major form within a certain dosage range. However, Win-2299 did not display this association of the 2 effects, since severe mental clouding occurred without obvious systemic toxicity. It is possible that confusional aspects may be more prominent for a given agent whose threshold psychotomimetic dosage is high relative to threshold dosage for any effect. Quantitative data relevant to this proposition are lacking for any psychotomimetic but are obtainable in principle. It is very probable, however, that absolute dosage thresholds for psychotomimetic activity correlate poorly with mental clouding. In ascending order, these dosages are very approximately: LSD (oral or intravenous) under 100 micrograms; Win—2299 (oral) and Nalline (subcutaneous or intravenous) 55.0-20.0 mgm.; harmine (intravenous) and mescaline (oral or intravenous) over 100.0 mgm. LSD and mescaline are at opposite extremes of an enormous absolute dosage range, and produce �89o CONSIDERATIONS OF PSYCHOTOMIMETICS practcially no clouding whereas the 3 intermediate agents elicit frank clouding at near threshold. There is evidence, however, that LSD and mescaline may produce clouding of consciousness at dosages well above threshold. Pennes has previously reported a sedative effect of LSD in 26.0% of a series of schizophrenics(8). The drug less occasionally (about 10.0% of cases) produced a confusional state(7). MacDonald and Galvin more recently reported a 58.0% incidence of mental clouding and confusion after LSD in 50 subjects. The psychotic subjects in their series apparently received the drug in dosages (per kilogram of body weight) up to 6.0 micrograms as compared with 1.0-2.0 micrograms orally in Pennes’ series(16). Mescaline sulfate (4oo.o—6oo.o mgm., intravenously) often produces slight drowsiness throughout the entire reaction and occasional confusional states(7). There may be an underlying similarity for all the drugs under discussion in the relationship of the visual hallucinogenic response to visual restriction and hypnagogic mechanisms. First, it will be recalled that visual hallucinations with the present drugs always disappeared when the eyes were opened. Wikler noted the same in post-addicts under mescaline(4). The authors have not noted this effect in frank form with either mescaline or LSD but have occasionally observed that hallucinations are reported as less distinct and vivid when the eyes are opened. Darkening of the room does initiate or intensify visual hallucinations with eyes open under mescaline or LSD. If eye closure and reduction of intensity of external light affect drug-induced hallucinations by the same mechanism, then the difference with respect to this mechanism may therefore be negligible between the present drugs and LSD. Such a mechanism may be related to that presumably operative in hallucinations and other mental disturbances recently reported as occurring with generalized restriction of sensory input(17). Secondly, the abnormal visual phenomena with the present drugs are probably best categorized as hypnagogic hallucinations or even more broadly as hypnagogic imagery or visions. This term is used because of the [Apr. invariable drowsiness (cf. Results, General) ; disappearance on eye opening is also consistent with the hypnagogic quality of the response. According to Ardis and McKellar, spontaneous visual hypnagogic images in normals are usually experienced in the drowsy state and with eyes closed. These authors also found strong resemblances in detail between mescaline visual hallucinations and normal visual hypnagogic imagery (18). Previous workers with Nalline have variously used the terms visual hallucinations, day-dreaming, vivid visual fantasies in a dreamy state, or nightmares. The apparent differences between the present drugs and mescaline or LSD may therefore be quantitative rather than qualitative. The conclusion would be that mescaline and LSD may also basically produce an organic reaction type. It is a familiar ob— servation that the visual hallucinations which are so characteristic of the drugs under consideration are relatively infrequent in chronic schizophrenia. These considerations obviously do not preclude various possible relationships between psychotomimetics and a possible endogeneous “toxic factor” or metabolic disturbance in the “functional” psychoses. Hoch and Wikler have recently and independently summarized the other implications of the drugs and the “model” psychoses for experimental psychiatry(19, 20). The indole nucleus, alleged to be speciﬁc for psychotomimetic activity(2I), is absent in mescaline, Win-2299, and Nalline. How— ever, with the exception of mescaline, the remaining 4 psychotomimetics contain a tertiary nitrogen grouping (2 in LSD). Since these compounds are otherwise grossly dissimilar in molecular conﬁguration (ﬁg. I), the entire structure undoubtedly has to be taken into account. Despite this well-known factor and the very small series of drugs, there are certain indications that the tertiary nitrogen grouping may contribute to psychotomimetic activity. In brief, some of the evidence relates to effects of apparently minor changes in the LSD molecule, effects of quaternization of VVin-2299 on its CNS potency(2), and comparison of the actions of serotonin with those of its tertiary amine derivative, bufotenine(22). However, in ad— dition to mescaline, the literature reports �HARRY H. PENNES AND PAUL H. HOCH I957] 891 other psychotomimetics without the tertiary nitrogen groupings: marijhuana, which is n0n-nitr0geneous(9) and 3,4,5-trimethoxy— amphetamine, a mescaline derivative(23). 9 W: "5 Some types of centrally acting drugs other OCH3 \ c2 “5 than psychotomimetics also possess the terFuther of OCH: analysis grouping. tiary nitrogen IE SCALINE on, these relationships will be presented elsewhere(24). There is no apparent common neurophar— macological basis for the psychotomimetic action in general and for harmine, Win—2299, and Nalline in particular(2, 5, 25). Win2299 is qualitatively similar to atropine in animals by virtue of its peripheral cholinolytic and central actions(2). The mechanism of production of abnormal mental effects ‘HCL HO- 0" C- 0' CH2. CH2- / similar be both for N\ drugs, Win—2299 apmay \°2"5 parently having a lower threshold dosage. 2299 (2 2 to recent speculations, some psy— According —-— chotomimetics may produce their effects as antagonists of cerebral serotonin(26, 27'). N-CH20H=CM2 The mental effects of oral LSD and intravenous harmine (both indoles and peripheral antiserotonins) differ in many respects (Results, General and Harmine) . The difference in route of administration is not a factor in 0n View of the ﬁnding of Hoch that oral and 0 "CL ' intravenous LSD have the same qualitative effects(28). However, differences in relative Structures of Some Psychotomimetics. levels contribute the to dosage apparent may FIG. I.—Harmine was supplied in 2 forms: as the base isolated from Banisteria caapi(I) and as the dissimilarities between the 2 drugs. c—N CH35 \ \ HARMINE NH LYSERGIC ACID DIETHVLAMDE C2 H5 6- D5 WIN- DIETHYLAMINOETHYL GLYCOLATE CH N CYCLOPENTYL THI‘ENVL) HYDROCHLORIDE G“ CH2 H ALLYLNOHMCRPHINE synthetically-prepared HCl-zHaO. The following dosages refer to hydrochloride form in each case. Harmine: oral, II patients, zoo-960.0 mgm.; subcutaneous, 6 subjects, 40.0-70.0 mgm.; and intravenous, II patients, 100.0-3oo.0 mgm. Win-2299 tablets: 7 patients, 2.0-I0.0 mgm. Nalline: intravenous, 12 subjects, 10.0-30.0 mgm. Intravenous harmine and Nalline were injected over a 20-30 minute period. Mescaline and lysergic acid diethylamide (LSD) were not given in this study. LSD and harmine contain the indole nucleus whereas the remainder do not. The tertiary nitrogen grouping is present in LSD (both in aliphatic chain and cyclic constituent), harmine (non-indole member), Win-2299 (aliphatic side chain), and Nalline (linking allyl side chain with ring member). Cf. Discussion. Both forms of harmine were supplied as the dry compound by Dr. K. K. Chen, Eli Lilly Laboratories, Indianapolis, Indiana. For parenteral administration, solutions in pyrogen-free distilled water, 20 cms.,3 were used several hours after autoclaving. Win-2299 was supplied by Sterling-Winthrop Research Institute, Rensselaer, N. Y., as the racemic mixture of the hydrochloride salt. Nalline was supplied by Merck and Co., Rahway, New Jersey, N- SUMMARY Harmine, Win-2299, and Nalline in single dosage produce many new mental effects in schizophrenics grossly similar to those elicited by mescaline and LSD. Many of the same effects are reported in normals after harmine and Nalline (other workers). Unlike mescaline and LSD at usual dosage levels, the present psychotomimetics regularly produce drowsiness and sleep along with the aberrant mental effects. The resultant state is partly that of “hypnagogic” visual hallucinations or imagery. The results with increased dosage suggest that the basic Allylnormorphine HC1= Nalline HCI; ampoules of distilled, pyrogen-free water containing sodium bisulfate, 0.2% and sodium citrate, dihydrate 1.5%. For intravenous administration, ampoule contents were diluted up to 20.0 cms.3 with pyrogen-free distilled water. �892 CONSIDERATIONS OF PSYCHOTOMIMETICS effect of these agents is to produce an acute toxic reaction type. The difference between them and mescaline or LSD with respect to clouding of consciousness and certain aspects of the hallucinogenic response may be quantitative rather than qualitative. The indole nucleus is not necessary in the structure of psychotomimetics since Win-2299 and Nalline are non-indoles. The tertiary nitrogen grouping may contribute to certain aspects of psychotomimetic action. BIBLIOGRAPHY 1. Chen, A. L., and Chen, K. K. Quart. J. Pharm. Pharmacol., 12:30, 1939. 2. Luduena, F. P., and Lands, A. M. J. Pharm. Exper. Therap., 110:282, 1954. 3. Wikler, A., Fraser, H. F., and Isbell, H. J. Pharm. Exper. Therap., 109: 8, 1953. 4. Wikler, A. J. Nerv. Ment. Dis., 120: 157-175, I954. Lasagna, L., and Beecher, H. K. The Analgesic Effectiveness of Nalorphine and NalorphineMorphine Combinations in Man. J. Pharm. Exper. Therap., 112: 3 56-363, 1954. 6. Hoch, P. H., Cattell, J. P., and Pennes, H. H. Am. J. Psychiat., 108: 579, 1952. 7. Hoch, P. H., Pennes, H., and Cattell, J. P. Proc. Assn. Res. Nerv. Ment. Dis., 32: 287, 1952. 8. Pennes, H. H. J. Nerv. Ment. Dis., 119:95, 5. 1954- 9. Turner, W. J., Merlis, S., and Carl A. Am. J. Psychiat., 112:466, 1955. Perrot, Em, Raymond-Hammett. Bull. Sci. Pharmacol., 34: 337; 417; 500, 1927. 10. 11. 1941. 12. 195513. [Apr. Iberico, C. C. Bol. mus. Hist. Nat., 5:313, Schultes, R. E. Natural History, 64: 120, Cardenas, G. F. Estudio Sobre el Principio Activo del Yagé. Thesis, Universidad Nacional, Facultuaa de Medicina y Ciencias Naturales, Bogota, 1923. 14. Albarracin, L. Contribucion al estudio de los Alcaloides de Yagé. Thesis, Bogota, 1925. 15. Goodman, L., and Gilman, A. Pharmacological Basis of Therapeutics. 2d Ed. New York: MacMillan, 1955. 16. MacDonald, J. M., and Galvin, J. A. V. Am. J. Psychiat., 112:970, 1956. 17. Bexton, W. H., Heron, W., and Scott, T. H. Canad. J. Psychol., 8:70, 1954. 18. Ardis, J. A., and McKellar, P. J. Ment. Sci., 102:22, 1956. 19. Hoch, P. H. Am. J. Psychiat., 111:787, I95520. Wikler, A. Am. J. Psychiat., 112 : 961, 1956. 21. Hoffer, A., Osmond, H., and Smythies, J. J. Ment. Sci., 100: 29, 1954. 22. Fabing, H. D., and Hawkins, J. R. Science, 123: 886, 1956. 23. Peretz, D. I., Smythies, J. R., and Gibson, W. J. Ment. Sci., 101 : 317, 1955. 24. Pennes, H. H. In preparation. 25. Gunn, J. A. Arch. Internat. de Pharmacodynam.. 50 : 379, 1935. 26. Gaddum, J. H. Drugs Antagonistic to 5- Hydroxytryptamine. Ciba Foundation Symposium: Hypertension. pp. 75-77, London, 1953. 27. Wooley, D. W., and Shaw, E. Proc. Natl. Acad. Sci., U. 5., 40: 228, 1954. 28. Hoch, P. H. Studies in Routes of Adminis— tration and Counteracting Drugs. Lysergic Acid Diethylamide and Mescaline in Experimental Psy— chiatry. New York: Grune & Stratton, 1956. ��Psychiatria et Neurologia Internationale Monatssehrltt tiir Psychiatrie und Neurologie Revue Internationale Mensuelle de Psychiatrie et de Neurologie International Monthly Review at Psychiatry and Neurology Editor: J. KLAESI, SchloB Knonau Redactor: E. GRUNTHAL, Bern S. KARGER Basel (Schweiz) New York Printed in Switzerland Vol. 135. No. 4/5, 1958 Separatum Sal-Hulda, 11.; Brunecker, G. 11nd Szdra, SL: Psychiat. Neurol., Basel 135: 285—301 (1958) Aus dem Staatl. Zentralen Neurologisch-Psychiatrischen Institut in Budapest (Frau Dr. M. Gimes) Dimethyltryptamin: ein neues Psychotieum Von A. SAI-HALASZ, G. BRUNECKER und ST. SZARA Einleitung Die ohere Stufe des Entwicklungsprozesses der Fachwissenschaften, die sogenannte experimentelle Stufe, beginnt die Psychiatrie fast als letzte der medizinjschen Féicher nur neuerdings zu erreichen. Den wirklichen Anfang bedeutet Beringers Monographie ﬁber Meskalin [1927], mit welcher zu gleicher Zeit die HaschischBeobachtungen von Frdnkel und Joel erschienen. Den zweiten groBen Fortschritt auf diesem Gebiet bildete die Entdeckung der Lysergséiurediéithylamid (LSD 25) durch Stall und Hoﬁmann [1943]. Der erste ausfiihrh'che Bericht Stalls [1947] bedeutete den Anfang einer groBen Anzahl von Publikationen. Das Ziel dieses Artikels ist die Bekanntgabe eines neuen Psychotikums bzw. dessen Wirkung auf normale Personen. Die Bewohner Haitis benutzten schon seit J ahrhunderten bei religiﬁsen Festen ein narkotisch wirkendes Schnupfpulver, das «Cohoba» genannt wurde. Mit Hilfe dieses Mittels konnten sie angeblich mit ihren «helfenden Geistern» in Verbindung treten, sogar auch von diesen Ratschlﬁgen erhalten. Das «Cohoba» wurde aus der Frucht der Piptadenia Peregrina gewonnen und enthjelt unter anderen Alkaloiden auch verhéiltnisméiﬁig groBe Mengen Bufotenin und N-N-Dimethyltryptamin (DMT), wie dies auch von Stromberg und Fish et al. bewiesen wurde. Bufotenin und DMT sind beide Indolamine und in naher Verwandtschaft mit dem biologisch hﬁchst aktiven Serotonin: �Sai-Halész, Brunecker und Széra 286 {\/\NH) /\——-—-—CH2—CH2—NH2 0H II |' OH A— 1 n —CH2—CH2—N/CH3 :1 \/\NH/ \cm. Bufotenin Serotonin /CH3 /\————CH2—CH2—N \CH3 b“ J \ \NH N-N-Dimethyltryptamin Bufotenin ist daher ein N-Dimethyl-Derivat des Serotonins, beim DMT fehlt jedoch vorigem gegenﬁber eine 5-OH-Wurzel. Das Bufotenin isolierte Handovski aus der Haut von Kroten [1920], Wieland hat es synthetisch hergestellt. Raymond Hamet gab Hunden intravenos Bufotenin und stellte voriibergehende BlutdrucksteigeAﬂ'en intravenos fest. gréBere Evarts, Tachypnoe Apnoe, spiter rung, Dosen Bufotenin und LSD-25 verabreichend, stellte bei jenen eine beinahe identische Wirkung der zwei Chemikalien fest: voriibergehende Erblindung, Ataxie und ein Zahmwerden. Er erklﬁrte dies alles durch eine Hemmung der sensiblen Reiziibertragung. Evarts nahm die Wirkung des Bufotenins und LSD-25 als Analog des Serotonins an. Nach Fabing ist Bufotenin ein in der Natur weitverbreitet vorkommendes halluzinogenes Indolderivat, dessen eine Hauptquelle die sogenannten Amanita-Pilzarten bilden. Fabing experimentierte an jungen, intelligenten Verurteilten: er injizierte intravent‘is wéihrend 3 Minuten Bufotenin. Es traten Erroten, Gesichtsperspiration und Kribbelgefiihl im ganzen Korper sowie Oppression in der Brust auf. Die Versuchspersonen sahen einige Minuten lang purpurne Flecke, die Storung der Raumwahrnehmung und Konzentration, daneben Depersonalisationsgefiihl und psychomotorische Unruhe dauerten fort. Bei groﬁeren Dosen war Erbrechen, Nystagmus und Mydriasis zu beobachten, deshalb hielt Fabing das Mittelhirn zum Teil als Angriﬂ'spunkt des Bufotenins. Die kardiovaskulﬁre Wirkung des Mittels war verhiiltnisméiBig gering. Die Versuchspersonen berichteten wéihrend 6 Stunden nach der Injektion iiber angenehmes Relaxationsgefiihl. �Dimethyltryptamin: ein neues Psychoticum 287 Material und Methode Unseres Wissens nach wurde die Wirkung des DMT am Menschen zuerst durch uns gepriift. Das DMT wurde von uns selbst synthetisiert nach der von Speeter und Anthony angegebenen Methode. Die salzsﬁurige Losung wurde als Injektion angewandt: die wirksame Dose war 0,7—1,0 mg/kg intramuskuléir, meistens gebrauchten Wir 0,8 mg/kg. DMT wurde an 30 normalen Personen, meistens Arzten, gepriift (I7 Manner, 13 Frauen; Alter zwischen 20 und 42 J ahren). Jede Versuchsperson wurde vorerst somatisch untersucht, und nur jene erhielten DMT, die vollkommen gesund waren und keine starkere vegetative Labilitéit zeigten. Auf den Blutdruck wurde sehr geachtet, da das DMT leicht starke Hypertonie erzeugen kann. I6 Versuchspersonen wurden vor und wéihrend des Versuches mit Rorschach untersucht. (Auf dessen Ergebnisse gehen wir hier nicht ein, da einer von uns1 auf dem III. Internationalen RorschachkongreB in Rom 1956 iiber diese berichtete.) Wﬁhrend dem Versuch wurden parallel zwei Protokolle aufgenommen und die Versuchs2—3 Tagen die subjektiven Erlebnisse nach aufgefordert, personen aufzuzeichnen; die Protokolle wurden dann durch diese Aufzeich5 Fallen wurde wiihrend des Experimentes EEG In ergéinzt. nungen durchgefiihrt. (Bisher noch nicht veroﬂ'entlicht.) Ergebnisse Schon nach 3—5 Minuten nach der Injizierung fﬁngt das DMT zu wirken an, und innerhalb einer Stunde léiuft die ganze experimentelle Psychose ab. Die Wirkung ist plotzlich und intensiv, mehrere Versuchspersonen berichten anfangs V011 einem weltuntergangsé‘thnlichen Erlebnis mit Starker Todesangst. In einigen Fillen war jedoch die Angst nicht so ausgepréigt, und die éiuBerst intensiven Illusionen und Halluzinationen fesselten die Aufmerksamkeit. Die Angstperioden wechselten mit solchen Starker Euphoric ab. Wéihrend des ganzen Versuches war das wellenartige Auftreten bzw. die Intensitﬁtsschwankung der gesamten pathologischen Phéinomene sehr charakteristisch. Wahrnehmungsstﬁrungen bzw. solche des Korperschemas, Depersonalisationserscheinungen, extrapyramidale Hyperkynesien, objektive Reﬂex- und Sensibilitﬁtsstﬁrungen fﬁrbten oft das Bild. Natiirlich waren bei den Versuchen auch die kultu1 A. S.-H. �288 Sai-Halész, Brunecker und Széra rellen und Pers6nlichkeitsunterschiede bemerkbar. Bevor wir die einzelnen Symptome naher betrachten, geben wir hier einige typische Protokolle wﬁrtlich wieder: Dr. J.N., Arzt, 28 Jahre. 10. 5. 1956. 50 mg DMT i.m. P.: 78/Min., RR 130/100 Hgmm. 3! Starker Schwindel und Kribbeln im ganzen Kiirper; hauptsiichlich sind die Lippen gefﬁhllos-eingeschlafen. 4/ «Alles ist glﬁnzender, die ganze Welt ist bedeutend heller.» 5/ «Als ob meine Stimme aus einer tieferen Kehle kﬁme. Das Zimmer ist gespensterhaft. Mir schwindelt. Ich amﬁsiere mich darﬁber, wie Ihr mich belauert.» «Ach, wie herrlich sind die Far-hen!» Er lacht und spricht andauernd. (Zwangslachen, Logorrhoea.) Maximal erweiterte Pupillen. RR: 160/120 Hgmm, P: 88/Min. Rhythmische Bewegung des linken FuBes. «Ach, neue Welle! Die Bilder kommen in solchen Mengen, daB ich gar nicht weiB, was ich mit ihnen anfangen soll! Zuvor waren sie noch angenehm, doch jetzt ist es schon zu viel!» Er lacht wiederum auf. «Alles ist so komisch. Die Farben leuchten ganz fantastisch. Die Gesichter sind auch ganz anders. Warum beobachtet Ihr mich so verdachtig ? » 10' «Ich sehe eine Farbenorgie, doch in mehreren Schichten nacheinander. Die Welt bewegt sich immer mehr.» 11' Er schmunzelt, spricht inkohéirent, bewegt sich viel und gestikuliert lebhaft. RR: 165/120 Hgmm. P: 88/Min. Er klagt ﬁber Dyspnoe. 12' «Ich fiihle in meinem Bauch Leere und trotzdem Fﬁlle, dorthin hat sich alles Schlechte verzogen.» «Hoﬂ'entlich kommt es nicht wieder.» «Man sieht seltsame Sachen, und trotzdem ist alles schnell vorﬁber, so wie auf der Wellenbahn.» «Die Wand bewegt sich auch, marchenﬁlmhaft. Ich fﬁhle mich ganz so, als ob ich geﬂogen ware.» RR: 155/120 Hgmm. P: 88/Min. Assoziationen aufgelockert, sucht nach Ausdriicken. Keine Dyspnoe. «Das Zimmer beginnt seine normale Form wieder zurﬁckzugewinnen! Nein, doch nicht . . . » Er setzt sich auf und sieht zum Fenster hinaus. «Nur wenn ich hinausschaue, fﬁhle ich, daB ich auf der Erde bin. Mir ist, als oh wir bis jetzt geﬂogen wﬁren! » «Ich habe das Gefﬁhl, daB dies ﬁber allem ist, ﬁber der Erde. Es ist beruhigend, zu wissen, daB ich wieder auf der Erde bin.» Pupillen noch maximal erweitert. RR: 145/110 Hgmm, P: 84/Min. Bewegt sich andauernd, gestikuliert viel. Sprache ist ﬁfters inkoh'arent, kaum verfolgbar. «Ich habe inneres Zittern, meine Gefﬁhle kann ich nicht gut ausdrﬁcken. Ich fﬁhle mich so, als ob ich hetrunken ware.» Er zittert. «Dieses Zittern ist gar nicht so unangenehm, es bedeutet, daB die Reise zu Ende ist, aber alles ist noch nicht vorﬁber.» Rhythmische Zuckungen des linken FuBes. «Jeder Anwesende hat gleichmiiBig gelbe Zﬁhne.» �Dimethyltryptamin: ein neues Psychoticum 289 28' «Alles hat einen ﬁberirdischen Stich und ist doch so real. Schade, daB alles in einem geschlossenen Zimmer geschieht. Mir scheint, daB ich zusammen mit dem Zimmer ﬂiege. Erlebnis der Reise. . .» Pupillen miiBig erweitert. RR: 140/100 Hgmm, P: 80/Min. «J etzt habe ich schon das Gefiihl, daB alles vorbei ist.» Ziindet sich eine Zigarette an. Die ZigaIette sieht er grﬁBer und umfangreicher. «Ich habe das Gefiihl, als oh ich lande. Die gehobene Stimmung léiBt nach.» Assoziationen noch immer gelockert. Hort in der Mitte angefangener Séitze auf, vergiBt was er sagen wollte, spricht iiber anderes. «Alles scheint gelb zu sein, hauptsﬁchlich die Schatten. Ich weiB, daB dieser Zustand aufhéirt, und doch. fiirchte ich mich, daB er weiterbesteht.» «Ich bin so nervos, als ob ich ﬁebrig wire. Es ist beruhigend, daB ich dauernd bei BewuBtsein war.» Klagt ﬁber Miidigkeit. «Alles ist voriiber, nur meine Gedanken schwirren durcheinander.» «Alles ist grau und farblos. Die Welt ist jetzt ganz ode.» AuBer leichter Miidigkeit beschwerdenfrei. Assoziation schon normal. «Ich hatte stets das Gefiihl, daB sich nur die AuBenwelt und nicht ich selhst mich verwandelte.» Dr. Z.J., Arzt, 30 Jahre. 1. 6. 1956. 60 mg DMT i.m. P: 72/Min., RR: 110/70 Hgmm (linkshﬁndig). 5' Er fiihlt sich ein wenig schwach. «Kollapsartiges Gefiihl.» 6' Ausgesprochenes Schwindelgefiihl. 7' RR: 130/90 Hgmm, P: 84/Min. Pupillen etwas erweitert. 8' Schwache Dyspnoe. «Das ganze ist eher angenehm.» 9' «Die Farben sind unveréindert. Mir schwindelt sehr. Leider geht es mir auch so mit dem Alkohol: mir schwindelt, ohne daB ich mich wohl fiihle.» 10' «Ich habe einen beklemmenden Druck auf der Brust, aber es kommt mir vor, daB ich auch ohne Luft existieren konne.» 11’ «Das silherne Muster der rechten Wand des Zimmers ist ganz reliefartig. Das Beklemmungsgefiihl nimmt ab.» 12' RR: 135/80, P: 88/Min. Rechter Patellarreﬂex verstﬁrkt, rechtsseitig Babinski13' 14’ 15’ 16' 17' 18' 19' Tendenz. «Die Gesichter haben sich veréindert, sind ganz mephistoéihnlich geworden.» «Uberall dominiert die silberne Farbe! Die Gesichter sind auch aus Silber und teuflisch. Die silberne Farbe ist schon, nur ein wenig furchterregend.» «Der eine Gummischlauch des Blutdruck-MeBapparates ist violett, der andere silbern.» (In Wirklichkeit schwarz.) «Die Gesichter sind asymmetrisch wie im Kino. Alles verandert sich im Raum, auch die Gesichter und Gegenstéinde.» RR 130/85 Hgmm, P: 88/Min. Reﬂexdiﬁerem der unteren Extremitiiten ist auch weiterhin vorhanden. «1111' schwebt alle im Raum. Bis J'etzt habe ich noch nicht die Rﬁumlichkeit der Dinge bemerkt. Die Anschauung des Menschen veréindert sich vollkommen.» «V01: ungefiihr einer halben Stunde konnte ich die Injektion bekommen haben. Mir kommt es vor, als ob diese Minuten viel reicher wﬁren, deshalb erscheinen sie mir linger.» �Sai-Halész,Brunecker und Széra 290 20' «Mein Uhelsein verstﬁrkt sich wieder, ich fiihle mich sehr schwach. Mir ist, als ob ich keinen Atemreﬂex hﬁtte; wenn ich nicht daran denke, wiirde ich zu atmen vergessen. » 21’ «Alles ist statuenhaft. Die Gesichter sind teuflisch.» 22' RR: 130/80 Hgmm, P: 84/Min. Pupillen mﬁBig erweitert. 23' «Mir fallen solche Details auf, die ich bis jetzt noch nicht bemerkt babe.» 24' «Ich fiihle mich vollkommen gewichtslos, gar nicht, als ob ich 75 kg wiege.» 25' «Es ist merkwiirdig, daB mir meine Hinde vollkommen fremd sind, als ob sie gar nicht mir gehorten.» 26' «Ich kann die Réiumlichkeit der Dinge besser beobachten; ich glaube, die Kiinstler sehen sie immer so. Wenn es so bliebe, wﬁrde ich Maler werden.» 27' RR: 130/85 Hgmm, P: 80/Min. Rechtsseitge Babinski-Tendenz besteht weiter. 28' «Die Gegenstéinde haben gar kein Gewicht. Ich glaube, ich konnte viel grijBere Gewichte heben als zuvor.» 29' «Die Gesichter sind noch immer statuenhaft.» 30' Er verlangt schwere Gegenstéinde und versucht, sie aufzuheben. «Die haben alle kein Gewicht.» 331' Er hort Musik mit geschlossenen Augen und lichelt. 32' RR 125/85 Hgmm, P: 80/Min. Keine Reﬂexdiﬂ‘erenz. Pupillen mﬁBig erweitert. 33’ «Die Musik ist schon und fesselnd. Als ich diese (Abendsternarie aus Tannhéiuser) letztes Mal horte, schwebte die Musik ﬁber mir, ich war jedoch auf der Erde. J etzt schwebe ich zusammen mit der Musik.» 34’ «Die Nebengerﬁusche storen mich sehr, schade, daB es Grammophonmusik ist.» 35' «Alles wird schon natiirlicher. Das ganze ist sehr angenehm.» 37' RR: 125/75 Hgmm, P: 76/Min. Pupillen méiBig erweitert. 40' «Ich fiihle mich schon halbwegs in Ordnung. Meine Hand gehort wieder mir.» 45' RR: 120/70 Hgmm, P: 80/Min. 50' «Ich bin ein wenig miide, sonst ist alles voriiber. Das Gewicht der Gegenstéinde kam auch zurﬁck. Es war merkwiirdig, daB sich am Anfang Angenehmes und Unangenehmes vermischte, in der zweiten Halfte jedoch war alles schon und I gut.» Von den retrospektiven Erinnerungen ist folgende ihres lyrischen und subjektiven Charakters halber von Interesse: Dr. E.Ch., Arztin, 27 Jahre. 50 mg DMT i.m., 27. 8. 1956. Teils fiirchte ich mich, teils bin ich sehr gespannt, was eigentlich auf mich wartet. Mein SelbstbewuBtsein mochte ich gem durchwegs behalten. Was werde ich wohl erfahren? Mit 16 Jahren hitte ich gerne Gott gesichtet — wird das jetzt kommen? Oder wird sich eine andere Zeit meiner Vergangenheit verlebendigen? «Guten Tag, Ihr Versuchskaninchen ist angekommen», begrﬁBte ich die zwei jungen Minner. «Ich messe IhIen Blutdruck, dann gehen wir ins andere Zimmer hiniiber. Der Blutdruck 120/90. Sie fﬁrchtet sich gar nicht», sagt der eine. Ich fiihle einen Stich, jetzt gibt es schon kein Zurﬁck mehr. «Sehen Sie sich gut im Zimmer um», hore ich, «sehen Sie auch aus dem Fenster.» Fliichtig schaue ich auf den Schreibtisch, die Stiihle und die monotone Wand. Alles ist kahl. Ich schaue durch das eisenvergitterte Fenster und sehe die groBen alten Baume. Ich sehe den déimmerigen Himmel, und auf einmal ﬁng es an... �Dimethyltryptamin: ein neues Psychoticum 291 Mir schwindelt entsetzlich, es trommelt in meinen Obren, mit meiner rechten Hand greife ich zum Hals, da ich dort einen ziehenden Schmerz fiihle. Mir schwindelt. — In diesem Augenblick bedauere ich, mich in dieses Experiment eingelassen zu haben. Ich sehe auf meine Uhr, es sind noch kaum einige Minuten vergangen. GroBer Gott, wann wird dieser Versuch ein Ende nehmen? Der Kopf des einen Kollegen zieht sich in die Lange, er bekommt Schlitzaugen. Das Gesicht des anderen wird ﬂacher und vierkantiger. Dieses eigenartige Licht, als ob der Schein einer Quarzlampe dammere. Meine Hand ist ganz zyanotisch. Ist sie wirklich so ? Ich ho're Sausen. Ich bin irgendwohin unterwegs, aber wohin? «Blutdruck 160», hﬁre ich, «Puls 100.» Das ist jetzt der Tod. Wie einfach alles ist. Das Sausen hat aufgehort, ich bin angekommen. Vor mir zwei stille, sonnenbeschienene Gﬁtzen. Freundlich nickend beobachten sie mich. Ich glaube, sie begriiBen mich in dieser neuen Welt. Es herrscht dumpfe Stille, wie in der Wﬁste. Ich wage nicht, sie anzusprechen. Das ist doch Agypten, diese die Siihne der Sonne, und ich bin endlich zu Hause. Zu Hause in jener wirklichen und schonen Welt, wo binter den zwei Gotzen sich heitere Menschen zwischen den hohen, gelben Sﬁulen und Statuen bewegen. Wie vornehm und einfach sie sind. Ihre sonnengebraunten Gesichter sind verklart, ihre Bewegungen frei und grazios. Weiter drinnen singen die Priester mit brausenden Stimmen. Der eine Gotze — nur seine Augen leben spricht mich an: «Geht es Ihnen besser?» «Es wird mir sehr gefallen, wenn das Ubelsein, welches der hohe Blutdruck verursacht, aufhiirt», antworte ich. Ich sehe mir meine Hand an, ein von mir ganz unabhéingiges, selbstandiges Wesen und dazu sehr schon. Die Form ist so wie zuvor, doch als ob sie mit einem goldbraunen Staub gepudert ware. Und die N age] sind rosa Muscheln. «SchlieBen Sie die Augen. Was sehen Sie ?» Ich gehorche. Aus der Dunkelheit sehe ich durch schwarze Eisengitter in den hellen Tempe]. Griiner Ranch qualmt darin und der Gong tont. China! Ich kann meine Augen nicht geschlossen halten, da mir schwindelt. J etzt zeigt man mir die RorschachTafeln. Ich kann mich so schwer darauf konzentrieren, es ist so langweilig. Jetzt erheben sich die hellen, metallschimmernden Wande, dann sinken sie wieder nieder. Es ist, als 0b das Zimmer atme. Auf der ganzen Flache kreisen vielfarbige — gelbe, hellgriine, rosa und blaue — Fischschuppen. Die glanzende Kugel der Lampe beugt sich kreisend naher. Ich sehe wiederum das Gitter, doch ist jetzt dahinter kein Ranch, sondern nur glatte runde grﬁne Steine. Auf meinem linken FuB kriecht etwas, doch sehe ich dort gar nichts. Alles bewegt sich und wogt. Im F ensterglas kreisen farbige Kranze und Fackeln mit ungeheurer Schnelligkeit. Ich mochte gerne erklaren, was ich sehe, doch .. . An den Wanden sehe ich das zischende, weiBgekronte, wogende Meer. Einige Wellen erreichen mit gedﬁmpftem Brausen den Strand. — «Debussy» — sage ich. Ich bin ein ganz kleiner Punkt, wie eine Bliite auf dem Wasser von den Wellen geschaukelt. Doch ich weiB, daB mir kein Leid geschehen kann. «Pupillen sind verengt, Blutdruck sinkt», bore ich. J etzt ist es schon still, die Schuppen kreisen immer langsamer, endlich bleiben sie stehen und verschwinden. Nur die seltsame Beleuchtung wéihrt fort. Das WeiB �292 Sai-Halasz, Brunecker und Szara ist noch auffallend weiB, alle Linien scharfe schwarze Konturen. Die Dimensionen sind sonderbar. Die ganze Welt ist furchterregend realistisch. Das ist die wahre Farbe und Form der Dinge. Geféihrliches Spiel, es ware so leicht, nicht zurﬁckzukehren. Ich bin mir dunkel bewuBt, daB ich Arzt bin, das ist aber gar nicht wichtig; Familienbeziehungen, Studien, Plane und Erinnerungen sind von mir sehr weit entfernt. Nur diese wirkliche Welt ist wichtig, ich bin frei und ganz allein. Zuriick, zuriick, drange ich mich. Ich muB den Weg zur realen Welt zuriickﬁnden. Auf dem Weg nach Hause treﬂ'e ich einen Bekannten im Bus. Ich beginne mjt ihm zu plaudern, damit ich die Realitéit der Beziehungen zu spiiren bekomme. Die am Wege stehenden Baume erscheinen grau und verblichen. Das Leben ist stumpf, unfreundlich und gleichgﬁltig. Ich bin ein anderer Mensch geworden, erfahrener und freier. J etzt verstehe ich schon viel mehr. Wenn wir die einzelnen Symptome der DMT-Psychose betreﬂ's Hauﬁgkeit untersuchen, finden Wir folgendes: 1. Vegetative Symptome wurden in allen 30 Fallen beobachtet. Das bestandigste Symptom war die Steigerung des Blutdruckes, die im allgemeinen 20—40 Quecksilber-mm erreichte, manohmal sogar noch mehr. Die hochste von uns beobacbtete Blutdruckerhohung betrug 70 mm, in einem Falle, wo der systolische Druck vor dem Versuch 140 mm zeigte und sich wéihrend des Experimentes bis auf 210 mm steigerte. Der diastolische Druck erhohte sich regelméiBig, doch in kleinerem MaBe als der systolische (meistens 10—20 mm, in einem Falle sogar 40 mm). Fast regelmaBig war die Pupillenerweiterung. Die Mydriase schien parallel mit den farbigen Halluzinationen zu erscheinen. Ob jedoch zwischen diesen ein kausaler Zusammenhang bestand, ist kaum wahrscheinlich. Eine Pulsbeschleunigung geringeren MaBes war auch in fast allen Fallen festzustellen. Objektive Atmungsstorungen fanden wir nicht, doch wurden von 23 Versuchspersonen (76 0/0) ﬁber Atemnot berichtet; diese wurde von einem Oppressionsgefiihl des Herzens begleitet. Dieses klinische Bild erinnert stark an das durch Serotonin hervorgerufene; es konnte vermutet werden, daB die molekuliire Ahnlichkeit der zwei Substanzen diese Erscheinung erkléirt: DMT verursacht auch wie Serotonin einen Krampf der pulmonalen Arteriolen. Die sympathicomjmetische Wirkung des DMT unterstiitzt diese Vermutung. Zur volligen Klarung dieses Mechanismus miiBten natiirlioh weitere Tierexperimente durchgefiihrt werden. Die sympathicomimetische Wirkung des DMT konnte nicht an allen Organen nachgewiesen werden. So fanden wir z.B. keine be- �Dimethyltryptamin: ein neues Psychoticum 293 deutende Hyperglykéimie und Tachypnoe. Die ganze vegetative Wirkung des DMT iihnelt mehr derjenigen des Serotonins als der des Adrenalins. 2. Sinnestiiuschungen wurden in 27 F ﬁllen (90%) beobaohtet. Diese waren in der Mehrheit optischen Charakters: helleuchtende, farbige Illusionen und Halluzinationen, die sich stets im schnellen Wechsel befanden. Bei geschlossenen Augen vermehrten sich die Halluzinationen und nahmen szenenhaften Charakter an. Eine unserer Versuchspersonen erzéihlte mit geschlossenen Augen: «Ich sehe F elsen, Téiler, méirchenhafte Gegenden, mit kaum einem Schein von Rot als belebende Farbe. Watteau-artige Bilder, dort sind jedoch die Gestalten griiBer. Diejenigen, die ich sehe, sind ganz winzig und verlieren sich in den Felsenrissen, kleine Anhiinger der furchterregenden Umgebung.» Oder spéiter: «Orthodox-griechische Einsiedler, die in F elsen gehauenen dunklen Hﬁhlen leben. An den Wéinden leuchten Ikone. Man spiirt, daB ihr ganzes Leben auf diese Heiligenbilder zentriert ist.» AuBer den optischen fanden wir auch — wenn auch seltener — akustische und haptische Halluzinationen ﬂiichtigen Charakters, die ebenso plﬁtzlich verschwanden, wie sie erschienen. 3. Stb'rungen der Raumwahrnehmung wurden in 22 Féillen (73 %) beobachtet. Die Dimensionen des Zimmers ﬁnderten sich am auffallendsten. Nahes und F ernes verschmolz ineinander. Die Form des Zimmers wurde ganz neu: oval oder vielkantig. Es konnte festgestellt werden, daB sich eben jene Dimensionen ﬁnderten, auf welche die Aufmerksamkeit gerichtet wurde. Wie auch in Meskalinund LSD-25-Psychose veréinderte stets jene Mauer die Lage, die eben angeschaut wurde. In einigen Fallen, in denen die Versuchspsychose Starker ausgeprﬁgt war, gingen die Raumdimensionen vallig verloren. Es stellte sich dann immer ein subjektives Erleichterungsgefiihl ein, sobald die richtige Riumlichkeit der Dinge wieder wahrnehmbar wurde. 4. Stb‘rungen des Kb'rperschemas erschienen fast immer gleichzeitig mit denen des Raumes. Es handelte sich um Symptome, die an den parietalen Symptomenkomplex erinnerten: die Versuchsperson bemerkte z.B., daB ihre Hand schon nicht ihr gehiire; oder wenn auch die GewiBheit bestand, daB es doch ihre eigene Hand sei, hatte diese doch etwas Selbstéindiges und Seltsames an sich. 0ft waren die St6rungen des Kérperschemas halbseitig; in 4 F ﬁllen dehnte sich die St6rung auf die ganze linke Kiirperhﬁlfte aus. �294 Sai-Halész, Brunecker und Széra 5. Zeitstc'irung war in geringerem MaBe in allen Fallen vorhan- den, erreichte aber nie eine grijﬂere Intensitéit. Solche Erscheinun— wie beim Meskalin-Versuch berichtet — daB Zeitsinn der ganz gen, verlorengegangen ware, haben wir nicht bemerkt. Die Dauer des Versuches wurde immer etwas ﬁberschﬁtzt. Eine Versuchsperson fiihrte das «auf die reichere Fiille der Minuten» zuriick. 6. Denkstb'rung. In 21 Fallen (70 0/0) fanden Wir eine ausgesprochene Auflockerung der Assoziationen. Die Sprache wurde inkohéirent, angefangene Siitze konnten nicht beendigt werden, da schon der néichste Gedanke im Vordergrund stand. Diese Inkohéirenz verursachte auch beim Protokollfiihren Schwierigkeiten. 0ft schwiegen die Versuchspersonen fiir einige Minuten, antworteten auch nicht auf Fragen; sie erkléirten spéiter, daB sie ihre Gedanken nicht genug beherrschen konnten, um etWas Verstéindiges zu antworten. In 5 Fallen hatten wir es mit paranoiden bzw. wahnéihnlichen Gedanken zu tun. Diese Versuchspersonen berichteten erst 1—2 Tage spater, daB sie wéihrend des Versuches ﬁberzeugt waren, man wolle sie tﬁten bzw. vergiften. DMT war das Gift, die Versuchsleiter die Mﬁrder. Eine Versuchsperson wurde Wéihrend des Experimentes sehr unruhig und muBte mit Gewalt niedergehalten werden. Sie erkléirte am néichsten Tage folgendes: «Ich fiihlte, daB ich vergiftet wurde und sterben werde und schon nichts dagegen tun konnte. Trotzdem kéimpfte ich einen seelischen Kampf, ob ich bis zum letzten Moment am Leben hé’mgen Oder ruhig sterben soll; das letztere war sehr verlockend, da ich mich sehr wohl fiihlte. Dieser seelische Kampf éiuBerte sich in meinem Motorium als Unruhe; ich spiirte und wuBte alles.» In anderen Fillen waren die Beziehungsideen nicht so ausgeprﬁgt, doch berichteten die Versuchspersonen nach einigen Tagen, daB sie betreﬁ's der Aufrichtigkeit und Zuverléissigkeit der Versuchsleiter ein wenig unsicher waren. Am nichsten Tage war dieses Gefiihl mit den eventuellen aggressiven Einstellungen zusammen verschwunden. 7. Aﬁ'ektive Verdnderungen. Euphorie ist eine verhﬁltnismﬁﬁig 0ft zu beobachtende Erscheinung der DMT-Psychose. In 8 Féillen (27 0/0) war sie stark ausgeprﬁgt, in 12 Fallen (40%) milderen Grades Oder nur auf kiirzere Zeit bemerkbar. 0ft trat sie zusammen mit Zwangslachen auf, in anderen Féiﬂen war sie mit Introversion verbunden; letztere wurde durch ein «verkléirtes» Lﬁcheln begleitet, das manchmal fast wéihrend dem ganzen Versuche dauerte. Die �Dimethyltryptamin: ein neues Psychoticum 295 Versuchsperson lag mehrere Minuten lang wortlos mit geschlossenen Augen und léichelte; manchmal jedoch weinte sie vor Seligkeit und seufzte: «Oh, wie wunderbar ist doch alles!» Wie schon bemerkt, ist die Angst eine der héiuﬁgsten Erscheinungen der DMT-Psychose. Am stéirksten ist sie einige Minuten nach Verabreichung der Injektion bemerkbar, wenn sich die Umwelt so plﬁtzlich und intensiv veréindert, daB die Versuchsperson die feste Umgebung verliert. Nur 4 Personen berichteten, keine Angst gehabt zu haben. In der zweiten Héilfte der Psychose tritt Angst Viel seltener auf. Nur eine Versuchsperson klagte wﬁhrend des ganzen Versuches iiber Angst und sagte: «DaB es nur nicht zuriickkomme ! » Was nicht zurﬁckkommen sol], konnte sie nicht erkléiren; sie antwortete: «Na ja, das Ganze!» 8. Bewuﬁtseinstb’rungen. Nur in 7 Fallen (23 0/0) haben wir eine BewuBtseinstriibung beobachtet. Sie war stets am Anfang des Experimentes bemerkhar, d.h. 8—15 Minuten nach Verabreichung der Injektion und dauerte nicht léinger als 2—5 Minuten. Wéihrend dieser Periode sprechen die Versuchspersonen nichts, und auch spéiter bestand eine Amnesie der Ereignisse, die inzwischen geschahen. Es blieb ihnen nur das Gefiihl, daB etwas Schreckliches vorging. 9. Neurologische Verc‘inderungen. Die Reﬂexe waren wéihrend des Versuches 0ft (63 %) erhtiht oder lebhaft. Voriibergehende pathologische Reﬂexe (Babinski usw.) fanden wir nur in 3 Fallen (10%). Im Motorium zeigten sich ausgepréigte Veréinderungen. Fast alle Versuchspersonen hatten eine hyperkynetische Zeitspanne, in der sich unwillkiirlich-extrapyramidale und Willkiirliche Bewegungen mischten. Nur einmal war die Hyperkynesie so stark, daB Gewalt angewandt werden muBte, um einen Unfall zu verhiiten. Sensibilitéitsstﬁrungen gesellten sich oft zur Stﬁrung des K6rperschemas. Meistens waren die Fehlleistungen seitens der Tiefensensibilitéit, Gewichtsschﬁtzung, Kﬁrperlage usw. zu beobachten. Die Oberﬂﬁchensensibilitéit war relativ viel besser erhalten. Sensibilitéitsstﬁrungen fanden wir in 18 Féillen (6000). 10. Halbseitigkeit der Symptome. Eine der interessantesten Beobachtungen beziiglich der DMT-Psychosen war, daB in Mehrzahl der F ﬁlle die Symptome halbseitig ausgepréigter waren. Dies war ebenso bei den neurologischen Symptomen wie bei den Halluzinationen und Kﬁrperschemastﬁrungen bemerkbar. Die linke Seite war stets die stéirker betroﬂene. Wir hatten Gelegenheit, 3 Linkshéindige unserem Experiment zu unterziehen; bei diesen dominierten �Sai-Halész, Brunecker und Széra ___—____—_——_—————————————-—-———~ 296 Abb. 100 % 1 80% 40% 20% s-aaa°a°-Eaa°a:a°§-Eé°-EE g be :1 :5 a; s: >., a "-4 0 '8 A: H m "‘ {-11 o I: cu 3'3 E,” H o9-1 >5 no 3:: g: .H .0 gcu 8 0 .=: :2 53 Q '8 au :5 uo .5.” 0 aa o 0 m C121 :o ‘53 a:3 (I) 1 :1 '-' :5 an .... f:O m ﬂw m a a)” ‘ M o CIT-I o a: ‘9 '8 w "" ho” s 2": cc 94 aH :o 2; 4.: '-' ﬂ tan 5:: 5 4:: 0 m F ‘3 w Q 5 E75 b; <‘. :1 H :o E E :1 «a p: '5cs o :1 g 3 g .... < g v-c an E o A4 v “-1 = 4 Q. m :1 I- :o gm 4-» ' 53 rd a a E :3 .ao _. g m o "=1 ° [—1 an g g c: "" ‘9 *8 6) u m g cc a 5.0 c: .2 s m die Symptome rechtsseitig. (Auf diese Erscheinung kommen wir in der Besprechung noch zuriick.) 11. Nachwirkungen. Alle Versuchspersonen klagten am Experiment folgenden Tage iiber Miidigkeit. Diese dauerte manchma] nur einige Stunden, bei einigen jedoch 1—2 Tage. Wéihrend dieser Periode 2 Nach ein 7 Tagen depressiv. %) (23 wenig Versuchspersonen waren Die in betreﬂ's alle 30 Ordnung. Personen vﬁllig Stimmung waren 1 der in wir Abbildung einzelnen der gehen Symptome Hﬁuﬁgkeit wieder. Besprechung Durch die DMT-Versuche ergeben sich 3 Tatsachen, die fiir das weitere Verstéindnis der sogenannten Modell-Psychosen éiuBerst interessant sind: und kurze Dauer der DMT-Psychose. 2. Halbseitigkeit gewisser Symptome. 3. Nahe chemische Verwandtschaft zwischen DMT und Serotonin. 1. Pliitzlicher Anfang �297 Dimethyltryptamin: ein neues Psychoticum Wirkung des DMT ist etwas ganz Neues unter der Psychotica. Meskalin fingt nach fast einer Stunde zu wirken an, Haschisch und LSD-25 wirkt noch langsamer. Aber auch die Dauer der Psychose ist beim DMT auffallend kurz, und zwar 40~60 Minuten. Um diesem Problem nﬁherzukommen, haben wir — wie schon berichtet - die Ausscheidung von DMT und 3-Indolessigséiure wéihrend und nach dem Versuch untersucht. Wir fanden, daB nach Verabreichung von DMT die Quantitéit der 3-Indolessigséiure im Harn stark zunjmmt und in den ersten 6 Stunden schon ungeféihr das Zehnfache der normalen Ausscheidung erreicht; ebenso erhﬁht sich — jedoch nur in geringerem MaBe — die Ausscheidung der 5-hydroxy-3-Indolessigséiure, was auf einen Zusammenhang mit dem Serotonin-Stoffwechsel hinweist. Im Harn fanden wir jedoch kein unveréindertes DMT, was bezeugt, daB das DMT im Korper sehr schnell und vollig abgebaut wird. Dies kann uns erkléiren, warum die Wirkung so schnell abléiuft und auch das DMT peroral unwirksam ist: wahrscheinlich wird es in der Leber abgebaut, bevor es die psychische Wirkung ausiiben konnte. Es bleibt aber noch immer die Frage oﬂ'en, warum das DMT so schnell wirken kann. Nach der Theorie von Rothlin und Patzig veréindert sich das Meskalin und LSD-25 im Organismus, bevor es eine Wirkung ausiiben konnte; es wéire eigentlich ein Umbauprodukt dieser Substanzen, das die psychotische Wirkung habe. Beim DMT kann kaum von so einer Transformation die Bede sein; das plotzliche Auftreten der Symptome unterstiitzt die Vermutung, daB das DMT selbst die psychotische Wirkung ausiibt. DMT wéire demgemﬁB das erste Psychotikum auBer Bufotenin — das selbst ohne Abbau oder Umbau die experimentelle Psychose verursacht. 2. Die Halbseitigkeit einiger Symptome ist eine der interessantesten Erscheinungen der DMT-Psychose. Es treten gleich zwei Fragen auf: a) wie ist es moglich, daB eine chemische Substanz auf eine Hemisphﬁre stéirkere Wirkung ausiibt als auf die andere, und warum stets auf die nichtdominante Hemisphéire ? b) hat die nichtdominante Hemisphéire eine wichtige Rolle im Auftreten der experimentellen Psychose oder wenigstens einiger Symptome ? Diese Fragen kann man heute noch kaum beantworten. Es wﬁre zu oberﬂéichlich, sich auf die erste Frage mit der Antwort zu begniigen, daB die nichtdominante Hemisphéire chemischen Intoxi1. Die rasche -— Psychiat. New-0]., Basel. Vol. 135, No. 4—5 (1958) 20 �298 Sai-Halész, Brunecker und Széra kationen gegeniiber mehr «verwundbar» wire; dies sollte sich doch dann auch bei anderen Vergiftungen zeigen. Oder aber ist der Kreislauf der dominanten Hemisphéire im Notfall zu besserer Regulation fﬁhig ? Die zweite Frage, 0b néimlich die rechte Hemisphﬁre im Auf— treten psychopathologischer Syndrome eine wichtige Rolle habe, wurde schon in anderen Zusammenhéingen beriicksichtigt. Hoﬁ und Pﬁtzl fanden, daB das Zeitraﬁ'er-Phéinomen nur bei rechtsseitiger Lﬁsion zu beobachten war and meistens bei parieto-okzipitalen Schﬁdigungen. In der DMT-Psychose zeigt sich ein groBer Tei] der Erscheinungen eben als parieto-okzipitale F unktionsstﬁrungen (visuale Halluzinationen, Kﬁrperschemastﬁrungen, Raumwahrnehmungs-Stﬁrungen usw.). Es scheint, daB die Halbseitigkeit bei der DMT-Psychose uns einen weiteren Beweis bietet, die Theorie von Hoﬂ und Pb’tzl zu unterstiitzen: eine rechtsseitige Gehjrnschéidigung iibt eine «bahnende» Wirkung beim Auftreten gewisser psychopathologischer Phﬁnomene ans. 3. In den letzten J ahren héiufen sich die Publikationen, die eine zentrale Rolle des Serotonins in der Funktion des zentralen Nervensystems annehmen (Brodie et al.). Es wurde auch angenommen (Woolley), daB der Serotonin-Stoffwechsel in der Genese der Psychosen, hauptséichlich der Schizophrenic, einen wichtigen Anteil habe. Wie schon erwéihnt, fanden wir im Harn der Versuchspersonne ungeféihr 4—5mal mehr 5-hydroxy-3-Indolessigséiure als bei Normalen; diese Substanz ist, wie bekannt, das Hauptabbauprodukt des Serotonins. Es gibt wiederum zwei Mﬁglichkeiten: entweder wird die 3-Indolessigséiure, also das Abbauprodukt des DMT, sekundﬁr oxydiert, oder aber mobilisiert das verabreichte DMT eine bedeutende Menge des gebundenen Serotonins. Im letzteren Falle ware die experimentelle DMT-Psychose im strengsten Zusammenhang mit dem Serotonin-Stoﬂ'wechsel verbunden. Hier k6nnte man nach gewissen Analogien einen in den zentralen Synapsen abspielenden kompetitiven Antagonismus der zwei Aminen vorstellen. Es miissen noch weitere mit radioaktiven Isotopen gezeichnete DMT-Experimente vorgenommen werden, um diese Fragen zu lﬁsen und auch damit einen Wichtigen Schritt zum biochemischen Verstéindnis der psychotischen Zustéinde im allgemeinen zu tun. Durch unsere ohigen Beobachtungen kﬁnnen wir auch feststellen, daB auBer dem Bufotenin das DMT auch eine bedeutende R0116 in der Gesamtwirkung der Piptadenia-Extrakte zu spielen habe. �M“— Dimenthyltryptamin: ein neues Psychoticum 299 Insofern unsere Ergebnisse mit den spﬁrlichen an Menschen gewonnenen Bufotenin-Beobachtungen zu vergleichen sind (diese sind wegen der intravenosen Anwendung des Bufotenins kaum moglich), ist es auffallend, daB das DMT eine periphere-vaskulﬁre, serotoninartige Wirkung in geringerem MaBe als das Bufotenin ausiibt. Dies kann vielleicht der strukturelle Unterschied, d. h. die beim Bufotenin vorhandene 5-OH-Wurzel erkléiren. Diese und die iibrigen Detailfragen konnten bloB weitere, an denselben Personen und unter gleicher Anwendung der 2 Indolamine durchgefiihrte Versuche kliiren. Z usammenfassung Dimethyltryptamin wurde synthetisiert, und dessen psychotische Wirkung untersucht. Nach intramuskuléirer Verabreichung von 0,7—1mg/kg Dimethyltryptamin tritt schon nach 3~5 Minuten ein psychotischer Zustand auf, der in vielen Erscheinungen denen ahnelt, die durch Meskalin und LSD-25 verursacht wurden. Die Dimethyltryptamjn-Psychose lauft innerhalb einer Stunde ab. AuBer der Beschreibung der Symptome werden 3 Probleme nﬁher untersucht: 1. Was kann die Ursache des plotzlichen Auftretens und schnellen Ablaufes der Dimethyltryptamin-Psychose sein. 2. Welche Rolle spielt die Halbseitigkeit der Symptome, also die stiirkere Schiidigung der rechten nichtdominanten Hemisphéire beim Auftreten der psychopathologischen Erscheinungen. 3. Welche F olgerungen konnen beziiglich der Bedeutung des Serotonin-Stoﬂ'wechsels im zentralen Nervensystem betreﬂ's der nahen cliemischen Verwandtschaft zwischen Dimethyltryptamin und Serotonin gezogen werden. Die Ahnlichkeiten und Unterschiede zwischen den Bufoteninund Dimethyltryptamin-Psychosen sollen weitere Experimente klarstellen. Re’sumé On a synthétisé la diméthyltryptamine et étudié son action psychotique. Aprés une administration intra-musculaire de 0,7—1 mg/kg de djméthyltryptamine, un état psychotique est apparu aprés 3 a 5 minutes déja. Il ressemhlait par beaucoup d’aspects a ceux qui sont �300 Sai-Halasz, Brunecker und Széra provoqués par la mescaline et le LSD 25. La psychose a la diméthyltryptamine dure une heure. A part la description des symptﬁmes on a étudié de plus pres 3 problémes: 1. Quelle peut étre la raison du début brusque et de la ﬁn rapide de la psychose a la diméthyltryptamine. 2. Quel role joue la latéralisation des symptémes ainsi que l’atteinte prépondérante de l’hémisphére droit, non dominant, lors de l’apparition des symptomes psychopathologiques. 3. Quelles conclusions on peut tirer de la proche parenté chimique entre la diméthyltryptamine et la sérotonine pour la signiﬁcation du métabolisme de la sérotonine dans le systeme nerveux central. D’autres expériences montreront les ressemblances et diﬂ'érences entre les psychoses a la Bufotenine et a la diméthyltryptamine. Summary Dimethyltryptamin was synthesized and its eﬁ'ect on psychosis investigated. An intramuscular injection of 0.7—1 mg/kg Dimethyl3—5 minutes a psychotic condition after and was given tryptamin was induced which in many respects resembled those phenomena induced by mescalin and LSD 25. This Dimethyltryptamin psychosis lasted less than an hour. Besides a description of the symptoms we have investigated three problems: 1. The reason for the swift start and rapid departure of the psychosis. 2. What is the signiﬁcance of the one-sided nature of the in of the disturbance the right degree is, that greater symptoms, non-dominant hemisphere when the psychopathological phenomena begin to show. 3. Having regard to the close chemical afﬁnity between Dimethyltryptamin and Serotonin, what conclusions could be drawn as to the import of serotonin metabolism in the C.N.S. Further experiments should clarify the similarities and differences between psychoses induced by Bufotenin and those by Dimethyltryptamin. LITERATUR Beringer, K.: Der Meskalim'ausch, Springer, Berlin 1927. — Brodie, B. B. et al.: Science 122, 968, 1955. — Erspamer, V.: Pharmacol. Rev. 6, 425, 1954. — Evarts, E. V.: Arch. Neurol. Psychiat. 75., 49, 1956. — Fabing, H.D.: Amer. J. Psychiat. 113, 409, 1956. — Fabing, H.D. and Hawkins: Science 123, 886, 1956. — Fish, M. S., �m Dimethyltryptamin: ein neues Psychoticum 301. N. M. Johnson and D. C. Homing: J. amer. chem. Soc. p. 77, 1955. — Fraenkel, F. und E. Joel: Z. ges. Neurol. Psychiat. 111, 84, 1927. — Hoﬁ, H. und 0. Po'tzl: Z. Neurol. 151, 599, 1934. — Page, I.H.: Physiol. Rev. 34, 563, 1954. — RaymondHamet: Compt. rend. Soc. biol. 135, 1414, 1941. — Rothlin, E.: Experientia 12, 154, 1956. — Speeter, M.E. and W. C. Anthony: J. amer. chem. Soc. 76, 6208, 1954. — Stall, A. und A. Hoﬂmann: Helv. chim. Acta 26, 944, 1943. - Stromberg, V.L.: J. amer. chem. Soc. 76, 1707, 1954. — Stoll, A.: Schweiz. Arch. Neurol. Psychiat. 60, 1, 1947. — Szdra, SL: Experientia 12, 441, 1956. — Wieland, H. und H. Mittasch: Ann. Chem. 513, 1, 1934. — Woolley, D. W.: Brit. med. J. 1954, 122. Adresse der Autoren: Dr. A. Sai-Halész, Dr. G. anecker, Zentrales Neurologisch-Psychiatrisches Institut, Budapest-Lipétmezb‘ (Ungarn). Dr. St. Széra, 113 Hesketh Street, Chavy Chase 15, Md. (USA). �, u '1‘ �Copyright, 1958, by the Society 'for'Experimental Biology and Medicine. Reprinted from PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE, 1958, v97, 4837486 A New Group of Psychotomimetic L. G. ABOOD, A. M. OSTFELD Agents.ale AND (23782) JOHN BIEL Divisions of Psychiatry and Preventive Medicine, University of Illinois College of Medicine and Lakeside Laboratories, Milwaukee During the past few years, much interest has developed in psychotomimetic agents, particularly with regard to LSD 25 and mescaline. At the same time, considerable emphasis has been placed on the possible role of adrenalin and serotonin in psychoses, particularly because they are structurally related to the psychotomimetic agents and are pharThe, role Of macologically antagonistic. acetylcholine and acetylcholine- like sub'stances, on the other hand, has received relatively little attention. Knowledge of the hallucinogenic properties Of cholinergic blocking agents,,such. as atroh pine and hyoscine, dates back to thetime of the ancient Hindus. Recently, a group of piperidyl benzilates possessing anticholinergic properties were synthesized by Biel and associates(l) as possible antispasmodics in the treatment Of duodenal ulcer(2). In the course of therapeutic trials, it was found that the tertiary amine hydrochlorides of the benzilate esters, although active anticholinergics, produced undesirable side effects, particu- larly hallucinations. The quaternary ammonium salts, on the other hand, were entirely devoid of such effects. We have recently, Obtained a series of such substances and examined their psychotomimetic effects on animals and human subjects(3). Methods. The psychotogenic effects of the N—methyl-3-piperidyl benzilate and related congeners were tested on over 40 human volunteers who were either normal or patients complaining of minor disorders. Although some of the patients had limited knowledge of the psychotogenic action of the drugs, the majority of subjects were completely unaware Of their nature. Ceruloplasmin determinations were made on many subjects, employing a method described previously(4). All of the agents were tested for their behavioral effects in animals, including some 30 Siamese ﬁghting ﬁsh, 50 rodents, and 5 cats. The action of these agents on the Siamese ﬁghting ﬁsh is comparable to those described 'for LSD by Abramson(5). In rodents there were marked behavioral changes, such as initial excitement and marked' hyperactivity, spon* Supported by grants from Mental Health Fund, taneous squealing, lack Of ”responsiveness to State Of Illinois, and Teagle Fn. stimuli, muscular weakness, (and lethargy. , _ 4 _ �NEW PSYCHOTOMIMETIC AGENTS The anticholinergic effect of the agents was determined on isolated smooth muscle preparations and the rectus abdominus according to the method of Chang and Gaddum(6). Results. Experimental ﬁndings have indicated that the compounds are extremely powerful hallucinogens, in many respects more interesting than LSD and mescaline. When administered in 5-15 mg doses, orally, to human volunteers, distinct auditory and visual hallucinations occurred within one hour in for recurred and periodically individual every periods up to 10 hours after administration of the drug. Hallucinations were accompanied by gross distortions of visual images and severe alterations in feeling state. A number of subjects exhibited paranoid and megalomanic delusions, while the affective states ranged from a feeling of unpleasantness to extreme terror. Some of the subjects actually carried on conversations with imaginary individuals involving situations dating back 10-20 years. The following are almost exact quotations from different subjects: “People from India are standing outside a tent. They have turbans and those are camels.” “I see six people sitting around a table playing cards . a monkey is over the table hanging by his tail.” “I am walking down a narrow corridor and suddenly stop and cannot move is beating . . . a band is playing . . . a drum 3/4 rhythm.” The subjects receiving 10 mg (orally) of N-methyl-3-piperidyl benzilate were in complete loss of contact with the environment for vis— dramatic While hours experiencing many ual and auditory hallucinations. In many respects these anticholinergic agents come closer to simulating clinical psychoses than do mescaline and LSD. Thus far, a number of congeners have been tested for both hallucinogenic properties and anticholinergic effect on the isolated colon (Table I). Of all the compounds tested for hallucinogenic properties, N-methyl-3-piperidyl benzilate is the most potent, with the Nethyl derivative being somewhat less effective. The tetramethyl derivative is considerably less effective than the N—ethyl derivative. The quaternary derivative is devoid of , psychotogenic effects. As for the antispasmodic potency, although the 3 substances possessing psychotogenic properties are perhaps the most potent, the remaining compounds are still quite effective. Ceruloplasmin determinations were made on all subjects, since this enzyme was shown to be increased in the serum of acute schizophrenics(4,7). The method used has been described previously(4). Preliminary observations have indicated that as much as a 50-75% elevation in the blood ceruloplasmin accompanies the hallucinatory episode produced by these agents. The enzyme increased only when marked psychogenic disturbances were apparent, returning to normal shortly after the psychogenic effects disappeared and while peripheral autonomic effects, such as mydriasis, muscular weakness, and dryness of the mouth, still persisted. A rise in ceruloplasmin has been shown to accompany changes in affective or feeling states, regardless of the mechanism by which the effects are produced (3 ) . Discussion. A discussion of the relative antispasmodic properties of this group of compounds appears elsewhere(1). It is apparent from the present study that in this series of compounds there is no direct relationship between the anticholinergic effect on smooth muscle and psychotogenic potency. The presence of the hydroxyl group in the acid moiety to yield the diphenylacetate ester is undoubtedly essential for hallucinogenic effect, while only slightly enhancing the anticholinergic effect. Since both the diphenylacetate and the benzilate derivatives penetrate the blood brain barrier, it would appear that the hydroxyl group is an absolute require— ment. The presence of a quaternary nitrogen in the piperidine ring only slightly inﬂuences the anticholinergic effect, but apparently pre— vents the compound from penetrating the blood—brain barrier. As a rule, quaternary ammonium compounds are not able to enter the central nervous system through the blood stream. Preliminary observations have shown that intrathecal injections of the quaternary compound into rats produce much the same kind of neurological and behavioral disturb- �_,,' _ a \ 4 l NEW PSYCHOTOMIMETIC AGENTS TABLE I. Structure-Activity Relationships of. Some Piperidyl Benzilate Congeners. Anticholinergic effect was determined on isolated rat colon with concentrations of about 10“ M. \ / Ill/Q ox R—O—C—C \ \/\O — Relative Relative halantilucinogenic cholinergic potency potency Name R X N—methyl-3-piperidy1-benzilate m 0H ++++ ++++ OH +++ +++ OH — + +++ I \N/ CHs N -ethyl-3-piperidyl—benzilate \/ N 02115 1,2,2,6 tetramethyl-4-piperidyl benzilate CH3 \N/(CHS) 2 CH3 N-ethyl-3-piperidyl-diphenylacetate \/ H 0 +++ OH 0 +++ N 02H5 m \/ /\ N-dimethyl—3-piperidyl benzilate N+ CH3 ances observed with the tertiary benzilates. At present, numerous other congeners are being examined for their hallucinogenic properties. Future synthetic work is contemplated in an effort to explore other structureactivity relationships from the point of view of hallucinogenic effect. In view of the work of others on anticholinergic substances, it may be predicted that the distance between the hydroxyl group and the piperidyl nitrogen is critical( 8,9). Introduction of alkyl groups into the molecule would, therefore, presumably diminish the anticholinergic potency, and it will be of interest to determine the relationship of such a change to hallucinogenic effectiveness. Summary. A series of synthetic anticholin- C'H3 ergic agents have been shown to possess potent psychotomimetic properties. Chemically, the agents are esters of piperidine and benzilic acid. Among the effects produced are megalomanic and paranoid delusions, visual and auditory hallucinations, and a partial loss of contact with the environment. A number of congeners of the compounds have been examined with regard to structure-activity relationships. J. H., Sprengler, E. P., Leiser, H. A., Horner, 1., Drukker, A., Friedman, H. L., J. Am. Chem. 1. Biel, Soc., 1955, v77, 2250. 2. Ewing, P. L., Seager, L. D., Keller, G., Dodson, D., J. Pharmacol. Exp. Therap., 1954, v110, l7. 3. Ostfeld, A. M., Abood, L. G., Marcus, D. A., �NEW PSYCHOIOMIME’TIC AGENTS Arch. Neurol. Psych. in press. 4. Abood, L. G, Gibbs, F. A, Gibbs,E ., ibid., 1957, v77, 643. 5. Abramson, H. A., Evans, L. T., Science. 1954. V120: 9906. Chang, v79, 255. H. C., Gaddum, J. H., J. Physiol., 1933, . t ' ' 7‘Akerfeldt, M., J. Pharmacol. Exp. Therap., Lands, 8. S., Science, 1957, v125, 117. A. 1951, v102, 219. 9. Goodman, L., Gilman, A., The Pharmacological Basis of Therapeutics, ed. Macmillan Co., N. Y., 1955. Received December 23, 1957. P.S.E.B.M., 1958, v97. DEPARTMENT OF EXPERIMENTAL rsvcumm HlLLSlDE HOSPITAL GLEN OAKS. N. v. MAY1 4'53 '- �Reprinted from the A. M. A. Archives of Neurology (5“ Psychiatry March 1958, Vol. 79, pp. 317-322 Copyright 1958, by American Medical Association Studies with Ceruloplasmin and a New Hallucinogen ADRIAN M. OS'I'FELD, M.D.; LEO G. ABOOD, Ph.D., and Knowledge of the hallucinogenic prop—erties of atropine—like compounds is cer— tainly as old as that concerning the effects of mescal and marihuana. It has been pos— tulated that the oracle at Delphi induced her prophetic vision with belladonna. Hughes and Clark1 quote a lively description of a 17th century American epidemic of atro— pine poisoning. Readers of English detec— tive novels or American Western stories are familiar with the deadly nightshade and Jimson weed, respectively. The recent synthesis of N-ethyl-3-piper— idyl benzilate hydrochloride, JB 318*,2 an agent chemically related to atropine (Figure), led to the present studies. Originally intended as an autonomic—blocking agent in the treatment of peptic ulcer, the drug exhibited hallucinogenic properties, so prominent as to merit further investigation.3 At the close of the conference of the Brain Research Foundation on blood tests in mental illness in 1957,4 several unan— swered or partly answered questions were raised or implied. What are the serum ceruloplasmin levels in disturbed behavior not of psychotic proportion? Does the con— centration of this protein vary with the severity of the mental disorder? Is its concentration in the blood increased during Submitted for publication Sept. 16, 1957. Department of Preventive Medicine and Division of Psychiatry, University of Illinois College of Medicine. Now at the Institute for Psychosomatic and Psychiatric Research and Training, Michael Reese Hospital (Dr. Marcus). This research was supported in part by the Mental Health Fund, State of Illinois; the Brain Research Foundation, and the Dan Crego Fund. *The material was supplied by Drs. John Biel and H. L. Daiell, of Lakeside Laboratories. Dr. John Biel cooperated in the study and made helpful suggestions. DAVID A. MARCUS, M.D., Chicago N—ETHYL—B-PIPERIDYLBENZILATE (JB 3l8) CHz—7CH—CH2\ N—CH: \ CHz——- CH——-CH2 / CHzOH l CH—O-C H ATROPINE drug—induced psychoses? And, ﬁnally, since ceruloplasmin attacks certain pyrocatechol (catechol) amines in vitro, what effect does an increase in these pyrocatechol amines in the blood have on ceruloplasmin? The present study, then, had the dual purpose of examining the psychotomimetic properties of ]B 318 and assaying the effects on serum ceruloplasmin of (1) JB 318—induced “psychoses,” (2) intravenous infusion of some pyrocatechol amines, and '(3) naturally occurring behavior disturb— ances of moderate severity. Experimental Methods and Results Studies with J B 318.—In all, 45 volunteer nonpsychotic subjects were studied. JD 318 was administered orally to nine subjects in doses of 10 or 15 mg. Three who took the agent were professional persons employed in the hospital; six were medical ward patients, selected only because their general state of health was satisfactory. The three 317 �A. M. A. ARCHIVES OF NEUROLOGY AND PSYCHIATRY professional persons had prior knowledge of anxious to repeat the experience. Seven the effects of the drug, whereas none of experienced visual hallucinations, and four the patients were told what to expect. Blood of these also described auditory hallucina— was drawn for serum ceruloplasmin deter— tions, which were especially prominent in mination before and at the peak of the three. The visual hallucinations usually consisted hallucinatory phase. Ceruloplasmin was measured by the method of Abood5 in of amorphous colored forms, whereas eight of the nine subjects. brightly colored, elaborate images were inThe determination was done as follows: frequent. In the ﬁve cases in which animal One-tenth milliliter of fresh serum was and human forms were reported the images incubated with 0.1 ml. of 0.1% p-phenylene— were usually related to speciﬁc events in the diamine and 1.0 ml. of 0.2 M tris(hydroxy— recent past experience of the subject. Most methyl)ethanolamine buffer (pH 6.8) for hallucinations lasted only a few seconds, al— a period of one hour at 37 C. After the though one subject reported images persist— addition of 2 ml. of distilled water the mix- ing for many minutes. Generally, but not ture was read at 490m“ on the spectro- always, the maximum hallucinatory effect photometer. An optical density reading of was attained when subject was kept alone 0.100 corresponds to an activity of IOMM in a darkened, quiet room. The auditory hallucinations consisted of substrate (p—phenylenediamine) oxidized of musical such mainly sounds, stand— 0.1 as whistling, hour ml. The of one serum. per ard curve was determined by oxidizing the singing, and band playing. A few reported substrate with puriﬁed human cerulo~ noises, such as sirens and hammering or banging radiators. Emotional disturbances, plasminrt such fear and as bewilderment, seem to acReactions related to the autonomic activ— visual whereas hallucinations, the company the 30 of about minutes ity drug began after oral administration and consisted of auditory experiences were not usually disthe following: dry mouth, blurred vision in turbing. Two be subjects to appeared paranoid all cases, usually tachycardia, facial ﬂushing, hallu— the during or immediately following and disappearance of the carotid sinus re— ef— While the cinatory central responses. ﬂex. There was no appreciable effect on fects ofthe drug persisted, the subjects blood pressure. Nausea occurred in two pa— showed reduction of intellectual a capacity, tients, vomiting in one. The autonomic recharacterized rela— short attention by span, actions began 15 to 60 minutes before the tive and anomia, inaccurate time grossly hallu— and outlasted the psychic phenomena All remained in judgment. contact with cinations by l to 24 hours. The peak auto— the actual environment, but the presence of nomic effects preceded the peak psychic familiar a person or object was required to effects in every case. enhance orientation and allay apprehen— Perceptual responses were characterized sions. by distortion of Visual images, visual and The following are taken essentially verauditory hallucinations, and alterations in batim from the comments of dur— a patient feeling state. All nine subjects reported dis— ing the period of hallucinogenic effect: tortion of visual images and an initial change “My arms are heavy and everything feels far in mood, characterized by apprehension and away. My head feels light. I’m very weak. . . .” “Lots of people are talking incoherently. I think lethargy. The general feeling tone was re— it’s Spanish.” ported as unpleasant by eight of the nine “The room feels distant. I wish I could lift my subjects, and none of the subjects were left is arm but I can’t. The and Dr. G. D. Cummings, of the Michigan Department of Health, supplied the puriﬁed human cerulo— plasmin. 1' 318 room a narrow, band is playing. The rhythm is M. . . .” “The room is a long corridor, and I’m in it and I’m 8 or 9 years old. I wonder how I’ll get out. I Vol. 79, March, 1958 �I CERULOPLASMIN AND NEW HALLUCINOGEN of .18 318 on Serum Ceruloplasmin’l‘ of Normal Volunteers TABLE l.——Eﬂect Before JB Ceruloplasmln Approximately Two Hours After J B 318 Subjects Who Hallucinated 318 230 242 304 224 188 230 241 2l 1 115 120 155 315 * 160 170 Subjects Who Did Not Hallucinate _ «——~ - _ _ -_ . __ -_ 143 296 The values are expressed as optical density X10 8. know I’m in bed and also in that other place. There must be more than one of me, and one is a little girl.” “People from India are standing outside a tent. They have turbans, and those are camels.” An electroencephalogram taken on one subject revealed no abnormality, even dur— ing a series of vivid hallucinations. Ceruloplasmin levels uniformly increased in the six subjects who experienced hallucinations and decreased slightly in the two who did not (Table 1). The parallelism of ceruloplasmin levels in schizophrenic psy— choses and those induced by JB 318 is evident. There was, however, no propor— tionality between the per cent increase in ceruloplasmin and the severity of the psy— choses. Nor were the ceruloplasmin levels during the drug psychoses as high as commonly occurs in acute schizophrenics?6 Studies with Pyrocatechol Amines and Human Subjects.—Pyrocatechol amines and their breakdown products have been increas— ingly implicated in schizophrenic psychoses. Since ceruloplasmin has been shown to at— tack epinephrine and serotonin in vitro,7 it was deemed worth while to infuse certain pyrocatechol amines intravenously and to gauge their effects on behavior and serum ceruloplasmin. There was a uniform slight decrease in serum ceruloplasmin with each agent, as well as with control dextrose in— fusion. The subjects were general medical patients who were either convalescing or not seriously ill. None had rheumatoid arthri— tis, liver disease, acute infections, or known carcinoma, conditions sometimes associated Oxtfeld at (11. with high cerulopla51nin.4'6 The infusions were all administered by an unfamiliar physician in a new setting. Apprehension was initially evident in the behavior and Speech of each subject. Common were such comments as “We’re on the same side, aren’t we, Doc. . .you won’t hurt me”; or “lf the test comes out bad, will I have to stay here [in the hospital] longer?” With a single exception, the subjects were relaxed, beginning about 15 minutes after perfusion was started. About half slept, and nearly all commented on how comfortable and tranquil they felt. None of the subjects on levarterenol, serotonin, or dex— trose reported any unusual sensation. The subject on isoproterenol U. S. P. and the two who received epinephrine experienced a rapid heart rate but no emotional disturb— ances. One subject who received epinephrine grimaced, tossed about, and was agitated during the infusion. Since the effects of the infusion on ceruloplasmin were identical regardless of the agent administered, the parallel decline in anxiety and in ceruloplasmin attracted our attention. It was postulated that if there were a parallelism between feeling state and ceruloplasmin, then both would be ex— pected to undergo an increase during peri— ods of disturbed behavior. 2.—E[fect of Various Agents“ onSerum Creruloplasmin of Normal Human Subjects TABLE Agent Levarterenol Epinephrine Dosage 10 jug/min. 10 jig/min. 20 jig/min. 5 pg/min. 10 ug/min. 10 ug/min. 15 Isoproterenol Serotonin Iproniazid 5% dextrose with water jig/min. pg/min. ng/min. 15 15 5 ug/m‘m. mg/min. mg/ min. 100 mg. orally 0.25 0.50 Ceruloplasmin Control 186 213 292 228 350 144 235 220 188 211 222 196 During Drug Eﬂect 140 232 225 191 347 102 205 200 214 189 224 1' 177 230 225 240 278 182 228 236 160 187 170 __- 141 150 TThis subject alone was markedly agitated during the infusion. N onpsychotic at present, he had been previously hospitalized six times for acute schizophrenic episodes. 319 �A. M. A. ARCHIVES OF NEUROLOGY AND PSYCHIATRY Ccruloplasmin* of Disturbed and Tranquil Subjects Who Were Not Psychotic TABLE 3.——Serum Disturbed Tranquil 262 250 220 222 136 157 154 272 240 lVlean * S. l). 348 230 282 410 263 202 170 181 118 186 156 230 170 120 166 The values are expressed in terms of optical density X10 5. This thesis was tested in 26 consecutively referred clinic patients. Previously, one pa— tient who could not speak English and three whose psychological states were not clearly discernible to the observer were not included, leaving a group of 22 patients. Each subject was interviewed in order to determine his general psychological state. Eleven exhibited disturbed behavior, such as weeping, pacing the ﬂoor, sweating, and tachycardia and/0r admitted to prominent feelings of anxiety and depression. An equal number whose illnesses were not viewed by them as unduly threatening were calm in the clinic setting. Ceruloplasmin levels for the two groups are shown in Table 3. No attempt was made to determine a pre— cise psychiatric diagnosis, but the behavior disturbances in the one group were of neurotic proportions. Increased ceruloplasmin levels in the disturbed group are evident and are signiﬁcant at the 0.001 level of probabil— ity. Comment The correlation of elevated ceruloplasmin with particular types of behavioral disturb~ ances apparently involving an alteration in “feeling state” raises the problem of the mechanism of ceruloplasmin production. In- asmuch as hallucinogenic agents, such as the present one (see also Alkerfeldtﬁ Abood“) seem to stimulate ceruloplasmin production only during the hallucinatory or psychogen— ically disturbed phase, a central mechanism would appear to be involved. It is of par— 320 ticular signiﬁcance that the onset of the enzyme elevation is within minutes after the occurrence of hallucinations or anxiety, suggesting a rather unique mechanism for enzyme production. Contrary to our origi— nal expectations, an elevation in blood pyrocatechol amines, which are apparently endogenous substrates for ceruloplasmin, was not, in itself, a stimulus for increased production of ceruloplasmin, but, rather, caused a decrease in many instances. What increases were noted in the infusion studies were apparently related to anxiety reactions to the manipulative procedures involved’in handling the subjects. Since, in the present studies, no noticeable alterations in feeling state resulted directly from the pyrocatechol amines, it remains to be seen whether in those instances in which such reactions have been attributable to infused epineph— rine8 an elevation in ceruloplasmin does occur. Future studies are aimed at the clariﬁcation of many of these points. The suggestion that changes in cerulo— plasmin may reﬂect alterations in emotional state has been proposed by others. Leach and associates9 have postulated that many environmental factors, including stress, can alter the enzyme level. Meduna4 described a patient who exhibited a high serum cerulo— plasmin >during an acute schizophrenic psychosis and a normal value during a lucid interval. Hoffer10 has noted an increase in a serum pyrocatechol oxidase (presum— ably not ceruloplasmin) during the acute phase of a schizophrenic attack. Schizophrenia is a genetic limitation involving par— ticular enzymes within the brain or elsewhere in the organism. In the face of environmental stress, such limitations be— come prominent, and metabolic products with psychotomimetic properties accumu— late." The psychosis itself is ushered in by the sensory distortions, altered feeling state, and hallucinations so induced. Sub— sequently, when the patient attempts to reconcile his present state with his past ex— perience, the disorganization of cortical function begins. Vol. 79,‘ March, 1958 �CERULOPLASMIN AND NEW HALLUCINOGEN Numerous reports”12 are available on the psychogenic properties of the bella— donna alkaloids, but the effects were quite variable and difﬁcult to interpret because of the many peripheral side-effects, particularly with atropine. JR 318 possessed about one—third of the cholineric—blocking effect of atropine on smooth muscle,‘3 and at the doses used in the present study produced a slight, if any, effect on blood pressure, heart rate, or gastrointestinal tract. Even the more superﬁcial peripheral effects ob— servable with atropine, such as mydriasis and dryness of the mouth, were occasion— ally absent with the doses of JB 318 used. With regard to the possible mechanism of JR 318 and other cholinergic—blocking agents on the central nervous system, very little'can be said. Although the evidence in support of the role of acetylcholine as a chemical transmitter in the central nervous system is not convincing“:15 disturbances in its concentration or action within the central nervous system result in a wide variety of psychic and neurological symp— toms. Many cholinergic agents, such as isoﬂuro— phatef“,17 produce central nervous system disturbances which are apparently associated with the accumulation of acetylcholine in the brain. The observations of Pfeiffer et al.18 that the “muscarinic” component of acetylcholine—like agents, such as arecoline and physostigmine, are of value in the treat— ment of catatonic schizophrenia, suggest a role of acetylcholine in mental disease. There would appear to be a conﬂict between the argument that a cholinergic agent is beneﬁcial in schizophrenia, while a choliner— gic—blocking agent is psychotomimetic; but the neural mechanisms involved in psycho— genic phenomena are much too obscure to justify the comment on this apparent dis— crepancy. What is signiﬁcant is the fact that acetylcholine does seem to inﬂuence psychogenic phenomena and may be of im— portance in the study of mental disease. Ostfeld at al. Summary A recently synthesized atropine—like compound, N-ethyl—3—piperidyl benzilate, induced altered feeling states, visual and auditory hallucinations, and increased se— rum ceruloplasmin in seven of nine patients. Infusion of four pyrocatechol amines— epinephrine, levarterenol, isoproterenol, and serotonin—appeared to have no effect per se on serum ceruloplasmin. Iproniazid, an amine—oxidase inhibitor, was likewise inef— fective. Serum ceruloplasmin undergoes small, but signiﬁcant, increases during psychiatric disturbances of neurotic type and proportions, and decreases by a similar amount during periods of tranquility. Department of Preventive Medicine, University of Illinois College of Medicine (Dr. Ostfeld). REFERENCES Hughes, J. D., and Clark, J. H., Jr. Strontium Poisoning: A Report of 2 Cases, J. A. M. A. 112: 1. : 2500, 1939. J. H.; Sprengeler, E. P.; Leiser, H. A.; Homer, J.; Drukker, A., and Friedman, H. L.: Antispasmodics: II. Derivatives of N—Substituted— 3-Piperidols, J. Am. Chem. Soc. 77:2250, 1955. 3. Biel, J. H.: Personal communication to the authors. 4. Brain Research Foundation, papers read at Medical Conference, Chicago, Jan. 12—13, 1957, by Akerfeldt,5 Abood,8 and Meduna. 5. Akerfeldt, S.: Oxidation of N,N-Dimethyl—p' plienylenediamine by Serum from Patients with Mental Disease, Science 1252117, 1957. 6. Abood, L. G.; Gibbs, F. A., and Gibbs, E.: Comparative Study of Blood Ceruloplasmin in Schizophrenia and Other Disorders, A. M. A. Arch. Neurol. & Psychiat. 772643, 1957. 7. Holmberg, C. G., and Laurell, C. B.: Investigations in Serum Copper: IlI. Ceruloplasmin as an Enzyme, 'Acta chem. scandinav. 5:476, 1951. 8. Hoffer, A.: Epinephrine Derivatives as Potential Schizophrenic Factors, Quart. Rev. Psychiat. & Neurol. 18:27, 1957. 9. Leach, B. E.; Cohen, M.; Heath, R. G., and Martens, 8.: Studies of the Role of Ceruloplasmin and Albumin in Adrenaline Metabolism, A. M.A. Arch. Neurol. & Psychiat. 762635, 1956. 10. Hoffer, A.: Conference on Biochemistry and Mental Disease, University of British Columbia, Vancouver, B. C., Canada, June, 1957. 2. Biel, 321 �A. M. A. ARCHIVES OF NEUROLOGY AND 11. Quigley, J. P.: Mental Disturbances from Atropine or Novatropine to Subjects Under the Inﬂuence of Insulin, J. A. M. A. 10921363, 1937. 12. Wangeman, C. P., and Hawk, M. H.: The Effects of Morphine, Atropine and Scopolamine on Human Subjects, Anesthesiology 3:24, 1942. 13. Ewing, P. L.; Seager, L. D.; Keller, G., and Dodson, D.: Cardiovascular Effects of Some Derivatives, J. Diphenylacetate 3-Piperdy1 Pharmacol. & Exper. Therap. 110217, 1954. 14. Eccles, J. C.: The Physiology of Nerve Cells, Baltimore, Johns Hopkins Press, 1956. 15. Feldberg, W. S.: Central and Sensory Trans— mission, Pharmacol. Rev. 6285, 1954. 322 PSYCHIATRY Koelle, G. B., and Gilman, A.: The Chronic Toxicity of Di—Isopropylﬂuorophosphate (DFP) in Dogs, Monkeys and Rats, J. Pharmacol. & 16. , Exper. Therap. 872435, 1946. 17. Rowntree, D. W.; Nevin, S., and Wilson, A.: The Effects of Diisopropylﬂuorophosphonate in Schizophrenia and Manic Depressive Psychosis, J. Neurol. Neurosurg. & Psychiat. 13:47, 1950. 18. Pfeiffer, C. C., and Jenney, E. H.: The 111- hibition of the Conditioned Response and the Counteraction of Schizophrenia by Muscarinic Stimulation of the Brain, Ann. Nevv York Acad. Sc. 662753, 1957. '- Printed and Published in the United States of America �DEPARTMENT OF PSYCHIATTY EXPERIMENTAL HILLSIDE HOSPITAL GLE. CAKS. MAY-1 4's; N Y. �Vol. 167, No. l MEDICAL LITERATURE ABSTRACTS neuralgic pain from herpes zoster, and in patients with tabetic crisis. R 875 was then given to 8 patients with psychalgia in whom a diagnosis of cenesthopathia associated with depression had been made. In these patients the drug proved to be ineffective; it was tolerated badly and the cenesthopathia frequently was increased. Thus, the effectiveness of the drug in patients with organic syndromes contrasted with its complete ineffectiveness in those with psychalgia. R 875 may be administered orally or subcutaneously; the intravenous route of administration is contraindicated because of the risk of respiratory accidents. Certain undesirable side-effects of the drug, such as malaise, nausea, vomiting, and oc— casionally drowsiness, require care in administering it; rest in bed is advisable, at least for the initial phase of the treatment. the Hearing Level Following Severe Poliomyelitis. R. Batson and F. McConnell. A. M. A. J. Dis. Child. 95:139-145 (Feb.) 1958 [Chicago]. A Study of The authors report on 87 selected, extensively paralyzed patients, between the ages of 5 and 37 years, with poliomyelitis who underwent detailed audiological assessment in order to determine the precise status of auditory acuity. The audiograms obtained from these patients were compared with those obtained during the same period from 2 groups of young adults without poliomyelitis. Near— ly all the pure-tone thresholds in the patients with poliomyelitis departed from the zero decibel reference level by more than 10 db., indicating some depression of hearing acuity as compared with the levels in the control subjects, which adhered ex— tremely closely to the zero decibel reference level, denoting normal threshold of audibility. Inspection of the pure-tone and speech thresholds in the patients with poliomyelitis revealed that more than 75% (28 patients) showed at least a slight depression of acuity which would be considered deviant from the norm. Numerous factors were considered in an effort to clarify the causative signiﬁcance of the reduction in sensitivity to auditory stimuli in the patients with poliomyelitis. Factors such as age, sex, and possible drug therapy were not thought to inﬂuence these results. It was believed that depressed hearing responses could not be attributed to emotional disturbances or lethargy accompanying serious illness, since the patients gave oral responses to speech-hearing tests which required more physical energy than the effort required for signaling in response to pure-tone stimuli. It was found that the duration of disability did not correlate well with the extent of hearing loss. Several patients who were ambulatory and others who were in a wheelchair throughout the day demonstrated the same defect. A signiﬁcant correlation, however, was observed between loss in hearing and loss in 117 vital capacity, in that patients with marked decrease in vital capacity were apt to show signiﬁcantly greater hearing loss. The signiﬁcance of this is not clear, and it may be only a reﬂection of the severity of the disease in a particular patient. Because there are many other clinical symptoms more distressing to the patient and the physician, and since communication with such patients is usually at close range, reduction in sensitivity to auditory stimuli can be easily overlooked even when it reaches moderate proportions of severity. The causative signiﬁcance of this ﬁnding is not clear. New Group of Psychotomimetic Agents. L. C. Abood, A. M. Ostfeld and J. Biel. Proc. Soc. Exper. Biol. 8: Med. 97:483-486 (Feb.) 1958 [Utica, N. Y.]. A group of piperidyl benzilates possessing anticholinergic properties were recently synthesized as possible antispasmodics in the treatment of duodenal ulcer. In the course of therapeutic trials, it was found that the tertiary amine hydrochlorides of the benzilate esters, although active anticholinergics, produced undesirable side-effects, particulary hallucinations. The quaternary ammonium salts, on the other hand, were entirely devoid of such effects. The authors recently obtained a series of such substances and examined their psychotomimetic effects on animals and human subjects. The psychotogenic effects of the N-methyl-S-piperidyl benzilate and related congeners were tested on more than 40 human volunteers. Although some of the patients had limited knowledge of the psychotogenic action of the drugs, the majority of the subjects were completely unaware of their nature. All the agents were tested for their behavioral effects on animals, including some 30 Siamese ﬁghting ﬁsh, 50 rodents, and 5 cats. The action of these agents on the Siamese ﬁghting ﬁsh is comparable to the action described for lysergic acid diethyl amide (LSD) by Abramson. In rodents there were marked behavioral changes, such as initial excitement and marked hyperactivity, spontaneous squealing, lack of responsiveness to stimuli, muscular weakness, and lethargy. The compounds proved to be extremely powerful hallucinogens, in many respects more interesting than LSD and mescaline. When administered in oral doses of 5 to 15 mg. to human volunteers, distinct auditory and visual hallucinations occurred within 1 hour in every individual and recurred periodically for periods up to 10 hours after administration of the drug. Hallucinations were accompanied by gross distortions of visual images and severe alterations in feeling state. A number of subjects exhibited paranoid and megalomanic delusions, while the affective states ranged from a feeling of unpleasantness to extreme terror. Some of the subjects actually carried on conversations with imaginary individuals involving situations datA _ �118 MEDICAL LITERATURE ABSTRACTS ing back 10 to 20 years. The subjects receiving 10 mg. (orally) of N-methyl-S—piperidyl benzilate were in complete loss of contact with the environment for many hours while experiencing dramatic visual and auditory hallucinations. In many respects these anticholinergic agents come closer to simulating clinical psychoses than do mescaline and LSD. Of all the compounds tested for hallucinogenic properties, N-Methyl-S-piperidyl benzilate is the most potent, with the N-ethyl derivative being somewhat less effective. The tetramethyl derivative is considerably less effective than the N-ethyl derivative. The quaternary derivative is devoid of psychotogenic effects. As for the antispasmodic potency, although the 3 substances possessing psychotogenic properties are perhaps the most potent, the remaining compounds are still quite effective. Recurrence of Glioma of Cerebral Hemispheres: Histological Features and Therapeutic Possibilities. I. Papo and R. Tritapepe. Minerva chir. 12:144-31446 (Nov. 30) 1957 (In Italian) [Turin, Italy]. A second surgical procedure was performed on 34 patients with a recurrent supratentorial glioma. At the ﬁrst operation this tumor appeared to be an astrocytoma in 7 patients, an oligodendroglioma in 7, a glioblastoma in 16, and a changing type of tumor in 4. Histopathological changes from astrocytoma to glioblastoma were observed in 1 patient 11 months after the ﬁrst operation. It is possible, however, that areas of glioblastoma were originally present. Atypical areas were found in sections of the oligodendroglioma in 4 patients, who were operated on, from 35 to 103 months after the ﬁrst operation. This phenomenon could justify the differentiation of the oligodendroglioma. The immature and atypical features of glioblastoma became more evident at the second operation. A type of glioma, which originally appeared to be oligodendroglioma with atypical areas, changed into glioblastoma in 1 patient 25 months after the ﬁrst operation. The longest postoperative survival period in patients with astrocytoma was 19 months, in those with oligodendroglioma 21 month, in those with glioblastoma 26 months, and in those with a changing type of glioma 6 months. The authors point out that in most instances there is reappearance of the symptoms of glioma rather than its recurrence. Astrocytoma and oligodendroglioma often change into glioblastoma. There is no evidence to show whether this is due to the intrinsic character— istics of the tumor, to the surgical intervention, or to the x-ray therapy. A gradual higher degree of malignancy seems to develop even in those gliomas which did not originally present a neoplastic structure. Surgical therapy, with rare exceptions, affords no beneﬁt to patients with recurrent glioblastoma but may be considered in patients with recurrent astrocytoma and oligodendroglioma. ].A.M.A., May 3, 1958 GYNECOLOGY & OBSTETRICS Induction of Ovulation in the Human: Therapeutic and Diagnostic Importance. H. S. Kupperman, J. A. Epstein, M. H. G. Blatt and A. Stone. Am. ]. Obst. 8: Gynec. 75:801-309 (Feb.) 1958 [St. Louis]. The authors explain on the basis of a diagram the current status of knowledge of the normal cyclic functioning of the pituitary-ovarian axis. A defect or alteration in any one of this normally sequential series of interactions can result in menstrual irregularities, ovulatory failure, and/0r amenorrhea. It was felt that speciﬁc hormone therapy in properly selected cases of failure of ovulation might artiﬁcially trigger the defective ovulatory mechanism. Since the proposed therapy theoreti— cally was to be speciﬁc for an isolated defect in ovulation, patients with other hormonal imbalances that secondarily inﬂuence the pituitary-ovarian axis were not included in the series. The patients who were euthyroid with normal adrenal function and who menstruated fairly regularly or who menstruated after therapy with progesterone and showed an absence of pregnanediol with a ﬂat basal body temperature were judged as having ovulatory failure and fulﬁlled the criteria established for the “potentially responsive” cases. Those whose only endocrinopathy was failure of ovulation received 20 mg. of conjugated estrogens (equine), administered intravenously as a single dose, not sooner than the 18th day of the menstrual cycle. Of the 40 patients treated, 31 were barren, and 9 were either single women with menstrual irregularities or married women practicing contraception. Nine pregnancies resulted among the 17 infertile patients in whom ovulation was induced after no more than 2 injections of estrogens given intrave— nously at intervals determined by the patients’ own basal body temperature charts. The history of infertility in the 9 women in whom treatment resulted in pregnancy ranged from 2 to 7 years. One of the nonpregnant patients had her ﬁrst spontaneous ovulatory menses in 3 years in the cycle subsequent to the menses induced by estrogens given intra— venously. Three other patients with a history of only infrequently occurring spontaneous ovulatory menses also had normal 28-day cycles for 1 period after that induced by estrogen. Moreover, 4 of the 9 pregnancies occurred during the cycle subsequent to the estrogen-induced ovulatory response. The negative responses were due to mechanical inability of the ovaries to respond to pituitary stimulation, i. e., polycystic ovaries of the Stein-Leventhallike syndrome, where the thickened ﬁbrous tuniCa presents a mechanical barrier to ovulation. Surgical exploration with bilateral ovarian wedge resection was advised in 8 of 12 infertile patients who were negative responders. In each of the 8 patients op- �COUNCIL ON DRUGS 1634 Orphenadrine Hydrochloride.—N,N-Dimethyl-2(o-methyl-a-phenylbenzyloxy) ethylamine hydrochloride—The structural formula of orphenadrine hydrochloride may be represented as follows: [CH3 CH Cy 0 CH2CH2N\ CH3 ' HCI CH3 ~ Actions and Uses.—Orphenadrine hydrochloride, the o-methyl analogue of the antihistamine, diphenhydramine hydrochloride, produces a reduction of voluntary muscle spasm. The effect is central, presumably by an inhibitory action on cerebral motor areas, and resembles the central effects of atropine. Orphenadrine exerts only weak antihistaminic and sedative eHects. It is not primarily a peripherally acting anticholinergic agent since, in therapeutic doses, it produces few of the typical effects on smooth muscle, the eye, or secretory glands which characterize atropine and other peripheral para— sympathetic blocking agents. The skeletal muscle relaxation is not of the type produced by mephenesin or zoxazolamine, since there is no evidence that it interrupts transmission through peripheral neuromuscular pathways. Nor is there any indication that it acts at the myoneural junction in the manner of the curariform drugs; it does not cause ganglionic blockade. Orphenadrine has been used for the symptomatic management of paralysis agitans (Parkinson’s disease). Subjective observations seem to indicate that the drug may bring about beneﬁcial effects in approximately half of the patients so treated. Rigidity is apparently relieved much more readily than is tremor; in occasional patients with severe spasticity, tremor may even be accentuated as the spasticity is relieved. Other salutary effects ascribed to the action of the drug include relief of oculogyria, sialorrhea, diaphoresis, blepharospasm, and disturbances in gait and balance. The drug also exerts a euphoriant effect which is useful in combating the depression and fatigue that frequently accompany this syndrome. In common with other antiparkinsonian drugs, the therapeutic effectiveness of orphenadrine diminishes with prolonged use. For this reason, and because it is considered somewhat less active than other antiparkinsonian drugs, orphenadrine is probably best employed as an adjunct to such other agents as procyclidine, trihexyphenidyl, cycrimine, or benztropine for the treatment of paralysis agitans. It may, however, be tried alone for patients who have become refractory to the other antiparkinsonian drugs. Because of its antispastic effect on voluntary muscle, orphenadrine has been proposed for use in a variety of clinical conditions which may be unrelated in etiology but in which pain due to J.A.M.A., July 26, 1958 skeletal muscle spasm is present. These have been described as sprains, strains, ﬁbrositis, whiplash injuries, noninﬂammatory rheumatic and arthritic states, and torticollis. Although such use might be considered a logical clinical application of the drug’s pharmacological action, the evidence available to date is not adequate to permit a sound conclusion as to the ultimate effectiveness of such therapy. Further studies are also needed to conﬁrm the possible usefulness of orphenadrine in the treatment of the extrapyramidal involvement associated with high doses of reserpine or phenothiazine-type tranquilizing agents. The clinical toxicity of orphenadrine hydrochloride appears to be low, at least with therapeutic doses. Thus far, side-effects have been limited to nausea, dryness of the mouth, dizziness, mild excitation, and occasional hallucinations. Most of these effects tend to subside or disappear with a reduction in dosage. Because of its anticholinergic classiﬁcation, orphenadrine should be administered cautiously to patients with glaucoma, tachycardia, or urinary retention. Dosage—Orphenadrine hydrochloride is administered orally. The usual initial dose is 50 mg. given three times a day. This dosage should then be ad— justed according to the clinical response of the individual patient and the appearance of sideeffects. Preparations: tablets 50 mg. Applicable commercial name: Disipal. Biker Laboratories, Inc., cooperated by furnishing scientiﬁc data to aid in the evaluation of orphenadrine hydrochloride. Pancreatic Dornase.—A stabilized preparation of the enzyme, deoxyribonuclease, prepared by fractional precipitation of aqueous acid extracts of beef pancreas followed by dialysis, sterilization by ﬁltration, and lyophilization. The activity of pancreatic dornase is determined by measuring the rate at which it reduces the viscosity of thymus deoxyribonucleic acid, potency being expressed in terms of units. One unit is an amount of enzyme which causes a drop of one viscosity unit in 10 minutes at 30 C, where the flow-time of water is taken as one viscosity unit. Actions and Uses—Pancreatic dornase is derived from beef pancreas, and, in contrast to the deoxyribonucleases produced by hemolytic streptococci (streptodornase), it is a single nuclease. Like streptodornase, it acts directly upon a substrate of deoxyribonucleoprotein (and deoxyribonucleic acid). The action of pancreatic dornase has been characterized as one of rapid depolymerization, with a resulting decrease in viscosity of purulent material. Pancreatic dornase degrades deoxyribonucleoprotein to relatively large-sized fragments, thus differing from streptodornase, which continues �Vol. 167, No. 13 COUNCIL ON DRUGS Mepazine Hydrochloride. — 10—[(1-Methyl-3—piperidyl ) methyl] phenothiazine hydrochloride—The structural formula of mepazine hydrochloride may be represented as follows: N-CH; < CH2 (II) .3 - HCI Actions and Uses—Mepazine hydrochloride is a phenothiazine derivative with actions and uses similar to, but not identical with, those of chlorpromazine. Although less potent, mepazine is not merely a weak chlorpromazine. Pharmacological studies indicate that it differs from chlorpromazine in that it does not lower the body temperature in rats as does chlorpromazine; it does not antagonize the waltzing syndrome in mice as does chlorpromazine; and it augments carotid sinus reﬂexes in cats whereas chlorpromazine inhibits them. The signiﬁcance of these differences with respect to its clinical usefulness is, at present, unclear. The drug is used principally for its calming or tranquilizing action in the management of neuroses and psychoses in which anxiety, tension, agitation, and increased psychomotor activity are predominant; it is said to exert a selective action to normalize the thinking process of mentally or emotionally disturbed patients. Because mepazine is less potent than chlorpromazine, it does not produce the excessive sedation, drowsiness, and depression which frequently accompany therapy with the latter drug. On the other hand, the diminished potency of mepazine makes it less effective than chlorpromazine for the long—term control of the most severe forms of agitation and tension; it has little or no immediate effect on acute psychotic disturbances. In terms of over-all psychotherapeutic effectiveness, mepazine might be considered to be intermediate between the most potent agents such as chlorpromazine and the milder agents such as meprobamate. Like chlorpromazine and other phenothiazine derivatives, mepazine hydrochloride exerts an antiemetic effect and may be used for the control of nausea and vomiting from a variety of causes. The drug has also been used for its calming effects in surgery, in obstetrics, and in anesthesia. Other reported clinical applications include use in narcotic withdrawal to control restlessness and agitation, in chronic alcoholism to lessen anxiety and tensions, and in advanced neoplastic states to reduce the 1633 quantity of narcotics needed for control of pain. However, sufﬁcient evidence is not available to establish its usefulness for the latter purposes. The acute toxicity of mepazine hydrochloride in experimental animals is less than that of chlorpromazine hydrochloride, and, in general, its clinical use is followed by a somewhat lower incidence of side-effects and untoward reactions. As already indicated, the usual doses produce a calming effect, with little sedation and drowsiness. Although jaundice has not as yet been observed with administration of mepazine, physicians should be alert to its possible occurrence. The drug should not be given to patients with a history of jaundice or liver damage. The most frequent side-effects of mepazine are atropine-like in nature and include blurring of vision, dryness of the mouth, and constipation. Since constipation can lead to more serious forms of intestinal obstruction, it should not be neglected; if necessary, laxatives should be prescribed. Less frequent side-effects include occasional dizziness, tremor, urinary retention, and transient hypoten— sion. The most serious toxic reaction to mepazine is referable to hematopoietic depression. As with chlorpromazine, the drug can produce leukopenia and granulocytopenia. It should, therefore, be used with discretion; peripheral blood cell counts are indicated at frequent intervals during therapy, and patients should be advised to report to the physician immediately upon the onset of fever, sore throat, or marked weakness. Because it potentiates the action of other central nervous system depressants, mepazine is contraindicated in patients under the inﬂuence of large doses of narcotics, barbiturates, or unknown large quantities of alcohol. Dosage.—Mepazine hydrochloride is administered orally. For the treatment of ambulatory neurotic patients, the usual initial dose is 25 mg. three or four times daily. This dosage can be increased every week by increments of 25 mg. per day until the desired effect has been attained. For those psychiatric conditions which are severe enough to require hospitalization of the patient, the initial dose is 100 mg. per day; this may be increased by 50 mg. every ﬁve to seven days. Maintenance dosage for such patients is usually 400 mg. per day or more. For the treatment of nausea and vomiting, the dosage ranges from 50 to 100 mg. per day. Dosage for use in surgical and obstetric patients has not been ﬁrmly established; single doses ranging from 50 to 200 mg. or more have been employed. Preparations: tablets 25, 50, and 100 mg. Applicable commercial name: Pacatal Hydrochloride. ’ �COUNCIL ON DRUGS 1632 the bacteria, as such, responded to the antibiotics, i. e., a transformation of the original bacterial arthritis into a chemical arthritis occurred. If the nodules were originally situated only in the skin (as clinically described) and only later appeared in the subcutaneous fat tissue (as described in the biopsy specimen and at autopsy), one could postulate that originally circulating trypsin caused vascular alterations in the deeper layer of the corium, with resultant skin nodules, and later the circulating lipase resulted in subcutaneous fat necrosis and subcutaneous nodules. Summary A chronic alcoholic patient had episodes of abdominal pain for two years, on the basis of a relapsing pancreatitis. Four weeks prior to his death, he developed swelling and tenderness of the various joints, with chills and fever. This could have been due to a bacterial polyarthritis associated with an acute pulmonary lesion such as pneumonia. The bacterial infection could have precipitated an acute pancreatic fat necrosis, on the basis of a Schwartzman phenomenon. Excessive amounts of circulating enzymes (trypsin and lipase) caused a striking involvement of the extrapancreatic fat tissue, cutaneous and subcutaneous nodules of fat necrosis, and necrosis of the periarticular fat tissue, initiating a chemical polyarthritis. The abdominal symptoms that appeared later were due to extensive J.A.M.A., July 26, 1958 mesenteric fat necrosis. The terminal jaundice was due to hepatocellular damage (toxic hepatitis) secondary to the pancreatic and extrapancreatic fat necrosis. The depression of blood calcium level was characteristic for extensive pancreatic fat necrosis and was due to saponification of the fatty acids liberated from neutral fat by the enzymatic action of pancreatic lipase. References 1. Roberts, N. J.; Baggenstoss, A. H.; and Comfort, M. W.: Acute Pancreatic Necrosis: Clinicopathologic Study, Am. J. Clin. Path. 20:742-764 (Aug) 1950. 2. Balser, W.: Ueber Fettnekrose, eine zuweilen todtliche Krankheit des Menschen, Virchows Arch. f. path. Anat., 90:520-535, 1882. 3. Hansemann, D.: Discussion in Verhandlungen arzt- licher Gesellschaften, Berl. klin. Wchnschr. 26:1115, 1889. Blauvelt, H.: Case of Acute Pancreatitis with Subcutaneous Fat Necrosis, Brit. J. Surg. 34:207-208 (Oct.) 1946. 4. Ponﬁck, E.: Ueber die sympathischen Erkrankungen des Knochenmarkes bei inneren Krankheiten, Virchows Arch. f. path. Anat. 56:534-556, 1872. Scarpelli, D. 0.: Fat Necrosis of Bone Marrow in Acute Pancreatitis, Am. J. Path. 32: 1077-1087 (Sept-Oct.) 1956. 5. Vogel, F. S.: Cerebral Demyelination and Focal Visceral Lesions in Case of Acute Hemorrhagic Pancreatitis, with Consideration of Possible Role of Circulating Enzymes in Causations of Lesions, A. M. A. Arch. Path. 52:355-362 (Oct) 1951. and Brakney, E. L.: Acute Hemorrhagic Pancreatic Necrosis Produced by Local Schwartzman Reaction: Experimental Study on Pancreatitis, J. A. M. A. 1553569574 (June 5) 1954. 7. Richman, A.: Acute Pancreatitis, Am. J. Med. 21:2466. Thal, A., 274 (Aug) 1956. COUNCIL ON DRUGS NEW AND NONOFFICIAL DRUGS Monographs and supplemental statements on drugs described here and in subsequent editions of New and Nonofﬁcial Drugs are based on the evaluation of available scientiﬁc data and reports of investigations. H. D. KAUTZ, M.D., Secretary. Mepazine Acetate.—10-[ ( l-Methyl-S-piperidyl) methyl]phenothiazine acetate—The structural formula of mepazine acetate may be represented as follows : N " CH3 < 0 CH2 ‘ u CH3C OH Actions and Uses.—Mepazine acetate has the same actions and uses as mepazine hydrochloride, except that it is administered parenterally. (See the monograph on mepazine hydrochloride.) Dosage—Mepazine acetate is administered by intramuscular or intravenous injection. For severely agitated psychotic patients, the dose by either route is 50 mg. three or four times daily. For the treatment of severe nausea and vomiting, daily doses of 25 to 75 mg. are injected intramuscularly. Dosage for use in surgical and obstetric patients has not been ﬁrmly established, but single intramuscular or intravenous doses ranging from 50 to 200 mg. or more have been employed. Mepazine acetate may be injected parenterally either as the full-strength solution or as a diluted solution. Chloride or alkaline solutions should not be used as diluents since they cause precipitation of mepazine acetate. Oral therapy with the hydrochloride salt should be substituted for parenteral injection as soon as possible. Preparations: solution (injection) 50 mg. in 2 cc. Applicable commercial name: Pacatal Acetate. �1631 DIAGNOSTIC PROBLEMS Vol. 167, No. 13 with antigenic properties may cause a Schwartzman reaction, and antigenic speciﬁcity is not involved, i. e., the provocative antigen need not be identical with the sensitizing antigen. It may be recalled that, in the case under discussion, the joint involvement was conspicuous early in the course of the disease. There was no deﬁnite evidence of rheumatoid arthritis, either clinically or pathologically. Bacterial polyarthritis, speciﬁcally of gonorrheal origin, should be considered, although a most careful search failed to reveal any evidence for a gonorrheal infection of the genital organs. Gonorrhea] polyarthritis in the early stages shows a serous type of synovitis, and cultures of synovial fluid may be negative. The association of polyarthritis with periarticular fat necrosis and pancreatic fat necrosis raises the following possibilities: 1. There may have been a rheumatoid of coincidence polyarthritis a pure with pancreatic fat necrosis, whereby the peri- The interesting feature of this case was the onset, with polyarthritis followed by the appearance of disseminated subcutaneous nodules, while the abdominal symptoms appeared later. The involvement of the pancreas proper, revealed at autopsy, TABLE 3.—Etiology of Acute Pancreatitis“ I. The common channel theory: reﬂux of bile into pancreatic duct secondary to obstruction of ampulla of Vater a. Calculus at ampulla of Vater b. Spasrn of the sphincter of Oddi c. Edema II. Obstruction of pancreatic ducts by 1. Stone 2. Spasrn of sphincter of ampulla of Vater 3. 4. 5. 6. Fig. 5.—Relatively well-preserved body and tail of pancreas. Large hemorrhagic, chalky, mesenteric mass extends downward from pancreas. III. Alcohol A. Acute B. Nutritional IV. Metabolic disturbances 1. Malnutrition (as it has been produced experimentally by ethionine) was not too extensive; it is possible that extrapancreatic involvement occurred early and was limited to the retroperitoneal space, enabling the escape of pancreatic lipase into the circulation by way of the lymphatics, circumventing the enterohepatic circulation. The resultant high lipase levels may account for the extensive involvement of the joints and skin. The various theories about the etiology and 2. Site Trauma VI. Vascular changes (Necrotizing arteriolitis; periarteritis nodosa) VII. Infection (e. g. mumps, scpticemic, acute cholecystitis?) VIII. Allergic a. Schwart7m3.n phenomenon * Extrapancreatic Fat Necrosis In Literature In Our Case + + ....................... Retroperitoneal fat tissue .................. + + Mediastinal tat tissue ...................... + — Subepicardial fat tissue .................... + Subcutaneous fat tissue ................... + + — Bone marrow ............................... + Central nervous system + (perivascular demyelinization) ........... + — Periarticular fat tissue ..................... + necrosis at the site of the original intradermal Mesenteric fat tissue Hyperlipemia V. pathogenesis of acute pancreatitis are summarized in table 3. An interesting recent theory6 relates acute pancreatitis to the Schwartzman phenomenon, whereby intradermal injection of a cell-free ﬁltrate of Salmonella, followed by intravenous injection of the same ﬁltrate, results in hemorrhagic TABLE 2.—-Sites of Edema of papilla of Vater Tumor of pancreas Squamous metaplasia of the epithelium in the ducts Surgical ligature —— V injection. Using this principle, injection of a bacterial endotoxin in sublethal doses into a pancreatic duct, with a subsequent provocative intravenous injection of the same endotoxin, has produced a fulminating pancreatitis in rabbits. Any substance Richman" (modiﬁed). articular fat necrosis occurred in a site of decreased resistance; but, despite the high incidence of rheumatoid arthritis and the relative frequency of pancreatitis, such a coincidence of these with periarticular fat necrosis has never been reported. 2. The pancreatic fat necrosis in the early clinically latent phase of the disease, with liberation of lipase into the circulating blood, may have led to a chemical polyarthritis due to extensive periarticular fat necrosis. 3. A bacterial (gonorrheal?) polyarthritis preceding pancreatitis cannot be excluded, despite the negative bacteriologic ﬁndings. One might speculate, on the basis of morphologic evidence of a chronic pancreatitis, that the pancreas was already sensitized. A bacterial polyarthritis could then have provided an antigenic provocation for a Schwartzman phenomenon, which led to an acute pancreatic fat necrosis, in the course of which large amounts of circulating trypsin and lipase were liberated. The circulating lipase caused a peri— articular fat necrosis, which in turn caused a proression of the polyarthritis, despite the fact that DEPAR MENT OF EXPERIMENIAL PSYCHIATRY HILLSIDE HOSPITAL GLEN OAKS, N. Y. JUL3 1 ‘5. �elements. 3. The rhythm of 4 -6 cycle/sec in the sub- cortical area disappears completely following administration of chlorpromazine in the dosage of 7.5—10 mg per kg, and does not appear even in response to painful stimulation with electric current; which undoubtedly indicates an inhibitory effect of chlorpromazine on adrenergic elements of these structures. 4. Administration of epinephrine against a background of a pronounced chlorpromazine effect produces a temporary decrease in symptoms of the chlorpromaaine effect on the organism. Accompanying this, there is a tendency to activation of electrical activity in all parts of the brain. 5. Comparison of our data with those in the literature leads us to the conclusion that the adrenergic substrate of the reticular formation exerts a complex inﬂuence on individual structures within the reticular formation as well as on the cerebral cortex. This action is apparently associated with metabolism of adrenergic substances, and for this reason it changes in a reciprocal manner as a result of the action of epinephrine and chlorpromazine. RE FERENCES 1. 2. AGAFONOV, V.G., Zhurn. nevropatolog. ipsikhiatr., 56, ANOKHIN, P.K., No. 2, 94, 1956. XX Mezhdunarodnyi kon— v Briussele (Collected gress fiziologov papers, 20th International Congress of Physiologists in Brussels), 151, M. , 3. 4. 5. 6. ’ 7. 8. 1956; Fiziolog. zhurn. USSR, 43, No. 11, 1072, 1957; Zhurn. vyssh. nervn. deiat.. 9, No. 4, 489, 1959. ANOKHINA, I.P., Zhurn. nevropatologi psikhiatr., 56, No. 6, 478, 1956. BAN'I‘SEKINA, M.M., Biull. eksper. biolog. i med., No. 8, 3, 1959. VERSHININ, N.V., Farmakologiiamchobnik) 137, M., 1952. GAVLICHEK, V., Fiziolog. Zhurn. USSR, 44, No. 4, 305, 1958. DOBRZHANSKAIA, A.K., Zhurn. vyld. nervn. deiat.. 9, No. 1, 22, 1959. POPOV, E.A. and T.A. NEVZOROVA, Zhurn. nevropatolog. No. 7, 559, 1956. 9. SHUMILLNA, 11. 12. 13. 14. 15. 56. A.I., Zhurn. nevropatolog. ipsikhiatr, 56, 10. ipsikhiatr.. No. 2, 118, 1956; Kinf. po vopr. elektrofiziolog. ts. n. s.. Tez. dokl. (Abstracts of Confsnnes on Problems of Electrophysiology of the C.N.S.), 144, M., 1958. BRADLEY, P.B. and A.I. HAUCE, EIG clin. Neurophysiol., 9, 2, 191, 1957. DELL, P., M. BONVALLET and A. HUGELIN, Journ. Physiol., 48, 403, 1956. GANGLOF‘F, H. and M. MONNIER, Physiol. et Pharmacol., acta, 15, l, 83, 1957. RINALDI, F. and H. HIMWICH, Dis. Nerv. System, 16, 5, 1955. ROTHBALLER, A.B., EEG clin. Neurophysiol., 8, 603, 1956. VOGT, M., Journ. Physiol.. 123, 451, 1954. THE ANTAGONISTIC ACTION OF CHOLINOMIMECTIC AND CENTRAL CHOLINOLYTIC AGENTS ON THE EEG OF THE RABBIT P.P. DENISENKO, Division of Pharmacology, Institute of Experimental Medicine, Um}! Academy of Medical Sciences, Leningrad (Received January 21, 1959) Today the presence of cholinerglc synapses in the central nervous system, particularly in the cerebral cortex, is considered an estab— lished fact. The cerebral cortex can be stimulated with acetylcholine (Markosian, 1937; Feldberg, 1950) and various "cholinopositive" substances — cholinomimetics (nicotine, arecoline) and anticholinesterases (physostigmine and diethyl p-nitrophenyl phosphate, or phos- phacol) — which, like acetylcholine, are capable of causing excitation of choline-roactive systems (Rizzolo, 1929; Miller, 1037; Stewart, 1952; Michaells, Finesinger, Ver— ster, Erickson, 1954). The rate of proﬁle- tion of acetylcholine in the cortex depends on the functional state of the cortex (Macintosh and Oborin, 1953). The establishment of the role and significance �of aeetylcholine in the activity of the cortex and other parts of the brain has aided in the under— standing and the correct evaluation and interpretation of the inﬂuence of cholinolytic drugs such as atropine, scopolamine, etc. upon psychic activity. ()1 the other hand, it has given rise to the synthesis and investigation of new sub- stances with cholinolytic action, inasmuch as this opens up an opportunity for entirely new methods in drug therapy of psychic and nervous diseases and increases the armamentarium of sedative and anticonvulsive drugs, as well as antidotes for poisoning with anticholinesterases. Among the cholinolytics known today there are a considerable number of substances capable of exerting a blocking inﬂuence chiefly on cholinergic structures in the central nervous system. Owing to the obvious predominance of central cholinolytic action over peripheral, substances of this type have, at the suggestion of S.V. Anichkov, been classed in a separate group — central cholinolytic agents.1 In chemical structure, central cholinolytic agents in most cases are complex esters of amino alcohols and aromatic acids, such 'as diethylaminoethanol and diphenylacetic acid. Pharmacologic studies of central cholinolytic agents are conducted by various methods, especially the methods of conditioned reﬂexes and electroencephalography; among others are experiments with convulsions produced by nicotine, arecoline, pentylenetetrazol, and other ' drugs. As research, electroencephalography is being increasingly widely used. However, out of the large group of cen— tral cholinolytic agents, this method has been used only for partial investigation of caramiphen (Pentaphen, Parpanit), benactyzine (IEMa method of 22, Diazil), and Z—diethylaminoethyl diphenylacetate (Diphacil, Trasentine) (Schallek and Smith, 1952; Paskov, 1958). In the current study an electrophysiological investigation was made of five new substances synthetized by S. F. Torf in the chemical lab— oratory of the Division of Pharmacology, In— stitute Fxperimental Medicine, USSR Acad— emy of Medical Sciences: Preparation IBM263 (benzene sulfonate 0f l—diethylaniinoisopropyl methoxyd l pheny lacetate . Preparation IEM-265, or Methyldiphacil (racemic l—diethylaminoisop ropyl diphenylacetate hydrochloride), Preparation [EM—268 (racemic 1-dimethyl aminoisopropyl diphenylacetate hydrochloride), Preparation [EM—273 (benzene— sulfonate of 2-methylcholine diphenylacetate), Preparation IBM—275, or Methyldiazil (racemic l «timethylaminoisopropyl benzilate hydrochloride». We also made a comparative study of the influence of certain other central cholino1 ‘The term "central cholinolytic agent" was approved and accepted at the 9th All-Union Conference of Physiologists, Biochemists, and Pharmacologists in 1959. 125 olytic agents, namely Diphacil, Diazil, Pentaphen, Aprophen (ﬂ-diethylaminoethyl diphenylpropionate hydrochloride), Diprophen w—di-Npropyl thiodiphenylacetate hydrochloride), and Tropacin (tropine diphenylacetate hydrochloride) upon the bioelectrical activity of the brain. METHOD Experiments were conducted on rabbits weighing 3 —4 kg with implanted nichrome or platinum electrodes. Potentials from the cortex (temporal and occipital areas), thalamus, and hypothalamus were recorded unipolarly. Experimental equipment consisted of a differential amplifier from the Moscow experimental shop and either an ink-writing or a type MPO—2 oscillograph. The amplitude—frequency characteristic of the ink-writing apparatus in the O — 70 cycle/sec range was flat to within 20%. The inﬂuence of the central cholinolytics, as well as of acetylcholine and cholinomimetics (nicotine and arecoline), on the spontaneous electrical activity of various parts of the brain was investigated. In addition, electroencephalography was used to show the existence of antagonism between these two groups of substances. No substance was administered to the same animal more than once a week. EXPERIME NT A l. RESULTS Before proceeding with the study of the in— ﬂuence of central cholinolytic agents on the electrical activity of various parts of the brain, we considered it necessary to determine how it changes under the influence of acetylvholine and cholinomimetics (nicotine and arecoline). This was essential because one of the tests in the study of substances of central cholinolytic action involves a determination of their anticonvulsive activity in nicotine and arecoline convulsions (Bovet and Longo, 1951; Kharauzov. 1954; Artem'ev, 1955. 1957; Zeimal', 1955, 1957; Golikov, 1956; Liberman, 1956; Sokolova, 1957; Smirnov, 1957; Fedorchuk, 1958; Jacobson, 1958). Intravenous injection of nicotine and arecoline (0.4 mg/kg) produces tremor and convulsions in the animal due to the stimulating effect of these substances on the choline—reactive systems of the brain. For further evaluation and analysis of the influence of central cholinolytic agents on the bioelectrical activity of the brain it was important to compare the picture of general excitation of the animal with the changes in the electrical potentials of the brain. Normally, the electrocorticogram of the rabbit was made up chieﬂy of waves of medium amplitude (30 -60 uv) and a rate of 4 —9 per second. Superimposed on these we re fast small waves with an amplitude of up to 15 av. Occasionally single high-amplitude waves appeared (5 —8 per min). As a rule, potentials �large doses (0.4 -0.5 mg/kugi. 1.9. .dosos which usually cause a convulsive seizure is animal. In the last case we recorded simultaneously the champs in brain potentials and of the thalamus and hypothalamus, were faster than those of the cortex but of considerably smaller amplitude (Fig. 1. 1-3; Fig. 2, 1-3; l-‘ig. 3). .l FIG. 1. Influence of nicotine and Diphacil on the RH; - - - somatosensory cortex; B hypothalamus. l normal EEG; 2 — 3 min after intravenous administration of nicotine in a dose of 0.43 mg/kg; 3 — prior to administration of Diphacil (6 days after the initial application of nicotine); 4 — 5 min after intravenous administration of Diphacil in a dose of 5 rug/kg; 5 — absence of stimulating action of nicotine (0.43 mg/kg) administered after Diphacil; 6 — 4 hours after administration of the preparations. A Cholinomimetics (nicotine and arecoline) were used in small doses (0.25 mg/kg) and the contractions in the hind limb. After the administration of choiinomimstios 126 �no FIG. 2. Antagonism of cholinomimetic arecoline and choline— lytic Methyldiazil displayed in the rabbit EEG. A — - somatosensory cortex, B thalamus. 1 — normal EEG; 2 — 3 min after administration of arecoline in a dose of 0.45 mg/kg; 3 restoration of original state; 4 — 5 min after intravenous- administration of Methyldiazil (0.5 mg/kg); 5 — absence of stimulating influence of are coline in the same dose after Methyldiazil; 6 — 8 hours after administration of the preparations. - the animal's behavior changed abruptly, espe— cially if administration occurred against a background of general depression which was usually observed after the rabbit had temporarily been in a darkened room. Whereas prior to the ad— ministration of the preparations the rabbit lay quietly in its stand with its head between its paws and at times even semi-asleep, following administration of nicotine or arecoline it exhibited unrest, turned its head, jerked, pricked up its ears and reacted keenly to any external stimulation. Mter epinephrine was given intravenously in the dose of 0.4 mg/kg, severe convulsive movements were observed lasting, with interruptions, for several min— utes. Along with the changes in the behavior of the animals already mentioned, there were also marked changes in the spontaneous elec— trical activity of the brain (Figs. 1 and 2). These changes took the form of an increase in amplitude and number of the high—frequency potentials and quantitative diminution, to and including complete disappearance, of high- �FIG. 3. EEGs in various parts of the rabbit brain before (upper oscillograms) and 5 min after (lower oscillograms) intravenous administration of central cholinolytic agents in the following doses: Diazil 0.5 mg/kg (A), Diphacil 5 mg/kg (B), Aprophen 2 mg/kg (C). Left, cortex; right, subcortical structures. amplitude slow waves. Changes in the EEG appearing after administration of nicotine evidently are not the result of induction of muscle currents but reflect changes in the electrical activity of the brain. inasmuch as they precede motor excitation of the animal. Such a supposition appears to be even more probable because 10 — 15 min after the strongest general excitation produced by administration of nicotine, the rabbit calms down (muscle tone becomes normal, movements decrease or disappear, and the animal reposes quietly in its stand) . Simultaneously with this, lowering of general EEG activity is observed, with an increase in the number of abrupt high waves and a diminution of the high-— frequency discharges. Comparison of changes in the EEGs of different parts of the brain discloses that follow— ing administration of nicotine cortical potentials show the first and strongest changes. Changes in the EEGs of the hypothalamus, thalamus, and other subcortical structures are less pronounced and appear later than the cortical changes. The other cholinomimetic, arecoline, in doses of 0.4-0.5 mg/kg also had a stimulating action: it caused unrest. convulsions, and tremor, which, as is generally recognized, are the result of the stimulating action of are— coline on the choline-reactive systems of the brain. The stimulating action of arecoline on ~ 128 the brain is reﬂected in the EEG to the same extent as is that of nicotine. As shown in Fig. 2, the amplitude of the fast oscillations, especially in the subcortex, rises sharply and the number of oscillations increases appreciably. Typical changes characteristic of excitation appeared in the EEG following intravenous injection of acetylcholine in doses of 0. l - 0. 8 ‘y/kg. In doses of 1 ~50 'y/kg acetylchouno produced such changes only du ring the first, very brief timevinterval after the injection; this was followed by a pronounced depression of electrical activity. Thus, in experiments with cholinomimetics (nicotine and arecoline) and acetylcholine. a characteristic picture of EEG changes a» crease in amplitude and number of fut rhythms and a decrease in slow waves) was produced which in combination with changes in the general condition and behavior of the rabbits (excitation, tremor, convulsions) permits us to regard, with a high degree of probability, the observed picture of EEG changes as a roll..tion of cerebral excitation. In addition, a clear—cut distinction was observed between the action of nicotine and arecoline on the cholinergic systems of the brain: the first and most marked changes uder the inﬂuence of nicotine are in the cortical EEG, but under the inﬂuence of arecoline, in the subcortical structures. The changes produced by �arecoline and nicotine are not identical in duration. The intensification of activity prochiced by administration of nicotine lasts a maximum of 10—15 min and is often succeeded by a general dqreesion of electrical activity. Potentials of normal magnitude and rhythm appear in l - 1 1/2 hours, but the sensitivity of the cholinsrgie systems to nicotine and mani— festation of the corresponding reaction to nicotine are not restored for 4 -—5 days. Arecoline a more lasting excitation which is succeeded by the normal EEG picture. 0n repeated one hour after the first injection, one may observe complete restoration of sensitivity b arecoline. Ahinistration of central cholinolytic agents gave opposite results. General calming of the animal was observed following administration of cholinolytic agents. This was manifested especially prominently when central cholinolytic agents were administered to animals which had not yet become accustomed to the stand and the experimental conditions, or when the prepara— tions were administered at the very beginning of the experiment when the rabbit remained somewhat excited. In such instances the ad— ministration of a cholinolytic agent caused jerking of the paw, attempts to escape the stand, head movement, and reactions to external stimuli (noise, light, and sound) to disappear immediately. Two to five minutes following admin— istration of Diphacil, Diasil, Pentaphen, Aprophen, and other substances in the group under investigation, the state of unrest was succeeded by general depression. of an intensity which depended on the dose of the cholinolytic agent. The rabbit lay quietly in the stand and reacted feebly to external stimulation. Simultaneously with the change in the state and behavior of the animal, characteristic changes were also observed in the electrical activity of the brain: slow waves (1 - 2 per sec) lg) to ”0 v predominated in the EEG. High— a potentials disappeared entirely or marke‘y decreased in number (Figs. 1, 2, 3). These cheapo in electrical activity following the injection of central cholinolytic agents could be registered in all portions of the brain which were under study. The intensity and duration of theee depended on the dosage of the agents admhistened as well as on their properties. This. similar changes could be observed following intravenous administration pm Motion frwy We of Diphacil. 5 mar/ks. Wen, Mammal-oil. 2 mar/ks; mg/kg; Diaail, 0.6 mg/kg; Methyl— easu. 0.1 mg/kg; and Diprophen, 15 mg/kg. other hand, intravenous administration cholinolytic agents in identical heee redted in dissimilar changes in the thalamus. and hypothalad cortex, such as Diazil and Methylmus. Motions dis-ll greater changes in the potentials of the structures than of the cortex. whereas administration of Methyldiphacil and Diﬂlacil renlted in greater changes in the cortex. Under the influence of Pentaphen. 1 it.eeet ~ ‘ I” h a“ Meal 129 131’ Aprophen, and to some extent Methyldiphacil, changes in the EEGs cf the cortex and subcortex were approximately identical (Fig. 3). Duration of the action of the preparations under study varied between 2 and 30 hours depending, apparently, on the dosage and their physico-chemical properties. The strongest and most lasting effect was observed after the administration of Diazil and Methyldiazil, and the weakest and shortest after administration of [EM-268 and Diprophen. Thus, experiments with central cholinolytic agents showed that they cause general depres— sion of the animal, a decrease in reﬂex activity and characteristic changes in the EEG (predominance of slow, high-amplitude potentials). Comparison of changes, following administra— tion of central cholinolytic agents, in behavior, general condition, and EEG, which were oppo— site to those seen after administration of cholinomimetics (nicotine and arecoline), per— mits the conclusion that the EEG changes produced by central cholinolytic agents reﬂect a state of cerebral depression due to blocking of the cholinergic systems of the brain. From our own and published data we knew of the antagonistic relationships between cholino— lytic and cholinomimetic agents that have been demonstrated on peripheral structures as well as in experiments with conditioned reﬂexes and with nicotine and arecoline convulsions. It was of interest to find out whether these antagonistic relationships are exhibited in the EEG. A special series of experiments were therefore carried out for the purpose of investigating the influences of central cholinolytic agents on the EEG already altered by the administration of cholinomimetics, and vice versa. It was found that central cholinolytic agents in definite doses prevent and cancel the action of cholinomimetics. As shown in Fig. 1, Di— phacil prevented the action of nicotine administered in a dose which usually produced a pro— nounced rise in electrical activity. Convulsions were the external manifestation of the stimulating inﬂuence of nicotine on the brain. Nicotine administered after Diphacil, Methyldiphacil, Pentaphen. and other preparations never pro— duced convulsions. Similar results were obtained wiﬂi arecoline: preliminary administra— tion of Methyldiazil prevented the effect of a convulsive dose of arecoline (Fig. 2). Figs. 1 and 2 show that normally both of these cholinomimetics exerted a pronounced inﬂuence on the EEG. Their administration in the same doses against a background of action by central cholinolytic agents was without effect; the EEG remained the same as after administration of central cholinolytic agents Diphacil and Methyldianil. In these experiments there were also data indicating a certain preferential antagonism batman arecoline and Diazil or Methyldiazil and between nicotine and Diphacil or Methyldiphsoil. Preparations such as Pentaphen and Aprophen prevent and cancel the action of - �arecoline and nicotine equally effectively. as application clinical for agents tion of these cholinolytics and tranquilizers. DISC U$ION REFERENCES experi— the of the course in clear It became experito an administration following ments that (Diphacil, preparations older of animal mental as and others) Aprophen. Pentaphen, Diazil, S.V.. In the book: Novye i eksperimente v sredstva lekarstvennye 1. ANICHKOV. and in experiments klinike (New drugs clinic), 5. L.. 1958. protivosudo— Izyskanie V.S., ARTEM'EV, 2. rozhnykh sredstv metodom eksperimental'anticonvulsive for search (A noi terapii agents by the method of experimental 1955; L. Dissertation. , therapy). i atsetilkholina rol' Fiziologicheskaia izyskanie novykh lekarstvennykh of role physiological (The veshchestv new for search the and acetylcholine drugs), 1. L.. 1.957. soveshch. dokl. Tez. GOLIKOV, S.N., 3. i claim. strukt. mezhdu sviazi p0 probl. the of (Abstracts veshchestv lekarstv. between Connection the on Conference 13, of Drugs), Action and Structure Tarw, 1956. dokl. Tez. iref. 4. DENISENKO, P.P., deiat. nervn. vyssh. probl. soveshch. p0 Problems on Conference the of (Abstracts of Higher Nervous Activity). No. 1, ‘6, 1... 1958. 1 mom. 5. ZEIMAL‘, E.V., Biuli. eksper.book: the in 1955. 42, 1, 39, med., Fiziologicheskaia roi' atsetilkholinai izyskanie novykh 106m rstvennykh of veshchestv (The physiological role new for search the and acetylcholine drugs), 79, 1... 1957. itoksiFarmakolog. LIBERMAN, 5.8., 6. kolog.. 6, 10, 1956. bioBiull. eksper. A.A., MARHEIAN, 7. 1937. 4 119, (2), med., log. Farmakoiogicholtm D.S., PASKOV', 8. GEM-275), Methyldiazil — agents well as newer — sigIBM-268 and (IBM-265), Methyldiphacil slow EEG: large the in develop nificant changes be— waves medium and waves appear and small be may changes These come less numerous. of cere— state of a manifestations regarded as confirmed interpretation an bral depression, the of experibehavior and condition the by mental animals. The depressant effect of central cholinolytic nature, cholinolytic of a is brain the agents on action the cancel and prevent inasmuch as they (nicotine, cholinomimetics and of acetylcholine stimu— a exert themselves which by arecoline), some is There brain. the on influence lating already which was antagonism, preferential discussed earlier. more one as serve hand, one on These data, synapses cholinergic of existence the of proof other the on system; nervous in the central the that proof convincing hand, they provide not characteristic is central cholinolytic effect of an but agents, cholinolytic individual only of of esters (complex entire class of compounds acids) which have amino alcohols and aromatic been called "central cholinolytic agents." and new that hope to Our data permit us found be posmay agents cholinolytic powerful Two action. central sessing a predominantly —- [EM-265 (Methyl— of the preparations studied — are (Methyldiazil) IBM-275 and diphacil) and tranquilizers as trials undergoing clinical cholinolytic drugs. 1 CONC LU SION'S to used was Electroencephalography 1. of properties cholinolytic establish the central complex representing of substances a number and aromatic diethylaminoethanol of esters acids. in manifested 2. A pronounced antagonism, central between exists EEG, their action on the agents. cholinomimetic and cholinolytic be— interdependence 3. There is a definite of action the and tween the chemical structure to the degree cholinolytic agents. According study under the preparations of vigor of action, of diminorder following the in may be arranged ishing strength: Methyldiphacil, and Aprophen phen, Diprophen. and IBM—268, Preparation chocentral the 4. The EEG data regarding esters complex of series of this ytic action recommenda— the which permits investigations u kharakteristika alkaloids Mann antikholinesteraznogv sredstva (Pharma— alkaloid of the characterizatmn cological Disantichoiinesterase), an nivaline as sertation, L.. 1958. rol' Fiziologicheskaia 9. SOKOLOVA, LA. . atsetilkholina i izyskanie novyldl vennykh veshchestv (The phydol“ role of acetylcholine and the 1957. 122, L., drugs), new 1 Parmakolog. 10. FEDORCHUK, IU. G.. 130 imh m ' toksil<olog., 4, 52, 1953. 11. KHARAUZOV, giperkine zov N.A., Farmakoterapﬂl tsentral'nogo proiskhoal- hyper“ deniia (Pharmacotherapy of of central origin). Dissertation. L.. 1954; Izbiratel'noe vliianie lekar not.” tsentral'nuiu na veshchestv nykh of influence (Selective nuiu sistemy -_., L.. system). nervous central the on ' ‘ �13. FELDBERG, W., Brit. Med. Bull., 6, 11, 312, 1950. 14. JACOEON, E... Antibiot. Med. a. Clin. Therapy, 5, 2, 89, 1958. 15. MACINTOSH, F. and P. OBORIN, Abstr. Comm. XIX Intern. Physiol. Congr. 580, Montreal, 1953. 16. MICHAELIS, M., J.E. FINESINGER, F. VERSTER and R.W. ERICKSON, Journ. Pharmacol., III, 2, 169, THE EFFECTS OF 17. 18. 19. ' 20. 1954. MILLER, F.R.. Journ. Physiol., 91, 2, 212, 1937. RIZZOLO, A., Arch. Farmacol., sper.,50, 16, 1929. Tsit. p0: Chem. Abstr., 24, 1158, 1930. SCHALLEK, W. and 1LT. SMITH, Journ. Pharmacol., 104, 3, 291, 1952. STEWART, W., Brit. Journ. Pharmacol., 7, 2, 270, 1952. HYPOCAPNIA ON THE FUNCTIONAL STATE OF THE RESPIRATORY CENTER G.L. FEL’DMAN, Department of Human and Animal Physiology, State University, Rostov-on-Don (Received January 8, 1960) METHODS The question of the physiological mechanism and biological function of sleep has long interested investigators (Legendre and Pierron, 1913; von Eoonomo, 1925; Hess, 1949; and others) and has also been the subject of syste— matic study in experiments conducted at the Pavlov Laboratory (Pavlov, 1911, 1923, 1935; Krasnogorskii, 1911; Rozhanskji, 1913; Petrova, 1941; Asratian, 1953; Anokhin, 1958). Ole method adopted for exploring the nature of sleep inhibition and its effect on normal behav— ior of the brain is that of artificial sleep depri— vation. Thus, as early as 1891, M.I. Manasseina demonstrated that keeping puppies awake for a period of 4 to 5 days will lead to death by degeneration of the nervous tissue of the brain Legendre and Pierron (1913) described histo— logical changes of the neurons in the region of the motor analyzer in the cerebral cortex of adult dogs deprived of sleep for 7 days. Prolonged sleep deprivation produces severe derangement of brain function, manifested in a derangement of the processes regulating biochemical activity (Fedorov and Sikolskaia, 1M1), nervous breakdown (Ukolova, 1959), and so on. Reports by N. Kleitman (1923), N. Kleitman and M. Li (1923), Tyler (1955), Bredlend (1955), and others, describe changes during experiments in sleep deprivation in The present study was conducted on 34 ani— mals (10 kittens between 18 and 30 days old, 13 kittens between 35 and 55 days old, 6 adult cats, and 5 puppies between 25 and 40 days old), with electrodes chronically implanted according to the method described by A. B. Kogan (1952). The electrodes were implanted in the region of the motor and visual analyzers of the cortex and in the subcortical sections of the brain. Potentials were recorded bipolarly with an interval between the electrodes of 3 mm for the surface electrodes, 1.5 mm for the depth electrodes. Recording was done with a two—channel electroencephalograph with optical recording or a four—channel ink-writing electro— encephalograph. Physiological tests were made of the effects of a sound stimulus (intermittent siren twice per second) and a tactile stimulus (an air current). Parallel with this, and with the same chronically implanted electrodes, determinations were made of the thresholds for direct electrical stimulation of the correspond— ing points in the brain. For purposes of comparison, we studied the intensity relationships for the motor components of the natural conditioned food reflex (Varukha, 1954) and coordination tests in which we analyzed the placement of the footprints made by the animals in walking. Throughout the period of wakefulness the animals were permitted to move about without restraint and were constantly observed under natural light by day and bright elect‘ric illumination at night. We kept the humans. Thus a study of the effects extended wake— fulness has upon brain function as revealed in the EEG and other indicators of. the functional state of the brain is a matter of definite interest. 131 �may be somewhat wider than the actual distribution, due to analytical errors and biological variation in the ratio of single bone to whole skeleton. It is predicted that in 1966 the average young child in the world will have a skeletal concentration of strontium-90 of about 4 MIC of strontium-90 per gram of calcium; that 10 percent may have a concentration of 8 one; that 1 percent may have a level of 20 uuc; and that none will have a level exceeding 80 one of strontium-90 per gram of calcium. References and Notes 1. Lamont Geological Observatory Contribution No. 347. This research is being supported by the Division of Biology and Medicine of the U.S. Atomic Energy Commission. Many individuals have contributed valuable suggestions and criticism. These include E. C. Anderson, C. L. Dunham, M. Eisenbud, H. Hollister. W. H. Langham, W. F. Libby, J. F. Loutit, L. Machta, W. G. Marley, N. G. Stewart, H. L. Volchok, and H. Q. Woodard. We also express our gratitude to the many medical doctors around the world who have assisted in essential sample procurement. Rieta Slakter is in charge of the Lamont analytical laboratory. R. Alley, W. Blake, T. Bott, J. Brokaw, D. IO :55» 5. 6. 7. 8. 9. 10. 11. 12. Harlin, M. Mandel,.._G. Markle, J. Rippey, J. Sonderburg, and R. lWoehr assisted in various aspects of the techniCal and secretarial work. J. L. Kulp, W. R. Eckelmann, A. R. Schulert, Science 125, 219 (1957). W. R. Eckelmann, J. L. Kulp, A. R. Schulert, ibid. 127, 266 (1958). The two commercial laboratories were Isotopes, Inc., Westwotid, N.J., and Nuclear Sci— ence and Engineering Corp., Pittsburgh, Pa. H. L. Volchok, J. L. Kulp, W. R. Eckelmann, J. Gaetjen, Ann. N;.Y. Acad. Sci. 71, l, 293 (1957); H. L. Volchok and J. L. Kulp, Nucleonicr 13, 49 (1955). D. L. Thurber, J. L. Kulp, E. J. Hodges, P. W. Gast, M. Warhpler, Science 128, 256 ' (1958). A. R. Schulert, E. A. Peets, D. Laszlo, H. Spencer, M. Charles, J. Samachson, Intern. ]. Appl. Radiation and Isotopes 4, 144 (1959). A. R. Schulert, E. J. Hodges, E. S. Lenhoff, J. L. Kulp, Health Phys., in press. J. L. Kulp and R. Slakter, in preparation. F. J. Bryant, A. C. Chamberlain, G. S. Spicer, M. S. W. Webb, Brit. Med. ]. l, 1371 (1958). Health and Safety Lab. U.S. Atomic Energy Comm. Publ. No. HASL—42 (16 June 1958). J. L. Kulp and R. Slakter, Science 128, 86 (1958). D. V. Booker, F. J. Bryant, A. C. Chamberlain, A. Morgan, G. S. Spicer, Atomic Energy Research Establ. (G. Brit.) Publ. No. HP/R 2182 (1957); F. J. Bryant, A. C. Chamberlain, A. Morgan, G. S. Spicer, Atomic Energy Research Establ. (G. Brit.) Publ. No. HP/R 2056 (1957). H. H. Mitchell, T. S. Hamilton, F. R. Steg~ 13. 14. Isosterism and Competitive Phenomena in Drugs q_ A study of structure-activity relationships in agents acting upon autonomic effector cells Daniel Bovet Making use of the considerable means offered by organic synthesis, many investigators have directed their efforts to the ﬁeld of therapeutics and have sought to lay the groundwork for a pharmaceutical chemistry or, better, for a chemical pharmacology. If such an ambitious program has not yet been fully realized, nevertheless, during the last ﬁve decades, one can notice the emergence of a few basic concepts whose usefulness continues to be conﬁrmed. This is particularly true of the concepts of isosterism and of competition. Numerous drugs were ﬁrst derived from products of biological origin, par- ticularly the alkaloids. The elucidation of their structure helped chemists to embark on syntheses of analogous compounds. In this respect cocaine, atropine, 8 MAY 1959 and morphine are good illustrative examples. The molecules synthesized according to their models exhibited clinically useful anesthetic properties, spasmolytic activity, or pronounced analgesic effects. In each case, chemical similarity produces in-some-way-related physiological properties. Analogous observations have subsequently been gathered in many other ﬁelds, but it has also become evident that sometimes very different, even antagonistic, pharmacological properties may be found in chemically similar molecules. Despite the fact that the concept of “antimetabolite” is based on rather old experiments, it was deﬁned essentially in the ﬁeld of “antivitamins”; the work of Woods (1940) and Fildes (1940) on 15. 16. 17. 18. gerda, H. W. Bean, J. Biol. Chem. 158, 625 (1945). H. Spencer, D. Laszlo, M. Brothers, ]. Clin. Invest. 36, 680 (1957); “Deposition and Retention of Ingested Strontium-90 in the Skeleton" (Washington, D.C., 23 Apr. 1957), committee report (ofﬁcial use only). C. L. Comar, R. H. Wasserman, M. M. Nold, Proc. Soc. Exptl. Biol. Med. 92, 859 (1956). C. L. Comar, I. B. Whitney, F. W. Lengeman, ibid. 88, 232 (1955). Consumer: Repts. 24, No. 3, 102 (March 1959). 19. J. L. Kulp, A. N. Kaufman, R. S. Slakter, W. R. Eckelmann, in preparation. 20. Health and Safety Lab. U.S. Atomic Energy Comm. Publ. No. HASL-5I (10 Nov. 1958). 21. L. Machta and R. J. List, “Stratospheric data and meteorological interpretations,” paper presented at a meeting on “ABC—sponsored Research and Development Related to the Collection and Classiﬁcation of Atmospheric Particulates,” held in Minneapolis, Minn., Oct. 1958. 22. W. F. Libby, Proceedings symposium on Noxious Eﬂects of Low Level Radiation, Schweizerischen Akadcmie der Medizinischen Witsenschaften 27-29 Mar. 1958, p. 309. 23. R. S. Russell, Nature 182, 834 (1958). 24. Unpublished data from the Lamont Geologi8—9 25. 26. 27. 28. cal Observatory, Palisades, N.Y. A. M. Brues, Science 128, 693 (1958). M. P. Finkel, ibid. 128, 637 (1958). E. B. Lewis, ibid. 125, 969 (1597). F. J. Bryant, E. H. Henderson, G. S. Spicer, M. S. W. Webb, Atomic Energy Research Establ. (G. Brit.) Rept. No. C/R 2583 (May 1958). the antisulfonamide component of yeast and its identiﬁcation as p-aminobenzoic acid found a large acceptance. The idea that a compound structurally similar to one normally present in the organism is able to interfere with the function of this metabolite could be applied in many ways. Its success, especially in enzymology [where, for the ﬁrst time, it was clearly formulated by Quastel (1925— 1928)], in chemotherapy, in vitaminology, and in endocrinology, obviates a detailed discussion of the underlying physi-L cochemical and biological principles. Instead, I would like to draw your attention to the importance of studies of competitive phenomena in pharmacodynamics, especially in the pharmacology of drugs of the autonomic nervous system. I would like to show how a very large part of therapeutical chemistry depends on the relations between many alkaloids or synthetic compounds and a few hormones, chemical transmitters, and products of tissue metabolism of rather simple chemical structure: epinephrine and norepinephrine, acetylcholine and propionylcholine, histamine, and 5-hydroxytryptamine (Table 1). Dr. Bovet is head of the department of therapeutic chemistry at the Istituto Superiore di Sanita, Rome, Italy. This article is a translation of his Nobel lecture, presented 11 December 1957, when he was awarded the Nobel prize for medicine and physiology for 1957. It is reproduced here with the permission of the Nobel Foundation. We are indebted to Dr. Ernest Schoffeniels of the department of neurology. College of Physicians and Surgeons, Columbia University, for the translation. 1255 �Drugs of the Autonomic Nervous System The history of the research in this ﬁeld is one of the most spectacular and successful chapters in the chemistry and physiology of the alkaloids and hormones. As far as transmitters of the sympathetic system are concerned, one may recall that the isolation of epineph— rine by Takamine (1901) was preceded both by empiric application of ephedrine-rich mahuang by the Chinese, and by the fortuitous discovery of the properties of tetrahydronaphthylamine by Bamberger (1888). The exact signiﬁcance of norepinephrine has been established only recently, by von Euler (1946). In the ﬁeld of parasympathomimetic agents, the observation of the properties of muscarine (1811) and the synthesis of acetylcholine (1866) preceded, by a century and a half century, respectively, the discovery of acetylcholine of Loewi (1921) and its isolation from tissues (1931). Histamine was synthesized (1907) shortly before its identiﬁcation in the products of animal and plant origin and before Dale and Dudley (1910) began their well-known studies of its pharmacological properties. The recent discovery of 5-hydroxytryptamine (Rapport, 1949) is the culmination of the work of Erspamer on enteramine isolated from enterochromaﬂin cells (1937—1952) and the work of Rapport, Green, and Page (1947— 1948) on the vasoconstrictor factor of serum, serotonin. The relationship between epinephrine, (CH2) /COO.CH2.CH2.N(CH3)31 “\COO.CH2CH2N(CH3)3 1 £5 E I34 8 0- 3 7 a% 2 w .=‘ - 3 g . 0 Fig. n=12345 Curarizing effect of choline esters 8 1. and dicarboxylic aliphate acids with normal chains. Curarizing activity was established in rabbits by measuring the “head dro P ” dose of the various compounds given intravenously. Curarizing activity reaches a maximum with succinylcholine and decreases with higher homologues of the series. [Bovet, Bovet-Nitti, Guarino, Longo, and Marotta, 1939] 1256 Table 1. Drugs with a competitive action with respect to epinephrine, acetylcholine, histamine, and 5-hydroxytryptamine. Adrenaline (noradrenaline) H \ CH0H.CH2rN/ , CH 0H Hydroxytrypt amine . . Histamine Acetylcholine CH 3 K CH3.COO.CH2.GH2.N\ 6213 CH/ H H \\N—c CH3 ’H NH-CH . OH CH 2. CH 2. H- cHz.CHz.N\H N/ \H H Sympatholytic Antihistaminics : Parasympatholytic Antihydroxytryptaagents : agents : .mines ” Ergotamine 929 F Atropine (spasmolytic Yohimbine 2339 R.P. (Antergen) agents ) Benzodioxane Curares: Pyrilamine d-Tubocurarine (933 F) Diphenhydramine Dibenamine Gallamine Antazoline Phentolamine Decamethonium Promethazine Succinylcholine Ganglioplegic agent: Hexamethonium Central ganglioplegic agents: Antiparkinson agents Antiphobic agents _ , tissue acetylcholine, and the nervous system was recognized early. In 1904, Elliot, struck by the similarity existing between the pharmacological action of epinephrine and the effect of stimulating the sympathetic system, proposed the hypothesis according to which epineph- rine is released from sympathetic nerve endings and transmits the impulse from nerve cell to smooth muscle ﬁber. Wieland in 1912 and Le Heux in 1919 tried to demonstrate that choline and acetylcholine were local hormones. Their hypothesis, we know, was successfully developed by Loewi, Dale, Cannon, and Bacq, whose experiments established the concept of chemical transmitters. The hypothesis of chemical transmission by acetylcholine ﬁrst proposed for viscera innervated by the parasympathetic system was later extended by Dale, Feldberg, and Vogt (1936) to the neuromuscular junction. Recent investigations on the physiology of the end plate have, in sum, conﬁrmed this mechanism. The reaction between acetylcholine and its receptor located at the postsynaptic mem— brane can now be integrated within the framework of electrophysiological ﬁndings, particularly those demonstrating electrical nonexcitability of this membrane and its great sensitivity to the transmitter (Kuﬂler, 1948; Castillo and Katz, 1956). To turn now to substances antagonizing these various hormones and transmitters, models for the synthesis of adrenergic and cholinergic blocking agents were furnished by compounds of biological origin, such as ergotoxine, atropine, and curare. The antihistaminics were studied later and represent syn- ' thetic products of completely original design. In practice, these drugs have been widely used in the symptomatic treatment of dysfunction of organs which are dependent on the activity of the autonomic nervous system: heart, blood vessels, bronchi, gastrointestinal tract, and uterus. The antagonists of epinephrine found their major application in the treatment of vascular disorders and hypertension. The antagonists of acetylcholine are used primarily as spasmolytic, mydriatic, and muscle-relaxing Table 2. Structural relations between and sympathomimetic Sympatholytic agents. [Raymond-Hamet, 1937; Bovet and Simon, 1936; Druey, 1936; Bovet, de Lestrange, and Fourneau, 1942; de Beer and Fassett, 1938; Hartmann and Isler, 1939; Gross, Tripod, and Meier, 1951] SYMPA'HOMIMEIIC AGEN’S /’ H0 \0H SYMPAYNOlVYIC AGENYS CHOHCHZNHCHg ACHECHENHE CH2CH2N(C2H5)2 V AC CH2CH2NHCH3 \v OCHZCH2N(C2H5)2 OH ANHCHECHzNH: N< V CH 2 mm L c (2115).? 93*” HUM HOMNH CH3 NCH3 o/\I~1chzc{r\m-<':H2 CHJDV OCH3 \N—CH; N CH2 C<NH—(IIH2 \N—CHg CH3 0H SCIENCE, VOL. 129 �agents. The antihistaminics are most useful in the treatment of urticaria, rhinitis, asthma, and other allergic diseases. For speciﬁc illustrations, I shall use examples from three different pharmacological groups. For the epinephrine group, I will consider ergotamine; for the antiacetylcholine group, curare; and for histamine, I will consider the syn— thetic antihistaminics. “ifssﬁm " , '" CH? C3 Synthetic Sympatholytic and Ergotamine-Like Compounds Sympatholytic drugs form a group characterized by common pharmacological properties. They act as competitors—or blocking agents, in AngloSaxon terminology—by opposing the effects of epinephrine and norepinephrine. Most characteristically, they block the hypertension and vasoconstriction produced by epinephrine. As is often the case, various drugs of this class were introduced empirically into therapeutics long before their pharmacological actions were established. As long ago as 1909, Froelich noticed that animals pretreated with small doses of the dextrorotatory isomer of epinephrine became resistant to the effects of the natural isomer. Today we explain this observation as resulting from a partial block of the receptors by a pharmacologically much less active enantiomorph of the compound. Later Loewe (1927), Kiilz (1936), and Raymond-Hamet (1937) described N-alkyl derivatives of phenylethylamine with sympatholytic properties; analogous properties were described in the phenoxyethylamine series (Anan, 1930; Levy and Ditz, 1933; Bovet and Maderni, 1933; Bovet, Simon and Druey, 1937), the phenylethylenediamine series (Bovet, de Lestrange, and J. P. Fourneau, 1942), the isoquinoline series (Hjort, de Beer and Fassett, 1938), and the phenylaminoethylimidazoline series (Meier and M'Liller, 1939; Hartmann and Isler, 1939). In each of these groups the structural similarities between the antagonistic molecules with either sympathomimetic or sympatholytic properties are evident (Table 2); the degree of substitution on the amine, the suppression or displacement of the phenolic function, the closing of a ring, are sufficient to reverse the pharmacological action. It is very important to notice that while the distance betWeen the amine function and the aromatic ring remains constant in both sympathomimetic and sympatholytic agents, the inhibitory 'molecule has always, in con: 8 MAY 1959 {gags seems i} {We casing mag, Fig. 2. Pachycurares. (Left) d-Tubocura- rine; (above) gallamine. Table 3. Classiﬁcation of the main groups of sympathomimetic and sympatholytic agents. ©-c-c—N ©—o-c—c—N ©mc-c-n Phenylethylamines Phenoxyethylamines Phenylethylene diamines Tiiii r i Sympathomimetic agents Phenolic derivatives of Phenylethylenediamine and Epinephrine its phenolic derivatives Phenylethylamines and their phenoxyethylamine phenolic derivatives Sympatholytic agents (aromatic series) N-Diethyl-N’-propyl-N’N-Diethylphenylethylamine N-Diethylphenoxyethylamine phenylethylenediamine Dibenamine Dibenzyline Tetrahydronaphthylamines, N-substituted Sympat/tolytic agents (heterocyclic series) N -MethyltetrahydroBenzodioxane: Phenylpiperazine Phentolamine isoquinoline Prosympal Benzylimidazoline Piperoxan Sympatholytic alkaloids Yohimbine Ergot alkaloids Table 4. Structural relations between sympathomimetic and sympatholytic agents: from epinephrine to ergotamine. [Marini-Bettolo, Chiavarelli and Landi, Vittory, 1950—1953; Bovet, Bovet-Nitti, Virno, Longo, Marotta, and Sollero, 1953] [NH _ CH3 CHOH-CHZ NH 2 ,NH2 / (31+2<:H2 NH2 GHz'ct' 0H3 OH OH Adrenaline Phenylethylamine Amphetamine Tetrahydronaphtylamine CH30H‘I3H2 IcorchH5 CH3 _ 843 LS alibi-c co C H2 -0H \Nz—CH 2 H 5-» 3 9| 6 1.5. _ CIH2 CH\ N/CHZ c,o\lI NH— N\ COG N‘ X30 ERGOTAMINE 1257 �The most active natural and synthetic tradistinction to the excitatory one, an amino group substituted by more, and heavier, radicals. Generally the inhibitory molecules also have a more stable structure and a higher molecular weight. sympatholytic compounds, whose effectiveness is sufﬁcient to permit their use in the clinic, are generally polycyclic or heterocyclic, with structures analogous Table 5. Investigations of synthetic oxytocic agents, derived from phenylglycinamide. [Bovet-Nitti, 1952, 1954] CH CH 3 3 NH- CH- CHZOH co- CONH-CIZHCHZOH CH2' CH2 N— CH3 CZ H5 NHCOCH2N< c2*‘5 8331.8. Ergometrine 62' " s CZ H5 NHCOCH2 N 1048 I €sz 1.3. ,6sz NHCOCHZN. H 0sz‘N- co- CHz-N c ’2 5 |062 |058I.S. 1.5. Table 6. Natural and synthetic curares: d-tubocurarine (King, 1935; Wintersteiner and Dutcher, 1943); 3381 RF. (Bovet, Courvoisier, Duclos, and Horclois, 1946) ; gallamine (Bovet, Depierre, and de Lestrange, 1947) ; succinylcholine (Bovet, Bovet-Nitti, Longo, and Marotta, 1949; Fusco, Palazzo, Chiavarelli, and Kniisli, 1949). “3‘0 <300 H 3 ‘ E"? 06H; on / ;.. C2H5 \ /"x I 1‘ ————©—o O—(CH2)5-—-0 I °2H5 3381 R.P. d-Tubocurarine ' O‘CHZ-CHZ'N(CZH5)3I ' on 2coocnzc H2N(CH3)BC! - , . o-cwcwmcm-I' 2 2. 253 or 0 Hz- CH2*N(CZH5)3'I ] _ . CHz-COOCHZCH2N(CH3)3C!‘ Succinylcholine Gallamine Table Subject Mammals Birds Amphibians (rectus abdominis) 1258 7. Pharmacodynamic properties of synthetic curares. Pachycurares (competing agents) : tubocurarine, gallamine Curarization Curarization Antagonism to acetylcholine Leptocurares (depolarizing agents) : succinylcholine, decamethonium Curarization (muscular ﬁbrillation) Contracture followed by curarization Acetylcholinic contracture to the above-mentioned compounds despite their complexity. Benzylimidazoline (Meier and Miiller, 1939) and dibenamine (Nickerson and Goodman, 1947) are related to the phenylethylamines; the aminomethyl-benzodioxanes (Fourneau and Bovet, 1933), to the phenoxyethylamines; and phentolamine (Gross, Tripod, and Meier, 1951) to phenylethylenediamine derivatives (Table 3). Studies conducted at the Istituto Superiore di Sanita by Marini-Bettolo and Chiavarelli, on the chemical aspects, and by F. Bovet-Nitti, Longo, Marotta, and Guarino on the pharmacological aspects, illustrate the usefulness of the concepts of isosterism and of competition in this kind of investigation. When the isolation and structural determination of the ergot alkaloids was achievedwresearches for which we are largely indebted to Stoll and Jacobs—— much work was done to prepare derivatives by partial or total synthesis; thus, dehydrogenated derivatives (Rothlin, 1947) and oxytocic derivatives closely related to ergometrine (Rothlin, 1947) were prepared, and the diethylamide of lysergic acid with hallucinogenic properties was discovered (Stoll). Since we proposed to investigate the structureactivity relationships of ergotamine, we used as our working hypothesis the con— cept relating structure to antagonistic action. At ﬁrst sight, the structure of the ergot alkaloids seems to be very different from that of epinephrine or of sympathomimetic derivatives of the phenylethylamine series. Nevertheless, since the skeleton of B-tetrahydronaphthylamine (2-aminotetralin) can be recognized in'the structure of lysergic acid, we decided to study compounds of this group (Table 4). Pharmacological tests with derivatives of relatively simple structure demonstrated the sympatholytic activity of 2-diethylaminotetralin (843 1.5.). Studies with more complex molecules, in particular the amide and amine derivatives of 2-tetralin, are a new step in the attempt to reproduce the essential portion of the lysergic acid skeleton. Using molecules of increasing complexity, one may go by successive stages from phenylethylamine to tetrahydronaphthylamine or to N-(2-tetra1yl) -N-methyl-N’-ethylB-alaninamide (916 LS.) and the ergot alkaloids, with a resulting progressive diminution at each stage of sympathomimetic properties and the appearance of sympatholytic properties. Oxytocic activity was observed in a large number of synthetic derivatives, SCIENCE, VOL. 129 �and this class of compounds seems very broad compared to that of adrenolytic substances (Table 5). In the course of experiments performed on rabbit uterus, isolated or in situ, several derivatives of aminotetralin and of aniline and even some aliphatic compounds showed strong activity. We may single out such examples as N,N-diethyl-N’- ( 2-tetralyl ) glycinamide (621 I.S.); N,N-diethyl-N’-3( 1048 4-dimethylphenylglycinamide LS.) ; and N,N,N’,N’tetraethylglycinamide (1062 LS.) (Bovet-Nitti, 1953). The main difﬁculty, apparently encountered also by other investigators, was the lack of parallelism between effects observed in laboratory animals and in man. Generally speaking, a satisfactory solution to the problem of syn— thetic oxytocies has not yet been reached, and the question is still under study. Antagonists of Acetylcholine: Synthetic Curares The problem of competitive agents that antagonize acetylcholine activity is rather complex, due to the multiple functions of this transmitter. Acetylcholine is the chemical transmitter in viscera innervated by the parasympathetic system; it has a role at the neuromuscu— lar junction, and it is liberated in ganglia during the passage of a nerve impulse. A surprising fact, which has been proﬁtably exploited in pharmacological investigations of competitive agents, is that compounds antagonizing acetylcholine differ according to the site of action of the local hormone. Thus, atropine and benzoylcholine neutralize the muscarinic effects of acetylcholine on cardiac receptors, on the intestine, or on secretions; tetraethylammonium iodide or hexamethonium block the nicotinic action of acetylcholine on sympathetic and parasympathetic ganglia. Finally, curares are speciﬁc antagonists of acetylcholine in striated muscle. With respect to the structure of antagonists, synthetic curares furnish us with a succession of examples comparable to those we have reviewed in the sympatholyticgroup. These investigations were begun in 1946, after King’s elucidation, in 1935, of the structure of one of the physiologically active constituents of Amazonian curares, and after the introduction by Grifﬁth and Cullen in 1942 of the chemically pure alkaloid as an adjuvant in anethesia. d-Tubocurarine, which is extracted from a menispermum, Chondodendron tomentosum, is found in curares prepared by the natives of the Upper Ama8 MAY 1959 , emcageugcagcagefcam Mammengmécm {1:39} CHQCG B Ci‘iéci‘ig ‘ ’ R;C8313 (CH333NCHgCRgu C0 CHg Fig. 3. Leptocurares. (Left) Decamethonium; (right) succinylcholine. zon. It is an alkaloid of the group bis ( benzyltetrahydroisoquinoline) , whose molecule has two quaternary ammonium ity, and this was also true for polyphenol ethers and aromatic esters. The latest investigations on the path to ultimate simpliﬁcation are concerned’ with the activity of aliphatic derivatives. In England, Barlow and Ing and Paton and Zaimis (1948) reported extremely interesting observations on the curare-like effect of decamethylene—w- functions. In research done with our colleagues, Viaud, Horclois, and de Lestrange, we ﬁrst looked for molecules structurally close to the selected model. By successive transformations, we were able to synthesize relatively simple derivatives with analogous properties (Table 6). From a series of new compounds with two quinolinic rings bearing quaternary ammonium functions, we ﬁrst selected the diiodoethylate of 8’ ,8’ ’ -diquinolyloxy1,5-pentane (3381 R.P.). This was the ﬁrst synthetic compound with curarelike action in mammals showing a speciﬁcity comparable to that of natural alkaloids isolated from curare (1946). It was then found that aminophenol derivatives which have neither quinoline nor isoquinoline rings had similar activ- bis-trimethylammonium hydrate (decamethonium). In our Laboratory of Therapeutical Chemistry at the Istituto Superiore di Sanita, the curare-like action of succinylcholine was ﬁrst recognized. This compound was synthesized by Hunt in 1911. The number and variety of compounds with curare-like action, the relative simplicity of their mode of action, and the possibility of precise pharmacological assay permitted a careful study of structure-activity relationships of synthetic curares. Solveni front D Iodine Carboxylic reagent Bromothymol blue 0 000 @%s + 60 O Enzymic hydrolysis (5%) 01 cm.{ R; 1 o O o @ @s....,...ho.... @ @ @ ® + a 2 § § Choline Succinylmonocholine Succinate 3 20 Control Non-enzymic hydrolysis (96) Fig. 4. Chromatograms of (a to e) succinlycholine at various stages of enzymic hydrolysis; (f) a mixture of succinylcholine and its products of hydrolysis; (g) 0.1 mg of succinylcholine after nonenzymic hydrolysis. [Whittaker and Wijesundera, 1952] 1259 �Fig. 5. Comparison between curarizing effects of d-tubocurarine (left) and of succinylcholine (right) given intravenously as a single fol— muscle of the Contraction anesthesia. gastrocnemius chloralose under (First line) the dog, continuous perfusion on injection or by lowing the.rhythmic stimulation of the sciatic nerve; (second line) control of the speed of injection; (third line) blood pressure. The record shows clearly the difference between the duration of neuromuscular paralysis following a single injection of succinylcholine (370 1.8., 0.05 mg/kg) and of d-tubocurarine (0.1 mg/kg). Also, on comparing the effect of a single injection of d—tubocurarine with continuous perfusion of succinylcholine (initial injection of 0.05 mg followed by repeated injection of 0.0062 mg at each signal), one sees that, for the duration of subtotal and reasonably uniform eurarization (about 80 percent, for 20 minutes), the reversibility of the effect is quick (about 10 minutes) after infusion of succinylcholine while it is slowly progressive (about 50 minutes) after injection of d-tubocurarine. [Reuse, 1953] I will mention only two important factors which inﬂuence the activity of bis-quaternary derivatives: the distance between the quaternary ammonium groups and the massiveness of the molecule. The ﬁrst factor is illustrated by comparison of polymethylene-bis-trimethylammonium derivatives (Barlow and Ing; Paton and Zaimis, 1948) as well as of aliphatic diesters of choline (Bovet, Bovet-Nitti, Guarino, Longo and Marotta, 1949) (Fig. 1). Careful pharmacological study showed that the action of new synthetic derivatives was sometimes quite different from that of the natural alkaloids. The differences between the action of decamethonium iodide and succinylcholine iodide on the one hand and the action of d-tubocurarine and of the tri— iodethylate of gallamine on the other were carefully studied by Paton and Zaimis, Brown and Dias and in our own laboratory. The British authors have proposed calling these two groups depolarizing agents and competitive curares. We proposed designating decamethonium and succinylcholine as leptocurares, and tubocurarine and gallamine as pachycurares (Figs. 2 and 3; Table 7). The advantage of our nomenclature lies in the fact that it does not presume the mechanism of action. The main differ— ence between the pharmacodynamic effects produced by the two types of curares is determined by the responses of amphibian and bird muscles. In birds, the pachycurares are typical curarizing agents, while leptoeurares induce con- ESHWEH H . CH, C“Cf~iLCHNH }; fag; \g‘fsfmwx ‘ as? N 1260 y 2‘ ecu, '2 CHECHEMCHM Fig. 6. (Left, top) Histamine; (left, bottom) pyridylethylamine; (above) pyrilamine. tracture that is followed by eurarization. In mammals the differences between the two groups are less sharp. The responses of muscle from different species or of different muscles from a single species are not always comparable. Also, intermediary steps seem to exist between depolarization and curare competition. The distinction between the groups, though relative with respect to the mechanism of action and the type of preparation used, are, nevertheless, useful if we want to compare relations between chemical structure and pharmacological activity. Clinically, the most important factor in classiﬁcation of curares is duration of effect. In this respect, the introduction of a short-acting curare, particularly succinylcholine, is an important step forward. The relative ease with which suc— cinylcholine is hydrolyzed by pseudocholinesterase and the very low toxicity of the products choline and succinic acid account for the brevity of action and the remarkable tolerance of the organism for this curare (Fig. 4; Table 8). The ﬁrst clinical observations concerning short-acting curares were published by Valdoni (1949) and Scurr (1951) and deal with suxethonium. The introduction of succinylcholine into anesthesiology was ﬁrst proposed in Sweden, by Thesleff (1951), Holmberg and Thesleff ( 1951), Tammelin and Low (1951 ) , and von Dardel (1951), and in Austria, by Briicke et al. (1951), Mayrhofer and Hassfurther (1951), and Holzer (1951). In the light of these various investigations, one may today recognize two methods of using succinylcholine: single injection when very short action is required (as for endoscopy or electroSCIENCE, VOL. 129 �Table 8. Hydrolytic products of succinylcholine. (CHgaN‘CiECi-izococ Hacib c OOCHZC HZN ’(c 1493.1’ -Succiny|choline 1'. (CH3)? CHZCHZOCOCHZCI‘ECOOH + OHCHZCHZN (cl-1‘3)3 I Choline Succinylmonoct‘oline l lrl(.7H3)3N CH2 CH 2OH+ HOOCCHZCHZCOOH Succinic acid Choline shock) or continuous infusion in surgical procedures of long duration. Two recordings from a study in our laboratory demonstrate results obtained with the two types of application. They show the superiority of continuous infusion of short-acting curares over the classical technique (Fig. 5). Antihistamines The last example I will use to illus— trate the concept of competition is concerned with compounds that antagonize the third local hormone, histamine. This particularly rich ﬁeld since the usefulness of these compounds has stimulated a great many investigations within a very few years. In 1937, in Fourneau’s laboratory, we began—A. M. Staub and I—to look for compounds antagonistic to histamine. Considering the number of features that histamine, acetylcholine, and epinephrine have in common, we looked for antagonism comparable to that exhibited by sympatholytic compounds toward epinephrine and by parasympatholytic compounds toward acetylcholine. We obtained the ﬁrst positive results in 1939 with thymoxyethyldiethylamine (929 F). Our experimental work was then directed toward deﬁning criteria for antihistaminic activity. Staub (1939) extended her observations to phenylethylenediamine derivatives. In 1942, the syntheses by Mosnier, the pharmacodynamic studies of Halpern, and the ﬁrst therapeutic results of Cuilleret, Thiers, Gaté, Celice, Perrault, Decourt, and Durel with dimethylaminoethylbenzylaniline, or Antergan, deﬁnitively established interest in compounds of this group. The role played by histamine in many allergic affections assures a broad area of clinical application of these compounds. After the pio— neers (Maderni, de Lestrange, and Benoit in Fourneau’s laboratory in Paris; is a Table 9. Principal groups of synthetic antihistaminics: 929 F (Bovet and Staub, 1937) ; Antergan (Halpern, 1942); antazoline (Meier and Bucher, 1946); diphenhydramine (Loew, Kaiser, and Moore, 1945); promethazine (Halpern and Ducrot, 1946); chlorphenamine (Tislow, La Belle, et al., 1949) ; pyrilamine (Bovet, Horclois, Walther, and Fournel, 1944); tripelennamine (Mayer, Huttrer, and Scholz, 1945) ; thonzylamine (Reinhard and Scudi, 1947). Antihistaminics related to: Sympatholytic agents onQ [OHS CH ocnac H2N(62H5)2 CH3 929F ”Q CH ‘0H 2 0H 2 Maria) 2 Antergon Q Spasmolytic agents 0 \ZCH CH Diphanhydramine O cuzcnmcusiz N \ N-CH2 _ Antozoiine 8 MAY 1959 :EH GHZCH2N(CH3)2 Chlorphenamino 2N(CH3) Pyrilamine N‘cnacnzmchu 3 CH— @001 ECHocH ZCHZNKSH 3’2 Promethazine \C Histamine Tripulennominc ﬂZOOCHS N/ \ZCHZCHZNCHa) Thonzylamino Table 10. Structural relations between histamine and antihistamines. [Walter, Hunt, and F osbinder, 1941; Nieman and Hays, 1942; Bovet and Walthert, 1943] NH /\ / / ’I CH2 CH2 NHZ , I, HISTAMINE Histamine action 2. N I Antihistamine action HQ": CH2 CHZN: (/\n-CH2.GH2.NHZO KEV) /J Nona \ ,/<CH 2 .0H 2 .NH 2 \ "[0142 A" (7N1ii KN 6H2 ii; N’0 2 ‘01:: CH 0 o \N ~ /-CH2CH2. NH2 “3 + K I R N: N [CH3 CH2.CH .N\ * CH% Viaud, Horclois, Mosnier, and Charpentier in French industry; Hartman and Hofman in Switzerland; Rieveschl, Scholz, Huttrer, and Roblin in the United States; Cavallini in Italy), about 500 chemists synthesized, in less than ten years, more than 5000 compounds in the antihistaminic group. Pharmacologists were easily able to recognize the competitive nature of the antagonism exerted by these antihistaminics toward histamine. Chemists, however, could not perceive any relation between the structure of antihistaminics and histamine which logically might explain such activity, nor could they ﬁnd a relationship among the various active compounds. It was therefore impossible to escape the conclusion that most of the results were rather empirical. From the pharmacological viewpoint, it was possible to distinguish three groups of substances (see Table 9) with antihistaminic action and relate them to (i) the sympatholytic group; (ii) the parasympatholytic-sympatholytic group; and (iii) histamine itself. To the ﬁrst group belong the phenolic esters (929 F) and the phenylethylene— diamine derivatives (1571 F) studied at the Pasteur Institute, Halpern’s Antergan, and the antazoline of Meier and Bucher. The compounds of the second group, from a chemical point of view, have more homogeneous structures, in 1261 �common with atropine-like drugs and other spasmolytics; some of these are, in fact, spasmolytic as well as antihistaminic (diphenhydramine). In derivatives of a-aminopyridine, which form the third group, the antihistaminic action is more speciﬁc and almost free of secondary effects. It is interesting to note in this group the isosteric reactions which account for the pharmacological activity. Walter et al. (1941) and Niemann and Hays (1942) have shown that a-pyridylethylamine derivatives have histamine-like activity, and that a fundamental difference exists between a-, [3-, and y-substituted pyridines in this respect. In this case, the analogy of structure which is not evident between histamine and pyrilamine (Neo-Antergan) may be seen between the groups a-pyridylethylamine and (it-pyridine ethylenediamine (Table 10, Fig. 6). A typical compound from this group is pyrilamine (see Fig. 7), but many other synthetic compounds of similar design have also proved to be active. Central Action of Transmitters The compounds considered so far do not exhaust the ranks of competitive agents. Pharmacologists are to some extent les enfants terrible: of physiology. They did not wait for the battle of the neuromuscular junction to be won before engaging in a more difﬁcult encounter. They proposed that the available evidence suggested the action of a chemical transmitter in the central nervous system, exactly as in the autonomic nervous system. Analyzing the collective results from various laboratories, Feldberg (1950) concluded that the theory ascribing a transmitter role to acetylcholine in the central nervous system was the only one able to offer convincing and satisfactory interpretations. Even if intervention of noncholinergic chemical transmitters in the central nervous system is not excluded, we must admit that our knowledge about the probable roles of norepinephrine, epinephrine, histamine, and 5-hydroxytryptamine is still quite incomplete. The physiological role of the reticular formation in the brain stem has been clearly deﬁned by Moruzzi and Magoun (1949). In the last few years, a considerable number of investigations have shown that compounds affecting the autonomic nervous system also affected this formation. Paradoxically enough, cholinergic as 1262 HISTAMINE 0.001 cm/H 0 20 .mm/Hg 200 100 0 15 PYRILAMINE HISTAMINE 1.0 0.001 “ j 1 V. 10 5 0 0 ‘_3lOsec Fig. 7. Antagonistic action of pyrilamine with respect to the vasodilating effects of histamine in cerebral circulation. The subject was a dog under chloralose anesthesia. (A) Blood pressure, femoral artery (mm-Hg); (V1) pressure recorded through a catheter introduced in a centrifugal direction into the external maxillary vein (mm-H20) ; (V2) pressure in the internal maxillary vein (mm-H20). Injection was made into the saphenous vein; dosages are given in milligrams per kilogram. [Virno, Gertner and Bovet, 1956] well as adrenergic substances affect the electrical activity of the cortex in the same way that direct electrical stimulation of the reticular formation does. Under well-deﬁned experimental conditions, acetylcholine (Bonnet and Bremcr, 1937) and epinephrine itself (Bonvallet, Dell, and Hietzel, 1954) provoke a transient activation in the electroencephalogram. The administration of either an anticholinesterase (eserine, diisopropyl ﬂuorophosphate) or of amphetamine (Bradley and Elkcs, 1953) produces an intense and prolonged desynchronization. From a strictly pharmacological viewpoint, the major interest in this type of investigation stems from the similarity in observed antagonisms between various groups of drugs in the central nervous system and in viscera innervated by the autonomic nervous system. As early as 1947 we suggested that in extrapyramidal syndromes some relation might exist between the central, “antiparkinson,” effect of certain tertiary amines and their ganglioplegic properties in peripheral ganglia (Sigwald and Bovet; Dumont; 1947). “Antiparkinson” drugs form a relatively homogeneous group comprising diethazine (Diparcol), isothazine (Parsidol), caramiphen (Parpanit), and trihexyphenidyl (Artane), as well as some antihistaminics (diphenliydramine and promethazine). Electroencephalographic studies (Fig. 8) have shown that three groups of compounds produce an electroencephalogram similar to that recorded during sleep: the parasympatholytics (scopolamine and atropine), the central ganglio— plegic or “antiparkinson” drugs (Table 11), and the neuroleptics (chlorproma- w; mwgwmmwww W MWMvM 51mm ‘ . -..,: p‘, 51%; g‘ﬁ‘kﬁﬁg‘ﬁ’?‘ “if“?'9““(high ‘) K $3.)wa ai’zfiig'f$6,133?3.25% “ if: (3:1‘331“ ii 4, ,. “‘ ;.§l(¢t {brave-112m}? Fig. 8. Antagonistic action of diethazine against convulsive patterns caused by nicotine on the electroencephalogram of curarized rabbit. (A) Blocking reaction after acoustic stimulation (black line). (B) Convulsive seizure by nicotine (2 mg/kg) in normal animal. (C) After injection of diethazine (5 mg/kg) a second injection of nicotine no longer produced the electrical changes observed previously. and the acoustic stimulus fails to produce the blocking reaction. [Longo and Bovet, 1952] SCIENCE, VOL. 129 �zine, reserpine). These also antagonize the cortical reaction elicited by external stimuli (stress) or by desynchronizing agents (eserine and amphetamine) (Bovet and Longo, 1956). The effect of such synchronizing agents may, as a ﬁrst approximation, be localized in the reticular formation and thus be comparable to the importance of chemical transmitters at this level. Many observations suggest that speciﬁc receptors fOr epinephrine, acetyl- choline, and histamine are speciﬁc proteins with a structural conﬁguration complementary to that of the transmitter. This concept was ﬁrst proposed by Fischer, who illustrated it with the now famous model of key and lock. his mechanism has been invoked to explain observations in physiological and chemical studies of taste and smell. Recently, Landsteiner and Pauling applied this idea of “complementary conﬁguration” in the ﬁeld of immunological reactions. At this point it would not be possible to consider the various aspects of reactions between chemical transmitters, inhibitors, and receptor proteins without taking more space than is available. The particularly simple case of binding acetylcholine with cholinesterase has been studied by Nachmansohn (1953— 1954) and Wilson (1954). They consider acetylcholine to be attached at two points, one electronegative and the other elcctropositive, and have drawn valid conclusions with respect not only to various anticholinesterases but also to a new group of drugs that reactivate the phosphorylated enzyme. If I cared to develop the extensive areas covered in this article I could include other topics and point out that different groups of compounds affect the metabolism of mediators because they are precursors or because they inhibit synthesis, slow down or accelerate liberation, or interfere with destruction. In every phase, investigations have been successful and the results appear to be very promising. Conclusion The composite picture I have tried to present, at the risk of relating many al— ready well-known facts, appears, despite inevitable gaps, very certain. If, in concluding, we rapidly retrace our path, we will see that in covering the vast ﬁeld of pharmacology, the structures of a small group of remarkably simple biogenic amines have led us, like the thread 8 MAY 1959 Table 11. Central ganglioplegic agents: diphenhydramine (Loew, Kaiser, and Moore, 1945) ; diethazine (Sigwald, Bovet, and Dumont, 1946; Bovet, Fournel, and Charpentier, 1947); caramiphen (Domenjoz, 1946; Griinthal, 1946); trihexyphenidyl (Doshay and Constable, 1949). / \ / \ CH-O-CHz-CH2~N(GH3)2 Diphenhydramine (Benadryl) -GO'O‘ OHZ'GHZ'N(02H5)2 Caramiphen <// \\> S N'CH2'CH2N(02H5)2 :COH'CHZCHZN > Diethazine Trihexyphenidyl of Ariadne, through the labyrinth of very a name always well-known and sometimes very close to us. The future of pharmacodynamics is, nevertheless, so rich and promising, and diverse physiological actions and chemical structures. It has been said that the art of the orator is to speak about what he knows and to hide his ignorance. I do not feel any need to resort to such an artiﬁce in presenting the current picture of the chemical pharmacology, because it is, in ﬁnal analysis, only a kind of “natural history” and classiﬁcation of organic molecules. I would say that the results obtained so far give rise to optimism because they let us catch a glimpse of the pharmacology to come as a well-ordered and well-deﬁned science in which foods, drugs, and poisons will be integrated in the metabolism of the simplest constituents of living matter. Finally, in recalling the great names associated with studies of the pharmacological agents that made it possible for us to reach our present level, I can only speak with emotion of all those who preceded me, particularly of my teacher, Ernest Fourneau, who wrote such a great and glorious chapter of therapeutic chemistry and whose name will forever be written in the history of this science. My feelings are sincerely divided between the immense pleasure I feel at the honor which is bestowed on me and my sense of inadequacy at being unable to repay my teachers and colleagues all that I owe them. This feeling is the more vivid because therapeutic chemistry is a very young science that has developed amazingly during the past half century; perhaps in no other domain does the part played by each individual appear so clearly and with such continuity as in our studies, where every formula bears it bears so many theoretical and prac— tical possibilities, that I cherish the hope that my future work will justify not only the marvellous distinction I have received today but also the conﬁdence and the friendship of my teachers and colleagues, whose works cannot be separated from those I pursue with confidence, enthusiasm, and love. Bibliography The following bibliography includes mainly general reviews; concerning studies published prior to 1948, the reader is referred to the work published in collaboration with Mme. F. Bovet-Nitti. Z. M. Bacq, “La pharmacologie du systeme nerveux autonome, et particuliérement du sympathique, d’apres la théorie neurohumorale,” Arm. physio]. physicochim. biol. 10, 467 (1934). D. Bovet, “Introduzione allo studio ﬁsiologico e farmacologico del curaro,” Boll. soc. ital. bio]. sper. 25, 539 (1949). , “Introduction to antihistamine agents and Antergan derivatives,” Arm. N.Y. Acad. Sci. 50, 1089 (1950). , “Some aspects of the relationship between chemical constitution and curare-like activity,” ibid. 54, 407 (1951). and F. Bovet-Nitti, Structure et Activite’ pharmacodynamique des Médicaments du syrtéme nerveux vége’tatif (Basle, 1948). “Curare,” Experientia 4, 325 (1949). , “Rapports de structure entre sympathomimétiques et sympatholytiques. De l’adrénaline a l’ergotamine,” Actualités pharmacol. N0. 6 (1953), p. 21. , “Le chlorure de succinylcholine, agent curarisant a breve durée d’action,” Sci. Med. Ital. 3, 509 (1955). , S. Guarino, V. G. Longo, R. Fusco, “Recherches sur les curarisants de synthése. III, Succinylcholine et dérivés aliphatiques,” Arch. intern. pharmacodynamie 88, 1 (1951). D. Bovet and V. G. Longo, “Pharmacologie de la formation réticulée du tronc cerebral,” Oomph-rend. 20éme Congr. intern. physiol. Bruxeller (1956), pp. 306—329. D. Bovet and P. Viaud, “Curares synthése: Chimie et pharmacologie,” Aneslhésie et analgésie 8, 328 (1951). F. Bovet-Nitti and D. Bovet, “Recherches sur les ocytociques de synthése: dérivés de la phenylglycinamide,” Arch. intern. pharmacodynamic 6, 327 (1954). F. Briicke, “Dicholinesters of -dicarboxylic acids ‘ 1263 �and related substances,” Pharmacol. Revs. 8, 265 (1956). W. B. Cannon and A. Rosenblueth, Autonomic Neuroeﬂector System (New York, 1937). J. Castilljo and B. Katz, “Biophysical aspects of neuro—muscular transmission,” Progr. in Biophys. and Biophys. Chem. 6, 122 (1956). H. H. Dale, “Transmission of nervous effects by acetylcholine,” Harvey Lecture Ser. 32, 229 (1937). L. Donatelli and U. Seraﬁni, Gli antistaminici di sintesi (Naples, 1951). J. C. Eccles, “The electrophysiological properties of the motoneurone,” Cold Spring Harbor Symposia Quant. Biol. 17, 175 (1952). V. Erspamer, “Pharmacology of indolealkylam~ mines,” Pharmacol. Revs. 6, 425 (1954). U. S. von Euler, “The nature of adrenergic nerve mediators,” ibid. 3, 247 (1951). S. M. Feinberg, S. Malkiel, A. R. Feinberg, The Antihistamines (Chicago, 111., 1950). W. Feldberg, “The role of acetylcholine in the central nervous system, Brit. Med. Bull. 6, 312 (1950). R. Fusco, G. Palazzo, S. Chiavarelli, D. Bovet, “Ricerche sui curari di sintesi, IV,” Gazz. chim. ital. 79, 836 (1949). L. S. Goodman and M. Nickerson, “Clinical ap- plication of adrenergic blockade,” Med. Clin. N. Am. 34, 379 (1950). H. R. Grifﬁth and G. E. Johnson, “The use of curare in general anesthesia,” Anesthesiology 3, 418 (1942). B. N. Halpern, “Les antihistaminiques de synthese, essais de chimiothérapie des états allergiques,” Arch. intern. pharmacodynamie 68, 339 (1942). , “Sur le mécanisme d’action des antihistaminiques de synthése,” Presse Med. 57, 949 (1949). H. R. Ing, “The curariform action of onium salts,” Physiol. Revs. 16, 527 (1936). S. W. Kuﬂler, “Physiology of neuro-muscular junctions: electrical aspects,” Federation Proc. 7, 437 (1948). O. Loewi, “Problems connected with the principle of humoral transmission of nerve impulses,” Proc. Roy. Soc. (London) 1188, 299 (1936). G. B. Marini~Bettolo, “Contribution a l’étude des alcaloides des Strychnos du Brésil,” Festschr. Arthur Stoll (Basel, 1957), pp. 257—280. , S. Chiavarelli, D. Bovet, “Ricerche sui simpatolitici di sintesi della serie dell’ergotammina,” Gazz. chim. ital. 80, 281 (1950). A. R. McIntyre, Curare. Its history and clinical use (Chicago, 111., 1947). D. Nachmansohn, “Metabolism and function of Manuel Luz Roxas, Agricultural Chemist Manuel Luz Roxas was one of the foremost scientists in the Philippines. His valuable services to the University of the Philippines as a teacher of chemistry in the College of Agriculture and the important role he played in the creation and organization of the National Research Council of the Philippines will be long remembered. Almost immediately after Dr. Roxas’ graduation from the University of the Philippines in 1911, with a BS. degree Hg? ‘ \ ._ Manogmmm OF in Agriculture, his ﬁrst research work appeared in the Philippine Agriculturist and Forester under the title “The pandan industry in Majayjay.” This was soon followed by three other articles in the same journal: “The cultivation of coconut,” “The effect of some stimulant upon rice,” and “The coffee industry in the island of Luzon.” Dr. Roxas pursued further studies in his chosen ﬁeld and in 1913 obtained his MS. degree at the University of the Philippines, where he then served as instructor in chemistry until he was appointed a university fellow to the United States. Evidently this appointment was in recognition of his unusual endowment with the “divine spark” to perform research. He enrolled in the University of Wisconsin and received his Ph.D. there in 1916. On his return to the Philippines, Dr. Roxas resumed his position in the Col-' lege of Agriculture in the University of the Philippines, where he was later appointed assistant professor, then professor of chemistry, and ultimately, professor emeritus of agricultural organic chemistry. He was also named Distinguished Alumnus of the University of the Philippines in 1932 for achievement in scientiﬁc research. All these deserved 11111111111111 131111111111 HILLSIDE HOSPITAL QLEN omsm. v. ' recognitions were due to his active labor in the ﬁeld of research, especially in agricultural chemistry and food technology; his 95 scientiﬁc papers were published in various journals, including the Philippine Agriculturist and Forester, the [ournal of Biological Chemis— try, Sugar News, and the Journal of the Philippine Islands Medical Association. The National Research Council of the Philippines owes its origin to the leadership of Dr. Roxas. He headed a committee that worked continuously in preparing the draft of the bill for its creation which was introduced in the House of Representatives. With the support of Manuel L. Quezon as Senate President and other leaders of the Philippine Legislature, and the cooperation of the then Governor General Frank Murphy, Act 4120 creating a National Research Council for the promotion of research along scientiﬁc lines was approved on 8 December 1933. Elected as ﬁrst chairman of the National Research Council, Dr. Roxas did a great deal in the organization of the different divisions integrating the Executive Committee of the council. For his distinguished and outstanding contributions in scientiﬁc research in the Philippines, Dr. Roxas may well be considered the “father of the National Research Council of the Philippines.” Manuel Luz Roxas was a man of sterling character, a good Filipino and patriot, simple and humble; all these qualities enhanced his merit as a true man of science. Our country can never repay what it owes him for his scientiﬁc labor and devotion to research. ANTONIO G. SISON National Research Council of the Philippines, Quezon City SCIENCE, VOL. 129 _ 3.1u1111959 the nerve cell,” Harvey Lecture Ser. 49, 57 (1956). W. D. M. Paton and E. J. Zaimis, “The methonium compounds,” Pharmacol. Revs. 4, 219 (1952). M. Protiva. “Chemie antihistaminovych latek a histaminové skupiny,” Nakladatelstvi L'eskolovenske’ Akademie véd (Prague, 1955). M. M. Rapport, “Serum vasoconstrictor (serotonin) : IV,” ]. Biol. Chem. 180, 961 (1949). Raymond-Hamet, “Sur un nouveau cas d’inversion des eﬂets adrénaliniques,” Compt. rend. acad. sci. 180, 2074 (1925). Rend. ist. super. sanita‘ 12, 1-264 (1949) (numero speciale sui curari di sintesi). Ibid. 15, 723—1040 (1952) (numero speciale sugli ergotamminici di sintesi). E. R. Rothlin, “The pharmacology of the natural and dihydrogenated alkaloids of ergot,” Bull. schweiz. Akad. med. Wiss. 2, 249 (1947). A. M. Staub, “Recherches sur quelques bases synthétiques antagonistes de l’histamine,” Ann. inst. Pasteur 63, 400 (1939). S. Thesleﬂ', “Succinylcholine iodide. Studies on its pharmacological properties and chemical use,” Acta Physiol. Scand. Suppl. 99, 1 (1952). D. W. Woolley, A Study of Antimetabolites (New York, 1952). �Cultural Determinants of Response to Hallucinatory Experience ANTHONY F. C. WALLACE. Ph.D. PHILADELPHIA �Reprinted from the A. M. A. Archives of General Psychiatry July 1959, Vol. 1, pp. 58-69 Copyright 1959, by American Medical Association Cultural Determinants of Response to Hallucinatory Experience ANTHONY F. C. WALLACE, Ph.D., Philadelphia Hallucination attracts the attention of the anthropologist for several reasons: First, because, as one of the most ancient and most widely distributed of the modes of human experience, most, if not all, human cultures provide deﬁnitions of and responses to it which are of interest to the descriptive ethnographer; second, because a vast quan— tity of content has been introduced into the cultural repertoire of mankind by halluci— natory ideation in dreams, visions, and hypnogogic imagery, and hallucination must therefore be considered in relation to culture change; and, third, because hallucination is often deﬁned in Western societies as a symptom of mental and/or physical disease, and anthropologists play a role in medical research in these societies. It is in the last context, particularly in the area of mental health research, that the present inquiry is undertaken. Cross—cultural materials on hallucination may be of interest in a mental health re— search context in at least two ways. First, and rather obviously, both psychiatrist and anthropologist will expect the manifest con— tent of hallucination to vary, as does the content of other behavior, to some degree with cultural setting, and they may be interested in the range, frequencies, and associations of various types of manifest content. Differences of opinion exist in Submitted for publication Sept. 3, 1958. This study was in part supported by Grant M-1106 from the National Institute of Mental Health, U. S. Public Health Service. Research assistants were Fred Adelman, Josephine Dixon, Joan K055, and Robert J. Smith. The writer has beneﬁted from discussion of methodological problems in psychopharmacology with Dr. Harry Pennes and Dr. Harold Rashkis, of the Eastern Pennsylvania Psychiatric Institute. 74/58 regard to the supposed variability of latent content: Lincoln, in his study of dreams in primitive cultures, and other psychoanalyti— cally oriented scholars have emphasized the universal presence in dreams of Oedipal themes and the classic “Freudian” sym— bols 13; less strictly psychoanalytic ethnolo— gists have not emphasized the presence of these themes so much as culturally and personally idiographic onesﬁ2'3 In any case, however, we shall not be primarily concerned with the content per se of hallucina— tions. Rather, we shall deal with the problem of the deﬁnition of and response to the experience, by the society, by the scientiﬁc observer, and by the hallucinator himself. The rationale for such an approach, in a mental health context, is twofold: First, knowledge of the range of deﬁnitions and response, and their cultural associations, may help in diagnosis and in communication with patients; and, second, it is likely that in some cultural subgroups in our society the nature of deﬁnition and response to hallucination entertained by hallucinator and his associates may aggra— vate or precipitate other mental disabilities in the hallucinating person. Indeed, the mental patient may suffer from added anx— iety precisely because of the nature of the deﬁnition of hallucinatory experience which he entertained prior to experiencing it him— self. Certainly among hospitalized patients in our society, the attempt to conceal halluci— natory experiences from the staff is both chronic and, in one sense, realistic: Staff members frequently take a negative View of hallucinations, and hallucinating patients are subject to measures which, from the pa— tient’s standpoint, may be punishments (de- �RESPONSE TO HALLUCINATORY EXPERIENCE lay in discharge, restriction of privileges, questioning on sensitive issues, subtle contempt, and even ridicule, from both staff and other patients) .23 Problems of Deﬁnition Uncertainties of deﬁnition impede re— search in the area of hallucinatory experi— ence. Although hallucination is commonly treated by psychiatrists as a symptom of mental disorder, its occurrence is neither a necessary nor a sufﬁcient condition for such a diagnosis. Most psychiatrists, furtherword the restrictions two on impose more, “hallucination,” excluding from its exten— sion those ideational experiences which oc— cur during sleep and assigning to it a generally negative valence. These restric— tions are useful in psychiatry in our own cultural setting, but they are not helpful in establishing a cross—culturally applicable deﬁnition (nor need they be, for a Western psychiatrist’s deﬁnition is to be regarded as only one cultural variant), since in some societies dreams and waking visions may be for many purposes treated as equivalent. For the purposes of this study, “hallucina— tion” will be deﬁned, very broadly, as pseu— doperception, without relevant stimulation of external or internal sensory receptors, but with subjective vividness equal to that aroused by such stimulation. Included in its extension, therefore, are dreams, the ter— of “hallucinations” psychiatric waking minology, and hypnogogic imagery; excluded is the fainter audiovisual imagery of reﬂective thought. There remains a some— what dubious category, occasionally referred to as hallucinations in the psychiatric lite-ra— ture, of perceptions whose subject matter is unambiguously provided by external stim— ulation but whose form displays subtle or gross distortion. The most familiar exam— ples are the undulating ﬂoors, stretched perspectives, echoing sounds, and other dis— tortions experienced by some subjects on administration of the so—called hallucino— genic or psychotomimetic drugs, and by normal subjects who have consumed nar— Wallace or alcohol, have been breathing anesthetics, or are in process of losing consciousness (fainting). We shall leave these phenomena out of the range of our deﬁnition, on the ground that a “hallucina— tory” dimension already exists, of vividness of subjective imagery in the absence of sensory stimulation, at all points of which the pseudoperception may be equally undis— torted, and relate these dubious cases, rather, to a logically independent dimension of perceptual distortion. The relationship between the two dimensions may, of course. be investigated empirically. A second major problem, in addition to the concept of hallucination itself, is that perennial ﬂower of confusion, the word “possession.” Casual observers and many anthropologists alike use this word in two very different senses: as a label for some person’s overtly observable behavior, and as a label for a native theory to explain this be— havior. These two uses are, unhappily, often confused. It may be best to state ﬂatly, at the outset, that I shall use the word “possession” to denote any native theory which explains some event of human behavior as being the result of the physical presence, in a human body, of an alien spirit which takes over certain or all of the host’s executive functions, most frequently speech and control of the skeletal musculature. A phe— nomenon of possession does not, therefore, for me exist; the word merely labels a theory. Now the possession theory happens to be frequently applied, in folk beliefs, to three very different classes of phenomena, for each of which other terms exist. One of these is hallucination; the second is hysteri— cal dissociation (including multiple personality, fugues, somnambulism, conversion hysterias, and hypnotic states); the third is obsessive ideation and compulsive action. Clinically, these are distinguishable phenom— ena. But any one, or group, of them can be, in folk theory, explained by the mecha— nism of possession. Unfortunately, some observers have, in their eagerness to empa— thize with their subjects, used the word cotics, 75/59 �A. M. A. possession to denote not only a type of folk theory but also whatever phenomenon their folk happen to use the theory to explain. In other words, if a people use the concept of “possession” to explain certain hysterical dissociations (such as the stereotyped fugues which are so commonly induced in many religious rituals), the anthropologist tends to say that the dancers in the ritual are “possessed”; similarly, if a people use the theory to explain hallucination (which is, incidentally, a less common use of the concept), the anthropologist may refer to hallucinators as “possessed” persons. Even more confusingly, the ethnographer may use the word to denote any person who is thought to be persistently inﬂuenced by a supernatural being, whether located inside or outside the person’s body. A third problem of conceptual ambiguity is the notion of trance. There would seem to be at least two major uses of this term: (1) to denote physiological collapse with coma or the occasionally concomitant delirious hallucinations; and (2) to denote (again) states of dissociation. The possi— bilities of semantic confusion are manifest. Problems of Methodology At ﬁrst, it was hoped that the Human Relations Area Files (HRAF), including the old Cross—Cultural Survey Files at New Haven and the completed portions of HRAF at New Haven and Philadelphia, would provide a sample of societies various of whose cultural features could be sta— tistically related to the phenomena of hallucination. The data contained in HRAF, however, even when supplemented by mate— rial from sources not tapped by HRAF, and by data on societies not included in HRAF, proved to be not amenable to statistical treatment, for three reasons: A sample which included representative cul— tures from all major culture areas was not available; the data were not comparable from society to society, because of the extreme unevenness of the reporting (rang— ing from no report at all to careful, exten— 76/60 ARCHIVES OF GENERAL PSYCHIATRY sive, and psychiatrically informed study), and the data provided were usually too crude to permit the discriminations which I regarded as signiﬁcant for statistical cate- gories. N0 quantity of time or money spent in HRAF and other library compilations can remedy all of these defects of the eth— nographic literature, and only a vast expenditure of funds in ﬁeld work could amass new and adequate data on a sufﬁcient num— ber of societies. The inference to be made is, rather, that the ethnographic literature available for areal or world samples, of the sort envisioned by Murdock 14 and others in connection with HRAF, is not suitable for statistical analysis with respect to all dimensions of anthropological interest, but is suitable only with respect to certain highly formalized and conventionally re— ported dimensions, such as kinship and subsistence activities. The cultures on which data were collected from HRAF in the abortive statistical phase of the study are the following: Abipone Achewa Ainu Andamanese Apiaca Apinage Aranda Arikara Assiniboin Balinese Bena Blackfoot Buka Bushman—Hottentot Canella Chuckchee Creek Crow Cuna Dahoman Easter Island Gros Ventres Hopi Ifugao Indian Yoga Kamilaroi Kwakiutl Lamba Maori Marshallese Plateau area (North America) Sherente Since nontrivial and signiﬁcant statistics appeared to be unachievable, the obvious next step was to consider what prestatistical manipulations of the data were possible and whether any of these might yield formulations of interest. Experimentation along these lines brought me to construct a rather tedious list of “existence theorems,” which I shall not reproduce here, but which proved later to be valuable in setting up the matrix of concepts. Existence theorems are Vol. 1, July, 1959 �RESPONSE TO HALLUCINATORY EXPERIENCE eminently prestatistical, but they are neces— statistical of description, sort to any sary since they deﬁne the relevant and nontrivial categories. An existence theorem is merely a statement that of the class A: there is at least one member concerning which the statement [9 in true; thus, for instance, the theorem where “there exists at least one (x) such that . . .” (3x)=df and (x):df “society” and A ber of the society as meaningless concatenations of visual and/or a u d i to r y pseudo-perceptions.” The whole of the theorem would read: “There exists at least one society such that hallucinations are deﬁned by some members of the society as meaningless concatenations of visual and/or auditory pseudopercep— tions.” From the existence theorems, derived from the HRAF cross—cultural ma— terials and from my ethnographic knowledge, the dimensions of hallucinatory experience shown in Table l were con— structed. These dimensions are offered as a formal frame of reference within which to observe cultural deﬁnitions of hallucina— tory experience, and as a rough statement of the range of cultural variability evident in the ethnographic record. With the foregoing semantic and methodological considerations in mind, we may proceed to discuss, informally and nonstatistically, certain implications of the ethno— graphic data. Conditions of Hallucination If one were to design an electronic brain which behaved in all respects like a normal human brain, one would have to include in its speciﬁcations both a capacity for hallucina— tion and a capacity to distinguish halluci— nation from sensory perception. Most human beings hallucinate (in the broad sense of the term which is employed in Wallace Communication Contains no information but is a meaningless pattern of auditory or visual images (:2 Contains information in the form of observation of phenomena that really exist somewhere (but are not messages) (1. Contains message from a supernatural being (ghost, soul, demon, divinity, etc.) located outside Ego’s body a . Contains message from, or is the experience of, a supernatural being (ghost, soul, demon, divinity, etc.) located inside Ego’s body ((5 Contains message from one part of self (e. g., own soul, conscience, memory, Id, subconscious, etc.) to another (6. g., consciousness, ego, etc.) or to other person as Contains message from a natural being communicating by means of radio, telepathy, or other means of telecommunication (1 1 B p12“hallucinations are deﬁned by some mem- 1.—Dimensiom of Hallucinatory Experience TABLE Mechanism of control Can be controlled by hallucinator and/or hallucinator’s fellows by manipulating physical condition and/or foreign biochemical factors ()2 Can be controlled by hallucinator and/or hallucinator's fellows by nonphysical means (such as will, prayer, ritual, worry, suggestion, autosuggestion, psychotherapy, etc.) I). Can be controlled by will of alien supernatural or natum being b I) 1 t b5 b. b1 b3 b 1A0 2 0 [Ab 3 b 2N) a I) 1A0 2A1) . Other (ﬁll) [Vb sz 3]) 0 Induction c. Hallucinator seeks to induce or repeat experience C 2 /—"C 1 D Concealment d1 Hallucinator conceals experience from group or denies oc- currence d 2 ,—/d 1 Punishment E e. Group institutes punishment and/or social extrusion e 2 He 1 Therapy 1“ Group or individual institutes therapeutic and/or prophy— lactic measures f1 fz Hf! G Role assignment g1 Experience qualiﬁes individual for valued social role (adult hood, shaman, healer, diviner, priest, etc.) g2 My 1 H Behavior guidance hi Content of experience may be taken as guide for individual and/or group action (other than therapeutic) irrespective of social role of hallucinator h: Content of experience taken as guide for individual and/or group action (other than therapeutic) only when hallucinator already ﬁlls certain social roles (e. g. shaman, prophet) h , Content of experience not taken as guide for individual and/ or group action (other than therapeutic) 77/61 �A. M. A. this paper), in one way or another, quite frequently; and there is no society, to my knowledge, in which hallucinatory experience is unknown. Hallucination is, in fact, one of the most widely distributed of the modes of human experience. Explicit re— ports of dreams, visions, and the hearing of voices are found in the sacred literature of the pre—Christian Near East; if mythology, ritual, and other religious behavior be re— garded as in part the legacy of such experi— ences passed on by oral or written tradition, we may suspect an antiquity measured in tens or hundreds of millenia. Under the general rubric of hallucination, however, there can be assembled a wide range of types of experience, from the Vivid and realistic supplanting of reality in ec— static visions and auditory revelations, to a relatively pallid verbal or visual imagery which blends imperceptibly into ordinary “thought.” These experiences are known from Western clinical observations to be prompted by the most various circum— stances: sleep, anoxia, pharmacologic agents, brain tumors, psychological stress, fatigue, sensory restriction, and others. Relatively little seems to have been done to relate the conditions precipitating and surrounding an event of hallucination to the content of the experience; ethnographic investigation may offer a few clues here. The speciﬁc conditions under which hal— lucinations have been reported in the ethno— graphic literature may be divided into the following categories : Sleep Fatigue Hunger and thirst Prolonged physical pain Extreme physical illness Social isolation Special exercises (breath control, posture, sensory restriction) Drugs Emotional stress in normal persons Mental illness It should be noted that these conditions are not logically independent, and that frequent— ly (and especially in voluntarily induced hallucination) two or more of the conditions are realized at the same time. Three observations are pertinent. First, in many societies relatively little signiﬁcance 78/62 ARCHIVES OF GENERAL PSYCHIATRY is attached to differences in the conditions under which hallucination occurs. In par— ticular, dreams during sleep, spontaneous waking visions, and induced hallucinations under drugs or stress may be given equal status and comparable evaluation. Western society is remarkable for the importance it assigns to differences in the precipitating conditions of hallucination; the most strik— ing example, of course, is afforded by the profound distinctions we draw among dreams (in sleep), delirium (in illness or intoxication), and “hallucination” in the restricted sense (in the waking state). Second, we must take note that, although not all hallucinatory experiences are regarded as desirable in any society, in primitive socie— ties it is very common for hallucinations with desirable content to be not only ac— cepted with pleasure but deliberately sought with the aid of such devices as hallucino— genic substances (e. g., some American Indians ingest parts of the cactus peyote and Paleo—Siberians, the mushroom ﬂy agaric) and various sorts of personal disciplines, ranging from breathing and posture exercises, through hunger, thirst, and isola— tion, to prolonged physical self—torture. The tendency to minimize discrimination among hallucinations on a criterion of precipitating condition of course does not imply any inability to discriminate between hallucina— tion and sensory perception; the preferential status of hallucinatory experiences is possible only when it is clearly differentiable from normal experience. Third, it appears that both the subjective feeling tone and the speciﬁc content of the hallucination are heavily inﬂuenced by a still more pervasive condition: the cultural milieu in which the hallucination, and particularly the voluntary hallucination, takes place. The latter point is worth elaborating here, although it anticipates some of the material to follow, because it is relevant to the methodology and evaluation of clinical research with hallucinogenic compounds under varying experimental conditions. Typically in such research the clinician administers Vol. 1, July, 1959 �RESPONSE TO HALLUCINATORY EXPERIENCE to a group of healthy urban adults, often medi— the with identiﬁed themselves persons cal or an auxiliary—medical profession, a substance which induces various instrumentally measurable physiological changes and observable alterations in behavior. The subjects are asked also to report verbally on their subjective experience. These verbal reports reveal a considerable variety of experience: Some subjects are euphoric; some are entranced by the intensity of esthetic pleasure they achieve in the contemplation of color, form, and movement divorced from meaning; many complain of anxiety, physical discomfort, various un— welcome perceptual distortions, and attitu— dinal changes; some hallucinate and some do not. These various reports and observa— tions are taken to indicate the psychological actions of the drug. Similarly variable re— sults, but usually with transient intensiﬁcation of chronic symptomatology, are given by mental patients from roughly comparable cultural backgrounds (but, of course, by virtue of illness occupying a very different social status). But no cultural controls are employed; and it is possible that to an unknown degree the subjective experience, and hence even the physiological measures, is inﬂuenced by the negative attitude toward any distortion of normal sensory and cognitive experience which many members of our society share, at least those people who do not customarily seek such special experi— ences as are afforded by narcotics and alcohol or by mystical or esthetic preoccu— pations. Some indication of the quality and mag— nitude of the possible effect of differing cultural attitudes toward hallucinatory ex— perience under differing conditions of drug administration is given by the differences in the experiences reported by normal white subjects after administration of mescaline and by American Indians after consumption 0d of introduction, and of intragroup per— sonality differences: ﬁrst, the inﬂuence of tains mescaline). The literature on the mescaline experi— ences of normal subjects is rather scattered, Wallace and some of it, particularly if it has an early date of publication, is unsatisfying because of the inadequacy of sample description and the disjointed and anecdotal style of presen— tation conventional at the time. Neverthe— less, the consultation of several prime sources “'25 reveals a reasonably consistent pattern of described phenomena, which con— trasts with the pattern described (also, unfortunately, sometimes in undeﬁned sam— ples) by anthropologists’ American Indian informants.”12'1“"!24 The fact of major contrast has been brieﬂy remarked in print by one of the—foremost anthropological stu— dents of peyotism, Slotkin,21 who observed in the course of discussion of attempts of white persons to suppress peyotism that “the responses described in clinical experi— ments on Whites are so different from the responses described by Indian Peyotists . as to fall into completely different catego— 2.—Contrasts in Prevailing Character of the Responses 0f_Climcally “Normal” White and Indian Subjects of M escaline Intoxication TABLE White Indian Variable and extreme mood shifts (agitated depression, anxiety, euphoria, depend— ing on stage of intoxication and personal characteristics) Initial relative stability of mood, followed by religious anxiety and enthusiasm, with tendency toward feel— Frequent breakdown of social inhibitions and display of Maintenance of orderly and “proper” behavior (“revivalistic" enthusiasm is socially proper in context) No report of suspiciousness “shameless” sexual, aggressive, etc., behavior Suspiciousness of others present in environment (reported to be uniformly present by Guttmann and noted in self by Kliiver) Unwelcome feelings of loss of contact with reality, depersonalization, meaningless“split-personality," ness, etc. Hallucinations largely idiosyncratic in content No therapeutic beneﬁts or permanent behavioral changes ings of religious reverence and personal satisfaction when vision achieved, and often, also, expectation of “cure” of physical illness Welcome feelings of contact with a new, more meaningful, higher order of reality, but a reality preﬁgured in doctrinal knowledge and implying more, rather than less social participation Hallucinations often strongly patterned after doctrinal model Marked therapeutic beneﬁts and behavioral changes (reduction of chronic anxiety level, increased sense of personal worth, more satisfac» tion in community life) 79/63 �A. M. A. ries; they do not seem to be talking about the same thing.” The salient differences in the reports are displayed in Table 2; the reader should note that a meaningful statis— tical presentation of frequencies of response types, while desirable, is precluded by the nature of the data available. These marked differences would seem to be plausibly explained by two related fac— tors which are independent of possible differences in racial physiology, of chemical action of the drug owing to variations in dosage, mixture with other agents, of meth— od of introduction, and 0f intragroup person— ality differences: ﬁrst, the inﬂuence of the setting in which the drug is taken (the white subject’s experiences occur usually in a hospital or university research setting; the Indian experiences, in a ceremonial lodge during a solemn religious ritual); and, second, differences in the psychological meaning of the primary drug effects when experienced. Certainly, gross enough situ— ational and semantic differences exist: White normal subjects generally take mes— caline once or twice, in a clinical research setting, with deﬁnite knowledge of an ex— perimental or a clinical purpose in the investigation, and without any commitment to or interest in peyote, or to mescaline in any form, as a personal religion; Indian peyote users take mescaline repeatedly, in a solemn religious setting to the accompaniment of serious ritual, with deﬁnite knowledge of a religious purpose in the usage and, often, with hope for per— sonal salvation, of which the vision is the evidence. The former factor—the setting— 5 been has reported by Fernberger to yield differences in content, which can to some degree be affected both by suggestion by the experimenter and by autosuggestion. The latter, the semantic, factor would seem to be signiﬁcant at the present stage of theory concerning the action of the hallucinogens, since it is recognized that both personal character and, perhaps, personally or cul— turally determined values concerning the “homeostasis of subjective—experience” may 80/64 ARCHIVES OF GENERAL PSYCHIATRY affect response to experimentally induced changes in sensation and perception.19 We quote the work of Hoch, Cattell, and Pennes 8 in this connection. We have pointed out that the alterations in the vegetative nervous system appear ﬁrst under the influence of mescaline, lysergic acid, pervitin, etc. This is usually followed by alterations of per— ception, bodily sensations, and changes in body image. In many patients it would appear that the perceptual alterations are conducive in producing anxiety, uncertainty, and, at times, rage. Seemingly, the perceptual alterations lead to a lowering of reality control, thence to tension and anxiety, which in turn lead to depressive, aggressive, and paranoid manifestations. Schizophrenic patients whose reality contact is already impaired are seemingly more vulnerable to drugs that have a disorganizing effect on reality perception. As yet it is unclear whether the emotional alterations seen in these patients are due to a physiological action of the drug per se or due to the experiencing of an alteration of reality and other changes on a psy— chic level. Interpretation of Content In most primitive societies, even if (on other grounds) the hallucinator is regarded as being ill, or the hallucination itself is unpleasurable, the content will not be re— garded as a meaningless concatenation of pseudoperceptions. The content of hallucination is sometimes interpreted as a message introduced directly into the subject’s consciousness by a supernatural being, directed either to the hallucinator himself or to the community through him as an intermediary. More frequently, hallucination will be in— terpreted as a real perceptual experience by the soul, which has wandered from the body and is seeing and hearing events involving real or supernatural persons which are occurring in another place, or which is able to see and hear events and supernatural beings present but imperceptible to others. The message—intrusion theory tends to blend into primitive theories of possession; in our society, it is expressed in the conventional telepathy, radio, radar, brain—washing, and electrical—current delusions and is classed as a paranoid mechanism, while the spiritual— perception theory is associated with extreme Vol. 1, July, 1959 �RESPONSE TO HALLUCINATORY EXPERIENCE religious enthusiasm. But in both theories, the content of hallucination is interpreted as signiﬁcant information. In at least two culture areas, that of the 17th—century Iroquois Indians of what is now New York State,26 and of Western society after the advent of psychoanalysis, a third theory also has existed as an alterna— tive explanation for hallucination. In this theory, the hallucination conveys an emo— tion—laden message from the soul, or some unconscious part of the mind, to the conscious self, and thus is a process of thought. This view, like the others, regards the content of hallucination as a message containing information. It appears to be a rare idea that the content of hallucination is mean— ingless, and one may hazard the guess that this notion is largely conﬁned to psychiatri— cally unsophisticated, nonparanoid, and tepidly religious, or nonreligious, members of Western society. If a hallucination is regarded as a mes— sage, there are evidently two approaches to its interpretation: to take the manifest con— tent literally, and to regard the manifest con— tent as a symbolic expression of signiﬁcant underlying ideas. The latter approach may entail various techniques, such as guessing and devices of free association, the consul— tation of a formal list of symbols and their meanings, and the more or less standardized derivation of meaning from the context of circumstances (such as ritual, illness, situ— ational stresses, and the like) in which the hallucination occurred. It is not important here whether or not there are, in truth, universal themes and symbols expressed in dreams and other hallucinatory experiences, as psychoanalytic theory and data suggest. The important point is that most human beings, in most societies, outside Western civilization, regard hallucinatory content as communication bearing signiﬁcant informa— tion which can be understood either directly or by the use of special methods of interpretation. Now this belief in hallucinatory content as communication, particularly when it is Wallace coupled with the conviction that the com— munication is not merely intrapsychic, seems to have an effect both on the content of hallucination and on the hallucinator’s, and his community’s, response to it. Halluci— nation in itself is not frightening, either to hallucinator or to his community, al— though the content may be; but even if the content is frightening, it is valuable knowl— edge. Hence the overt response to halluci— nation will very likely be markedly affected by its classiﬁcation as communication. It is to the topic of response to hallucina— tion that we now turn. Response to Hallucination The difference in response between Eng— lish white and Australian black to a course of hallucinations in a mourning woman is vividly illustrated in the following anecdote, reported by Parker,15 the author of a study of the Euahlayi tribe of Australia. Our witch woman was rather a remarkable 01d person. When she was, I suppose considerably over sixty, her favourite granddaughter (lied. Old Bootha was in a terrible state of grief, and chopped herself in a most merciless manner at the burial, especially about the head. She would speak to no one, used to spend her time about the grave, round which she ﬁxed upright posts which she painted white, red, and black. All round the grave she used to sweep continually. More and more she isolated herself, and at last discarded all her clothes and roamed the bush 5. la Eve . . . as she had probably done as a young girl. She dug herself an underground camp, roofed it over, and painted enormous posts which she erected in front of her “Muddy wine,” as she called her camp. She never came near the house, though we had been great friends before. She used to prowl around the outhouses and pick up all sorts of things, rubbish for the most part, but often good utensils too; all used to be secreted in the underground camp. She never talked to anyone, but used to mutter continually to herself and her dogs in an unknown tongue which only her dogs seemed to understand. We thought she was quite mad. One day, while we were playing tennis, she sud— denly, muttering her strange language and dancing new corroboree steps, clad only in her black skin, came up. Matah told her to go away, but she only corroboreed round him and said she wanted to see 81/65 �A. M. A. She danced round me for a little time, then sidled up to me and said: “\Nahl [negative or “no”] you frightened, wahl me hurt you. I only womba—mad—all yowee— spirits—in me tell me gubbah— good—I lib ‘long a youee: bimeby I come back big feller wirreenun [as a medicine woman] wahl you frightened? I not hurt you.” And after crooning an accompaniment to her steps, off she went, a strange enough figure, dancing and crooning as she went towards her camp; and not until the spirits gave up possession of her did she come near the house again. I used to tell the other blacks to see that Bootha had plenty of food. They said she was all right, the spirits were looking after her. Lunatics, from their point of view, are only persons spirit-possessed. Gradually old Bootha, clothed as usual, came back about the place. Strange stories came through the house back to me of old Bootha. She was very ill for a long time, then suddenly she recovered, not only recovered but seemed rejuvenated. We heard of wonderful cures she made; how she always consulted the spirits about any illness; how there were said to be spirits in some of her dogs; how she was now a rainmaker, and, in fact, a fully ﬂedged witch. me. . . . The reader will note a typical Western attitude toward the “lunatic,” a blend of amused contempt, pity, and anxiety, and also the native woman’s awareness of the attitude, and her effort to clarify the white man’s misunderstanding by explaining that her hallucinatory experiences were “good.” Noteworthy also is the satisfactory (both to the woman and to her associates) social remission, which was achieved in the course of becoming a shaman: a remission which, I suggest, was facilitated by her anxiety— free acceptance of hallucinatory experience. This anxiety—free acceptance of, and willing— ness to describe, hallucinatory experience contrasts vividly with the common shamed, fearful, self—doubting attitude of Western patients, who frequently try to conceal the fact that they “see things” or “hear voices,” and sometimes “confess” (as the psychi— atrist puts it) to hallucinations only under very careful questioning. Response to hallucination may be considered both as a matter of the hallucinator’s response to the experience and as a matter of the response of his group (and the two, 82/66 ARCHIVES OF GENERAL PSYCHIATRY of course, may be equivalent). As I have indicated, in primitive societies the fact of hallucination per se is seldom disturbing; but the content itself may be disturbing or not, depending on the nature of the socially appropriate response. Dreamers or vision— aries may resist strenuously the hallucinated suggestion that they undergo an arduous process of becoming a shaman, or that they accept the role of berdache (an institutional— ized inversion of sexual role among the Plains Indians), or that they commit some act, like murder or incest, which violates social norms; they may be stricken with panic at learning of approaching community disaster, or that they have been bewitched, or that they will be captured, tortured, and killed in a future war. Similarly, the hallu— cinator’s associates may respond with dismay, or with enthusiasm, to the wishes of his soul, and may institute protective meas— ures to avert harm from him or from them— selves, may induct him into the special social relationships indicated by his vision, may conduct the indicated medical treatment, or may take his revelation as a code for social reform. The signiﬁcant point is that it is the content of the communication which is the focus of interest and the fulcrum of action rather than the fact of hallucination itself. Let us now consider, by contrast, the responses to hallucination typical in Western societies. In some social groups, particularly religious sects, hallucinatory experience with supernatural ﬁgures ap— parent in the manifest content is interpreted as divine, 0r Satanic, revelation, and is responded to either by acceptance of in— junctions discovered in the content or by repression, or even punishment designed to drive out “possessing” devils. In psycho— analytically inﬂuenced groups (which prob— ably include a considerable proportion of the urban population of Western countries), dreams are interpreted and used as a basis for psychotherapeutic action, but waking hallucinations are regarded as symptoms of serious psychic illness. And in the rest of Vol. 1, July, 1959 �RESPONSE TO HALLUCINATORY EXPERIENCE the population at large, waking hallucina— tions are probably regarded primarily as indications of “nervous breakdown,” or even “insanity.’ The latter unfavorable social diagnosis is very commonly followed by the social extrusion of the hallucinator, with or without prior medical advice, into a mental hospital or some other socially restricted environment, or at the very least into a quasiostracism at home or in lodgings. Police force is available and not uncom— monly used to sanction and to effect this extrusion. In medical circles, despite recog— nition that hallucination in many conditions is a secondary symptom, and despite the insistence of workers like Boisen that “what the voices say is the important thing, not 1 hallucina— the mere fact of hearing voices,” tion is commonly taken to be a grave sign. In some of the research literature, indeed, hallucination is treated as if it were the essential feature of psychosis. Now it is reasonable to suppose that most persons, when they hallucinate for the ﬁrst time (certainly when the ﬁrst waking hallu— cination occurs), are aware of the culturally standard interpretation of and response to hallucination in their society. Even if they do not accept this interpretation and re— sponse as wise or proper, they will be aware of its probable evocation in others. If this is the case, then it is likely that the person’s interpretation of, and response to, the fact of his own hallucination in a given context (as well as its content) will be a function of the way in which the fact (and content) of hallucination is deﬁned by his culture. The function should determine in part his ’ emotional experience both during and after the event, and possibly (by cultural suggestion) its perceived content as well. 'We may ask, at this point, how much anxiety, self—depreciation, and cognitive dis— tortion are added to the miseries of mental patients by the circumstance that they have learned to fear waking hallucination in the course of living in a society in which waking hallucinatory experience is almost uni— formly negatively valued? (The scientiﬁc validity of the valuation is irrelevant.) Furthermore, we must question the completeness of any research into the psychophysiological action of the so—called psychomimetic drugs, of sensory restriction, and of other hallucinogenic procedures which fails to weigh not only the magnitude but also the direction of the probably mas— sive contaminating effect of cultural sug— gestion upon the subjects. For what is measured is not just the action of a drug or other procedure, but the action of the procedure plus the subject’s interpretation of and response to this action, plus the feedback effect on the continuing action itself (Figure); and all of these actions, inter— pretations, responses, and effects are factors with direction, as well as magnitude. There may be much that the therapist can do to alter the internalized cultural deﬁni— tions of hallucinatory experience in his patients, if he wishes. But it is research problems that chieﬂy concern us here. It would be possible in clinical research to con— trol for the direction of cultural effects by employing as control subjects persons whose subculture differs sharply from that of the Hallucinatory pseudo— perception SPECIFIC HALLUCINOGENIC STIMULUS CONDITION cognition of Situation -””'“°'°‘ , . -39. “—3). _____ Musculofure 1’ Vaugned'gme" "em”s ' . WWW / ‘ . personal-3y . 2‘ .. dynamics , Internalized cultural 15" definition of situation 9 MOTOR vEggAL *{ RESPONSE Mediation of response , , to hallucmOgenic stimulus by facets 0m; subjectlve experience. _ - - 9 NERV° Wallace 83/67 �A. M. A. experimental subjects in its deﬁnition of the expected experience, and by ensuring that the experimental conditions for the controls were sufﬁciently close to culturally normal conditions for them to permit generalization from past learning. Furthermore, it would be possible to select subjects systematically on criteria of personality, of past experi— ence, and of attitude toward the expected events; and it would be possible to vary deliberately the general situational structure with other variables held constant, both by physical manipulation and by deliberate in— struction and suggestion to the subjects. Such procedures, incidentally, should also be considered in relation to other than halluci— nogenic compounds; they evidently would apply to such drugs as tranquilizers, sedatives, and energizers, which on other evidence also depend in part for their effects on relatively unexplored interactions with personal dynamics and sociocultural milieu.18 Methodologically, such manipulations are the reverse images of the controls imposed by the placebo—and—blind (or double—blind) techniques and of analysis—of—variance tech— niques involving multiple pharmacologic agents; whereas the placebo-plus—blind, or variance—analysis, design varies the chemical agent and holds situation constant either by randomization or by laboratory control, the method of cultural and situational controls would hold the drug constant and vary such aspects of situation as the physical experi— mental conditions, instructions to personnel, and character and background of subjects. Drug and cultural controls should ideally be combined in one design. Summary The paper brieﬂy examines the range of cultural variation in conditions inducing, interpretations of, and responses to, hallu— cinatory experience. The published data suggest strongly that internalized cultural deﬁnitions of hallucinatory experience have a profound effect on the responses both of mentally ill and of normal persons. Meth— odological controls for cultural differences 84/68 ARCHIVES OF GENERAL PSYCHIATRY are indicated in research with hallucinogenic substances. Eastern Pennsylvania Psychiatric Institute. REFERENCES Boisen, A. T.: The Exploration of the Inner World, New York, Harper & Brothers, 1936. 1. Eggan, D.: The Manifest Content of Dreams: A Challenge to Social Science, Am. Anthropologist 2. 54 :469, 1952. Eggan, D.: The Personal Use of Myth in Dreams, J. Am. Folklore 68 :445, 1955. 4. Fernberger, S. W.: Observations on Taking Peyote (Anhalonium lewinii), Am. J. Psychol. 3. 34 :267, 1923. Fernberger, S. W.: Further Observations on Peyote Intoxication, J. Abnorm. & Social Psychol. 5. 26:367, 1932. Guttmann, E.: Artiﬁcial Psychoses Produced by Mescaline, J. Ment. Sc. 82 2203, 1936. 6. Hoch, P. H.: Experimental Induction of Psychoses, in The Biology of Mental Health and Disease, 27th Annual Conference of Milbank Memorial Fund, New York, Paul B. Hoeber, Inc. (Medical Book Department of Harper & 7. Brothers), 1952. Hoch, P. H.; Cattell, J. P., and Pennes, H. H.; Effect of Drugs: Theoretical Considera— tions from a Psychological Viewpoint, Am. J. Psychiat. 1082585, 1952. 8. Huxley, A.: The Doors of Perception, New York, Harper & Brothers, 1954. 10. Klﬁver, H.; Mescal Visions and Eidetic Visions, Am. J. Psychol. 371502, 1926. 11. La Barre, W.: The Peyote Cult, in Native American Culture, Yale University Publications in Anthropology, No. 19, New Haven, Conn, Yale University Press, 1938. 12. La Barre, W.: Primitive Psychotherapy: Peyotism and Confession, J. Abnorm. & Social Psychol. 42:294, 1947. 13. Lincoln, J. S.: The Dream in Primitive Cul— tures, Baltimore, Williams & Wilkins Company, 9. 1935. Murdock, G. R: World Ethnographic Sample, Am. Anthropologist 592664, 1957. 14. 15. Parker, K. L.: The Euahlayi Tribe, London, Archibald Constable & C0., 1905. Petrullo, V.: The Diabolic Root: A Study of Peyotism, the New Indian Religion, Among the Delawares, Philadelphia, University of Pennsyl— vania Press, 1934. 16. Vol. 1, July, 1959 �RESPONSE TO HALLUCINATORY EXPERIENCE Radin, P.: The Winnebago Tribe, Washington, D. C., Bureau of American Ethnology, 37th Annual Report to Secretary of Smithsonian In— stitute, 1915-1916, 1923. 17. Rashkis, H. A., and Smarr, E. R.: A Method for the Control and Evaluation of Sociopsychological Factors in Pharmacological Research, Psychiat. Res. Rep. 9:121, 1958. 18. Rubin, L. S.: The Psychopharmacology of Lysergic Acid Diethylamide (LSD—25), Psychol. 19. Bull. 54:479, 1957. 20. Slotkin, J. S.: Menomini Philos. Soc., n. 5. 42:4, 1952. Peyotism, Tr. Am. J. S.: The Peyote Religion: A Study in Indian—White Relations, Glencoe, 111., Free Press, 1956. 21. Slotkin, Wallace 22. Smythies, J. R.: The Mescaline Phenomena, Brit. J. Philos. Sc. 3:339, 1953. 23. Smythies, J. R.: A Logical and Cultural Analysis of Hallucinatory Sense—Experience, J. Ment. Sc. 102:336, 1956. D.: Personality and Peyotism in Menomini Indian Acculturation, Psychiatry 15: 24. Spindler, G. 151, 1952. 25. Stockings, G. T.: A Clinical Study of the Mescaline Psychosis, with Special Reference to the Mechanism of the Genesis of Schizophrenia and Other Psychotic States, J. Ment. Sc. 86:29, 1946. 26. Wallace, A. F. C.: Dreams and the Wishes of the Soul: A Type of Psychoanalytic Theory Among the 17th Century Iroquois, Am. Anthropologist 602234, 1958. Printed and Published in the United States of America 85/69 �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. 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Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/18207735ad5546b08aac89618232e7bc.pdf 66f756c9dd21d0500a4b4e9773773d3e PDF Text Text ��Wm « . . ”1%! W3 l/W W "79"! - duh [cow ~ 4444...; n— wlamaZu-ﬂ nag ‘3 073 /3 W _———_—_é¢%0u_LL__p_J_ 1w... mug: . j” / 3 H4 Ito :98 ��'VfJii MMud‘vue I7M¢2+ ? la Mal. .max Q ,4”; . 9:19 M00 4/73 ,“ K We; /a¢/If ,, (14.2...e‘23m,“ L DF/Wdﬁ ﬂan" 714 - “7‘ 44.4.5 44W r M , %W(“ W77 27/56:.) xéa/av-p 2/3“; 413»; Ma... 7w,» #1W 1‘ I; a.“ me: ‘M‘M w 4‘ 7‘ WWW/3,1:I/7 w»! AWL—«awe; CK’S") mm) M �7 7 4%? % ,4» 014/.- a‘,‘” __n ”ViV W ,, (A. 2‘ MW "5 11M; r W ��‘ WMA (“Av/Jaw AJa—lnw.m.5¢nﬁ¢ ��M Wf - I7 ‘70 [Lav/2.». 5’52 31 ,9: d3: ��ﬁbrw Dr? ' D.- £44415" Iv ~43 VP-’YV MED-thaw Masha“. -6” 'DFP- m 51am JV 1 ‘ ��\ \-_' <f/ e4 AM (3 ��73/4 r 4/»! / 4? ��" ,; . “A; 7 m 7V ��Ph. i74800 MECHOIYI® CHLORIDE (METHACHOLINE CHLORIDE U.S.P., MERCK) a SHARP DOHME MECHOLYL* Chloride produces the same physiologic response as does acetylcholine, which, when released at nerve endings, produces parasympathetic stimulation. In therapeutic doses, MECHOLYL slows the heart rate, lowers blood pressure, constricts the bronchioles, dilates the peripheral blood vessels, constricts the pupils, Increases intestinal tone and peristalsis, causes salivation and ﬂushing, and stimulates the detrusor muscle of the bladder. In general its eﬁects are the opposite of those produced by epinephrine. Its action is much more prolonged than that of acetylcholine and it is, moreover, devoid of the nicotine-like effect of that substance. METHODS OF ADMINISTRATION MECHOLYL Chloride is a potent substance and careful consideration should be given to Its dosage and method of administration. For *MECHOLYL is the registered trade-mark of MERCK & CO., Inc., for its brand of methacholine. [i] stopping an attack of paroxysmal auricular tachycardia it should be given by subcutaneous iniection (never by intravenous or intramuscular injection), and the same method of administration may be used in treating scleroderma, chronic ulcers, Raynaud's disease and other vasospastic states, although in the latter conditions better and more prolonged eﬁects are obtained when it is administered by the method of ion transfer For administration by mouth (iontophoresis). the less hygroscopic MECHOLYL Bromide is supplied in tablet form. Atropine intravenously immediately terminates the action of MECHOLYL. A syringe containing a suitable dose of atropine sulfate [0.6 milligram (l/iOO grainI] should be available for immediate intravenous iniection if the dose of MECHOLYL Chloride causes undesirable symp- MECHOLYL Chloride is supplied in ampuls Since MECHOLYL constricts the bronchioles containing 25 milligrams (0.025 gram) of the powder. Solutions for subcutaneous iniection are prepared by dissolving the drug in sufﬁcient sterile distilled water to make it possible to measure accurately and administer easily the dosage desired. WARNING Injections of MECHOLYL Chloride should be given subcutaneously only. lniections should never be given in- travenously or intramuscularly. PRECAUTIONS The patient should be lying down during the administration of MECHOLYL Chloride to minimize the effects of lowered blood pressure. [2] toms. Overdosage of MECHOLYL may produce momentary cardiac arrest. The Trendelenburg position, to give the cardiac center the beneﬁt of any circulation present, is sometimes beneﬁcial in such an emergency. and may produce an asthmatic attack in those subiect to this condition, it should be used with extreme caution, if at all, in cases where there is a history of asthma or hypersensitivity. Substernal pain following the administration of MECHOLYL is said to be rare. However, the use of this drug in patients subiect to angina pectoris is not recommended. USE IN PAROXYSMAL AURICULAR TACHYCARDIA One of the most efﬁcacious uses of MECHOLYL Chloride is in terminating attacks of paroxysmal auricular tachycardia. It is, however, not effective for prophylaxis or for continued treatment in cases of frequent recurrence of the arrhythmia. [3] �not recommended for the treatment of auricular fibrillation, auricular ﬂutter, or paroxysmal ventricular tachycardia. It is DOSAGE The initial subcutaneous dose of MECHOLYL Chloride should be limited to IO milligrams (0.01 gram) to test the patient's tolerance. Careful preliminary testing of the patient with a small dose will not nullify the effect of a subsequent dose, and is advisable if there is any doubt of the patient's ability to tolerate the drug. treating paroxysmal auricular tachycardia in patients under twenty years of age, IO milligrams given subcutaneously usually terminates an attack. In older patients, 20 to 40 milligrams may be required; obese patients sometimes require more. In Slow absorption of the drug due to inadequate local circulation may interfere with the therapeutic response. If the attack is not terminated in two minutes, compression of the vagi, together with gentle massage at the site of iniection to promote absorption, is suggested. Conversely, if absorption is found to be too rapid, further absorption may be retarded by applying a tourniquet above the site of iniection. The eﬁects of MECHOLYL may be terminated immediately by atropine. [4] and larger dose (if that given ﬁrst fails to interrupt the attack) may be given 20 to 30 minutes later, providing no severe reaction has occurred following the ﬁrst dose. Quinidine in moderate doses (not more than 0.2 gram four times a day) usually does not impair the MECHOLYL effect. Larger doses tend to inhibit its action, although MECHOLYL has been known to “break through" the depresr slon of quinidine. 174800 For oral administration or administration by the method of ion transfer (iontophoresls)—Ph. A second I Gm. bottles. 10 Gm. bottles. MECHOLYL BROMIDE (for oral administration only) is supplied in Boxes of 24—200 mg. (0.2 Gm.) tablets Bottles of 500—200 mg. (0.2 Gm.) tablets OTHER USES OF MECHOLYL CHLORIDE been used (by suba number of other condi- MECHOLYL Chloride has cutaneous iniection) in tions, particularly in certain vasospastic diseases, such as Raynaud’s disease, in chronic ulcers, and in scleroderma. If a test dose of IO milligrams of MECHOLYL Chloride has been well tolerated, the subsequent dose may be increased cautiously up to 25 milligrams (0.025 gram). In these conditions, however, the much more prolonged eﬁect produced by MECHOLYL Chloride administration by the method of Iontophoresis (ion transfer) or by the oral administration of MECHOLYL Bromide Tablets is preferred. MECHOLYL CHLORIDE is supplied ,snm DOHME SHARP 8: DOHME as follows: Philadelphia, U. S. A. For subcutaneous iniection— DIVISION OF MERCK a: CO. Inc. Boxes of 6 ampuls each containing 25 mg. (0.025 Gm.) of the dry powder. I 5 I P- IB-413 [6] Printed in U.S.A. �For the Medical Profession only ‘ANECTINE’® CHLO RIDE BRAND SUCCINYLCHOLINE CHLORIDE INJECTION 20 mg. in each cc. Multiple-dose vials of IO cc. (for intravenous use) ; n’l ' ix, use 'v 6’ ‘ " ' e .,'alysis. While respiratory depression is usually a r single dose of the drug, or following ’M‘uV-r-mtous administration, cessamore prolonged respiratory there may on occasion be depresoion requiring adequate respiratory exgen by the administration of supplemental or controlled . - -. . ‘ANECTIN E’ Chloride brand Succinylcholine Chloride Injection is an ultra-shortactmg skeletal muscle relaxant; that is, following intravenous injection of small procedures. The quick return of spontaneous respiration is a deﬁnite For more prolonged relaxation advantage. ‘ANECTINE’ may be given by continuous intravenous drip; tachyphylaxis does occur and cumulative action is not seen. The degree of relaxation not be ordinarily may controlled by the solution. Upon stopping the intravenous drip, adjusting the rate of ﬂow of narily resumes within a minute and spontaneous respiration ordirecovery is complete within 5 minutes. CHEMICAL PROPERTIES Succinylcholine chloride, also to as diacetylcholine chloride, is odorless, crystalline substance referred a white, which'is readily soluble in succmic acid bis (ﬂ-dimethyl—aminoe‘thyl) water. Chemically it is ester dimethochloride, and its formula is as follows: i ' ' ’ Cl CH2COOCH2CH2iV(CHa)3 CH2COOCH2€H2N(CH3)3 :I'he ester linkage is rapidly hydrolyzed in alkaline solutions but is in acrd solutions. In order to relatively stable promote stability, solutions should be refrigeration. It appears that succinylcholme is rapidly hydrolyzed kept-under followmg its PHARMACOLOGICAL ACTION ‘ANECTINE’ causes muscular transmission at the myoneural paralysis by producing a blockage of nervous junction.This action was ﬁrst reported et al.1 Independent studies by Bovet The at Wellcome Research Laboratories have been conducted on the synthesis2 and pharmacology“7 of the drug. de Beer and his associates3-7 have found that doses as low as 0.05 mg./Kg. given cats are effective in producing intravenously to muscular relaxation, and that intravenous doses of 0.1 mg./Kg. or more produce and complete muscular characterized by short durationprompt paralysis which is of and action extremely rapid recovery. Repeated injections produce reproducible and phylaxls nor signiﬁcant cumulative predictable muscular paralysis, neither tachyeffects being seen. When given by intravenous drip, a predetermined degree (scratic of relaxation in a cat nerve-gastrocnemius muscle) could be closely approxrmated by adjusting �The administration of doses of ‘ANECTINE’ sufﬁcient to produce complete neuromuscular blockade has not caused any signiﬁcant. ghange in blood pressure (except for the typical asphyxial pressor response in the absence of adequate respiration). No,evidence of any histamine-like depressor action has been found, thus differing from observations with d-tubocurarine. The ECG of the caﬁ was unchanged during a 2-hour infusion maintaining complete paralysis. ' ‘ ‘ Acute toxicity studies in albino mice showed the intravenous L.D.5o to be 0.55 to 0.59 mg./Kg. Complete paralysis resulted, with marked dySpnea and anoxia; death was apparently due to respiratory failure. Those mice which survived the initial symptoms exhibited disappearance of anoxia and dyspnea in 2 minutes and had completely recovered within 30. minutes. Chronic toxicity studies on albino rats showed that the intraperitoneal injection of -1' mg./Kg. or less, twice daily over a period of 4 weeks, produced no evidence of toxicity. important.diﬂ‘erence‘between ‘ANECTINE” and d-tubocurarine is that the former is not antagonized by anticholineste'rases. On the comrhlti’, 5.14.911 drugs as physostigmine, lThis rostigmine (neostigmine) and procaineaapnoli‘asgmthg 5;th 1:8 :11 would support the theory that syuccinylcholine'is hydrogze succinylcholine. by cholinesterases and that interference with this enzyme actiOn results in per- -. sistence of activity of the drug. Edrophonium (Tensilon) also prolongs the action of succinylchohne. An- ' ,. ' CLINICAL INDICATIONSUKNI) DOSAGE ‘ 1 Short Duration: ‘ANECTINE' Chloride brand Succinylcholine Chloride Injection is indicated for the production of muscle relaxation during surgical procedures, 3,9,13il5-17 and in conjunction with electroshock therapy.13,14,16 In view of its very short duration of action (usually about 3 minutes following a single intravenous injection) succinylcholine is ideally suited for procedures ;requiring 'only brief relaxation, .such as endotracheal intubation, endoscopic examinations, orthopedic manipulations, short surgicalvprocedures such as tonsillectomies, and electroshock therapy. As described previously, intravenous administration of the drug produces relaxation within a minute, which lasts about 3 minutes and is quickly followed by recovery of spontaneous respiration in those cases where apnea hasoccurred. Dosage for. Short Procedures: The average dose for’relaxation of short duration is 20 mg. (1"cc.) ‘ANECTI‘NE’ Injection given intravenously (Foldess)... The optimum'doSe will vary among individuals and may vary from =10 to 30 mg." for adults (0.5 to 1.5 cc.). Following administration of doses in this range, relaxation develops in about 1 minute; maximum muscular paralysis may persist for about 2 minutes, after which recovery rapidly takes place within the next few minutes. However, very large doses may result in more prolonged apnea. ”-21 Obviously, facilities for supplemental or controlled respiration with ,adequate exchangeoi oXygen should be available at all times. In order. to'avoid carbon dioxide accumulation and hypoxia, supplemental or controlled respirationgshould b? provided during respiratory depression without waiting for the development 0 apnea.. , Prolonged Relaxation: Although ‘ANECTINE’ isfshort—acting, prolonged relaxation may be obtained by repeated injections or, preferably, by maintaininga continuous intravenous drip.8,3o By adjusting. the rate of ﬂow, the desired degree of relaxation may be obtained and maint‘air‘ie'd‘, and the degree of relaxation can be changed within 30 seconds by changing the rate of ﬂow. Upon stopping the ﬂow of the intravenous drip solution, relaxation. quickly disappears. In those cases where respiration has been depressed it usually returns to normal_within a. few minutes upon stopping the intravenous drip, V. Dosage for Long Procedures: The-'aVerage dose for continuous intravenous infui‘ sion is 2.5 mg. per minute for adult patients. For convenience'in preparingsolutions for intravenous drip there are available ‘Anectine’ Chloride Solution, 50 mg. per cc., 10 cc. ampuls and 100 mg. per cc., 10 cc. ampuls. The, contents of one 500 in mg. 10 cc. ampul may be added to SOD-ecstetileiisotonic saline solution to an prepare (1 0.1% mg. per cc.) ‘Anectine’ Chloride Solution; the contents of one 1 Gm. in ’0 cc. ainpul‘maybe added to 1,000 cc. to prepare an 0.1% ‘Anectine" Chloride Solution. This concentration is suitable for continuous intravenous infusion, See literature accompanying ‘A‘u‘ectine' Chloride Solution,’5_0fn‘1g./cc., 10 cc. ampuls, and 100 mg:‘]cc.,«10 c‘c‘. animals for details regarding use of'r'this‘product for obtaining ' ' r‘elaxatiOn. Solutions for prolonged intravenous drip jay also be‘ prepared. for a dilution of‘An‘e’ctine’ Injection, 20 mg./cc. in appioprrate proportions. ‘ NOTE: Succinylcholine is rapidly hydrolyzed by alkaline'solutions and therefore loses potency rapidly. it mixed with thiopental sodium (pentot‘hal sddium). Such mixtures, if used at all, must be used within a few minutes ofvprepatationq however, separate injection of ‘ANECTINE’ is preferable. Succinylcholine chloride is quite stable when storedqunder refrigeration. 0n long standing at room temperature potency gradually decreases; however; solutions may be kept as long as 3 months at room, temperature without signiﬁcant loss of potency as determined by biological assay. , , ' !~- ‘ �.m . . CONTRAINDICATIONS AND PRECAUTIONS The drug should be used only by those skilled in‘ the administration of sppplemental *oecontrolled. respiration and facilities for this procedure, including adequate respiratory exchange with oxygen, should always be immediately .. available. “'V ' 'ANECTINE’lis not an anesthetic agent and should not be regarded as a substitute for anesthesia; 'its‘Ause“ does not take the place of givmg an adequate amount of anesthetic agent. Some anesthesiologists believe that rapid injection is responsible for the muscular twitching that is seen just prior to relaxation. These fascrculations may be due to the‘rate’of injection of the drug, and may be minimized or avoided ‘by giving the injection more slowly/,8,”8 While respiratory depression is usually of very short duration following a 'single dose of the drug, d" following cessation of continuous intravenous administration, ‘LiiCl‘C may‘e..-.§ribcc{i.iongespeaially with excessive doses, more prolonged respiratory depression 1.9-2]- requiririg controlled respiration and the administration of oxygen. The duration of the effect of ‘ANECTINE’ may depend on plasma-cholinesterase activity.94,2°,27 Patients’with severe'liver disease, severe anemia, severe malnutrition, and possibly those suffering from' polyphosphate insecticide poisoning may have a decreased plasma-cholinesterase activity which may intensify and prolong the action of ‘ANECTINE’, especially if large'doses are used.23,29 In such cases, in addition to the usual measures of controlled respiration and administration of oxygen, it may be desirable to administer plasma or whole blood for the purpose of restoring cholinesterase activity,” Neostigmine and other anticholine’sterases, as well as edrophonium (Tensilon), do not antagonize the action ,of~‘ANECTINE’, but on the prolong its contrary eﬁ'ect. They are therefore contraindicated as antidotes for ‘ANECTINE’. Intravenous injections of proCaiiie likewise may prolong and intensify the action of ‘ANECTINE’. There is evidence that intraocular pressure is increased slightly following injection of ‘Anectineflﬂ “This effect is seen immediately after the injection and during the fasciculatory phase; it' subsides as complete paralysis supervenes; it appears to be the result of brief contraction of the extraocular muscles. This suggests that ‘Anectine’ should ’be usedl‘with caution, if at all, in intraocular surgery. The opinion is expressed that the effect is probably not sufﬁcient to contraindicate the drug in general, surgery or electroshock therapy for patients with "' glaucoma. ‘ r‘ .- .KBIBIZIOGRAPHY 1. 2. Bovet, D., Bovet—Nittl, F., Guarino, 3., Longo, V.G., and Marotta, M.: Pharmacodynamical property of certain derivatives of suc’cin'ylcholine with curate-like action: esters of trialkylethanolamine of dicarboxylie aliphatic acids. Rendieonti Istituto Superiore di Sanita 12:106, 1949. Phillips, A.P.: Synthetic curate substitutes from aliphatic dicarboxylic acid aminoethyl esters. J. Am. Chem. Soc. 71:3264, 1949. Castillo, J.C., and de Beer, E.J.: Poteii‘tiationbl' curarizing action of diacetylcholine (succin lcholine) by aliphatic dicarboxylic acid aminoethyl amides. Federation Proceedings 9:262, 19 0. Castillo, J.C. and de Beer, E.J.:_The neuromuscular blocking action of succinylcholine (diacetylcholine). J. Pharmacol. 6: Exper. Therap. 99:458, 1950; de Beer, E.J., Castillo, J.C.,1.Phillips, A.P.,3Fanelli, R.V., Wnuck, A.L., and Norton, S.: Synthetic drugs inﬂuencing neuromuscular activity. Ann. New York Acad. Sci. 541362, 1951. Wnuck, A.L., Norton, 5., Ellis, C.H;, and- de Beer, E.J.: Production of controlled neuromuscular block by infusion of diacetylcholine. Federation Proceedings 11:403, 1952. Ellis, C.H., Norton, 3., and Morgan, W.V.: Central depression by drugs which block neuromuscular transmission. Federation Proceedings “11:42, 1952. Foldes, F.F., and McNall, P.G.: Succinylchélinei A new’a‘ppréach to muscular relaxation in anesthesiology. New England J. Med. 247596, 1952. Brucke, H., Ginzel, K.H., Klupp, H., Piaffenschlager, F., andWerner, 6.: Muscle relaxing effect: of bis'echoline e'sterof dicarboxylic‘acid in narcosis. Wien. klin. Wchnschi‘. 63 :464, 1951. Ginaiel, K.H., .Klupp,.H.,; and Werner, G.: Pharmacology of ”bis—quaternary Yammonium a, compounds. Comparative tests withisome aliphatic dicarboxylic acid esters. Arch. int. Pharmacodyn. and Therapy. 87:79, 1951. 7Gi'7nzzei,9§(l‘.H, Klupp, H., and Werner, G.: A‘dicholine ester with greater curare effect. Experentia . a. Arnold,‘0.H., Bock-Greissau, W., and Ginzel, K.H.: Wien. med. Wchnschr. 101:492, 1951. Thesleﬁ‘, S.; Pharmacological and clinical tests with LT 1. (0.0—succinylcholine iodide). Nordiak ’ Med. 46:1045, 1951. Holmberg, G., and Thesleff, S.: Succinylcholine iodide as a muscle relaxant in electro—shock treatment. Nordisk Med. 4621567, 19SL‘Abst. in J.A.M.A. 14821064, 1952. Dardel, 0.37., and Thesleﬁ, 8.: Clinical results with succinylcholine iodide, a new muscle relaxant. Nordisk Med.‘46:1308. 1951. Thesleﬁ‘, 5., and Dardel, O.V.:'Clinical report on succinylcholine iodide. Presented at 26th International Congress of Anaesthetists, London, September 3—7, 1951. Abstracted in J. Am. MJWom. Assn. 7:58, 1952. " 3. 4. 5. 6. 7. 8. 9.' 10. 11. : 12. 13. . - , ‘ 14. 15. ‘ 16. ~ ' �I7. Mayrhofer, 0., and Hassfurter, M.: Surgical risks in patients with cardiac and vascular disorder. Wien. klin. Wchnschr. 63:88.5, 1951. 18. Holzer, 1-1.: Wien. med. Wchnschr. 102:112, 1952. 19. {IggerfgIséKd Prolonged respiratory paralysis after succinylcholine. Correspondence. Brit. MJ. 20. Love, S.H.S.: Prolonged apnea following scoline. Correspondence. Anesthesia (London) 7:113, 1952. 21. Gould, R.B.: Succinylcholine. Correspondence. Brit. MJ. 1:440, 1952. 22. Bovet, D., Bovet—Nitti, E, Guarino, S., Longo, V.G., and Fusco, R.: Investigations on synthetic 23. 24. 25. 26. 27. 28. 29. 30. 31. curarizing drugs. III. Succinylcholine and its aliphatic derivatives. Arch. int. Pharmacodyn. and Therapy 88:1, 1951. Poulsen, H. and Hougs, W.: Letters to the Editor, Lancet 2:199, 1952. Foldes, F.F.: Letters to the Editor, Lancet 2:245, 1952. Kay, H.T.: Letters to the Editor, Lancet 2:200, 1952. Evans, F.T., Gray, P.W.S., Lehmann, 1-1., and Silk, E.: Sensitivity to Succinylcholine in Relation to Serum-cholinesterase, Lancet 1:17.29, 1952. Bourne, J.G., Collier, H.O.J., and Somers, G.E-:ASuccinyIchoIine (Succinoylcholine)—MuscIe »S[« Relaxant of Short Action, Lancet 1'§2.£5, 1952. Lehmann, 1-1.: Letters to the Editor, Lancet 2:199, 1952. Hampton, L.J.: Personal communication. .L . ,r .:l Diacétiyilchdlihe I" and Little. M., Jr , Hampton, L.]., Grosskreutz, D.C.'. (Succin’yIcIroIine): A Controllable Mu'scIe Rel’axant. Presented before the Twenty-seventh Annual Cpnzress of Anes‘ ” ‘h thetistSyVirginia Beach, Virginia, Septemher 22-15,..1952. " " ‘1 ' Lincoff, H.A., Ellis, C.H., DeVoe, A.G., de Beer, E.J., Impastato, D._I., Berg, 5., Orkin, L., and Magda, 1-1.: The EEect of Succinylcholine on Intraocular Pressure. Am. J. Opth. 40:501,1955. — PREPARATION FOR IMMEDIATE INJECTION OF SINGLE DOSES FOR SHORT PROCEDURES ‘ANECTINE’ CH LORIDE mo SUCCINYLCHOLINE CHLORIDE INJECTION 20 mg. in each cc. multiple-dose vial: of IO cc. For intravenous i'nieetion V Also available: FOR PREPARATION OF INTRAVENOUS DRIP SOLUTIONS ONLY ‘ANE CTINE ’ C H LO R I D E m SUCCINYLCHOLINE CHLORIDE STERILE SOLUTION 50 mg. in each cc. IO cc. ampuls (Total contents 500 mg. Succinylcholine Chlorlde) To be diluted before using FOR PREPARATION OF INTRAVENOUS DRIP SOLUTIONS ONLY HIGH POTENCY ‘A N E C T I N E ’0 CHLORIDE SUCCINYLCHOLINE CHLORIDE STERILE SOLUTION 100 mg. in each cc. 10 cc. ampuls (Total contents I Gm. SuccinyIchoIine Chloride) To be diluted before using ‘Aneetine’ Injection is supplied in the form of a sterile isotonic aqueous .rolution. ImtoniCity 15' achieved by the addition of a :uitable quantity of sodium chloride. \\ .” p,“ BURROUGHS WELLCOME & CO. (U.S.A.) INC.,TUCKAHOE, N.Y. Associated Houses: LONDON BOMBAY by 731 MONTREAL BUENOS AIRES Printed in u.s.A. SYDNEY CAIRO JOHANNESBURG DUBLIN AUCKLAND 41 I o o 6 �Poloni, A.: L'Acetilcolina nel liquor dei malati di mente. Hancenze di effetto curarosimile del liquor di echizophrenici sul mnecolo acetilcolina e en dorsale dell: saga, I1 Gervello g1: 81-1oh, 1951. Translation of EEEEEEE‘ author, using the method of Tower for the conservation of acetylcholine in spinal fluid, and the dorsal muscle of the leech for the test, has made the fol» lowing observations in several trials, making use of the spinal fluid of 10 normal subjects and 110 mental patients, of whom 50 were schizophrenics, 10 progressive paralytica and 50 subjects with other forms of mental disease: The (1) That the spinal fluid of normalaubjects cistains acetylcholine in a to 1:1G' concentration varying from 1:1 (2) That the spinal fluid or schiaophrenice in 9h$ of the case: does not contain ecetyloholine bet a substance which produces an action antagoMstic to acetglgholine, 7; weble to that of ”curare", in a concentration of 1:1 to 1:1' .... (3) In the spinal fluid‘of the progressive paralytic: one encounters the some curare-like subetance nut in a lower concentration than in that of schizophrenics. (h) The spinal fluid of persons affected with other forms of mental sick— ness, as well as that of normal subjects, did not contain the curerelike substance in a discernible quantity, but only acetylchcline, which was found in greater concentration in the hystericale and epileptice, in lower concentration in senile psychotics and alcoholics. This emphasizes the pathologic vale of the report obtained from the spinal fluid of schizophrenics and progressive parelytics and suggests the hypothesis that the curare-like substance is trimethylamine, product of the excessive catabol~ ion of choline, of which the author has found an abnormal urinary excretion in schizophrenics; (In the some paper, in a footnote, the author eliminates trimethylamine, since does not have aurora-like properties.) it �CHOLINERGIC ASPECTS OF CONVULSIVE THERAPY Max Fink, M'.D. �\ From ‘ the Department of Psychiatry, Washington University School of Medicine and the Department of Psychiatry at the Missouri Institute of Psychiatry, University of Missouri School of Medicine, SUOO Arsenal St., St. Louis, Missouri 63139. MH-072u9 and MH—2715, MH—927, grants part, IVE-11380; and the Psychiatric Research Fomdation of Missouri. Aided, in IX: 65-8 2-25-66 by USPHS Revised for the Jowmal. 06 vaouA and Manta! Disease. �CHOLINERGIC ASPECTS OF CONVULSIVE THERAPY While the mode of action of convulsive therapies remains enigmatic, one theory holds that the early development and persistence of changes in brain function are requisite to changes in behavior.“3’21,22 useful index of neurophysiological change is the appearance of high voltage electroencephalographic slow wave activity.22 '23 While the biochemistry of this activity is A poorly understood, demonstrations that it is inhibited by anticholinergic corrxpoundsl9920’3""56 suggest that cholinergic systems may play an active part. The EEG patterns and the response to anticholinergic drugs in convulsive therapy are similar to experimental and clinical head trauma and to a lesser extent, to spontaneous seizures. impulses has been extensively studied since the early descriptions by Dale12 and Loewi.38 A constituent of nervous tissue in a acetylcroline is liberated during the excitation process. It is rapidly hydrolyzed through the mediation of aoetylcholinesterase and is rapidly reconstituted by the bound form, �choline—acetylase system.‘+5 Free acetylcholine has not been measurable in normal cerebrospinal fluid despite the rapid breakdom of bound acetylcholine during periods of activity and excitement.63 But the normal have measurable cholinesterase cerebrospinal fluid does activity.“1 ChoLéneILgic Mme/ta 06 CILanLoce/Lebm mena. Free acetylcholine was found in the cerebrospinal fluid of cats within a few minutes after experimental head trauma and persisted for varying periods up to 1+8 hours. The quantity of free acetylcholine varied between 2.7 and 9.0 gamma/ 100cc and the amount was related to the degree of induced trauma.6 Concurrent electroencephalogram first demonstrated high voltage fast activity, interpreted as evidence of an intense neuronal discharge, which was succeeded by-a short period of flattening of all recorded electrical activity. These phases were followed by prolonged periods of high amplitude sharp waves in the delta frequencies. The behavioral changes related to the degree of induced trauma and to the amount of measured free acetylcholine. With higher levels of acetylcholine, Bornstein reported greater degrees of EEG abnormality and greater changes in consciousness. Spontaneous post-traumatic seizures were also amount related to the of free acetylcholine measured in the cerebrospinal fluid. �Bornstein applied acetylcholine to exposed cat cerebral cortex. When the concentration of acetylcholine was or less, high amplitude sharp the electroencephalogram. to 2 waves When of low frequency appeared in the concentration gamma/100cc, the electroencephalogram parallel to the post-traumatic records. Investigations in neurological patients McEachern demonstrated 1 gamma/10000 was increased flattened in a fashion by Tower and free acetylcholine in the cerebro- spinal fluid only in patients with recent head trauma, recent grand—Hal seizures or after electroconvulsive therapy.63 Free acetylcholine varied from 0.2 to 100 gamma/ 100cc. In assaying spinal fluid cholinesterase activity, they noted a sharp rise in the butyrylcholinesterase fraction and a fall in the acetylcholinesterase fraction in patients with head trauma and following convulsive therapy. however, the cerebrospinal although it ' After spontaneous seizures, fluid did not exhibit such inversion contained free acetylcholine. They concluded that the level of free acetylcholine varied directly with the degree of cerebral damage and that reversal of cholinesterase fractions was a more sensitive indicator of cerebral damage. Electroencephalograms taken at varying intervals following trauma also indicated a relation between the degree of EEG abnormality and the appearance of free acetylcholine in the cerebrospinal fluid. �Increased acetylcholine in rat brain after traumatic shock was also reported by Kbvach, at a£.35 This acetylcholine activity vitae. was inhibited by the administration of atropine tn electrographic, behavioral and neurologic signs of head trauma were blocked by the parenteral administration of The atropine, as were similar clinical changes occurring after the intracisternal addition of acetylcholine.6 0.5—1.0 mg/kg applied these observations to the treatnent of closed head injuries. In 20 patients with varying degrees of trauma, he administered atropine subcutaneously in doses of 0 .1 mg/kg, Ward noting clinical improvement in some and electrographic effects in others.67 a reversal of the The same changes in the' .*-‘_ post-traumatic electroencephalogram were reported by Jenkner and Lechner in a study of diethazine, another anticholinergic single intravenous dose in forty patients resulted in nornalizing the abnormal electroencephalogram in twenty—two drug. A and marked improvement in six others.33 Similarly, in experiments of post—traumatic shock and cerebral edema in animals, Denisenko reported a blocking of the clinical changes by such anticholinergic compounds as methylbenactyzine and adiphenine (Trasentin).13 ThuA, the amount 06 Mae acetytchloune may tamed/52 éptnat ﬂuid 60110“)th cmtnocuebaat mama and the tn the, amount 06 - ‘ -A,‘r �ghee acety£cho£ine, the degnee and type 05 e£ecthoencepha£nghaphie in carded/C behavion abnolzmablty, and changed phenomena, which may be deduced by appear/L aA the adminibtnation Lute/mutated anti- 06 chounugie daugb. Bluuln acetylchoﬂéne and antéehounugic dhugb. The effects of the direct application of acetylcholine to the central nervous system may also be blocked by anticholinergic drugs. The administration of the cholinesterase inhibitor di—isopropyl fluorophysphate (DFP) elicited high amplitude rapid frequency patterns similar to status epilepticus and some posttraumatic states.2'*’31a32a68 These EEG effects were blocked by small doses of parenteral atropine and scopolamine. The' EEG geat increase in acetylcholine after tetraethyl (TEPP) was measured and pyrophosphate related to the toxic effects and the induced convulsions .29 ’59 Chatfield and Dempsey prepared exposed animal cortex with prestigmine and evoked electroencephalographic spike activity. prior administration of atropine blocked the appearance of spiking, or if present, this electrical activity could be The eliminated by atropine.9 In contrast to these findings, Brenner and Merritt applied topical acetylcholine in concentrations of 2—1/2 to 1096 to the exposed cortex of cats and noted no effect. on the electro— encephalographic changes after intravenous atropine (1 mg/kg) .7 �The concentrations of acetylcholine in these experdnents, however, were higher than the topical applications (1-H gamma/1000c) and the intracisternal (0.2-10 gamma/10000) injections of Bornstein.6 Brenner and Merritt also noted electroencephalographic effects similar to acetylcholine after methacholine (Mecholyl) and carbamylcholine (Doryl) in concentrations much lower than the acetylcholine concentrations. They ascribed the increased effectiveness of these cholinergic drugs to their lack of sensitivity to cerebral cholinesterases. 6mm Atady a necuAa/Lg Ceaebao¢pina£ Fluid Acetyﬁchoﬁine and Seizuneb. One view Thug data M9, conﬁuwxg and to quaiiﬁy thié iAAue. of acetylcholine metabolism finds it in nervous tissues in an inactive and bound form. During periods of activity, acetylcholine is liberated at the cell membrane where it is rapidly deactivated by cholinesterases. The amount of bound acetylcholine is the resultant of the continuous processes of synthesis, liberation 'u and breakdown.15 It has been postulated that the level rises falls during waking activity.15’29’“5’6° at al. reported increased free and total acetylcholine during sleep and Tbbias after chlorofornland pentobarbital anesthesia in rat and frog brain but no changes after strychnine or picrotoxin convulsions.5° �(microacetylcholine of level the neasured Richter and Crossland in and rat sleep anesthesia during tissue) brain gamma per mg. brain to be 300% The difference levels. post—seizure than higher rate resynthesis the as however, transient, in tissue levels is gamma/gm/minute).“5 (7 high is brain in rat for acetylcholine Crossland a£.16 and at Elliott confirmed by These observations were and Merrick.11 Giarman and Pepeu reported the increase in be roughly to various depressants following acetylcholine nervous central the of of depression the degree proportional to Buck, and Maynert activity.29 motor in system and the reduction sedation during levels acetylcholine brain however, studying elevated with associated were sedatives concluded that some existed.39 relationships rigorous brain acetylcholine but that no of. observations In part, this may be related to the earlier in measured synthesis acetylcholine McLennan and Elliott that narcotic of low dosages by accelerated rat brain slices is dosages.”° by-high inhibited but drugs, in fluid the in spinal Free acetylcholine was reported an patients, epileptic patients with epilepsy.1°’63 5.0 0.02 to of in quantities demonstrated free acetylcholine Of 56 Acetylcholine gamma/100cc. 1.0 of with an average gamma/100cc extent the seizures, of the frequency to related levels were since time the and to abnormality, of electroencephalographic �the last seizure but bore no relation to medication, type of epilepsy or level of cholinesterase activity. Elliott at al. also noted free acetylcholine in the spinal fluid in concentrations up to 3 gamma/100cc after pentylenetetrazol (Metrazol) convulsions.16 Tower and McEachern viewed the increased acetylcholine as a by—product of the seizure and not causal.63 Studying the hypothesis that seizures were induced by the accumulation of acetylcholine, Tbrda neasured the level of acetylcholine in brain tissue after pentylenetetrazol convulsions. She noted a rise in the acetylcholine content of brain before and a fall during the convulsion. Below certain levels of acetylcholine, convulsions failed to occur. She suggested that the fall in . tissue acetylcholine during a convulsion was due to the inhibition of acetylcholine synthesis by increased concentra-’ tions of metabolites such as annenium ions.51:62 Giarnen and Pepeu also measured changes in central nervous system acetylcholine following various stimulants.29 Only after nethacholine and 3, 5—dimethylbutylethyl-barbiturate was there a significant change in the acetylcholine level. They noted a decrease in association with induced convulsions. With other drugs which they classified as stimulants (LSD, iproniazid, iproniazid + hydroxytryptophan, and iproniazid were no changes in the acetylcholine level. + DOPA) there They concluded that �despite intense excitation produced by these compounds, there were no changes in acetylcholine levels unless these were accompanied by convulsions. (The between these observers and Cone may be differences in observations at at. related to the differences in measurenents, fOr the latter and Tower and McEachern methods measured changes of biochemical reflecting free acetylcholine only, while Giarman and Pepeu measured total acetylcholine including bound and free forns of acetylcholine.“°). Thane btudieb Auggebt that aae accompanied by an tncteaee tibeaated 6aom tté Apontaneoub on tnduced 4etzune¢ tn tnteaeettutaa ﬁnee aeetytchottne bound ﬁonm whtch may be aeﬁteeted tn the Aptnat staid. Ceaebnat activity and eetzuneé enhance aeetytehottne deatAuction, toweatng txnbue teveZA 06 aeetytehottne, white eteep and anebthebta augment aeetytehatine paoduetion ineaeaetng ttbbue tavetb. ' Centaat Menuoue SyAtem Cholineeteaaeee. Tower and McBachern also measured spinal fluid cholinesterase activity.63’5“’65 By reporting cholinesterase activity as a ratio of the rate of hydrolysis with two substrates compared to an acetylcholine substrate, acetylcholinesterase/acetylcholine and butyrylcholinesterase/ acetylcholine ratios are derived. Normal cerebrospinal fluid contains these esterases in the ratio of 33:17. �-10In patients with head trauma, Tower and MCEachern reported an inversion of the cholinesterases with an increase in the butyrylcholinesterase of the spinal fluid and a decrease in acetylcholinesterase activity. The extent of the cholinesterase related to the severity of trauma and to the degree abnormality. A similar reversal was observed in patients reversal of EEG was undergoing convulsive therapy. In patients with elevated spinal fluid acetylcholine spontaneous seizures, however, no change in the after ratio of cholinesterases or total cholinesterase activity was found. Changes in cholinesterase activity may be related to changes in cell membrane permeability. Acetylcholinesterase is found in highest concentration in the central nervous system while butyrylcholinesterase predominates in other tissues, especially blood serum. With increased cerebral acetylcholine, vasodilation predicted, with vascular fluid transudation varying with the extent and duration of the vasodilation.35 Spiegel, Spiegel—Adolf, and their and increased cellular perneability may be co-workers demonstrated such perneability changes and increased conductivity of the tissues associated with the appearance of various ions (as potassium and phosphate) in the spinal fluid following electrically induced convulsions.5"'58 electrolytes as nucleic-acid splitting enzymes Such non- also increased. �-11- Changes in cellular permeability may be the basis for the high concentrations of acetylcholine and increased concentrations of butyrylcholinesterase after induced seizures or head trauma.65 That changes in cholinesterases may be large and measurable is suggested tte recent demonstrations that neural stimulation by and learning produces changes in brain weight and acetylcholinesterase reports, Pryor and Otis studied the effects of repeated induced seizures in Wistar rats.“3 After Following these activity.37’“9 as little as u weeks they observed increases in brain weight and in acetylcholinesterase activity which was related to decrements in behavioral perfornance. persistance of acetylcholine in spinal fluid after head trauma and after seizures despite increased cholinesterase The activity may be acetylcholine— the of the related to sensitivity acetylcholinesterase system to concentration relationships.8’“1’55 At "physiologic" concentrations, hydrolysis of acetylcholine is rapid (3—H ndcmoseconds) but at higher and lower concentrations, the activity falls off quickly. In contrast, the butyryldholinesterase~acetylcholine relationship is non—specific rate of hydrolysis increases with increased concentration. These relationships relate to theories of the induction of seizures. While the usual concentrations of acetylcholine at and the cell membranes are destroyed by the specific activity of acetylcholinesterase in a few microseconds, an excessive concentration following excitation may exceed its rate of �-12- hydrolysis. The seizure threshold induced, with the seizure itself may be reached and a seizure adding to the amount of free acetylcholine. Increased acetylcholine affects vascular and cellular perneability altering the concentrations of various ions, including butyrylcholinesterase in tissues and in the cerebrospinal fluid. Through the activity of this esterase, though of low efficiency and depending on concentration acetylcholine is reduced in tissues to levels for the action of acetylcholinesterase. ChoZanAzcnaAeA appcanb in the Apina£ 6£uid kinetics. more direct a4 a ncﬁﬂcction 06 theta incncaAc in inzcnchZuzan gluidb ac6u£xing diam changcb in cc££ mcmbnanc pcnmcabizity accompanying incncabcd EEG Hypcnbynchnony and Induced Convu£5ion4. of high voltage EEG slow wave The acctchhoanc. significance activity for the convulsive therapy process has been repeatedly described."’?-’23’50,51 In the usual course of convulsive therapy, interhtreatment electroencephalograms record progressive increases in amplitude and in theta activity and a reduction in beta activity. As treatment continues, delta activity appears in bursts and eventually is the dominant activity in all leads. These changes are directly related to the number and rate of induced convulsions, and is not specific for a method of induction. While some relationships to type of electrical current has been observed, all seizure inducing methods —- electrical, intravenous chemical or inhalant -— exhibit the same type of EEG pattern changes.21’22a23:3° �-13The early appearance of high degree hypersynchrony and its persistence throughout a treatment course has been found to be prerequisite to improvement. Both the electrographic and the behavioral changes of induced convulsions are transiently reversed by the acute administration of experimental anticholinergic compounds.19’2° The intravenoue injection of diethazine, bonactvzine, the piperidylbenzilates JB—318, JB—336 and JB—329 (Ditren), and subjects. WIN-2299 induced EEG These EEG desynchronization in psychiatric changes were associated with behavioral alerting, anxiety, tremors, illusions and hallucinations. In patients who had recently received electroconvulsive therapy there was a reduction in slow wave activity and a reversal of euphoria, denial and confusion. Atropine, in low doses, was also associated with EEG desynchronization accompanied by tachycardia, nervousness and tension. At higher dosages, hypersynchronous slow waves followed by lower voltage, poorly organized delta activity with superimposed beta activity was accompanied by progressive confusion and disorientation. effect of anticholinergic drugs on the slow wave activity of convulsive therapy was also assessed by the chronic administration of atropine (5 mgm per day) and scopolamine (1-3 The during the weeks of treatment. The amount of EEG slowing was significantly less than in a control group.66 The samples were too small for a clinical correlation but the data is consistent mg) �-1uwith blocking of the clinical effects of electroconvulsive therapy. Marked improvement was reported in treated, none of scopolamine-treated and in 5 controls receiving unmodified replicated ECT. of 2 1+ 7 atropine— of the 6 This study was not by the authors who suggest or population changes may have results in a second study.“ that dosage factors contributed to the different - AA tn cueblcat tJLauma, the demographic changes induced convuutoms may be modiﬁed by the 06 antichounugtc dlLugb Auggebting 06 Want/cation that tncneeued amounts acetytchoune on tncneated chounugtc aecepttvity ts amounted with the htgh voltage Atow wave activity. 06 Acetytchoune and Induced Convutbtont . Despite a constant application of treatments, however, there is great variability in the time of appearance, the duration, anount, and sensitivity to modification by alerting, hyperventilation and barbiturates of the electrographic slow activity in psychiatric populations.30 These differences relate to differences in central cholinergic activity. The failure of certain patients to develop hypersynchrony may be associated with the absence of free acetylcholine and with minimal changes in cerebral function, wave �-15thus precluding a clinical response to induced convulsions. Tower and McEachern in their study of craniocerebral trauma, included observations of six psychiatric patients undergoing convulsive therapy.63 Studying the patients ments they reported free spinal after 3-7 fluid acetylcholine in treattwo patients; and an increase in butyrylcholinesterase and a decrease in acetylcholinesterase with a reversal of the ratio of cholinesterases in five of the six patients. Concerning the one patient in the series who failed to show either free acetylcholine or a cholinesterase ratio reversal in the spinal fluid, the authors stated; "It is interesting that this patient was the only one of the six to show no response to treatment." From these observations they concluded that the spinal fluid' <3; changes in induced convulsions were more like those of 4 ‘4‘ craniocerebral trauma than those of spontaneous epilepsy. «3-.3‘ Other evidence of alterations in the perneability barrier may be seen in the demonstrations of an increaSed concentration of cocaine in brain tissues three days after a series of induced convulsions.1 The change 12 in concentration of this large molecule, ordinarily absent in brain tissue, was associated with the appearance of hypersynclu'ony (delta bursts) in the electroencephalogram, �1 -.,,-_..._. -15Fhom theae oboehvationb we would conclude that induced convuibioni, like chaniocehebhai thauma and Apontaneoui Aeizuheb, ane aAAociated with an incheaie in ghee acetyichoiine in inten- cebtuiah 6iuidA, attuing cuebhai pumeabifity and enhancing the appeahance is maintained Lb . one 05 cholinebteJLaAeA. The Level 06 ghee by hepeated induced Aeizunei . heﬁiection ieveu 06 aLCULed aitehed pehmeabiiity 06 06 EEG acetyichoiine hypmynchlwny acetyichoiine and the eiecthoiyteb and otheh Aubitanceé, inciuding choiineAtULaAeAs. The changeé in intuceuuiah elect/w- .oi.m_m_._._.. _ ..l.__a u.- iyteé, inciuding aeetuichoiine phovide the biochendcai AubAthate 601:. the pelwibtent behaviouai changed and EEG hypwynchnony ﬁoaowing induced convuibianb. An ww...-._.~__.-m~ 06 application the phedietion o6 06 these conciuiioni is been in the btudieb the convuiAive thehapy heéponbe and the ctaiiisication as psychoaei. ~--....-_ Choiineétehabei and the Ciaibiﬂicatian 06 PAychOAeb. ._‘ 4» .. V Punkenstein at at. reported a relationship between the blood pressure response to methacholine and the clinical response to convulsive therepy.25'27 Immediately after the injection the blood pressure falls, usually returning to the baseline within 5-20 minutes. A return within 5 minutes Of methacholine places the patients in Groups after- 20 minutes \‘ \e I, II or III; places'the patient in while a return Groups VI and VII. �-17Group I and Group II-III respectively, while and 97% have a 9% and a 35% Gkoup VI and Group VII recovery rate, subjects have 89% recovery rates to induced convulsions.27 Group I to III reactors may be looked upon as patients in whom is rapidly hydrolyzed; while Groups VI and VII have a slow hydrolysis rate. (The response to injected epinephrine was suggested as a second criteria in the classification, but is of limited discriminating value.”8) methacholine While we have no biochemical explanation fbr the differences in the metabolism of methacholine in these psychiatric groups, it is possible that the blood and tissue cholinesterase activity levels of Groups I—III is high while that of Groups VI-VII is The low compared to general psychiatric populations. differences in blood cholinesterase levels in normal and mentally ill subjects have been extensively studied. Despite differences in nethods,“’5 elevated cholinesterase levels compared to normal populations have been reported for depressive subjects,"""’5"‘7952 schizophrenic subjectslh’28’53 and a mixed psychiatric populations .“2 Alpern reported lowered cholinesterase levels in schizophrenic subjects.2 While these studies appear inconclusive, they provide data that the variations in blood cholinesterase levels are generally greater and frequently elevated in the mentally ill. Negative reports include the failure by Ellman and Callaway” to confirm Rubin's study; and Altschule's review of the data suggesting �-13no abnornality ' of cholinesterase levels in the mentally ill.3 that cholineAth play These Atudteb AuggeAt meaAuAeA may a signiﬁcant note. in the thuapeutéc aupome to canvutatve the/mpg and in the pathoggnebta 06 paychobu. �-19; CONCLUSIONS This review summarizes some of the available data suggesting that cholinergic mechanisms may be central to the convulsive therapy process. Induced convulsions are associated with cerebral vasodilaticn and increased cellular permeability, followed by the appearance of increased amounts of enzymes and electrolytes in intercellular and cerebrospinal fluids . The increase in acetylcholine, vasodilation and increased permeability appear as interrelated phenomena associated with ' trauma, seizures and induced convulsions. These biochemical changes acconpany increased hypersynchrony which is recorded as EEG slow wave electrical activity in scalp electrodes and which can be nodified by the acute and ' chronic administration of anticholinergic drugs as atropine, benactyzine, diethazine, procyclidine and various piperidyl— benzilates . In these regards, induced convulsions are more similar to cerebral trauma than to spontaneous seizures. in cerebral biochemistry alter cellular activity sufficiently to affect consciousness and the behavior of subjects . Failure to induce persistent biochemical changes, including the The changes concentration of acetylcholine, results in failure to produce behavioral change. �-20There is, as yet, no consistent evidence for differences in the sensitivity or dependence of populations on cholinergic mechanisms. Differences in the rate of development of cerebral changes to the sane number and frequency of induced convulsions classifications of the nentally ill based on the blood pressure response to methacholine suggest, however, that such differences may be significant in the pathogenesis of different and .._..__...V ___,‘~,‘....____... ' «uAW—‘wﬂﬂw ,1“ psychoses . �REFERENCES 1. Aim, B., Strait, R. L. A., Pace, J. W., Hnenoff, M. K. and Neumphysiological effects of electrically Bowditch, S. C. indnced convulsions. Arch. Neurol. Psychiat., 75: 371-378, 1956. 2. Alpern, D. O. i kholinergicheskaya Aktivnost kholinesterasy reaktsiya kmvi pri shizofrenii. 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Cholinesterase patterns and acetylcholine in the cerebrcspinal fluids of patients with craniocerebral tram. 616. Canad. Jo Researdl, Sect. E, 27: 105-119, lgugo \ Tower, D. B. and McBachern, D. of cholinesterases in human The content and characterization cerebrospinal fluids. Canad. J. Research, Sect. E, 27: 132-145. 1949. 65. Tower, D. B. and McEachern, D. II. Acetylcholine and neuronal activity. Acetylcholine and cholinesterase activity in the cerebmspinal fluids of patients with epilepsy. Canad. J. Research, Sect. 66. Ulett, G. A. E, 27: 120—131, 19u9. and Johnson, M. W. Effect of atropine and sc0polamine upon electroencephalographic changes induced by electro—convulsive therapy. Electmenceph. Clin. Neurophysiol., 9: 217-22u, 1957. 67. Ward, A. A... Jr. Atropine in the treatment of closed head injury. J. Neurosurg., 68. Wescoe, w. The 0., 7: 398-402, 1950. Green, R. E., McNamara, B. P. and Krop, S. influence of atropine and scopolamine on the central effects of DFP. J. Pharmacol. Exp. Then, 92: 63-72, 191.8. �for Ihe Bio Sciences Informgﬁon Exchange. . . . . NoI' for publlgnhon pubhcahon or Prepared j DEPARTMENT OF HEALTH, EDUCATION. AND WELFARE ——1 m”: PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH "one: or ; . s SUBMITTED TO! ‘Public Hoalth Service. NeIionaI lnr+i+u+es of 'n-r OF Paganini “mmame ‘ and Give names. department. and ofﬁcial Win ‘l'ifles RESEARCH Hulfh. ' ‘ ' rnoJEcIr;”.-\ Div. of Research Grants. Bofhesda l4. Md. ' , in Spinal Fluid § 7 a—sm. (022 , ' , PROJECT NO. (Do no? use this space) and. U lemme} l Read" Injuries“ ' , I of PRINCIPAL INVESTIGATORS and ALL OTHER PROFESSIONAL PERSONNEL engaged on the proiecf. 11.9., Rmsurgem, mums: Gluing Instructor in NeuroIn. surgery. Dartmouth Radical School Smutﬁadgs. i. . John P. Wilson, Ph.D., Assistant meensor 1n the Physiological Sciences, Dartmouth Medical School I NAME AND ADDRESS OF APPLICANT INSTITUTION: ' Hitchcock Fomdation Hanover , New Hampshire SUMMARY OF PROPOSED WORK — (200 words or less —- Omlf Conﬁdential data.) In In Bio Sciences lnforrnaﬁon Exchange summer!“ of work In progrcss are exchanged wlﬂn qovernmonf and privan agencies supporﬁng research In modiul and rant-d ﬁelds and an forward“ to invosﬂqaton such informnﬁon. Your summary Is to be usod for rhese purposes. vbnqm study of in. neq'tylnholine MW: of spinal fluid mama“ in hudinjxaﬁu, utilizing the biéh'nsa'y author! am! Young; Mariana, has A, bun Wt“ tale .mn. In! study Indiana the presence put of «cannon», smtonin.‘ and one. unidentified in the period following head injury. mezpmponod “any: is an extension of this Mainly ml: u.m1n tissue as will as tpifail fluid. and ~11; aging. in addition chain: 'analysis for these one 3mm” (spectrephntnnuomter). during tha We“ f.‘ Silbmitted beginning SIGNATURE OF PRINCIPA INVESTIGATOR for periOd I. September 1956 A , ldenfify fhe Professional SchooI (medical, dental; public healfh. graduafe. or ofher) wifh which this proiecf should b idenfiﬁed: mm, INVESTIGATOR —— mm Romanian .. Do NOT um:- Ti—u: :nnn'n- I 11 ed. �12/17/56 smmc comm wanes WW3 rwml :5an or ~ may mam Acrmr! IN BLOOD ml mm... m) mma: )5.“th for the at mum of t papa-1m mutation mod for): Gil-13:1 mm th Mien, in Matt“, Mm mum Samar, Brooklyn, «.2... Pom-my 15, 1957. A with. m mom-mm nth-ad in ”portal for tho «5mm; a! W My W m W tar um» 91' m «mu-cm» Minty. Though of W31. “14 «mm-nan (2.39) and on m thalliutan» in min-.1 fluid. the mum. in nanny applaud. to the may.“ of and and «11:, um mm, m. on» biological num. Only 0.3 um, :1. of 13311:]. fluid at 0.001 I1. at m mu «um: knyltuooblno 10 why-d a lmdng incubation, m um is nquirod for a in dnmtion. W but”, pa 8. 1! “Situated by am“ 51 tol- trickle”— mm into a calorimeter tube. notummm¢1smwwnmmrm~wmmm «.1331. uotio acid, cum-1mm, ind daunting m thus Whom. Thu than that map mu :m an: m mt: with ”Miami” to product Absorption mm a. 510 tho a. ma to format ton, color with an New”. want, m m M. or new in. y. an be both may.» mum the cam in not by Adding *Mn 1397" u in spin]. ﬂuid, um sham-mu 1: n «1mm Wu: mum-m), (lawnmmmwmmm dot-ruin“ 0! W “machinist-mu. mm of mm in various Mansion. fluids at. amounts-nod and coup-rd to tho ﬁndings in pun-nu with mm dim». Th. nor-:1 W “01ka Yb Ind!!! W10»). alto mu .ployd to “My «batman. that action, no): u LSD, which is a mum inhibitar of 10 �WW. Wham” mtahmtortothnmnmwwwcm hr this mu the awyummm - hm“: - WOJn1¢romoerquythu¢ummmmmtof tm»mmlibcatdhyumc lauwrkmwamwmawmmmnmm mum at m mm, 9.3. mm mu m... 3 601m, 3., m4 Gold-abut, m, a. 3mm. My», 1, 21.6 (1956). �we «mwmman. m: 31.3mm, wmmmc cmmms, m 1'3ch W W, W W. 'm .m no Magnum - Lon; Inland for of a n.‘., 3661“,, 1) m ”may, not M1» on an. ”WW- mm» harm), and for tho Illa; than 111:“ mu u spam. mum mum“ of and and ”both“!— mum.» 1mm in fan madman. a: aninitiou 1: Mm a. "mm m mm and tin-Sr to u» » W in mu W. W]! ma ‘ wat u Wtimﬂu York Mm, 11.0%ch cm 15, 19,7! “W nautical mm: m mm. mu that: m s: muons; mm; (nmalm, mom. mm of atypical alkaloid- m- mm», mthmuumbounafmuc mp: mkummcut 1n thiamine, and Wow. I'm: sum in : Mia «fat mm, 2) awn-s in ”WM 111le 20mm rm- the 91‘ m from macros! M Marina. municidanﬂmdtmmdwmﬁkh wish alkaloid! W I” be much. duration at diam-ranting nut-win 1:: tbs who «Wu. to We 03:10:13.1" I couple“ uh“ for henna; m6. mutating than and hack «mm ma mum-1a, «man. um, mad tmtm into a. null value at cthylm mum“. Tho aim a truncated m M Wu to dryness, thin upon-d out on mt» pupa. Separates: of tho 1: want either by handing cur-anaemia an; Mme).- 1anmmppmu1n mmmnarmmuostmtmamm mum. at mun, ms. mu. am.» 3min. m �“ cam mum «an an a! mt thomh with H» (521:1), or by in 1n 1:: m3. m- petition :5me“ W (m bola). At oommdm mum m «a «a: 1m puma). um ﬂax-1p: , the. club“ with 1106M, tht «ma by mpontm in «11ﬁlth ﬂaking. mud tub», than mm. arms. and Wm mama. m this point than W WI m MinnaﬁyotwlwtomdbthnMaunm«maintain-momma mummuawxomumqmmutmmmu W. M Mal-Inﬂux com-mm; 1m «mum at out amen my be gland mm, thmhthMmWw5uw, mat. mad ”imam, mmtmu, WWI» W mama. W W bah structural {mm at th- '13., and to! 16 drug: tar in pasture m dam-trusting the with ml: w. metric Rub dag mhmtmthmmmoﬁhmcamwath WWIMtMO. Amioutm of tin mm to ﬂu arm. a! “Mum“ prior to m {allowing 4mg than” will I» mean“. �(Effect a! In a Was Mona an 3% Theory of convulsion for amriigmﬂme report to this society we noted the relational” between the degree of induced delta eetidw during the course or therapy and the behavioral response to electroshock. Thane patients, in when big: éegreee of delta nativity were induced early, and were sustained, miteeted the greatest. degree: at helmvieral change, as well as a significantly greater percentage of inprovemrt. and recovery than these patients in when only law degree: a: delta activity were We (Fm: m: m. 1957). In the past few years, a variety of reports relating changes in £me( 1‘) leetylchoum and oholineeternae in the spiral fluids of patients (Subs, Herd) 1rd minis 0 (Bernstein, Teller and HeEnohern) following head the obsem’cime that cholixm'wbic agents may by trauma (32mm, Bard, Jemmr) alter the EEG m; putterne induced and by electreeheck (Inuit), led us to investigate the role of autylcholine-eholinestemee metabolism in acctroeheck therapy. In 1956 Ulett reported that atropine or schpclmne, when administered row! the clock schedule blocked the appurme of the delta activity on a. we hm com to mandate with electroshock therapy. meet. noted, however, �that his patients nurtured numerous madcaiubla aide effecta during these mutations. (19%) had Previously, mm (1950 ramming the suggestion of Bernstein new that atmpine mama bath the EEG patterns and the mumlogm signs induced in an by head trauma. Here, too, the side effects wen marked. In 1953. W:- md Lechmr ropertad that mum-a1 effects similar to atropine mm intend in patients with 610W 11-. in tram, head on also reported the effect at normal subjects. the EEG hypothesis of the we of nation lanthanum is a soluble We: Wr “was: dry with. at“ comlaiva mama» aethnsm the bmdyoardia, «11m: moment neumplvuiolagicnqdapﬂva than”. coupow with Wologic to atropine. In maximum animals. hymns 335; Media 1.1m. and 111mm: of patients ﬂaring electroshock Warsaw; and to relate than them findings to the ham and whim by Maine min- we purpose of this repwt to describe the effects of is dicthuine um; Thcy EEG blocks slowing of the heart; Wasp-m, «ﬂatten. induced by ucatylcholme, main ugal uni hypotenaion. m ma fasciculation e and pilocarpmﬁ and induces �~3- m: shock ﬁreﬂy-two paymttric patients, in-vurioua stages of electron- treatmnt in an studied. the EEG these 351 upon-ward. voltm’ury purchiatric hospital have been WW Follow laboratory. Wtemd intmmny at a routino amtration, 4mm” both the were 25 mm the habtwioral m per minute, for a total errata. Prior and a to the W Mahatma, period were upeonaordad. Running 'dmg record again tested in recording, diamante unstmtured historical intervicw regarding, and meordeﬁ EEG EEG an BEG at the rate or 290 to 250 nan, depending upcn drug maximum, aubjoots Imam periods were mntinued until mummm Wanna patterns on visual \. inspe ction. m m: (a) Neal: follwed by n fooling of Q. 11!. subject; manifested spontaneous gouging initially; dryness of the mouth and, a thickmsa of speech. They nohd heaimde and makneu of the increased mathsmou and difficulty in W were Psychiatnc/cleaﬂy mnifoctad in between 13 and 30 mm attaining mm am noon rammed by eyelid closure. subjects. In the not. pound titer drug mutation, ax subjects spontan- �.3. 0011333” med fouling: of «mm mums mm amnion illusions, about than" 111mm, the setting of the «auras or our icientity. by the um: and Myrtle Such and m: pm- patterns were transient and had diaappuamd‘ of the expat-meat, usually vitiun three hours. In um subjects, mesing august-loan and panic led to, a «mum at an wrung. amt Hero, too, mummm at minimisation War was mum: tune hours. (b) In previous studies, we had noted the intimate rolaﬁommP hem ehangan in syntactic language 1:3th with mmm induced by allotmm. changes diothaaino inﬂamed In In subjects alteration in mm prior to abatmshook, in syntactic pattern at an “lurking” musty. 3&3er with tielta activity, We}: clinical amnesia {anthems of an ”alteration in cerebral function, diathaninu induced a appearance or animation of amt: languaga ambnl patterns. indicative tmient. dis- The pct-5.06 01' ohms” in language in mum-rent with 63mm in eloetmmephalom. (a) Patterns: In all words, than dosymhmiaaum or fmqmneics. Them m. M 15 in 3. MW in wltage and a decrease in pruinamo at In patients without. delta activity (magmas), �.5. me «mum ‘ppannoa or small by the T123543 5.- W8 of 198 voltage 6-? cps uctivity. are Monstmtcé in Slidoa 1, not. appear slower to be alterad. 0131.2. The basic alpha rate does Mishap in voltags and appaamnoe of The fmuweies with mwmtmtion in blockad. In patients with vu'ying ”thaw waiting voltages: W 1m voltage m and burst «halite. in 3 is a decrease ntdxitw diuppoun; and 31m and am Wotan hem This change It wants times {bits or Maud high voltage dean from convulsive urea-am, them are now: in Sudan ham. «W «mm Manny and voltage 1m, 15mm. mm Ghana's Ind h. mm: is West in all 6100mm imam. during drag mumum, and persists far one Concurrent with electroencephalogram changes, uillon}. and language patterns at the pm-dnjoatioa language in 313% m putter”, Nauru: awn uppured. ciascxﬁbed. With the to three as the ho- mum the para-injection behavioral and �as w: ﬁtness obaorntions confirm the report of Jeanne: and Manner of tho affects af diethaaim altars moot-d: subjects. in’*uonm1" we also note that diam II‘ with mammal: induced delta activity in a fuhion dearth“ similar ta atropine and ocopolnmine, l5 ty- Ulett. Memo". Shea patterns are similar to the affect of these anti-showman conpaw-ads in records 1'0le head tram. In the» subjects, intmvma ammo caused immediate changes bath in the we and in behavior. It is appsrmt, Wafers, and that. it; its: duration of activity is most mum). for the @0an mm. mutual: aim audits by mmus obumra at new man attracts of head ﬁrm point to an inﬂate of muralagie dyst‘motion, the :2» mwlohonm 1n the the madly affects the centre). nervous when, basis fer the owned EEG alteration; and the 1m). at spinal fluid. the effmt at ttmpine both an mm a» continuum tin-tho: support to ﬂu chm: of relationship batman the dome an mm» m wbjoets with heaé mm mm Wim Em putt-rams. of mmm. In those studies of Wain. and u the patterns and has nutylcholmo chatmahook, the intimate relationship 13¢qu EEG bonnie: �.7. m trauma... m ﬂuid m mama. beam On We the bases note the parallel to we observations» in head of, these observatim, as wall as studies at spinal chanmmmu lavela, would magi-st that [the (Tower and mwem, Mammal substrate in similar to that. of head tram. Fink and W22), of the electmshack promos: Electroshock my be Ionized upon as a continua-d mothod of inducing cerebral dysfwc’oian for its bazaviaml “Tact. Purim pmidas 13m atudiaa have (1th that. alteration in cerebral mm: pbyuiologic basis for the behavioral changes in electmahock (Fink and Kahn, 1957). Such altamtion in embm mum pmidol m milieu for a change in the eat-mum's adaptation to his environment. aspects a? behavior, in pemaptim, mum lama, mood, recall, memory, m affect, the basis for the therapist's ovalmtim ate. Margo mange, and of immanent. studies of ﬁiathudm amplify this neumplvnolegia mm“ The hypothesis of electroshock by suggesting the type of Minute mat. Marlins both the Wuhan biennium and the beluvioral chm. �m: Dicbhaam, a patent mﬁwohcainergic unwound, 1:1th was upemmntnny intuwnmsly in wyuhiatric subjects in various sages at commlaive thanpy. mectmmcephalogma minimum theme in voltggs, a. and observatmm or éeaynchronixatim of fmquencioa, hyperventilation Manson in mean}: mmmt print dnlta activity. accords with delta activity sham! ammu- changes with mama‘s-anus of delta burst activity. Gmmt pat-amass with the ahetrogmﬁxic effects, behavioral and language indicative of a reversal of the electroshock affoct. were charred. It is maelndod that: (a) Disthuine is a patent anti—cholimrgia amount! that readily enters the antral not—mus system upon intmmm ministration. (b) The Modalities}. butts ras- Fm changes in electroshock is to this of head trams; and (s) therapy The may biocheniml lie in buis of the mode of action or m cmﬂsive the acetylchounoocholmatemu system. ��(glum‘ﬁrzr Wﬂ «/¢V7/‘ “W“W WMWW— #MZ ; _WMQ!4¢W MM ‘ é; 7% WM/ 64331” .461 ha— @fﬁ/If/y EEQaQ/JW gag/M1114. ﬂ 64x7 ��14.3.,“ , / -4I/ . .. M... �é“; sessé c W ﬁg? ngz/ & W‘Za- MWX m ’55 2 “a! gégil Mara. 461/ 4. .4“) ¢ MM: Wu W Jeni #M“ K/m 1» 14:44::____ ��/Z¢, Aﬁfﬁgg L££A4AIZI~ mWMmQ ("43 2% 2 . @a M 3" ��/ / 'v-—-9:' wpw'.” v -' MIG/’4 4trsmg+¢zi9 - ._ ~‘ ~ . " . Dr ��10/ M‘ £77. ~———-—-—-————-——__ / 1 w W? WW M tr M WM mu 5 m; Mar fir WM ltra in x1“! EEQ. 32 ' #2 Cf; .- .20 _ Wa MAX—«l 4.4.!” . #34“... 4'“ ‘7 AIM xcreq cwé‘.’ :4. ('3) M44. Min-A- ��“0011/ /;4a+ a” ._—————-9 ,4¢,,‘“‘“':_:=, l/aw M #u/t. 410/ ﬁ’é‘fu’” S“ v MM ��[f7 x, W/ r{ /¢C// A"! wax / (31) I) 2 %%l -———-> MIL. ”cw / ) ��ﬂew- �O EST —_WU. ”WXW IK. Bag 11“» “~ f ‘ 4W Iy .NQ W .CW ‘e’ Iaéas/uue' ‘ MM? c) jivfeaﬂﬁuﬁp 041.. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Files: Acetylcholine and Cholinesterase, 1956-1966 (folder title 1/4). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-003-0-001 Date A point or period of time associated with an event in the lifecycle of the resource 1956-1966 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/9528d68ea90232ebce57ade28fbef74f.pdf 93461c25c5f8ae971bd4c1aadc2a1278 PDF Text Text I; I Mnémc . ' Recent studies changes in the 7&4 ’demonstrated that a necessary change in behaviort was the development of early mg sistent signs of altered cerebral function of slomgga ”a was a “f7 in these laboratories re-evaluating the role of cerebral mechanism of electroshock pie-requisite for ?. [ours Wt (Fm/IL indeay and per- which electroencep/alographic and/(ah , r:f.:'6) any. mes may of this observation remained unclear until the recent reports of Ulett describing the ability of premedication with high doses of atropine to pre- We wt}; (WMI‘Collowing 5 vent the appearance of the EEG suggestion of this report, we delta abnormality a . nth the investigated the roles of acetylcholine and cholinesterase in electroshock therapy. The data amply demonstrates a close relationship between the degree? and persistence of the ele ctroencephalographt‘cr abnomality and the appearance of measurable quantities of free acetylcholine in the m ‘ mm“ as“ as well {:5mm of. to ﬁcholyl-cholinesterase, The I q ”'2 ('7’de } Loewi u W? normal ratios of” cholinesterase WW of the ‘ p $.00» . 1 f .— p. role of acetylcholine in the transmission of nervous impulses has been a subject Edi} W x 072/) Q). for study since the first description of The arguments as «If theWeﬁ‘ects 4 (ﬁes r’ to whether actylcholine is the main or only �agent in the transmission of the nervous impulse are not of primary concern It is sufficient to here. of nervous tissue; that note that acetylcholine it excitation process; that exists in a it is bound form and a normal constituent is librated during the a is rapidly hydrﬁlyzed through the specific action S of cholinesterase; and as rapidly reconstituted by the choline-acetyléueg fluid iﬁ: Richter Crossland - 1916). Furthemore, normal cerebrospinal I‘M? Mariam ”‘?¢‘94) 4.94mi m‘t‘uﬁv contains no free acetylcholine deSpite the rapid breakdown of system ( & a, bound acetylcholine during periods of activity and excitement. The cerebra- spinal fluid normally has a definite level of cholinesterase activity, which is principally of the "true" or mecholyl hydrolyzing type{ IVMﬂM/“V 4“} "Romsuetkg. any). .111 the absence of free acetylcholineﬁand under the ”normal" conditions described! ﬁe electroencephalograms fail to (a) Effect of Cranlocerebral Trauma: variables was lationship of described by show any . The consistent abnormality. earliest changes in these 0 glmstein (l9h6) in a classical study of the re- changes, degree of experimental head trauma, and levels of cad/w»?!grew oft! cats free acetylcholine in the 09!. stu subjected to varying degrees EEG 0 a of head trauma, B/mstein first showed that free acetylcholine appeared in {Yaszwm the CSF ‘ céE. within a few minutes; and persisted for varying periods up to M hours. There was a positive relation between the degree of 17am and the quantity �-3gamma 9 per cent. cu- electroencephalograms demonstrated patterned changes. Initially, the of free acet’lcholtne which w Eg-rwﬁﬁal varied-khan 2.7 and 9.0 Ocn Com-raw records were filled with high voltage .fast activity, 516 int'preted as an intense neuronal discharge; only to be followed by a short period of flattening of all #01 recorded electrical activity. These periods were "followed by prolonged periods of high amplitude sharp waves in the delta frequencies. Mt 0 Ulth thes/e'zlectroencephalographic changes, Bﬁrnstein fur- ther noted that behavioral manifestations w{ he werencorrelated with degree of the of as as free level well acetylcholine traumal/ ”in; highest levels of acetyleholine; he noted the greatest degree of abnormality as well as the greater severity ””77? M u/ the of WW t'anges a the appearance ofAseizures. _ W, diva EEG alteration in consciousness, 7393!. rnnumnrm further substantiate these observations, B/grnstein applied acetylE Y 105553 choline to the cat cerebral cortex. When the concentration of acetylTo and choline was 1 gamma per cent or less, he observed high amplitude \sharp waves of low frequency in the electroencephalogram. creased to .7lmaém WAC/c! the concentration was in- he ~Wana Mada per-cent, the electroencephalogram we. fad-w 2 gamma 74: When Tower and McEachern (1919 a) flattened,‘ m repeated thﬁe studies in human cases: w �cere‘rospinal in the fluid only in patients following head trauma, recent grandmal seizures and electroshock therapy. to 100 gamma In cent. addition, per terase activity of the. ific cholinesterase spinal fluid. (benzoylcholine Specific cholinesterase ( mecholyl The free acetylcholine varied from 0.2 Tower and Mc Eachem assayed the choles- They noted a sharp - splitting)fraction rise in the nonspecand a drop in the - splitting) fraction in the patients head trauma and those following electroshock therapy. No with such inversion was demonstrated in the fluids containing free acetylcholine following spontaneous seizures. These authors also conclude that the level of free acety- lcholine varies directly with the degree of cerebral damage; adding, however, that the degree of reversal of the cholinesterase fraction is an even sensitive indicatbr of cerebral more damage. In most of these subjects electroencepéhlograms were taken at varying intervals following trauma. Here, too, as in Bernstein's experimental study, there Was a direct correlation of the extent of EEG abnormality and the appearance of free acetylcholine in the cerebrospinal Thus, we may conclude that craniocerebral fluid. trauma results in the appear» �-5. in the spinal fluid; and that a ance of increased amounts of acetylcholine direct {KN rJ relation “between the amount of acetylcholine, the degree and type of electroencep‘llographic abnomality and clinical behavior. (b) Effect of Atropine on post-tramuatic EEG and Behavior: In his studies, Bernstein, administering 0.5 0 atropine, demonstrated a reversal or a blféking of the EEG - 1.0 mg/kg. effects of trauma, depending on the relation of the dose to the trauma. Atropine also modified W the behavioral and neurologic signs of trauma. In the experimental condition of [Mrﬁﬁc/UEPNM acetylcholine, which induced EEG and clinical ﬂanges similar +1.14 to head trauma, Bornstein also demonstrated the blocking and reversing effect of atropine. Ward ( 1950) applied these ideas to the treatment of human cases of closed head injury. In 20 patients with varying degree‘ of trauma, he admin- istered atropine subcutaneously in doses of 0.1 mg/kg.. In selected cases he noted dramatic clinical improvement which action. He \ .traum.we. also noted, alographic effects of IA) lg. m M ATTRI Ben-5;} to he atropine selected instances, reversal of the electroenceph. In the study of another anti- �To“) f \DIW I cholinergé' drug, "DIPARCOL" ‘6' (diethazine), Jelkner and Lechner( 1955) re- port significant alterations in the post-traumatic electroencepbdogramio A single intravenous dose in no instances of abnormal electroencephalogram re- sulted in nomalizing in More 22 instances and marked improvement in six others, recently, Ulett and Johnson (1956) demonstrated the of peripheral atropine IL’ .0 to block the same effect occurrence of slow wave activity follow- ing electroshock therapy. This study suggests the possibility that the same biochemical condition underlies the electroencephalographic abnormalities in head trauma and One in electroshock. report stands out in contrast to these findings. the§5 In ex- periments Brenner and Merritt (19h2), applying topical acetylcholine in con- centrations of to 232‘ intravenous atropine to the exposed cortex of cats, noted no effect of 10% ng/kg) on the electroencepahalographic changes. It is important to note however, that the concentrations of acetylcholine in these experiments was significantly higher than the topical applications “a, 0.: ML andnmtra-steruc (0.2 Merritt, however, make - 10 gamma) (1-34 g7ama%) injections of Bomstein (19h6). Brenner aha-4.1L note of electroencephalographic effects similar to ace- 0 tycholine from mecholyl (acetylbetamethylcholine) and d’iryl (carbamylcholine) , ‘ each in concentrations much lower than the acetylcholine concentrations. �-7. They ascribed the increased effectiveness of these cholinergic drugs to their lack of sensitivity to cerebral cholinesterases. A - variety of experiments utilizing DFP (di-isopropyl fluorophosphate) a compound with irreversible anti-cholinesterase effects - demonstrate‘ the developnent of high amplitude rapid frequency waves similar to status epileptic“;s as well as lesser degrees of abnormality noted in post-tramnatic states _ wich et a1, 1950; Frefdman _e_t_ a}, 1929; and Hampson gt a}, 1950.) A! .. (Hit In these studies, too, the electroencepahalographic effects were blocked by small doses of atropine. In another laboratory study, Qhatfield and posed animal cortex with activity. The Me PR0 ST! Dempsey (l9h2) prepared ex- NW and evoked electroencephalographic Spike admestratgﬁof prior atropine blocked this spiking, or if present, the alnormality could be eliminated by atropine. Thus, from a clude variety of experimental and clinical studies, that electroencephalographic activity as a result of trauma, To PM; AL ‘5“ we may con- induced by acetylcholine, either application or interference with normal cerebral metabolism, can be blocked or eliminated by atropine. �-8(c) Role of CembraSpinal Fluid Acetylcholine in Seizures Acetylcholine is normally present in nervous tissue in a bound, in- active form. During periods of activity, the free acetylcholine is liberated at the cell ”I; The membrane, where it is rapidly deactivated by cholinesterasmﬁ- level of central nervous system a acetylcholine is this ant of the processes of synthesis, liberation and breakdown. It the result- may be post- ulated, there/jars, that the level will rise during sleep and fall during act- ivity. this hypothesis is tge That (1949) and Elliott, , was demonstrated by Swank and Henderson (1950) liquid air quick-freezing methods, Etc.“ ter ANIM in “8.1 experments. was 300% higher than ' micrograxmna the post seizure level. tissue levels is transoi'ent, however, as the 7 in rat brain is high (1 gr: . and Crossland demonstrated anesthesia and sleep level of acetylcholine (measured as brain tissue) Richter and Grassland ’R’tSW ”thesis The By using that the per mg ' difference in rate for acetylcholine J Elliott 33 a; confirmed thez'e (I950) gaxmna/gm/minute). observations. In addition, they noted that after metrﬂzole convulsions Jﬁi FK’EE acetylcholine was always demonstrable in the spinal fluid in concentrations up to 3 gamma per cent. In spinal fluid studies in Tower and Me man, Cone, Tower and Me Eachern (19h8) and Eachern (19h9 B) also demonstrated significant quantities of free �.9acetylcholine in patients with epilepsy. 0f 56 epileptic patients, meaSurable demonstrated/free acetylcholine in quantities of 0.92 to 5.0 with an average of 1.0 gamma per cent. gamma “¢¢ ‘7.) ()7 per cent, acetylcholine level was directly The related to the frequency of seizuresf/ the extent of electroencephalographic abnormality, and the relation of time of / n01 ., M sampling l 14¢, tonlast seiZure. It bore I relation to medication, type of epilepsy or level of cholinesterase act- ivity. As to whether the acetylcholine appeared in the spinal fluid is a by- product of the a M V“ ' s I o n / conclusion; or whether C the increase in acetylocholine was a is problematical. a, increased cause of the seizure, lieve that the Tower and [{cetylcholine liberation itself but related Me Eachem (19h9 B) be- is not due to the seizure to the basic process causing the seizure. I In a study of thfhypothesis that the accmuulation of acetylcholine is basic to the seizure process, Torda (1953), induced convulsions in animals by met zole. She determined the level of acetylcholine in brain fore and during convulsions. She W tissue be1' ' . noted that convulsions are preceded by a rise in the acetylcholine content of tissue; that the content gradually $118 during the convulsion; and that * 5423..) occur. Furthermore, she postulated convulsions u WAS 8. certain levels, convulsions failed to can?» send 3 factor} which in physostigmine probably acetylcholine, but in electroshock seizures was not. �Shendllu concluded was due that the fall in tissue acetylcholine during a convulsion to inhibition of acetylcholine synthesis by increased concentration?- Sec” of metabolitesnas ammonium ions. While considerable argﬁihent waxes about the significance of acety- lécholine in the mechanism of seizures, it is apparent that free acetylcholine appears in the Spinal fluid following seizures; that activity and seizures enhanceﬁiacetylcholine; dfstruction/lowering tissue levels of acetylcholine; while sleep and anesthesia Aﬁgment acetylcholine production increasing tissue levels. �W!"— " WM—w-"ﬁ ' TNT <- Mm; E Aest‘ I. / I w- . , » urr u ' , M 0' - ,,._ -m—~ I 4,4 " 6Z7 v - ,1 5 M 1,;“414, m. -w—.‘ —V<.._—. .Avv»/— up ~~r .-———:v mm” M: . ~ . w.,-- ”v7 /’ W“, .. -v. .. . . . wﬂnm .,,_.V,r, _.._ .<‘._,._r_.__.=_,,m,_qw ' -. ‘ EE < ,. ’ I I: l -7' ['4imzzm4m-‘ean-,g-gﬁc ‘ ~ — ‘ , / -~—...:.;_.-f.._ Mg; ((244.4'4/pv A , , ,.. / /' l . ’ / 3 ‘ j Z e" . ��-« ”tum-35$: 434.. \2 as: {525% mthhw ‘3‘ M . {3%. «3%. Ma g. 7 \i‘xw _. , n ﬁwkﬁkxﬁhﬁ \.m§\. 5n Q“ W; ‘53 h}. 41“; 7 53.3% _ x w x ”‘1; (“VM , «$ka ��the level of free acetylcholine and should follow a decay rate equal to the EEG WWI-£6 rate of in desthtion. Since previous studies demonstrated that Ron hypersynchuy was a necessary pre-requisite to clinical response to electroshock therapy, it may be stated that the absence of free acetyl- choline precludes changes in cerebral function and thus precludes a ical response to electroshock. Certain assumptions 61M (1/ .WQS in \mﬁxam em . may be made regarding M‘ W£%,ML 4W; Cholinesterase I is found in clin- WM“; all 4 {a ;ﬁb€,¢.¢£ £0»£u64* ' ' highest concentration in the central W, W nervous system; while cholinesterase II is predominant inAblood serum. With the increase W! M/mx.dv£[7 in acetylcholine levels, in the intercellular fluids M Wftoaow M 6i mm ‘5‘”; vs odilation and increased cellular permeability degree of transudation of vascular fluids may be I: into the dependent on the extent and duration of the / predicted, with a intercellular spaces tasodilation, (Kabat gt 3;.) 19118); ration changesggﬁztlt high ncentrations of 15?; , enzymet, th 4/ rate of hydrolysis idndecreased, ' achnﬁnson and Rothenberg, �@ Tit/4M ﬁgﬂﬂﬁ W05! M. r ' ”1“." I (m0 4» w- ar A » W M L’ M.%u 7 . WW1 ’53), do W MW; - ’ . - W I44"! %_ /o¢ /ZM"‘ �2% Mwaﬂ.‘ éﬁ 7M/Cc 42 d a >/~7‘$[ 6a 56) iwwwh‘ 4M 444W ' 'wZ/zé 9“. ﬂ A—ﬁr7:9%__~_ ��__ _%j%i%% __M __~__ Meg/Eran!» , , M W/ 8&9- afﬂt ‘9 _4€§./_""f. ' 1% ﬁﬂwjg; W M; ___-#__ ��F:+r§¥¥33~%¢;*‘ '77 , "“37 ' \. *Q W~~ -~’ vM—w7ﬂx-«7A 77.7.«7-«7 . .ﬁW-M 1'} f MW~ §' \»M ‘ \ ﬂ r \- j "39% \~§\-&3~ .uxawk , 7 - 7 «.77; 7 777 , 77.7—7— ...-< w... 7- W - 7 7 7 7 77 77.3, 777 a Q7 M353; --:-..___7—a.7..7 ' 77.7.7 1377-3 ~&\ 71;;7.}7c§?§37\7:s7 sw C\ hﬂa§»3~§~3~ 77-.. 7.7.77 ‘ 7- 7., 7 x 77 5g .v‘wz\ if»; ~ \ f ��I: she/ﬂ ammunummmmmmmmemw at our.Mating um 'mmsmmmmaozmmmmmmumu Meat 11: than Inherited“ ﬂu 1-01. mmpn—mquuiuformmhmurnammtot mhwpmtsim ddﬁndocobulmuondmam Wcummawmmm(mmmv$6h topmtmawotthamdalhtmutw(mttmdm 1956). rationing the Inseam at this report, In investigated the , of acetylcholm Ind cholinoatome in diam-tutu n clone of w’ My. «f ﬁfe? ":9- ‘ therapy. as. data amply the dean. and persistm of the ham 1".th 010W 113109 mm 75:, role: “humility math- I'm acetﬂdwlim in :ppm of measurable quat- the cerebmpinal fluid as wall as an in- moralenrucetvlchdjnohthotmumornemmpnmm Mamamrormsmmtmtmumotmwxm affects by Dale M1 (1911s) Ind/(1921). ' rho W: n to another «1th 4 ' �“wwwmmmtu‘mdmammmm of M 0mm hon. It in affluent to who that mtyldmnm 1| nmmlmtitmtofmmmmy mtnmmmabmtmaaa is liberated as. an mum normal cut-Ironing]. 1.913%) than“ th- or activity and that m ﬂuid contains an hm saga-mt. no true of bdund 1?. iallnpidly mtylchoum (faster and McEachorn new periods The comma-121ml dummy; nomliy has ﬂuid lenl of Munster-nae activity, Men is principally of the mM W was; a: Manning and .- mam mmtitutod mun (mm-a 6mm - 19M). Funk-awn, «citation W through by during thy W (W n “two" deﬁnitm- and Rothanborg: 1935). hmmdfmmtylchonmmdwwrthc'mml"condium (a) fact. :10 mmbrd Tm: th- mliast chug» in than Wmaomumwaommmwmuauummdm vngaumpdEmm,mdoxpommhudtm,mdm otrmumymwminthoembmpamnm. human-numbMtedtonqingdogmluthomtrm,homu1nnruahamdthattm �v r A—w— WWW—«WW. W-_-m_w..__quw$ mtmmmwnmcsruuunarummmmm per-1m for varying poriodl up to Mm. that m a. pain» mum ‘mmmmammmmwnttnomwmma mamaandsammmh human; mum, W was rm activity{ inmlytohtoﬁmdbyawm tbs records won filled with high voltam urpntodalunmﬁeuo neuranldiachatgoy period of mtumd We. {humus of :11 room-dud Glacial-191 activity. Thou period: ~mwwwmm—n -M." mthntoﬂmndbypnlowmothighwnwbshammmh fw. summogmmc . tbs delta. than With that behavioral as wen u . i changel, - Barnum 11mm:- new Nautical! an duo 00th with dogma of tum, with the 15931 of tree mtylclmline. with highest levels a: mmmmwmmuudagmotmmnmwumuum the in alteratim in seventy gm‘bar ma the 1'0 Wmu.» o: apontanam farms:- ahounotothnupoud mam, change! Wanna: animus. those chain-mum, in m. Bantam applied acetyl- «teen-balsam. Unauthomntntimot amylmmlgmporom.arm,hooblemdhighmpntudu �Mmsdloufnqumyintheauctmmoplhlom. manommutation an increased to 2 gun pen-cont, the ﬂattened; in a tnhiun pal-Inn}. to the Tatar,“ kaW mammpmlogm pout-twat“ a) repeated mm. § rum. mm mum-um otnxwingtmofwmandoﬂm»wm¢nsordem. 13112 mmmmmmmrmmmmmnmwm mummmwzm,mmiummmm therapy. murmmtyloholimuxﬁsdhuOJwMgmmrmt. In muQMrmm-aemmdmmmmmiuwatmm ﬂuid. Mm:MmmmmpMcmmmM(m wmmntm) - (tn-chem fondling dug: in the lpociric chainsaw emitting) fraction in the pntiantl with head trams mm W. tho fluids outlining mean faction m a lo s'ugh hint-310nm and We Wadi: rm antyloholim tanning mutations mum. more also conclude ﬂat the Laval a: nu agctymm uric. Wummmotumbmmgm,mr. than: Mmdnﬁmldmmnmmmtnmummmw sitiw indiutor of mm m. �Inn-tatuaumjomwmrmunmnmh— iamla tanning. m. Hun, too, an in Bernstein's W cm, Mmammwmumamumtdmmwwum adenwmmmaﬁWMd. mmmmmludnmtmmnmmnmunthaw ”ammuarmmmmmmnudgmum adfmtrahﬁondmhomﬂnmtofmwlm,ﬂum mmdwogmowwmmhémmﬁ Banners gm Am 9&th of (12) In u.- on BEG and mms, Barnum, maturing 0.5 - 1.0 lag/kg. um, mumudamdor&umdmm¢hm¢tmb Mam'unumorunmmmm; Atmpimdsomdm tho Word and usablogic aim of tum. In tho maximum eon-.- .wmgm mmmwmm,mmaumnwmm dmm of mmcistam induced Km and clinical m: rmrsing arrest. or «3mm. m<m>mmmmmmmathmm¢ WWW. mmpumummmotmhmintend atropin- aubomunly in data «(0.1 W0. In about! an! �.__.. _“_«, _._.__,,....<.,.___,. W7. w _. mmwmmummmmmmnmwam actim. ”waww", .. __._ 7 bmmnmmma,mrmafﬂualectw 'exmpmpmpmo effaahl .w M” wwwmmwv—WWWWWV.W_ 0239113301110 «um. hmsmammu- am, Inn-mm (mm). mwmuﬁﬂ mmamwmmwmmnm.” AWWMHMMWOIWW mmmmmmammwwmmomn: IMW,Mtandemm(1956)Wthume£fm -A——.~-T.v _ ofpoﬁpheglatnﬁminﬂocﬂngthemmotdmmwacﬁuw following unattached: the sm Wen]. mm. 00:811th mm saw mggom tbs Minty any mm. the mmmmmmum WWW mu- MWMdsmmnmmnmmgﬂndi-nga. Inmates- 3m: W mmmm in Wmmdzimloﬂwtmmedmnaotmu,wbudmdfm parjnants and Hewitt (1913); topical .ofinWatnﬂmﬂM/kﬂmthooloatmmmm xtumrwmmmhmr, thatthecmnmumofmamwm mmmnmamswmwmmmmmmappuuuéu (Mm$)mmmmmm(o.2emm)mmatnom �thin (W). 3m: and ”.11“. of hm“, mar, WW]:- ognplun affects 81:11” to noetycholino (WW), chonu) and duty]. than th- mmm mmm. 1mm at that. cholinorgic drugs mums. IA - n van-Low ma at expert-ants nah in commutation! Inch lover my mum ﬂu 1mm attach thou-lack.“ to um with incur-11:10 2m mmm (awwmﬂ- DFP muutytomhnl (div-1W}. Imam“) cumin-stoma. strum - mum- thadaubmtnthighmpnmdonmdfuqmymvelmumm mnpueusuuuumm dugmoxabmmutymmnmt-W mm 919;. (Es-non. museum, too, 1950; mag, 192m and Ema-ca mmmmmnphicoftoctImnWby Inn dot» at am. In W as. 1950). mama-y mm, tantrum and 3-way (191:!) pm mud dwtmmphdomplﬁc m1 mmuw. ﬁnpriarWtimotnmpimelm, expand cox-u: with procugdno md ovum, mmmntyoomuonmmmbyatm. m.rmanneworupommae1mmam.mmm and. tint datum-MW activity induced by mtyldzoune, um �tuna, uI combs-alum unbeblocbdoralmmmbyatmm. topical tpplmuen or interference with mum. of am run. may. mummpnmtmnemuamuam, mmmotacuuty.mrmmmunhenuumw maxi-,1Ihonit1lnpiﬂym1nudbycholmmnu. thunder Wmmauwlm ilyﬁnnﬂaruulhntd’ﬁbpmm at manna, ulnar-1510:: and mmmuuuu - this mm is true um It N ha mm, Wm. dudngnlupmdhﬂdnﬂngmiﬂw. nut m Maud by aches:- and 02-083de (1919) NW§.mmﬂdeM'(19SO)mmupemu. 11mm: on quash-trauma methods, Riches: and cm wining dam-mad um (many-dam mwmmmxamwm prn.mmm)ulwmmmmtmm an wmmmmnmymnummm rats. for Micheline 1n nth-11:1 18 high (1 gulp/mu). Elliott ggmmjmmunu'obsemum. 111mm, thqmtndthat snot-mm mmmrmmwmmmmmn �_...—_——___w wv—wwrvnvr—ﬁwwv—wvw th‘smmnmmmtmﬂmuptoJEtmmm Intpdmlﬂuidotﬂiuinnn,“m,Tmrundﬂon(19hﬂ)md mwhmmm alumnae-ad mimt managed rmmmmupumuumomm. 0t56wihpthpt1mﬂ.hh (1919 B) (Wmmmnmmmwmnm'mmuuudoawa mmoem,umqmndeJMWM. magnetism:- mmmnmpdmmmotmymmot WWw,wmnuumor‘motmm¢ “Whitman“. Itbonmnhﬂmtomdicgﬁm,typadepﬂsply armaehammnuacuuv. hummumtymwmmmamuam mammumrmmmmamwmma _munofthaac1mn,1apobmm rmrlhdmmm (19193)» mmmwmmnumumtmuwm iwmmnudhthohsdcmumth-mum. ht’ahwdmlwmmmdmdmw lib-intact): «13m process, rm (1953).1ndnoodoauvu1d.min mwmtruoh. Sheatoxudmdtholmlofmtyldxolim 13an - �”memcm. mmmtommmmm,addbytmommmmmmmmtdusmj anthem” Mfmsdumgwmmgwdmtmmmmh,m Wmn,mmudtmtm, .MhWWumpmmyaummm,bﬂh mmmmtmrmnmm WWWM. maimhiladtoopw. Wmammmmmummumotmtymmm that: by increased mam-cums ﬂ ”tam“. such a min in. M13 mm nrgunent mm the significance of newb- ‘Wmﬂnmcmdms, niaappumtﬂmttmmwh mwmmmmdrmmm; thitmvityuﬂ mummammamum, «mm; mm sloop mug-mm, M W mammal-19701.net tum @tyldzonm product“ mm with than muse: 80m omimumdchmgummmm,2mrmdncm(mwhw (a) , Walnut! ”1:413:de «shun-ammo activity. «Wmaammmrmmmmmm Twin.- Minster». �"w ——_<__~___..——ww—m_mw—.wrw “—vwr , wwwv I (”ta-m“, .. ”apedtic',: for Mahlﬂgdw mid: he a ma: Spain-o{r 21w for WW; and «shaman-a II ('psendo", ﬁes-Specific,“ a!" WW Warsaw-MW). m have 6133mm ram «Wrormmawmmmoum. differential a..—vnv—_——-_ nu cholimteme activity an mm he» 083 Bach/Ann and mm 1133a, This qualitative dintlnctim. W Rpm-ting the 138111158 substratu’to mtylchonnc, but a ratio of the activity mtylcholm mum-nu, an Wm (mu Wm - me). autumnal m the zonal as: consist: a; mm necholyl and haul- m nuns are found: In mch ntiol non-1 of 33:17 for lack/10h to sub/Ash. manor “pawn" amt-Suez- with a mi]. ‘ non-speciﬁc eaten“ emporium. In patients with hand .‘IZ chainsaw” activity. tram, I'm and kitchen report a sweat may, manu- mum. the county of mammmm eorrdnﬁm between ﬂu extent at tho th- dagm of Wu. tuna and usert. that. there in a definit- mend both with �r,_._W__,__.___._... Inpuumvith mmmmammuvmru: unatotopmmuiznm,hmr,mm1nthonuodobd139mm or total audits-Item activity“: round. Imrandlhmm (191:? g), in than study érudounbnl at tram, n- W‘mmmtmmtmmmw. 3m» &pm WW, zuwnzmmmnmmmgmmmmmw ﬁmw decram c‘Wmﬂthnmerulofth Wotan“, amr 3-? am Mupomd rm mtylchanm m..1? ratio at abolition-M7411 ﬁve pt tho :1: patient.“ Fro-than ohm» nmmwmmtmmtmwmmmmm nor: 1113 than. of crunooerehnl um than that: found in opium. kmtmmpmmmmmmmmmwum Momtmwaweamna ratio reversal,- fb-ymwﬂn ummmmtmnpcmntmaaamlymotmmumwm to want." W �mrmmyaahmmmu. Alia, fmmcwdmrmﬂ pungent m ot’l'mrmdgcﬁcehcémb), mtthctcguths fwdtoMspimlncid WWW thalamus tomcat-ant, penuts us to considor the yummy basic to the anaemia of the um:- that such hm 9:.th pmceu. Ghana‘s: .g. . ocmlusians Certain further deauctiom and agaafalectric m mmmgmmma mum. The pmscuce intcmnnhr ﬂuids Mean alcctmcn Maximum; The pen-- mduccaachangeinccn— ﬂax-activitywith‘anmmu when acetylcholina induce; to gradual pastime. tom: “trim ofﬁo mtylchaum inﬁll WW, nﬂwted in tb nudomeofhwanmmncmtelymﬂm �»;y- mmarmmwmmmwwrmamnuoqmmw an at new destruction. 31m. pm” IMO? Mutated tint lmonnnnmmmnmausaxnmumuypnhunmxuwintnhumnxmqmmnijhmbmahock thonpy, it my be stated that the absence a! {mo acetylchcnne pm- cludu chmgu 1n eczema]. {motion and thus pracludu n clinical aspen-e to electroshock. ‘hﬁhhnummmummsnybomwbrqpnnmgdumpainaﬂluuwmmepmb usability at! explaining the increald 1n Ghanaian-Ame activiw. I is round in highaat cannuntrttian in the central narvoun estemse Quintet-rue aystaum while n is pram in other games, especially blood serum. choline- With the increase in mtylchoum levels in the inter-cellular ﬂuid: as a result. of stimulation and convulsion, “sodium and increased cellular pemeability may bawm¢mum,muhacbgmouttnmmmmmaaatwumnurﬂmuh1Mmibuhﬂmm celluhr spaces dependent on the extent and duration of the ﬂuctuation, (but �r_"__. m,_m into tbs spin-1 fluid; and that thus the electrolytes increased, than siwmsnt increase in changes . mm in permsbmty of calls may ﬂms such u nusledc‘soid Splitting was s amps“. pmids the basis for the sppomncs of high concentrations of scstylchouns and for increase concentrations of Cholinutsrus II, (Tatar sad With the increase HcEschom 19h? in cholinss’oerssa activity, should not the free sooty. lchouns be rapidly destroysd? ﬂuid after trams a). To what melanin cam it's persistence and seizure be «embed? An explanation is available in the for this discrepancy observations 0: Hush-am and Rothsabsrg (191:5). continue! by Tower and Ks ﬁschsm (191396) and Burgaa and the Intosh (1955), tylchouas - shonnsstersse I system “humanips. At ”physiologic” extremely rapid (3-4.1 1vity in spinal is cmcsntrations, mdrolysis microseconds) but falls of! very ﬂuidly extremely sensitive to (Haldane at higher and lower of, ill-t the sea- montrstion acetylchonne is consentmtims, set.- tbs Cholinesusrass II cum). In contrast, acetylchonns uhtionship 1s non-specific, and the rats at hy€re1ysis incmsss with concentrsum. 0011 mums, insstarase this I, in the 11:53 acetyai‘shonm functional with nouns]. st. 1m_ls o: soatylsholins is dsstmysd by the specific. oMsr 0! milliseconds. Where wvity of chol- the excitaﬂea is such as to - �1nd. to an of “casein mm by concentration of sootyloholino in nervous tissue, the rots momma. ‘aooodoo. choline mounts, the ssisuro threshold dissociation in sootyloholino - unt vaaouur ad As is ruched the oonoontntion o: oootyiand c soisuro occurs. 1h. _ cholinostorsse I motionﬂzip vaults in s per- sistonoe of acetylcholine. rho «ism-o, In. acotylchouns. ‘ itself, perhaps adds to the Ian]. at inc'mmd mtylaholino airing.” rapidly. with result- 1'1» permeability connineffects and the appearance of increased names») mmoimnuooohomonom II. Itumoouvuyorwo onlym, though of lot sfﬂciomy, roduoos tho sootyicholins ~«mum of cholinostonso and 69th on concentration aworim, 1on1, InAhours to kinetics that - to levels for the plvsiologic I. Altontionintlnbloodbnin pewbmty humorbyths cantimingsutim omo observed in pout-electroshock oioctmooophnogrm. 1: evident in the mount apart no Aird 33 g (1956) Such s possibility- «annotating a significant increase in tho concentration or odd-inc in bmin tissuo 3-day: utter s ashes of 12 elects-om. an on. shows #olooulo, ordinarily obsent in brain tho clung. tism, in omcantntion of this mg. to b. con-eluted with the spposmoo �, w— _, N‘erm—. #179 WW ducal unu, however, the 1:: mt subjects. the ma 1tuntoa 311 com awumum of trout- «‘WW AM» 7 ms extent; miuuw to «- Despite a Maﬁa: nry may in the of high dogs-ea hypersymhmy, m: by Alerting, mule the duratiamdﬁ' hypnrvmtmum populating. me and wly appearance m persist-mo Wont the tmtamt cont-u, has been described In a neceﬁnry pu-requinita for imprwmmt following shook( nuke: Kuhn. 1956). Batman certain patients to dovdop 137”“an aholine Ind Manama: Assuming my be um mechanism Perhaps and gloom- of.macs-mug the failure them staring of acetyl- nﬁud. is. that a gnnd m1 leisure indicative of the developmnt of tissue 1min or free acetylchonm in mass at the I; hub- at. at hydrolysis by Mae-unl- that the electroencephalographic Wrenchrany in a reflection of tbs persistence of this almond. concentration of acatylcholineg than tho diffemnco in paint: who maintain hypermchrm and those in when it rapidly (tumour-O Ida] disappem, 15 a nﬂactim of the theta.“ of the wonmatemmcetyldmum hydrolysi- Byataa. Persistent. Mommy "cults non decreased "to of �rw‘“. a“ + V ‘. , “m---“vmw hydrolysis of acetylcholim. .Ismbmmmmmdm'oomct, dWrmorbothof the following postulates m opantin an patient: with persist-mt hyper”:— chm. 1) Western” spread batman the the tiam. opt“ ammunition, so that than in a great Imam.- substrate concentration and those present in with high gootylchaline) Ind/[Y 2) Gunmetal-nu m I~1a in 108 1113.1”, lo that the cmntntian kenotion a: this mm opemtim, thong) at a slow decay rate. Conversely, in patients with short ed lampemymhm, cholineatomaelandnintismandspimlﬂuidm Anthem, at” the appunnce of high oomentratiom of acetylcholine stuns!» the production or tissue cholinestemse I in the central Frau tho lucid studies of ”am-noun (195$), a stated in depnasive psych” induced mtylchonne my pncnorbid m1. (1 nervous system. dim rahtionahip batman cm— Mutton of tum cholinestcmse‘ I and level . /) luv-750.. of nervous nativity can be mmpnuul depression) , than the choc:4 . g.» alumni“ I to production a maul. Waters” amt. m �g; hmmmmmwmmumummm _atummuv1ty. Wuﬂaweiwtnmwmmmd WWNWPGW. Itilmww mmmxmmbymmmxx. rhpbhodpmmnotnb mrmcmwmohdmmumbéomuam matm.g.g.nntommzomm. hummus-Wm” mmumuimmsmwmmmducmx,n,mmm Mgmwmmsmuﬁamwmm tomato: Wumumdmmum. mmxnﬁmmaﬁw mtnuuummmmmamnumw;sssmnm �4t). awn-mwmm. the l «tutor cautnlnorvm ”Input Immuoimumm” 1, human tn: of our): and sustained ma levels of :cotylnhouno m Khan, the Wencﬂlhareaaidhrpndicumnm data Wmnohm and 910nm spinal ﬂuid mum to a slow 1nd of chainsaw” activiw. at peripheral “mat-.1431 w chained: neat: 1| thn hypotheti- roaming central nervous syntax nictivity to “rte elect—reducer. �thmmphmdem, 1) mammmamnmmmnud. It'snhuato 3) Whmdduudbwhmcuaoﬂurmmﬂmﬁxm ﬁn" memm—Wrww. «swim 1nd... W tht ‘3) a) shamans activity and patterns ethical norm all at up blame mm a m” a) ‘) 1’) at. of W at M “1 frequency at emu-mu (patina-1) mung; Momummy. mm 1 .7 �NEW» J? I i . , \J Danae ReleefAeetylchenne / bu]. ' E ”Km m Mm at i E Wvulsulﬂ 45% (”<— thenpyﬁdmtnted thet/ Gen-change in behevie 6 wee the development or slowing up he"? as f Wheat oheervetion W - we. index (Finkw and ﬁlm, mined unclear until the «out report! J’ the than; at Mention with high deeee of atropine s f1. E «‘1 E {E ""1? ijmtmg Week WWM”) ﬁcdw- View. describing "‘" hum-tomemﬁemmenw E)W” “M" “ W131- '7: the role of care- Wrelrequeite , ?:- Conan/.hve in the melanin o: WW0 E F amazes - 7'3""‘ early and persistent eight of altered cerebral Mention 2 E 15:7 umrmwwww22". 'W‘m~" "M" m-dbe’prevent the appeennce of the EEG delta abnormality (meet um John-on, name“) 1d; 1956). Following the mggomm at this report, we role/ Convu' | £09 of eeetylchame and cholineetereee in therepy. The data up]:- m E W ”‘35“: e m clue relationship ehetreeneephalogrephic S‘ounvxﬁ ities of free eeetylchonne 1n Wane ~> between the degree and persistence of the led the appeuenee of measurable quant- the eerebreepinel fluid as wall as an inn. vereim of the annual ratios of bensoycholmemlinemme to monomehenmetereee . W he role. of ecetylehenne 1n the bum tea! study since the Loud tnnuﬁdan first eﬂeﬁe—by m1. (1911:) and/(1921). the 3 description of We. W of nervous impel-ea he: as to whether gmmm "’ �lawmanaalyﬁgentmthomaiuionofmuwmmmmmt cf pm", man: here. It in mnmnt a normal constituent of nervous is liberated m it mm in n baund torn and tiuuo; that during the excitation process; that through the specific notion of that mtyldzonm 1: Minute” 11'. in rapidly hydrolysed aid as rapidly raconttitutod by tho Wtyhu‘ Bysm (Righter h mainland - new]. «3&0;me ﬂuid 191m) damn W W contain- no 1910).. in» mtylcholim (Tower and 1493116th mo rapid breakdown o: bound acetylcholine during periods of activiﬁy and excitement. cerebroapiml fluid manually has The chain-stance activity, principauy ”ohm hydrolysing typo (Warm and of the ducribed, eloobmemelﬁdlogma Effect. :3 crab fail to 'tm‘ or w condition- Wm Show Tram: W Bothenborg. 1915). In tbs shame of fmo «Mammalia- and under the (3.) Fummm, any conailtant abnormality. 506-) ﬁﬁMU Jeotad to varying degree: of had tram, Bomtainﬂﬁut abated that (I 4 In. �‘1'. acetylchmne uppeu'ed in the 08? within a _ few aw” minutee etterhtnme and Wm up“: Wﬂoeitiwhnktm persisted for verying periods up to he hams. hw_¢,_e./ ”MK“ at tame/:1 ﬁe quantity of tree W... W”-~Nu '{L versed heaven 2.? and 9.0 pm per cent, Mi 'Wgne 7__ ‘ , “MM . Wu} Mm amount-m. electroencepﬂlogrm 1111:1113, the Vracorde were mud filled with all patterned changes. high voltage recorded electrical fut Witty. 1n:1 short mm in immune. my!» mum F. - activity. mane periods then Inﬂated by prolonged perloﬁe a! high amplitude sharp the delta “V, z.- terpreted as an intense neuron-J. discharge; only to he followed by m “I. were 0.190 correlated with degree of tame, WW mtylcmhemthegmteetdegneotmmmntylmthe M seventy-M WM. as well all with the level of tree mtylcholine. with highest levels W MA. 5(- in containment-change- in greatef and '20 J gamma“-/' ‘ period of ﬂattening of Iﬁ‘J‘ eponteneoue of. name, poet~tremt1c eeimree/ 0/1/24. Wow furtmr substantiate these abstention, Bemetein applied ecet choline to the apoeed cat oerehrel cortex. acetylcholine use 1 gm When the concentration of per cent or lose, he observed high mutude �W“ sharp ms at low frequency castration m immune! to mum . m (£2, patimto therapy. gm pan-09111.; Eu mount "(19349 a.) :1me mpeutud was found Wham the can. the electmcaphalogm in a fashion pummel to the poototnmtic Tower and @ 2 in the electroencepmom. ”com. by}; WI W ”arm. thou studios in in up «rebroapiml ﬂuid only 13' '7 adtmm,moentgmm«1uuure3}nd’m that :m neotylchguna varied IMOA to .100 gm per ant. In ”1 addition. Inner and Mencken-n assayed the cholkutenu activity at the spinal “Maternal M (W ﬂatwf/ m. W W fluid. They noted a sharp rise in the mamaiﬂc oholinesterase (berm. Molina-splitting) .WW” with”. taunting thanpy._ Ho such inversion m dmmstrated 1n the fluids containing tree acatylohonm following Spontaneous seizures. than: authors oL ‘ do. concludcﬁt the m1 of tree acetyloholm varies directly with the degree of cerebral W P. .._ ‘ 3% dam; Mr, rover-:1 of tho ohalinenterue slum inﬂate:- nt con-bra dunno. adding, tau a, that the traction/tram non m �W -5- want-)Ww an m at (g m of those i P 5 tervala tanning MA mm, direct cox-“hum of the _of Em Mommy m appearance of true uoo‘ylgaolmo in the nnbmspzlml Tf (-l [I m. I' that. eminent-b211, traum- WM ﬂ” W/ m I 1" m?! mes-d a in- the ﬂuid. . min-11mm- ofﬂaoctyldmnno in tho Imus]. ﬂuid; and, that the” bemoan mum the dim: degree pthmtylcholiﬁ, aim wt at and type ()3) {“49— . ‘ varying 1 . lA~ mammognphic nbnomlity/ an!" clinical War. am Am g. mtg-swan at EEG and Behaiorz ﬁw‘x mu Mud- W u“ /w mama-d {munching at mam attests/Mb— . W j—h‘ “1.31m °£ 3th. 6‘“ W ”ﬁshnet-n1 a and neurolcgic {.1336 of W *h tum. trams. 4;; W ”1.574; Mn“ 2 “:86 awn/9 Men of 'mtncistorml acetylchoune, which induaod Em and clinical . W effect of utmpdm. closed head In 20 clung” 11:11:: to had Ward (1950) tum, Bgmatoin applied axons 1331117. 1m: 06 31.10414. _ Water! ibis—W to the trentmt of 0... human pttienuuith varying agree of iatarad atropine subcutaneously in dam o: 0.1 when In cues 9f m, , be achin- M can! �r WWWmmmm—W’mmww E aux. mmmmmmlmm'mmm rmml at tho electro- ,_ .W. . A E. enceprmlognphclc effects . W ~vm1Wv—wr E m. cholinergic drug, a! alterations in the report 31mm Inﬁm study of author anuJaguar and Loom (1955) 915::th We Ammumtmnmmhommammmmm E E «(At a_ 833”“me r A-..“ ‘ m . __V W tu: 9.11.4447 M W mudmmmnmgmzzmmmmmdwmmcmm of atropino in blocking the following the 010% and Johnna (1956) WW w W and I in m Wm of that wave activiw therapy. this study suggest; an biodmictl in head mm.- Mutated the smith“ ﬂat uﬁdeﬂ; th- chctmnoepkﬂommic \ I \\ E I ‘ _ manpoz'tstandaoutinconmsttothuennmngarlnﬁwhm_ ' \ pennants Brenner and Merritt. (19M), applying topical aoéﬁyldzoline 1n concentratiomctﬁtomitoWWcomdmu,Wmdfm i or intmenma atropin- (1 E E It is important to not. the r ‘ 1r E nag/lag) on hmr, oloctraomphnlom that the concentrations of “Mabel!” in thésa expemnta ma signiﬂmﬂy higher than the topim¥ upplioationl . r E . L E «hang». (1-1; game. S) and than intncistamn1(o.2 . - 10 N , Born.of gum)1njecti%a 1 .:/\_ .\ �mm Banner and (19115). ognphic affect: 01101130) and than tbs imu hunt, annu- to doryl hunter, m not. of 0100th :cetyuholina from mecholyl (nootylhetmthylo (Micheline), not: in mneontrations 193$).de concentration. mh 1m:- Thq ascribed the manned effect- at those abolinergic drug: to their lack of maitivity to cerebral mums. mm high «11 u n epileptic”, mm In (W, ﬂan at 913;, am. In author 1950; degrees a! abnomlity noted in mhtmmtie boom 339,, 1919; and Emma 23$.19So). m1 if present, ﬂu», mentor} The tho in: warn W by ‘ study, Ghntﬂald and aorta with prosuwm 39m activity. or 1075531; studios, too, the olectmneoﬂnlognphie effects .1111 date! exposed W «puma. npid fnquencykw similar, to status Dempsey (19152) and «oh-d pnpmd eloctmemoptnlomma prior aduiniatntim of ntropinn blocked this spiking, Ibnomlity could be 15leth by atropine. a variety of upexdmntul and clinical elude that eloctroenuphnlogmphic nativity induced by studiu, u- my con- uctyldmuno, nth»! �w .—-——\W- W.. 'WM as e result at Btu-Lug tram, topical application or interference with nee-all period! of aetiviﬁy, 3% free acetylcholhe in liberated W, mm, when it in rapidly Mum by 01103111081283”. {mu—ML WAammchmne 115M101: at ma We, hm. that the than the Th9 10701 mint, of remnant of the processes It may be postulated. therefore, m1 mm rise during aleep and run mmiﬂw. this methane is true and is at the cell That we: denountrehd by Richter and Cree-land (19h?) Swank and Render-eon (1950) in animal uporlmntn. m using liquid air quick-freezing methods, Edema: and Greenland denomtrated that. mm the anesthesia and sleep 1M1 at wetylehonne (manned ea per a. brain tissue) was 300% difference in ﬂame level: rate for acetyleholme in 21g f” (1950) Maw, “ _ Vﬂ ' *~-~r-—.._ (ﬁtter mtmole camﬂei brain is however, an the meynﬂxeeia high (7 W‘“ observation» The game/alum“). Elliott W‘mey H“ , 0,94» A noted that ”W «J'N'n‘ﬁ' a free mtylohnline was always demmatrabh WW”, x. is tme’imt, at 6611th these higher than the poet eeiaure level. in - �-7 w» mmmwmm_—-— '“ " ' - : qumm unmadﬂﬁdmmcmquptoBmwmt. m, In ’lpin-J. ﬂuid audio. in fear and Kahuna!!! (191:9 B) Illa Geno, Tan:- and He Enohem (191:8) and mmm woman!) in patients with opuspay. free (77%) mud lignuieant quantum: at Of 56 OpilOPtic W mammal.- rm miyloholine directly ranted to the momma to the last minute. W ‘in quantities of 0.02 to 5.0 at cultures, the extent It hon no mention to mansion, cm emulsion, orwhetharthe «nun, that. the 3pm ﬂuidisabyb mummammoamumd-s is prom-untied. Tm: and When: hem-ad mtylchoum liberation in not itself m‘mntod to the mic is buie to the scum process due mung ﬂu ”inure.” process, Torch (1953)/ induced» animals by metruole. She dctomined mm; type of epilepsy mm.“ line ot‘ I “ﬂammumymmmauzymm or the mo-ammm af-f;m abnormality, ml the mung»: of or lavai of choljnaatemne activiw. product of the M; J gum per cent, with In may at 1.0 gum per cent. 16791 ﬂuent“, tin level 01' (191:9- B) to up be. “ism § mm Won: 1:: mammalian in bran �Mam berm nadduring W Wm. mm¢me convulsions rise in mintymmum Mutant of tissue; that tho by a my» mum Mfﬂndudngﬂwcmnlﬁm3umﬂutbomcemm15,m whim failed to occur, )hrﬁzem/de a - \\\_~_,_.H_. than” K.’ as during u convulsion We»; H111» duo V‘; to inhibition at aoetylchenno mama; martial. argument” about. the MWWM’ZMMM choline the W Mum mﬁummum Inch 3: ram-m; ' mtylchaum; while sleep and W . mtautivity tum 1m].- nf and - 15min. WW magma: mem- mum 0.th mtylchoum produnﬁan abut-ration: of change: in mtylchonm, armor and of of W»! Gmtlnt War/wed...“ 03m. Mun 1m. W Mb... in clam ﬂuid Jan-L, dostmcum, lowering mowing J.» —_‘_..~... . ,‘_‘ manned concentration- at by tum, /" prob-Lb acatylohouna, but in m msm"ﬁot¢&nmumtthofmmmmw in mm poetuhud /,:v’ . ‘ whim: z” with When: (1916),..— min-1 fluid cholinemmu activity. are normally fwd 1n the spinal fluid: than Two W Minuteman-I �\ } 0m”, - ~apec1nc',§ or ity for wetylcholine; and hm mxéming)mm Bath W W Wyn for Mom and differential rite pend” qualitative distinction... cholirmstame activity a, memo. has a high cholimtarwo 'II (.“psaﬁdo', 'nm—apecitio,' or Mam-manning). dittemnt. rates a! madam—1 1 .éetymxoam, but Mandamus. By Thin ‘ ”porting the M ratio of the activity ”errand and prf W(mﬂ1M/Aah Wk”: bent. oylcholiué swam—ates to an aoetylcholim substrate, m_ meio- are round: WMw-‘C/WLW M osr contains antenna in an _ Thus, normal 68! consists ntio - /1,u?l’zjdua.2 mo)‘ In such 0133:17 for n“ non-specific ester-nae component. In institute with hand tram, Tour and Warn report ‘5 dwinzfTr W the dog-reset mmtyg ﬁzz-J2 65.x; tram and‘tho “Av-o: ”” mu it" ,g 3 nAsimﬂmt correlation batman the extent of the chalkenamc reversal “in with ' 1 WW a)”; M minly of imposing" octane“ with a . no I , the oWncomalogmphin 33 3 Jr”? �In patients with 130de mu ﬂuid hétylcholm activity a I result of Ipcntenoouc seizures, hammer, no change in the ratio of chol- inestemea or total cholineeternae activity an Wm Manx:- Tower and a their study of creaioocrehral (19w 3), in ‘:A six portede psychiatric phtienta mapping in: * ﬁle rm. W); W patients utter 3.7 troatmntc, theymported {1; m M decrease cholimntame, a “I. tram, re- therapy. ﬁtm- rm ioetylohonne act- a: cholinectemco with a revered of the 5 W We: W ratio of chcnneetoru? in five of the six patiente. Fro: tho/e oblont “time more (V they concludejthnt the apinﬂ. ﬂuid Wax: are- “Du—4 ' in lib those of cmniooemhrel tum than then found in opucpcy. haul-ding the one patient in the series who {tiled to show either 1“ﬁeyW“ tat "It {mnwetylcholim or a cholincaterace ntio reversal, 0 u mum-ting that this patient was the only om o: the six to chow no recponce to treatment .' �Ducunm m , but than variant obnomtiom, In my comma that therapy induces spinal ﬂuid changes mm otrmrandwchem (191:9 rum to maps»). ﬂuid b), ﬂu W 111m cerebral tram amt. that onlytho gamma, railed ta show a response to peanuts us to consider the pwnibmty that such biochemical “t, basic to the machinist o: the W at alas-uric current through brain ular activity with an .inemaae to inﬂuee a grand mal'acisun. in m. Thu tmtnant, We m process. cnmlusiom certain further deduction: and ‘ago than than. an mamas poasibla. the pun-- manna: a change in cell- mtylnhnuno to level: uranium. presence at! free :1lech in tho �enema—II in Mt in other tam, W blood anew man. With a. 1mm in acetylcholino levels in the inter-canning fluids an a result of . mum amm'umnmdtmundmmmmmmmm annular ms dupendantm ma ottoman duration or themuon, (mm. ngm)vltmwpmwmwmbmmsmmmmw 81:6.me in mm mom (19M. "s2. W» M. '53). Thu I!!! convulsion, 3111:9301 and modihﬁna and nomad annular pemahility my �throws mumm;mmtmbmehmmud, luxuriant mmmmmmumw-m splitting m. 4 mummramtydmmmmmﬁomtormtw _ wwmumamwmmwtermmmtma ﬂmmm ’n. (rmr w mm 1916 B). mammmincholmMmae activity. mummfmmwb 1mm replay be ﬂuid nth-r m doatroyud? and re whet We. ”ism I» «edited? :1: can . . it’- pal-datum in in amplmtim for this (1180mm ammuntheobumtmormmmmm.mm" tyrower and He Enchun (1919c) and Bax-gen me monoun- At ”physiologic“ mantmtione, m «2% (m rapid (3-15 dam) mtnﬂm. mm: but at. higher and fans acetylnhoum nation-hip 1: with (195$). thet the 33.6w sensitive - chonmteme-I cyst. is mtienehipe. 1v1ty he Intonh cm). Wu, mg. with hem-1 ne- to concentrationor. acetymhenne 1s Mr concentmtiona, set- In contrast. the [hasten-e411 and the mm rd: of hydrants 11mm levels of acetylohnnna et eettutyoreheaamteytheepune «name-nu, theseemohenne inseam-I, 1n the order or nimucom. . more 3% annotation W - �loaf» In main menu-luau or mwlaxolm in mm tissue, at hydrolysis Mascara-2‘1: by ehouneumtn, my As tha rah an mutation at acetyl- thaimnthrydzouu mammalian”. occurs. In. dissociation inpootylcboum - Ghanaian-a I whammy results in a par-- mm,1tu1f,par}upalddstothtlmlof unﬁt-#61:. with munnu mom-ea untmoeofaoetylchonne. nu ﬁtym. mm gym: pemmuw grim .W 1mm muesnmnummmmnmumﬂ.'1t1umauuwottua ant. vascular and 0mm, aid the or mummcm,mmmmnmmmmmt, ypuulbi uduoeathnm‘ylcholmm, action at ' mmudm,umrermmo1agu muons-I mm,muhasentumm,ubccomnmummw �all?» . ! I W dwwm{mubm)nmmmmm hmumnamwaotmmmmmmuu Wuhnecmﬂmdmmpnvmmmmtmmm due” mu, )2pr m, extent) its in lost abducts. Ila-pelt. n m up at uppunnoa mum: m vuy greatly in of mg: dogma WW. nut.- daumua: m 2171 to modiﬁcation by ﬂex-ting, ituntosa- has bean W applicatiu: of b mmmﬁan and hub-- w psyuhntzic popﬁhtion. me and 1t! any appearance courts, trait“: Want yum the 63mm u n uncanny pn-mquuiu for Mt following 01.0m— m( ampmumwmm'z Pcmmiomudwm. M&Km,1956). ButmtutbcmhmiumucﬂnngtheMnno! dialing and Mentor-Ion m be nut-d. Assuming that a grand Ill is. seizure indicative of the MW of tism le'nlloffmo mmmnm-«mnudwwwmm-I/ ’md ehctmphdognmc hyperqnchmil a reflection at u: um. the per-31m of thin abnoml commutation a! Micheline; than the difference upmummnmmmmmmmman W(Mhouni Wm, 13 a nﬂactian of tho mm m W «we. d tho dammsuwtymm Persimt types-3mm units m- M nt- of �.vp—v—vW—yw—qw—nw « W ‘13mzmmmmmmm.dummorwd WWW. of ! ﬁn {ma-mg postulates are opontiiu k £3 menu with pom-tons E chm; l E W . Westerns-i 18 in low cWﬁﬁ;u tint 12W in a great 1) . spread tho hm tho amigo]. mum- aubatmh Mutation and at Wanna-II 131m. no that tho concentration 135mm. of chum on oporatiw, [and hi. W1: a lion docq nu. Camel-loin in patients with short hypersy'mhm, Whoomrnae-I and-II in tissue mm and spinal a. ”7 fluid am we produotion of tissua cholimsteaé-a-ao-I 1n the oentml nervous syntax. W mm WW ame-I my“ aim-rm tho lucid studio! o: (1955’), mutation of Mam? cholimateroao-J ﬂ ‘ 35 4‘— high. \Purmemon, the appeal-once or nigh concentration of acetyldxouno am in I new with high mummy 2) and those pmsent and a direct mum}: between on» level of aetiuty can deMa’o be ‘ do... 91»th 1M Manon» my stunts chainsaw-1 pmduotion to o m zoom. stated 1:: Massive psycho-3 (fungus-.1 60pm). than tho Wu! mu. Eﬁofji 1 �‘ .53.- In moth-r cutout, those studies of outcome reactivity. “Eadie: _ In have opplioation imp-W by to the woman Watch an! other: havo damn-tram a mhtiomhip between the blood pressure reopen-o of patients to inject“! mohohl and ahock. Namely]. Ward“, is ﬂair mama). naponaivity to alcoho- a potent oholinugio agent which induces sweating; and vuadﬂation, momod peristalsis. It is rapidly cholimutoma-I and slowly by cholinostam-ﬂ. Tho W 15'de w pressure of sub- mu an: arm- mused menoml and Muml to the baguun. 1n n variablo length of tin, 3.3. the to natal-unto ' 20.119112“. more than Patients whoa- blood pressure “mummswmmomieduaroupl, II, QMIII no notions; those whose blood pressure “has 20 or more 11mm to rotum to o MWImotonhwooﬁm WM M”! mt ntouitthdthonupII-vmructomaﬁimute. hmmmmnmtonmoMmmmwpﬂIn9ﬁmmxy buoﬂmueroupvlmdmmcum. , g" Wilt-v rats. (momma at, 1952.) ' hmmmzummuummupumumm-mmA Wmédmlylio a lion npiﬂyhydmlyudy than the W81. nu. V. may Gmumm potiontahan m» predict. Hanson, that tho tholinoutenu ‘ uuuwmnmdwxammuldbohighyuhuoﬂmmuvﬁy \va x �a. dwnamwum. Homnhnrcaamrpnmnm mmurwmmmmdemM4,mumuu mammmmwmmmnmmmm mammmmﬁarhmammmmmum mmaudpwmmwmmmumpmu mwnmmuammmmuwumm. �Wmmamnﬁanummotmm-oraammmm W emmwmuummamyummtmwmm l quire #11: veriﬂmtim. 1mm For this purpose mutionahipo ho WM Wash-at 1) it in anaemia. ' murmumaammmmmnm. typo, OllQWﬂogrlI patterns. m and magnum at suggest-d that an mam. 1‘4an A1», the “mum 2)Rohumdmchmty1choumuvohtothomnicalmd patina“. 3) mung» 1:: indie” or mama brain nmcuon othorthnn mama: such mtylrhmao 10701:. h) mums; of cholinoatenae actimy and patterns or blood spinal ﬂuid to: 41)le b) We!“ a) ram otdwoloznant of 3m , d) amber and frequency of tmtnentl a) antennae (perimnl) mativity f) 60mm]. meti‘rityo 14 .& 7’ 5. Wm n... WWWM? éIJMW~ 4* , um and �111: 7-3-6A (I: on rue ROLE or AcsrrtCHOLrue ' ' 'vh .d) AND CHOLINESTERASE 'IN'OONVULSIVE THERAPY -« IStudies evaluating the role of cerebral changes in the mechanism of cenvulsive therapy have demonstrsted that the develogpent of early and persistent signs of altered cerebral. function are prerequisite to changes in behavior (Pink and » t A ~A. . at ': n . ' .c. ‘ I: ‘c .' V A s ', <:-~t ‘ Kahn,‘l956), In these studies, electroencephalographic slowing was the nest significant.index This ohzrvation remained un-v clear until the reports of Ulett describing the effects of pre- medication with high doses of appearance in the atropine preventing of the EEG delta abnonnslity (Ulett and Johnson, 1956). Following reniewed the suggestion of the we report. role dt acetylthis cholinestersse in-‘convulsiva' therapy. ‘he data suggests a close relationship between the degree and persis of the electroencephalographic slowing end the appea ence of and choline measurable quantities of free acetylchnline in theygnrebrnspinal / influid as well as an inVersian of the aerial ratios of benenycholine. . 'cholinesterase to lecholylcholinesterase. that: The role of acetylcholine in transmission of nervous the impulses has been studied since the first descriptions of Dale (1915) ..snd Loewi (1921). The srgunenta as to whether actylcholine' is the main or only agent in the trans-ﬁssion of the nervous, impulse are not of primary concern here. .It is sufficient that acetylcholine is a normal constituent of nervous tissue; that it exists in a bound torn and is liberated during the excitation is that process; it rapidly hydrolyzed through the specific'action~ - A ‘ " . A .1 F .v «an ‘ -< _- : .V. l antes-.3 var-I‘m.- ,, . “be”: wMYJ/I'" 44:: gauges-5mm �. .1 of cholineeteraae and as rapidly reconstituted by the choline- I ' acetylaee system (Richter &.Crossland, 1969). Furthermore, normal cerebrospinal fluid containe _ free acetylcholine despite the rapid breakdown of (Tower and HcEechern, l9b9a) bound no acetylcholine during periods of activity and excitement. 'The cerebrospinal fluid normally has measureeble cholin- esterase activity, principally of the "true" or mecholyl ’ hydrolyzin3 type (Nachmeneon and Rothenberg, 1965); ' In the absence of free acetylcholine and under the conditions described, electroencephalograme_fail to consistent show any ‘ I abnormality; .. ‘ i (a) Effect of gregiggerghggl . 3 Exagggz .1n n study of cats subjected to varying degrees of head trauma, Borenetein (1946) reported that free ecetyltholine appeared in the CSF within a few udnutes after experimental head trauma and persisted for varying houret acetylcholine quantity of periods up to £8 free _The varied between 2.7 and.9.0 gamma percent, and-the amount weeV poeitively related to degree of trauma...‘ Conconntant electroencephalo3raes demonatrated patterned chan3ee. Initially, the records were high , filled with n fast activity, interpreted as voltage intenee neuronal discharge; only to be followed by a short period of flattenin3 of ell recorded dectrical activity. These periods were then followed by prolonged periods of. hi3h amplitude sharp waves in the delta frequencies. The . behavioral chan3es were also correlated with degree of trauma, as well as with the level of tree acetylcholine, with ,higheet levels of-acetylcholine. Bernstein reported the greatest _‘-_... �_, ‘ 1 , _ ,. .3 w. a yawn-mun?” lift!“ .1»? . .. my vmr in?! 0...“, yr,“ y». my -1,“ 'V'W'FM' cream-ls“. . _ . .~ > I -3degree of m abhor-slit” the greatest. and thence; in consumes ' furthermre. spontaneous post-Ftrat-oticseisures livers also related to the of tree aco'tylcholino- appearing iii the apical fluid. 1 “t l..,‘_.‘.__.. l... V A t ‘ ’ further substation ,theae‘ohsarvations, Bonstsin applied .acetylcholine to the eiposed cat cerebral cortex.' "h. the concentration of sutylcholine use percent or less. he To , ‘ . . ' EI - . line ‘ observed high amlituda sharp waves of low froqmncy in tho electroencephalogram. When/the concentration ‘ves increased to 2 3—: perceot,’ the electroencephalogr- flattened in. afashion parallel l to the post-trematic records. ‘ . Tower and HcIIchem(l9lo9a)'-Iropa_ated neurological pstients. thssa studies in Irse acotylcholins ass 112 foond in the cerebrospinal fluid only in the patients with. rocoot hood trams, ~recent grand-ml seizures or convulsive therapy.- The free acetylcholine varied from 0.2 to lOO' 3‘s perceot. lnladdition, Tower end lichchern assayed the cholinesterasa activity of the spinal fluid; They noted ashsrp rite in the “nonspecific cholinesters'se ‘ fraction '(hensc'ﬁiholine-splittiog) and a drug in the specific choliioesterasefractiou (escholyl-splittioc); in the patients ‘ with head trams and those'follwiu in Mlsive thereby. no ~ - such inversion was ’d-oustrstod it: the fluids containing tree acetylcholins fondling spontuooos soisores; These authors concluded that the level of tree acetyleholino varies directly} the degree of cerebral dance; «nesting, haever. that with. the reversal of the oholinostersse' frantic: cos ‘a sore sensitive indicator ot-esrshral donate-V ,' I. ' _ ' ’ �7-1-2 intorvalo following varying at cm in loot of theoe anhjeeto. .‘lhe nthore reported a direct Electroencephalocrnooere trano - m and the appearnce of the of ahnorn'lity degree correlation oerobroopinal fluid. in the of free acetylcholine _ two Theoe ' increeoe the etudiea indicate. that crnioeerehral tron-a nay nomt of free acetylcholino in the opinal fluid; ’wt of froo that a direct relation eniota between tho acetylcholine, the degree and type of eioctroondphalouraphic and abnormality. and changeo in clinical behavior. ' Bornotein adainiot'ered O.5-l.0 tog/its atropine after hood traumawae tho induced anddennatrated blocking of mifeot no effecto. Following the experitrana.~ induced intreciotornal which ecotyldlouno. addition of jof and neurologi'c eigno behavioral nntal 2 clinical change. oililar to head trouno.'lornatoinohoerved 1 blocking effect or atropino. zoo and , Vardf1950) applied theoe idoaa to tho treatnont caeeo. .. of hulah ' of closed head injury. .In 20 patiento with varying degree of trau'oa.‘ he adminioterod atropine outmoly dooea of in 0.1 tog/kg. In one eaoao'henot'ed'clini'éel ignorant. and in tho of electroencephalographic of the 1 othero, revoroal effocto am: ntioholinargic of 'otndy a another dm. tragna. In Lechnar (1955) reported oinificant altoretiona in the poet- and » tranatic electroencephalogrn. inota‘nceo ' in 22 of A. oingle iatrovonooo dooe in abnornal electroenoeph'aloorno reoulted in inatoncea and unto-a iaprovooont 1. eix othoro. ‘ 1.0 nor-dieing ! o , �. 3 Iv. . . p 5 u ' .. ' ‘ , . V“ U - 'F ‘ ‘ ' r ‘‘ Ulctt and Johnson (1956) donoootntd tho I... ’oﬂoct'ot Antroptno 1n blocung tho oppnronco of no: 111601” couwlo1n. oct1v1ty vi. than". an' mood: tho study oouuto tho that 0.- Motbdcal .chauo. oloctMuphoch on... 13 hood ; m... cod 1: ,.- i . “owl-1o...1:: oootrut t6 thou 11.11:. In an: out undo noon 0. mod-onto Broom: .d Hordtt _(1m).__m1y1og top1c‘11'ocoty1f161111.11 ,' - 1 ’ thou. of tom! 1o concoctrouooo o1-2-1l2 «to; noted no offoct of clocttooocoohologuohu that tho mtntw. no “unfunny atom an... 11: to tho otrop1. of oootylohou. 1o than tho tinted lad-or tho .rooot) ,m :5 ~ ' I m2. W at onoophalogtophic otfocto won Modal by . ‘_- A #ﬁ.1w-_ ‘ moot“. . -V . in ﬁ...___‘..-% 1.,mr-4gmv4._.ﬂ 41V W to 6.1;.an about:- ‘Wq 1950) 11.. 1950).. Inothou 3 . 1 «duty of 1.011qu nth choumtoruo' 1nh1b1tor on (614.9:ny (Imam-photo) Mutton 1113b qutodo 1‘.“ (Money pot... “-11“ to out. 1n opuoptmoo. u -11 u 1.3.: «lop-o. of no.6 .' 1969; and v _ tho potont post-truth: . _' . ototuﬂlltnttcmuot 11., - on tho h w ‘ motion. to. thutlod o1 logo1t1v1ty A . _ . tut1oom1hoyucﬂbold01Wdfott1Mﬂthou- at"... ‘ 1"...“ § (mutants). I _. '34; (oatylutuothylcho1bl a“ by: -chol'yl 111 commutati.oh 1.» ti.” on. .otylobu. concou“ch ennui-31c. drugs to w...h- hM-—mbvwmmr wWe... am (OJ-IQ ‘ A quuuuu'u (1-1 3-1 oloctroooooohologrqluc oflocto 011111: to 4 ﬁlls) to ooto. '- ‘ (1 1-..... earth: Mt tho. Wu 1; atria-tuna 'o’z Wain (1946). mm: .11 smut. potent) at] ow w. m new”. at .1... too, tho “cotto- 0.11 dam of otrop1oo. �- 6.In another_laboretpry study, Chetfleld and Dempsey (1942) 'ptepered exposed animal cortex with proatlgnlne and evoked electroedcephalographic spike actlvlty. The prier.edu1nlstratlon of V . _ ‘ 'atroplne blqcked’thls spiking, er if present, the abnormality could be elimlnated-by ettopineuv Thus. from a _ variety of experimental end cllnlcnl studles; __ we A may conclude that.eletttoencephaldgtaphic aetlvlty_1nduced by ‘ acetylchallne. either as a result of trauma, topical applleation qr [ntefitxcnce with cerebral metabolism, can be blocked gr ellmﬁnated 5y atrnpxne (a) ‘Role of Cerebtnaplnal Fluid W...‘ " Acetyicholtne normally appears to be present-1n nervbus tissue in bound. inactive farm. 'chollne 15 activated thus the During periods of liberated at the cell by Ac cholinesterese. activity, free acetyl- membrane, where The it is rapidly de- level of-bqund acetylchcllne ls resultant of the processes of sinthesis. liberation breekdpunw It may be and postulated, therefore, that-the level wlll rise during sleep and fall daring ectlvity. ‘That this hypothesis '15 true was demonstrated by thhtet and Crosslend (19a9) and Elllatt. Swank-and Henderson (1950) in anlmal experiments. By using ltquld-alr‘qule-freezlug methods. Rlcﬁter_and‘Croaslapd demonstteted that the anesthesia and sleep level of acetylchollne {measuted as microgtemﬁe per mg: brain tiesue) was JCCZ higher- poet thaﬁ the seizure level“ ‘The d1£fetence_1n tissee levels is trapslent. however. as the tesyntheels rete for acetylchollhe 1p rat brain is high (7 gimme/gm/mlnute). lﬁlllett‘et a1. (19$0l; a �- 7 _ AIter metrezole convulsions, confirmed these observations [they also noted that free acetyl~ was choline ttatione always demonstrable in the spinal fluid in concen. up to 3 V . l genus per cent.> ln spinsl.£luid studies in and and Tower (1948) Cone, Tower and Menschern men, Mcéechern.(l949h)-slso denonstrsted significsnt of free eoetylcholine in pstients with quantititCe 56 enileptic patients. 49 epilepsyl"0f (77X)'demonstrsted’messursble free acetyl— chuline in Quantities of 0;02'to 5;O genus oer cent. with an average per.cent. lhe acetylcholine level was directly reletedl extent eelzures; of electraencephslogrephic the to the frequency of ebnormslity..snd the telation.of the time of coupling to the last of.l.0 gamma seizure. It hare no relation'to indication, type of epilepsy or“ .Ievel of cholinestetese sctivity.ll ' . , Whether the acetylcholine appesttng in the ~ '. A 3 g. spinal fluid is a by-broduct of the convulsion, or whether the incress} in acetyl- I]choline is'n cause of the seisure, is problematitel. McEachern (l949b) Tower and believe that the increased scetylcholine libetstion' ls not due to the seizure itself but related to the basic procees' causing the seizure; In a s“dy of the hypothesih that the accumulation of scetylcholine is basic to the seizure process, Terds'(1§53) induced Canvaeions'in animals by nettezoles She_determined the level of scetylcholine in brsin tissue before and during convulsions. .She noted that convulsions ere preceded by s " rise in the scetylcholine content of tissue; that the coucanc‘grueuaiiy fells'durins the convulsion; and that below certain levels, convulsions failed to ‘occur.v She suggesteﬂ that the fell in tissue scetylcholine during convulsion use due to inhibition of see.tyleholine synthesis by concentrstious of metabolites such so smunnium ions. increased a ' �While ebout erguneut the role of acetylthere.ls considerable choline in the mechanism of seizures. it is probable the: free acetylcholine ie increased during seizure. and appears in the cerebral spinal fluid; that activity and eeizures enhance acetylcholine destruction; lowering tissue level. of acetylcholine;‘ WW while sleep and enestheeie.eugmeot acetylcholine production, . increasing tissoe levels. 7 l. . rd) Concomitant with their observations of changes in acetycﬁbline. Toqer and Mczechern (1949) oeaeured spinal fluid cholineetereee activity. ‘rwb types of cholinii lesteresea are normally found in too ebinel fluid: .cholioeeteraee-I ("c-me". "specific" or-necholy'l hydrolyzinﬁ), which has a high: ' nod specificity far eeetylcholioe; cholineeterdIo-II ("peeudo"." epecific". or beozoylcholine-hydrolyzine). -Both coupounds hydrolyze' - ‘ ecetylchollne, but have different rates of hydrolyeie ftr mecholyl "and beoZOylcholine. -Thioldifferehtiel rate permit! duelitetive' distinctionse of the .By repertins the cholioeetereoe ectivityJee e ratio. activity with uncholyl and benroylcholine substrates to on retidio ere found: cholinesterene-l/ choline-tereue-II[acetylchbline.(with Ash/Ash - 100). acetylcholioe substrate, acetylcholine and ln-such ratios normal CS? two contain: eatereeee in the ratio of 33:17 ‘ior choliuentereee-I to cholioeetereee-II. Thus; noruel CS? consistedllllllli with of "epe¢i£ic” utterance a euell non~apecific eetereoe component. mainly ' i In patients udth heed tron-I. Toner end Holechern reportm m inverting of the eniupte of dbollniptirg‘le with d lignIIiCInt meg. mime unionist-nan meme decreaue in choline-cerebe-I ectivity.- betweenthe current or the cltolihbotereee of mm fluid and e They eleogreQOrted a Mﬂel correlation with the severity �of cm... W the of electroencepheloirmhic and with the degree I II I abnormality; '- . ,I" In patients with increeeed result of spanteneoue eeieurne. of. 1 e 395-1221: r" , eoihel'tluid ,ecetylchoiine howewet. no cerebral ad Tower tum, ee e thmge'ingthe ratio. cholineste'raseslor total" cholineetereee ectivity‘ w _ wee found. nonethern (194090. in their etudy of crazie- reported obeervetione in eix peythietrit petiente undergoing convulsive there", \Studyiegthe patients otter 3-? treatments; they. reported tree ecetylcholtne activity in the Iepinel fluid in two petiente; end en increeee in cholineetereee-II and e decreeee' in aoli‘neeteree'e-I with e revel-eel of the retio of cholineetereeee in five 6! the eie petiente. In: the,” Nobeervetione, they - like thoee of ctmiooen‘hrel tron-e epilepe'y. petient in the Veeriee who foiled to ehow. free eoetyltholine or e cholineetereee retio either Mani-in _ Regarding the one the eoihel fluid. they Petient wee wtou:_"1t.ieinteteetlnsthet thie no" one-of. theeie tee-me. to only. to a... the tree'tneut". .. . I 1 ' I DISCU§§ION . Fran theee verioue met-yetioneQwe hey contlode thet canvuleive therepy iodueee epiunl fluid like cerebrel sore ehmgee emtw thn than of maintained. we chpredtet trans” , epilehey. If the perhllel ie‘ ot the degree ehhtitn new electroencephalogrmhic ebnouelity, the acetylcholine, end e— , thaaee the thetfluid epinel in cootlmd induced céwuleione were sure thihkthoee found in . “arena of free revered of cholineetereee ectivity retioe �-.10 _ the splnal field and the nunber and frequency of lnduced cone vtlslons., Also, item the observntlans of Tower end McEachern 1n (1949b), the cemment thst ohly the patient who failed to shew. -§pinal fluid changes-talled'to show a response to treatment, ptrmits us tu consider the possibility that such biochemical bas1c therapy of the the chmges are to ccnvulelve medical“ process. cpnClualonsiare pnsslhls'. ad The hasssge of electric current: through breln sw‘stencesilnduces in change sctlvlcy with an increase 121 free a deductions Certain further mm“ . acetyl-. choline to levela'suffictenti‘to1nduce a grand nsl seizure. The . presence of ' ' free acetylchollne 1n the intercellulsr fluids electrical hyperaynchronyr‘renscted lathe .386 as delta? slwlng-r The degree of hyperaynchrow sc'mrate-ly reflect} the, decay acetylchollne of should fonds! free a ad rate equal level S1nce studiesthe purines of deatrhctlon. acetylchollne rate to demonstrated. that EEG hypersﬁchtony use: a, necessary ﬁrvrequlsite induces. ' . ' ' to the cllnlcsl respome 1n central‘slvsthﬁapy. it my be stated .mu'mm chances that the dunes of free aestylchollne in cerebral fulcrum ad thus prilud'es s clinical rem the 1ndueed convulsions. tn Certain eat-muons nay be ends regardles changes In cell embrace permeability as emlal’nlng the incresse in theme-:- .estetasd activity; Chollnesterase-l ls feud m htgheat concen- ' tratlran . 15 ~- 1n the centre} nervms system; predominant in other tlesues. especihlly the increase in eoetylchollne ‘ anus chounfcsmrsse-II Innis blid serum With 1h the 1ntercel§lulsr cerebral fluids as a result of stlmletlon and cmwlslhn, vasodilation and increased cellular permshillty be Pradicted’;’ my ' D E .MLr-JM: 4‘ . ‘ . M. -. . t a ‘- . �~11} thﬁ inch:vasculdglfluids'tnto with a degree of ggancudatian of dnrittan of thg'. and ch. on dlpcndcnt spaces nxtcnt cellulnr vnddtlptlio-n _do occur numétous wag (um 0:11., 19m, anpiy.dcnonstrstcd ‘Ihnt ouch ”manna chm ' SﬁlejiIFAdolf 8910331 1n and by répofti (1961; '62, 'bb,"£§;.'53)é - . . denunstrat§d They cdnductivity cbhvulsldnn e1.c:r1c.11y_iuaucgd tacguased.che that Idikqgo pot-saint as ﬁargous of ions. 1n n cf the clouue; resultud thh lldid§ el§ctgolyths the while phbiphatQ, that and ipingl into and nan-cltcirolytés nngsnittcant 1n .tncraalcd. incrpaso 1h Gunﬁght prﬁibiliﬁy nucleic-acid abutting 'enzyus. of £011; may'thtu prﬁvida thé basil for-thudappoarahco of high ‘w-u 'contgntrati§u§ of a¢§tylch611ns and for lqcrcnand cancantgattons' of cholineaterasefll (Tower 1nd1HcBIéhern.19b9c)." _ . within. 1n;glil%;1n‘ch011héytct‘ne‘acglgitz; free act-tylﬁtoiiné _rnp1d1y> b0 dutioyoih? T.“ wit ohoﬁﬂd not tﬂe $phdnsn can ind uéttbed? agitate-ht. sbtml' fluid. arm: ugh; m panache-e. in. 1‘ qbuertitiann. EB. thin‘diactcpcdcf nvnillbla in An éxplanattqn.for ' Sy :kuurgxl (19.005). Nachuntoh of Mun-ad and__loth¢nber3 . McEdchcm (1969c) .ind poison and HuprtoIh (1955),.{thaf the acetylcholinc-cholthél'brabe-I'uyatﬁu is vary aanptttvi~co:¢on¢aq4 itdtibn relpttonshlpq; At "physiqlogic" éoncentrdtlons, hydtolysis , - and, buc'd: 1i higher of ncntylcholigi tdpid‘(3—6’nucranecoudn) qu1c¥1§itiL}dqno off cutv,). activity £111: lower cqngcptrgtionl. rtiatiénﬁhip to chbltneutaraac-Il-acutylchollno In conraac. the rafd with egocenttaiian. hydrolyita-tncfgases of the and non-specific. i . 'um. nor-.1 um. {mama mu- n: «manna. a cell ' Qéttvity' chi geocylchbltnn ipqctftc by thidgntioﬁjd npnbr-neny tho f ;_1 ‘jt �.i. V-“ wry...” m.“ r'rr'l r . v: _, r“'\7ﬁ"x.:r'7m¢rm., _ ’0"; 3 Of cholineaterase4l ithhe order of niliiseconds. . _Where - . . 'l excitation 3 A a , lead% to an'excesaive‘concentration of acetylcholine in nervous tissua the :nté othydtnlysia I by cholinesterase-I is F 4A A 'A’Q": exec-eded. thu con:enrration of acetylcholine mounts, the seizure threshold is reached and a seirure cccurs. The dissociation in ncetyichoiine- A3 m}! 1 “+4—ow cholinestern5u—Z zclationahip chnlinn The neiznrej liree acetylcholineul itself, The results in a perniatcnce of acetyl— pernapa adds to the level of “gt“..i. increased acetylcholine diffuses rapidly,» with resultant vascular-and cellular_permeability effects and the iPPEﬁvahcé cf inzréaaed ions in CéF; ﬁnd also etficiencf, increased cholin- r LAM; astsrawemii. 4 Aﬂnmnmm. It 15 the activity of this enzyme}.th0ugh'cf lqw- 3 and dependent on concentration kinetics that rdduceﬁ’ the acetylcholine leval;yaperiod I . j ' , of houra to days. tb levels - .__\._-xw-:‘.mz...' for the p‘Eaiologic action of cholinesterase-I 1“ Alteratian in the blood brain permeability barrier by the f ~continuing action of acety-lchoiin e may be the biochemical aub'5trntc {or the hvpcrsynchrony so often obServed in past~electro~ «nu—“\me'mut maﬁw—«A .hnck-electraencephalogramst Such a possibility is evident in the' I 'i ' ' report by.Aird et all (1956) demondtrating a significant increasn in the concentration of cocaine in brain tissue 3 days after a' 'seriea'of 12 induced convulsions. ‘ g of concentration tiisued to he His data about the change in i, . 1M . ' - ' In ..—.u..‘,~«.r.n.v.— 9-1.4.L — .1. “F... thi a large molecule, ordinarily absent in brain torrelatcd with the appearance of bypersynchrony ’ I (delta.bursta) in the elecnroencapnalogran. In our studiea of thc appearanca cf clactroencepnalographic he, have confirmed tire many changes with acmvulaimi .previous reports tnat convulsive thctapy induces hyparsynchrony in most subjectst Despite a constant application of treatments, ‘ a �«.13-‘ electro- however. the time-of'appeatancé. duration and extent of the graphic slow ' 1' A . 'ventiiation it; its sensitivity barbiturates - all QAV$f and populations. and - The to wodification by aierting,'hypervary greatly in psychiatric appearance degree of hypersynchrony, high early beeﬁ has the course; tieatmeﬁt persistencv throughoﬁt described as a necessagy prerequisite for improvement following Electroshock(Pink and Kahﬁ..1956). But what is thé~mec§anism" "undcrlying the failure of certain patients_to deielcb hyperaynahrony?_ Perhaps-thgse studies of aceryléhollne and cholinEstﬁraﬁes may be rélated. ‘Assumiug that a grand mal seizure is indicative of the at‘ttssue levels 9f free acetylchnline In eicess of "' ﬁhu fate of ﬁydzoiysis by cholinesterase~I;-and_thét the electroencephalographiC.hypatéyuchrony.13 a reflection of the'peraiatenCe, development ' of this.abncrmél concentration of acetylcholihe; than the differencé 1h pugzehts who maintain.hyperaynchrony"ind those lh'vhom it ‘rnpidly (fgv hears) disappears. is a reflection 0f the kinetics of the ch01tngsterase-acegylnhollne h§dtofysis systeﬁg Persistént.. hypersynchrbnj Insult; from dccteiqéd rate of hydrdlyeﬁs of ’cboline.v ¢ ‘arahstn-nﬂ acttyl- ,. _If the hypothclla~prevtouely'deducgd are cattact; nithér-ane» ‘ . . V ' . , f u-ww-xa..yrmwméw.w}v-JH‘ or both bf the felLowlng postﬁlateg‘are operative in patients with 99 tslsteﬁnt hypersy nebr‘ony: (1) is a ‘ . Chaitaeﬁteraseél is in low great.spread betweén the apt! thosé preéent '_and 1n cancentratton, an that théte' trace concentration the ttésue with high acctyicﬁolxne;vandlor' '(2) Chalinesregage-Ii is a1 enzym¢~aub low, so that the concentration Ltwetzks cf chis‘system are opcratxve, though at a slow decay .. .13...- ...,.__..J rate“ �‘ _ fonversoiy. :u patientc with short-lived hyper:yuchruny. Cholin- cetetaee-I and -II in tissue and spinal fiuid may be unusually - Furthermore, the‘appeatﬁnce at high concentrations of acetyl-~ Ichcline stimulates the production of tissue chclinesterdse-i in the(antral nerVDus.system.- From the lucid studies of Nechmanaon (1955). a direct relatzonship bétwéen concentration of“tiesue cholin-- estethee~1 and level of nervous activity can be deduced. It 109' ievels of cholinestereaeél can be dull- demonstrated in depressive 'psythoseé (? menonaueal deptession), then the electrcshock_induced _acetylcholine may stimulate cholineetetaee-I production to a mare normal. pre~morbid leverm , cantext, these studies 1n_enqrher problem of autonomic reactivity. may have application to the. ‘Rncent qtndies by Funkenltein and others have demonstrated a relationship between the blood presents of patients .respbhsefto injected mecholyl and their event-n1 reopensiyity to ' :i' ” ' - 'Hecholyl which a induces“ cholinetgic potent is agent electsaShack. ' “ ~2i: tachycatdia, ic?‘ perietaISist sweating. incteaeed and vagadilation. chnlin~e hy hydraitzed cholinestetaseél and slowly by ls rapidly estetaee—II. 5;.. atter injected fails vatinb'le length of time, blood pressure of subjects return. to the baseline in a five to more than 20ninutee. Patients rthalyi i The and presiﬁre'l whose blood 5 the minutes are classified as Group I. baseline in to returns those whose blood pressure takes 20 or more '21! ':an reactions; minutes II to return to‘a baselineg‘es Group The Gtoup 1 reactors have a 92 improvement ' VI and VII reactions. 'IlllI-I-I - rate with canvuisive {1- - H; i ~ therapy. and the Group II, II-III reectorl : 352 rueovery rate In a i contrast, the Gto up VI reactors have a 892 and the Group US;da~9§1~agent-uzeaauuzyq:ate.£runktntto&n-otqe3~y¥$953-- I ; 1 �“ VII a 97! recovery as patients in 2W4"??-:'£€i§:?fjw*ja 15 _ Groupu_ I to may llI may be looked ubon the injedted mecholyl is hydrolyzed; rapidly while the Group V! and VII patients have We a slow hydrolysis rate. predict, therefore, that the blood cholinestereee ectivlty.-' levels of Grouce l-III would be high; while the activity of Groups Vl-Vll would be low we recall here a similar prediction cholinthe date central for of nervous levels item Iy regarding esterese~l, in which the develovuent df early and sustained EEG hypersyhchrony and elevated epinel fluid levels of acetylchdline related to low level of cholineeterase activity. _Thus, the date of peripherelystlmulatiou by cholinergic agents is A ,was congruent to the hypothesiq regerding central nervous‘system‘reP activity to electrcahock. cammsmus: This survey of the literature of the roles of acetylchollne of cholinesterase in convulsive therapy hue led to a number speculetione which require yeriflcetlan. 'For this purboee, it and 3 is ‘ suggested that en-investigetion of the following relationships, 'be undertaken. (1) Level of free_ecetylchollne iu the epiqal fluid. 1‘3. type; cbnvulalye frequeucy. to number and therapy relation Also. the essociated electroencephalogram'patterns; Reletidn of such ecctylcholine levels to the clinicel (2) behavior of patients. (3) than z‘ 3;“:Ww’gwwm‘us rate (Funkenetein $5321" 1952); ;Patients in Funkeaetein whom .24; EEG in indicec of altered brein function other with such ecetylcholine levels. Changes ’ , .7 ., _ �{4); Reiéttoh chalineate'fﬁe gétivify of blpbd scrim andpspinu fluid to: (I) ﬁattémﬁ of and ‘ age, , (b) alméta (c) rate bf deveiwopt'zent of‘ EEG (d). numbg: ,md fréqqencyof . f ‘ treamhts . (e) ,aﬁtbn'omc (heriphgnli reactivity -(.f)',cerébu1 reacthﬂty‘ ‘ ‘ , 3 . gpexfsonauty Run: ofatroptne“. physos‘tiglnlne'admini‘attatian on (’8‘) (5) hypersyhchrony ‘qliﬁical behavtdr. , _- ‘ ~‘ E36,“, j 4 �III: 7-3-6A ‘r (1:, ﬂab-(i) ‘ ON THE ROLE OF ACETYLCHOLINE AND CHOLINESTERASE IN CONVULSIVE THERAPY Studies evaluating the role of cerebral changes in the mechanism of convulsive therapy have demonstrated that the development of early and tunct persistent signs of altered cerebral are prerequisite to changes in behavior (Pink and on Kain, 1956) - was the most In these studies, electroencephalographic slowing s significant index. This obhrvation remained un- clear until the reports of Ulett describing the effects of pre~ meo11ation with high doses of atropine in preventing the appearance of the EEC delta abnormalitv (Ulect and Johnson, 1956). ’Followlng the suggestion of this report. - we Eg 5: reniewed the role of acetyl— choline and cholinesterase in convulsive therapy” {é to data The lg; ve x close relationship between the degree and persistence? of the electroencephalographic slowing and the appearance of Suggests a T: .¥ measurable quantities of free acetylcholine in the cerebrospinal {g fluid E; as well as an inversion of the normal ratios of benzoycholine- cholinesterase to mncholylcholinestersse. I h:§ . . Ihe role of acetylcholine in the transudssion of nervous impulses has been studied since the (1914) and Loevi (1921). first descriptions The arguments as d of Dale to whether actylcholine is the main or only agent in the transmission of the nervous impulse are not of primary concern here. .It is sufficient that acetylcholine is a normal constituent of nervous tissue; thst exists in a bound form and is liberated during the excitation process; that it is rapidly it hydrolyzed through the specific action g) �oi cholinesterase and as rapidly reconstituted by the choline— acetylase system (Richter normal cerebrospinal a Crossland, 1949). Furthermore, fluid contains (Tower and McEachern, 1949a) no free acetylcholine despite the rapid breakdown of bound The acetylcholine during periods of activity and excitement, cerebrcspinal fluid normally has measureable cholin- esterase activity, principally of the "true" or mecholyl hydrolyzing type (Nachmanson and Rothenberg, 1945); In the absence of free acetylcholine and the conditions under described, electroencephalograms fail to show any consistent . abnormality. Effect of Craniocerebral Trauma: .In a study of cats subjected to varying degrees of head trauma, Borenatein (1946) (al reported that free acetlehcline appeared in the CSF within a few minutes after experimental head trauma and persisted for varying periods up to 48 hours. The quantity of free acetylcholine varied between 2.7 and.9.0 gamma and the amount wasl percent, positively related to degree of trauma. Concommtant changes. electroencephalograms demonstrated patterned Initially, the records were filled with high voltage fast activity, interpreted as an intense neuronal discharge; only to be followed by a short period of flattening of all recordedeaectrical activity. These periods were then followed delta frequencies. behavioral changes were also correlated with degree of‘ trauma, as well as with the level of free acetylcholine. with highest levels of acetylcholine, Bornstein reported the greatest The m �consciousness in change the greatest degree of EEG abnormality, also seizures uere and furthermore, spontaneous post-traunatic the in appearing related to the amount of free acatylcholine spinal fluid. applied' Bernstein observations. these To further substantiate when the cortex. cerebral exposed cat scetylcholine to the he gamma 1 less. or acetylcholine percent was concentration of waves of low frequency in the electrosharp observed high amplitude encephalogram. When the concentration'vas increased to 2 gamma parallel fashion in-a flattened percent, the electroencephalogram to the post-traumatic records. A 112 in studies these Tower and McEachern(l969a) repeated the found in was Free acetylcholine patients. pneurological head trauma, with recent the in patients only cerebrospinal fluid The free acetyltherapy. convulsive ‘recent grand--nal seizures or from 0.2 to varied choline lGO gamma percent. In addition, Tower spinal the of and HcEachern assayed the cholinesterase activity cholinesterase the nonspecific in rise fluid; They noted a sharp fraction (benzcyhholine-splitting) and a drop in the specific the in patients (mecholyl-splitting), fraction cholinesterase therapy. No those convulsive following with head trauma and in free containing the in demonstrated fluids such inversion was acetylcholine follouing spontaneous seizures. These authors directly acetylcholine varies concluded that the level of free that however, damage; cerebral of with the degree suggesting, sensitive more a was fraction cholinesterase of the the reversal indicator of cerebral damage._ -' �- 4-following intervals varying taken at were Electroencephalograma direct a reported The authors most of these subjects. trauma in of the of degree correlation EEG abnormality and the appearance cerebrospinal fluid. the in of free acetylcholine trauma craniocerebral indicate that These two studies may fluid; spinal in acatylcholine the of free amount the increase free of the between amount and that a direct relation exists electroencephalographic of type and acetylcholine, the degree behavior. and changes in clinical abnormality, (b) Effect of Atropine on Bernstein administered 0.5-1.0 pggt-grggggtig mg/kg EEG 5&4 thgviog; atropine after head trauma- EEG effects, manifest of the blocking demonstrated and induced was the experiFollowing of trauma. behavioral and neurologic signs mental addition of intracisternal induced which acetylcholine, trauma,“Bornstein' head to similar EEG and clinical changes observed a blocking effect of atropine. human of treatment the Wardflgﬁo) applied these ideas to degree with varying 20 In patients head injury. closed of cases of doses in subcutaneously of trauma, he administered atropine and in improvement, clinical noted he some cases In mg/kg. 0.1 the of effects electroencephalographic the of others, a reversal Jenkner anticholinergic drug, trauma. In a study of another the in putreported.simificantl'alterations (1955) Lechner and 40 in dose intravenous traumatic electroencephalogram. Asingle normalizing‘ in instances of abnormal electroencephalograms resulted others. in 22 instances and marked improvement in six _ �- 5 - atropine effectwof Ulett and Johnson (1956) demonstrated the sane conVulsive‘v illoﬁing slow wave of activity the in blocking appearance biochemical‘nechanisnl same the therapy. This_stndy suggests that ’ . V ' under£:5the electroencephalographic changes in head cranes and in . *-',._—s Mov ~...,_..-—~ in contrast to these findings}: In their i _. M. . experiments Brenner and.Herritt (1962), applying topical scetyle in concentrations of 2-1/2 to choline 102 ‘ to the exposed cortex of cats, noted no effect of intravenous atropine (l nglkg) on the electroencephalographic changes. lt_is iaportant to note, however, that the concentrations of acetylcholine in these experiments than significantly the topical applicetions (1-4. was higher 3“. I percent) and the intracistsrnal (0.2-10 galls percent) injections Bornsteind(1946). Brenner and Merritt. houever5'slks_note of of electroencephalographic effects similar to acetycholine free mecholyl (acstylbetanethylcholine) and doryl (carbanylcholine), each in concentrations Inch lover than the acetylcholine concen- effectiveness of these incteessd the ascribed trstions. lack drugs cholincerebral of to sensitivity to cholinergic their They ‘ estereses. A I variety of experiments with the potent cholinestarsse' inhibitor DFP . .31. induced convulsions. due report stands out a.m- fluorophosphate) demonstrated high (di-isopropyl amplitude rapid frequency 885 patterns similar to status epilepticus, as well as lesser degrees of abnormality noted in post-traumatic stete!!(ainnich, et el., 1950) Freedman et a1., electrohempson the 1949; and et al.. 1950). In these studies, too, encephalogrephic effects were blocked by snail doses of atropine. -——.‘ Cs- �In rustle? labcratbry study. Chétfield and Dempsey (1942) evoked and anxmai prestigmlne :ortcx expasud ytch prepared r9103hdlU.YJDF1C Spiﬂe autlwtzy. electro- prior.admznzs:ration of The 'uzrcane biotk\d this 5:1 1:5. a: if present, the abnormality v?u.d be viim‘:1th by atrepir~ 7C 1 trtn 'hu.. a variety of experimental clznlcal scudzcs, and 'har eie-ttnuvcethIographic acti;1cr ._:ti;:hrr;:¢. irhc: -T;t'!‘!". ‘th as 3 wﬁ tnd¢¢¢d bv reswlt of trauma. topical appl;astict or :rrvzral m;:a‘clzﬁn, can be blscked ur elzmztated ltz'tln|k‘ -. (r) ‘3}.: 'x '.;re:.cwg:n31 ~ a:e:yL.n;1;1¢ ﬁcrtully appnars :; “Jqu, ;v¢;ttae iczm. It trcaxd;un {L58 Ln 4 The level of spund acetyichclinc is v c: the pro: I! 3325 cf synLEcsig. liberation an; may be Lcscuiat is true :45 npmanstratpd 1W: -. nex.{;3;. pr-Sen: 1: vezvous 11554t a I u . therefore, that the level bill during «lead and fall duslng activity {111352. 9v'xn a“ ‘T ac:1;i:;, r:ce acatvicell membrane. where it is rapidl; de- Activated ty challnestarase. c::.:an; bv . Du::n3 pazxud$ of :hu;in# is liberated at the ;h;. the .,‘.‘.:l Au€£.luld.;‘£- "‘ r.u.J 2 by thhte: Pyzdur$;n (1950? and La That this hypothesis Crosaiand {19u9b and aagzyz uxanrimun;s Sy Richter and Grassland qu1ck-freézing methods. asxrg liquid air deﬁoﬂSLYdtzd that the anesthesia ard sleep level of acetylchoiin‘ .Lgustcd mi:ragra:13 per 25 :Fdn fn» Ln»? uvi;urc lcvc; Itdnxieﬁt .. ?. .5 (D N mg. The brain fiSbUd} was 3092 hich? difteteECe in tinauc levels 13 .5 the resynthesis rate for azetyluhclihe in m rat braxn is high (7 gammaigm/clnute). 'Elliott er a1. (1930} :. par-- �After metraeole convulsions, free noted that also XIhey acetylobservaticne, these “K ;3r?ic~‘i n ; chul;ne :ws always demunstzable in the spinal fluid in concen- tratians to up In spinal 3 gamma per cent. man, Cone, Tower and HtEechern fleid studies in ahd Thuer and McEathern (1949b) ‘1348) ti quantititls 86 also demonstrated significant free acetylcholine in patients with epilepsy‘ 'Of patiehts. epileptic Lhuiine in quanti'iea 49 (7723 demonstrated 0:02 tc of SP0 gamma naeeurable free acetyl- per cent. ith an average was related level directly acetylcholine pu:.cent. Ih: (L the frequeﬁcy cf seizures; the extent of electroencephalzgraphic t6 the last of relation of time the sampling and the abnormality, cf 2 O gamma It bore seizure. no relation ta medication. type of epilepsy or level at cholinestetase activity. Whether the ', a . a the in fluid is spinal appearing acetylcholihe ty—prcdcct of the canvulsion. or whether the increase in 9 - catae of the Seizure, is prshlenlticela acetyl- Tower and chachern (1949b) believ that the increased e;e:ylchcline liberation (T; itself but related is not due to the seizure caaeing the seizure. A“ In a to the basic preceee s“dy ef the hypOthesls that the accumulation acetyleheline is basic to the seizure process. Torda (1953? indured convdsxcrs in animals by metzazcle She determined the level of acetylcholine in brain tissee before and during convulsions.» convulsichs byla She noted that preceded are rise in the acetyicholine content of t:ssue; the: the content gradually falls during the convulsion; and that below certain levels, convulsions failed to occur. 3 She ccnvulsioc suggesteﬂ that the was due fell in tissue acetylcholine during to inhibitien of acetylcholine synthesis by incrcdeed reagentratiacs of mezabclites such as ammonium ions. �While there is considerable orgumcnt about the role of the machanism of seizures. choline in it is acetyl- probable thot free atetyltholice is increased during seizures and appears in the spinal fluid; that cerebral activity and seizures enhance acetyl:hcline destruction. lowering tissue levels of_acetylcholine;while sleep and anesthesia augment acetylcholine production, V inLrGaSXSg (d) tissue levels. Svstoo Nervous Centrai Cholinestegase: Concomitant with their observations of changes in acetycholine, measured spinal fluid choliuesteraee activity. Tower and Hcﬁachern Two (l9é9) types of cholinii esterases are normally found in the spinal fluid: cholihesteraso-I i"true". "specific". or metholyl hydrolyzing), - which has a high specificity for acetylcholioe; and cholinesteraBe-II ("pseudo","nonspecific”, or beozoylaholine—hydrclyzine). Both compounds hydrolyze acetylchcline. but have different ratio of hydrolysis for mecholyl and beozoylcholite. distinctions of the .By This diffexehtial rate permits qualitative reporting the cholioesteraso activity as 5 ratio activaty with mecholyl acetyicholine substrate, two and benioyloholine rati$ are found: substtates to an cholinesterasevl/ acetylcholine and cholinesteraoe-II/acetylcholine (with Ash/Ash - 100). in such ratios manual CSF contains esterasea in tho ratio of 33:17 for cholinasterase-I to cholineateraee-Il. Thus, normal ‘ CSF consists- inly of "specific" eaterases with a small nonhSpeciiic esterane component. traoma, with head Toner and Kcﬁachotn report an patients inversion of the amounts of cholineoteraies with a significant In increoae in the cholinei‘trase-II fractiOn of spinal fluid and a decrease in cholineatorase-l activity. They also reported a correlation between [la extent of the cholinesterasc rcvérsal with the senority �the electroencephalographic of trauma and with the degree of ‘ abnormality. scetylcholine a as patients With spinal‘fluid increesed .In however, the ratio in change no sponteneous of seizures, result found. actitity was cf :holinesterases or total cholinestereee (e) Effect of ﬁle trnehock on at A Tower and McEachern’(l9493), esterases: it oline and Ch in- in their study of cranio- psychiatric trauma. in patients six reported observations cerebral Studying 3-7 after the patients convulsive therapy. undergoing the they.reported in activity free acetylcholine treatments, . ’spinsl fluid in increase in cholinsstersse-II patients; and a decreaee in cholinestarase-I vith a reversal of the rstio llron'thess Of the six patients. of cholinestersees in five and an two in changes fluid the concluded spinal that they observations, cdnvuleions trauma craniocerebral those like more were at induced than those found in * epilepsy. Regarding the one patient in the series who failed to show cholinestsraee in ratio reversal or s free scetylcholine either the spinal fluid, they wrote: "It is interesting that this response shun to no of to the six one the was only patient treataen.." . DISCUSSION From these various observations, vnlsive therapy induces spinal fluid we may conclude changes more that con- like cerebral is. 'trauma than those of spontaneous epilepsy. If the parhllel of. the degree maintained. we can predict a relation between of abnormality, the appearance free electroencephalographic qcetylcholi1e. 3nd ; ra"97331 of cholinestcrane activity ratios ' �‘“ the L-L Fpl'd: fizid and the number and frequency of induced-con; xtisisrs. Alsu. irsm the Observatians of raver (1959b), 1hr ccmnent that cnly the patient suing? ELUiJ ;hangua us in ptrmits :hnngcs are filled who and McEacharn failed to Show to show a response to treatment, cozsider the pcssibility that such biochemical basi: to the :cchanism of the achuleive therapy process. Certain further deductions and conclusions are possible. rhé brnin subrtances of induces through electric current passage change a in cellular activity with an increase in free acetylchclinc to levels sufficient‘to induce a grand mal seizure.i The preaence 3f free acetyltholinc_in the intercellhlnr fluids electrical hypersynchrony.ref1ecced in the induces , slaving The degree of hyperaynchroqracturately reflecth the level of free acetylcholine and should follow to the rate of acctylcholine destruction. demonstrated that 1c the as delta EEG a decay rate equal Since previous studies hypersynchtony was n_neccssary pre-requisitc EEG clinical responsc in coavulsive thcrapy, it may be stated that the absence of free acetylcholine suggests minimal changes in cerebral function and thus pracludes a clinical reapanse to the induced convulsions, bc made regarding changes in Certain assumption: may membrane cell permeability as explaining the increase in cholinf esterasd activity“ Cholinesterase-I is found'in highest concen- trarian in the :entral nerQOus system; while cholinﬂesteruse-li is predominant in other tissues, especially bloba sdrum. ~With the increase in acctylcholine levels in the intercellulur terebral ilwids as a ‘ xesult'of stimulation .-J.-;'..L ..i ;w::tjs;; and convnleibn,‘ :uliuau: gartelhllzty may be predicted, �.. 11.. interthe fluids into of vascular with a degree of transudstion of and the duration the on extent dependent cellular spaces vssodilstisn (Rabat et all. 1948). 'Ihst _do such permeability changes in and Spiegel-Adolf by Spiegal demonstrated amply occur was ; . demonstrated They '53). 'é8, '6h, '42, (lQél, numercus reports cenductivity the increased that electrically induced convulsions cf the tissue; resulted in a leakage of various ions, as potassium and phosphate, into the spinal fluid; md that while the electrolytes iignificsnt increase in non-electrolytes permeebility in Charges nucleic-acid splitting enzymes. i .creased. there was a Wes of cells may this provide the basis for the appearance of high :ﬁccentrations of acetylchdline and for increased concentrations - oi chalinesterase-Il wt ch~he (T owe: and Mczachern l9h9c) incevihy in cholinesterase activity, shculd not the free acetylcholine be rapidly destroyed? To what Mechanism can seizure be ascribed} its persistenze in spinal fluid after An explanaticn for this descrepancy is available id the ebsersetidns trauma and cf Nachmsnson and Rothenberg (l9é5), hy confirmed McEachetn (1949c) end Bergen and Macintosh lever and ' (l955),lthet the scary!:hcline-chclineglerssc-I system is very sensitive to concen- tration relaticnships. of acetylcholine At is rapid "physiologic" concentrations, hydrolysis (3~4 microseconds) but at higher and quichly_(hsldene off curve). lower concentrations, activity falls relationship is In conrast. the chdlinesterase-Il-acetylcholine nGt'EpCCllli, and the rate of hydrolysis increases with csncentration. Thus, with normal functional levels of scetylcholine membranes, the scetylcholine is destroyed by the at cell specific activity �where'exzxtJZLcn -:41 in the Urdu: of "111;3dC9ﬂdi '!;U&uLVc '1..‘q;. :rL:.:1"-"wf cchaevtratton of acatylcholisu in “Bfiohs is Hytirwﬁxw ‘; ‘b: ‘*::e:tr3:icn f :lr311rﬁ:ster.19a—I t.s ex;cc:J¢d_ Ev: {Htéskrld the seizure uf acatvlzholivc mount:, The :2 I tree acetylahoiine t"r‘1"; -~'.' *1 I: ~~II .r‘;c1nn;y. The “erhaps adds to the level of rapkdly,« diffuses ucstylcholtne increased a; the actlvtzi cf thia enzyae. Jun LCgﬁﬁduﬁt ad Lu CUCLUDCYaCXCn A ‘Lc acetylcholice level’ f): fke shwcx persistence of azwtyl- a the and pctmrubility effects vaatulax-ind cellular £53; cholxn~ Inzteased 413: and .v‘retued inn. 1n 1" t.~':t"’ '¢ ’.vnshiv rzeults in nex:;ra. itself. The Etna 'W' disscnlation in acet/isholtné~ a tﬁOugh c1 low klnolizs that lchls period of heurs to days. to p cholineatetaRP-I. of action /w;alcgic (lottrtcnvcphgiagraMs Suuh a posstblllty xs ev.5c:t in the' I Tcpﬂ$2 by Axrd e: 1n 1n-.e;ae a democdttating (1936) sxgniticact 1;. erin gdcszte in of cuvuent::;103 the ‘ 12 L9LC€RTT¢L10a itisund Cedutuw ’v‘ tiesue is data induced convulsionq. 3 da,; af e' shows the change in brain in absent tﬁis ordinarily nnlecule. large ct of wﬁtﬁ hypersynchrvnv the ;nTT91aLcJ Appearance ta be eleCtroancephaiogram‘ the in (deitu bursts} electroencephalographi: of of the appearance In 0d: stLdica nuwbuni' the many confirmed have we changes nuth hypersynchtony induces therapy convulsive previoug reparas that of treataents. application constant a Deepitc in maqt Suh‘c~(w ' #cmwnlsiozs, _ �FLHCLICof the Jnd 54r3:1cn extra: ILmv of Appearance, (it “VlﬁVﬁf, ‘rT'XXATXOH 315 *"ri‘::w“" . ‘ {v hyperaler21u1. c;d1‘i:1L1‘" tc senaazxvzty its Qaca graph;; 5ch I herb:tgrates all cgrly appearrnce TLQ vary greatly in géyzhiatric of?.igh degree hvpe: vnchrany. bwaa has tzcatmunt the ::.r:‘~‘ 1:* ::§ 33:1IHEE'CV (Lfvgghiji 31¢;Yihﬁﬂ as a nuccaaary E'sctrgﬁﬁ”( t-tr': 'quh:iwlrr 2H: and Kihn. 1956). Bu: what 1: ch; meghanism' imitate of caftain pﬂttents_zo deveiop n3persy1.Lrauy be and acccyléhriine may chottneqterases of <tgiiee - L%ewﬁ 9:;L4y3 greraqgtsira to: inprrvcmeu: folluwing \s-uﬂ.' .la "Z¢piwﬁx seizuze ls :ndznattnc o: thy *EA: 4 armnd m;. ; {13:uc KQIHL; 2f {tee a»:'{2.chv'LHv in ‘HH and ghnlznugcaraae-i; by ," -«;c *nd~a;;z‘s n. erlag'-.5;; hypetsyncnrcnv La 1 iKSQ$E a! that the alertrc— ref\r\::LLn cf the pvrstazunce the ditfctence then 3f acetylcholinu; c~rven‘:¢;2cn Phﬁ”':d1 ‘32: 9‘ u. :rﬂ-tr:: -in ra:a;¢1r ry;c:e,n :n:;r.v in- at in whom it Persistent .frizzc=2-r3we-QLPn;l;bol{we hydrolysln system. {La 3 Lh of ace:"Lhvnral of atu I decreased fr3a rate I h5“a7annchtnn", resulcs K . . V s-prrvlousiy deduced are correct, ezther one 'J 9" 0' LI V 1 rv- in .A 0‘ t r9 n ’ I‘ ‘1 ,— P" patients with (a as are operatlva pcstula: suing .cr'xst.uz hyﬁvrzy nebrbny: (" 1% :‘i attrast-I IS in law s: rte er: in LF: tisSue t2) h‘ Yh<‘ 2 Cb'litugrpzata—II is :oﬁc=n£r3££nu , «12L h1gh Kev, so %: that thc:e a;¢:ylchclzne; and/3r that the noncancraziou at though are 02e241122. g; 5. suqtyt 'h:..- 1 slaw decay rash o �I ‘, f)‘:W-‘rvrs. t“: " st: gfztzl Ira in» ‘.-* “2:- 1" 2 ~ 3 :: "ca proqz tlcn <th .L . Fran Chv a:v:yl- nzgh cgnawnLratiors or :"l':us:eraae—I stuchn suuid . attivit" cad be (;Q55!. . of Wacnmunsan ill-n If can be deduzcd“ 13w demorstracad in dapre:?£ve yzr~xe5 g‘ acnopausal depr¢sszct), then the electroshock induced ' $:L:V1-‘QIIUL 1¢v-:rimula:2 ;%;l;ne {grasp-I graduation to a more usn“ku: Eu ,4 -\ \ v 1‘! :g: - - cgﬁu"'crac#3 c r .t “.CE Ha4.3: xu“ « chhriy. 2 z: ‘“"gi;ia:: r, tzarv122d;3, an r31): l éﬁn y‘;rra L) txue to more than -;‘.c;- upnli:ation cm Rucent szudius by Funkeaatein and. rglarlcsshlp Fatwaer the blond p:e>3ure a "aren* L!(11FP:51~ ‘gegt whicb iﬂduces swancpag, and in;:¢n.cd peristalris. 20 minutes. 5 minutés are :lauSLfied as Gtaup 1. .1, 20 or were c ‘JYI .3. 'daczsrs have h.'..~¢‘ax:u.-, ax a 92 Improvemant C’W‘Tiht, the Group ‘,~.. , .._..- V1 sir-.1 GK'C‘J-P charapv, and the Group II—III reactors a 'IIIII-III I: Patients whcsa bleed preséﬁre 'na.r1:#e: zhcsa vF‘ue blaod presecrc zukej 92:13:: 2:. (ha :1: b43313: in.a varlnc;e {ength of time. t;ﬁh.ﬁ$ to [J3 baseline in xrd .L‘ :1J11e3_may hive untrrgvi: [EdQLIUity ‘Ezm 01 '\ Iiﬁ.~it. tigsc 4 if tiaaué ;nclltester85&—E in the ogzuac‘ ctaLentrat on 0‘ chxuu 'hcixn— aid snvgi cf rer"ccs 3t _ _‘ c..". x‘ _ "\c_r..e— ‘ ’P?‘ é ratu with Louvulsive 35% recovery rate reactor: have MW. -......»n.a.cac textzmw a 892 and the Group I‘*'Hal-*mHO‘vw-Iy9ﬁ-’ ' In ,- �ﬁll a: 31., 1952). :e:c"crﬂ rate (Funkensteln 9—“ -Pa7;ean in Fuzkensteln Grcups l to Ill may be looked 972 a ;: Ew;l;ui- :1 "him ET n 'J' m C‘. '1 de Ch: 1716 and VI; V1 upon tad weuhalyl is r2p;dly hYJrolyzed; patients have a-slow hydrolysis rate. predict, therefore, that the blood cholinesterase activity. levels of Grorps I~III w0uld be high; while the activity of Je may Grazps Vl-Vll would be low We recall here a siuular prediction rega:ding the ds:a fur central nervous system levels of cholin-A 11 which u‘rergse~l, the development of early and sustained EEC hyperaynchran) and elevated spinal fluid levels of acetylchclinc relatvd to was a law level of cholinestarase activity, 1. 43"¢ cf 9:11pﬁnral ‘u: V \ u \ . azngtuast 0y 8 cbslincrgic agcntz is the hypotheeib'regarding central nervous sysrvm re? :5 aztivitv :2 :zzm‘;atl>n Thus. a ., ”w“ “a ~c:r.shuix. a A,~‘ ,.-."..( 'c-~ :AJ'L H—-—.- as... ThLG survey of the litarature of the rJlos acetylzholin (f "V .o. :hclinestarase in ccnvﬁlslve therapy has led to a aﬁd speculations which require verification. For number of this purbose. ‘t L Rdgglilhd that an-investlgarion of the ftlivwing relationships :elztlon :c :3Evulslve therapy - type, ,0 J I v o 9 L." I in 14" number and fttquency. .ociated oleczrcencephalogram'partarns. h Relsclcn of such a;eryl:hollne levels to the clinical behavior oi patients. (2) (3) Llaé BE“ Changes in lndices of altered braih function other with Such acetylchcline levels �(L) 'Relaciou of :holinesherase accivity 1:03 serum and splnal and patterns of fluid to: (a) age (b) diagncsis (c) rate at development cf (d) number and frequency of EEG hypersynzhrocy t:eatmehts reactivity (e) autcacmlc (peripheral) reactiﬁity [csrebral (i) if») «g; _pe:sona11ty Rut at" :nLrIL Eshxvic: atropine. 'physcgstigmine adrainistmticn on ’ EC,“ � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Files: Acetylcholine and Cholinesterase, 1956-1966 (folder title 2/4). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-003-0-002 Date A point or period of time associated with an event in the lifecycle of the resource 1956-1967 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/22ce0e2ce2b39aba2aae8d5d1394cc60.pdf 2c9db7ac17279fda4146fb703f39bab1 PDF Text Text ' """ "r ' " WWO WW WW3. IN Max Rink, -*-' '"I’W v“ ”kw "FWHWOMV'.’ v.3. "m qr min...“ .7... W 14.1). mthofPoydmiatry of School Missouri Meir» , of MRI-nit}; Psychiatry, at the Nissan Institute of 63139. Macaw}. St. Innis, Annual Street, and Vii—072w, bin—927, m—zns, usms in part, by gums Missouri. of Formation :3 Iii-11380; ltd the Psychiatri 5WD W. VII: 7—25—65 Ram ��Wm, lQNQe) . The activity md emitement (Tracer and oembmepiml fluid does have measurable cholinestemse activity, however, principally of the ”true” or maholyl hydrolyzing type (Madmen and Rothenberg, 19%). In the absence of free acetyldroline and mder the cmditims described, electmenoephalogrm fail to (e) Show almorulity. mummy: Meta of Crmiooembml Trauma: Free mtylcholim was found in the cembmepiml fluid within a few minutes after experismntel head trauma in cats and persisted for varying periods up to #8 m9 (Bernstein, 19%). The quantity of free mtyldmline varied between 2.7 and 9.0 gamma percent, and the was related to the degree of induced trauma. wt electmemeptulogmm demstmted patterned Carma-rent charges. The records were first filled with high voltage fest activity, interpreted as evidence of an intense neuronal discharge, com to he succeeded by a short period of ﬂattening of all recorded electrical activity. These phases were then followed by prolonged periods of high amplitude sharp waves in the delta . freqmncies. The behavioral changes related both to the degree of trauma wt of mtylcholine, md the of measured free acetyleholim. With higher Bernstein reported greater degrees of abnormality and greater charges in omecioumess. poet-tnunetic seizures were levels EEG Spmtmeoue also related to the ammt of free mtylcholine warring in the spinal fluid. �Bernstein applied amtylcholine to exposed cat cerebral cortex. men the concentration of acetyldroline was or less, high wlitude shup the electromoephalogrm. waves When of 1 gm percent low frequency appeared in the concentration was increased tOngmepemnt, theelectmencephalogmflattmdina fashim parallel to the post—tramtic records. Investigatims in neurological patients by Tower and HcEadrem (1909a) damnatmted free acetylclwline in the cerebmepinal fluid only in patients with recent head recem grind-mu seizures or after electmvulaive Free acetyldxolhe varied from 0.2 to 100 gm tram, therapy. percent. In assaying spinal fluid dnlineetemae activity, they noted a sharp rise in the nonspecific dmlimsterase fraction (bmwyldwlineaplitting) sad a drop in the specific dwlinesteraee fraction (mdmlyl-eplitting) in patients with head trauma and following convulsive therapy. The cerebmapinal fluid did not exhibit such inversion, although it contained free acetylcholine, after spontmeous seizures. They cmcluded that the level of free aoetylcholine varied directly with the degree of cerebral dmage and that reversal of the cholimvterase W was a m sensitive indicator of cerebral (image. Electroencephalogrm, taken at varying intervals following EEG of between the degree relation indicated a tram, also abnormality and the appeamce of free acetylcholine in the cerehmeﬁinal fluid. �. r -; o-Tn- "W wu-rm- V“ 7 ~ MNIWWF‘. «wwwnmw' . ”3-.— :Nr‘ ‘mw— l‘.«nmw~.—WMM v-y »".\—- (max .9 w— , r‘ "murmur 1 Wm" q‘ 4;. These observations were recently oonfimd by Kovaoh, wounded increased aoetjldxoline in o: 1.1;. rat brain after traumatic shock, and an inhibiﬁn of this activity by the ministration of atropine to the muscle preparation. Tim the «want 05 {no aootgtchoune may ammo in tho who Aptaol staid {cunning WWW mum and the. mount 05 (no acugwwune, the dean.“ and typo cg mmmcapmogwuc «bloom/aim and «Maya in clinical bohavion appeal: cu Wound phenomena. (b) Antioholinegﬂo m and tram: oleotmgr'aphic, The bohavioml and neurologio signs of head trauma were blocked by the parenteral achinistmtion of 0.5~1.0 m/kg atropine (Bomtein, 19%), as were similar clinical changes: oomrring after the intmciutornal addition of acetylcrnlino. Ward (1950) applied these observations to tho treatmm: of closed head injuries. In 20 pttiants with varying dogmas of tram, he amtiniotomd atropine subcutanowsly in doses of O .1 mg/kg, noting clinical in soon and a reversal of the oleotmgraphic effects in others. Similar alterations in the poat-trmnnatic electroimprovement encephalogram were reported by Jenkner and Igdmer (1955) in a rtudy of diethaxino; amthor antidxolinergic drug. A single introvomm dose in forty patients maultod in normalizing the ' abnormal electroencephalogram in six othom. in twentyi-tm and marked ingrovemt .mr—‘xv �T-W‘vw 'h'mivu‘ -.-. ~.w—w.y‘~ WVMMW'Wn-uvw‘w—W 1."'"q'( v -— m7 "In“? - "mmwuﬁwuwmw‘vu “m""vw -WW’-xm -~ wr: TW'f..‘-|‘.Yr 1m Sinilar oboewatiam have been reported with mthylbezuctyzine md in minal exporimnts of post-trumutic shock and man 03mm}. Odom: (mm, affect of atropine Thu 1&5). assessed in the convulsive therapy was process by Ulott and Johnson (1957). With the administration of mnpordaydvmtngmwoeksthepatimts moeivnd oleotxoshodc therapy, the of slow wave activity atropinewto mt oigxificmtly lass than in a omtrol grow who had not monivod tho atropine adhinistmtion. (In a later study these was authors failed to replicate this study, suggesting that dosage factors or popllatim ohms-m multo [Johnson 93; &, may haw contributed to diffemnt 1960]). Similar affects mm obacmd with experimental antioholixnrgio was diothaxim, banaotyiim, the pipaddylbenzilates (Pink, 1958, 1960). The intruvonms injection of and JB-329 (Ditm), lid WIN-2299 JB-318. JB~336 111de ES damchrmizatim in psychiatric subjects. Those EEG ohmgos were associated with bahaviml alerting, anxiety, tram, illusions, and hallucina— tions. In patients the than had recently received eloctmomvulsive a reductim in slow wave activity md a manual of euphoria, denial md oonmsim. Atropine in low thumpy, dam, was was associated with tadnvoardia, mass E88 desyndumization acoarpmiod and Maxim. by At higher dosages, hypcnyndum slow wows, followad by lower voltage , poorly omitted delta activity with super-imposed beta activity wm associated with progressive confusion and disorientation. ”I..- —w m hwy”.-- �.erw—spmﬂlwtvnvamnw." w— r..«wwruun-x...—..,«».w..i. in combat Both Wguphtc mm"._., w-uvw-m .7..-7._~.-—v-—wwww..— um ~— ._.‘...,W wan rvw—Hw. ;W.——»—.- w—u w "r - , -— wwv—ku.“ and induced convulsions, the. ehahgu my be modiﬁed by the. WWMOR antichottuugte MA, Auggutbig that tamed manta 96 acetytehaane on. chawvigtc unpuvttg 4'4 undated with the. high vauaga Alon) wave activity. 05 Wed (0) Brain Similar EEG mﬂlcholim and mtfahnlimggzc ahmgaa and similar blocking by my mticblinergic drugs has been obserwd following the direct application of amtyldmoline to the central nervous cystem. The achinistmtim of a cholimtemse inhibitor Df'P (di-isagpmpyl fluoroplvsphate) elicited high unplitudn rapid frequency EEG patterns similar to of poststatus epileptiws, as wall as changes similar to M stma (Madam £314, 19‘69, Samson gt 9;” 1950, mid Hindi-m 333b, 1950, and Weasel 93.31;, 19%). These EEG traumatic effects were blodmd by small. dose: of parenteral atropine and in amtylcholim after awpolmim. The mat tetmthyl pyrophosphate (TEPP) was masumd and related to the toxic misfostatims and cmwlsims induced (Sim and inm Pepcu, 1952; Stone, 1957). Chatfield and W (1M2) prepared exposed miml cortex with pmstiminn and cvdcud oluhmnoephalogmphic spike activity. Thu spiking, or prior mismtim of atmpim blocked this if present, thc «mutuality could be eliminated by atropine. In contrast to that: findings, Bmmor and Merritt (19%) applied tepical acetylduolim in concentrations of 2~1/ 2 to to the exposed cortex of cats, and noted no effect on the 10% w- «ﬂu-xwa—VVlwu- ��“mun-ny- rw-WV‘VKwnZw'w—w "1W:wmwvtwwav 1W”'_<1>vwnv.<_wum,vwwv ]- ‘_ VFW, .. .- w n - ~-....Vr.ﬂ.--“ “W,- ..‘,_.,‘......_,.,.‘ -.v—--Y‘. ,-. -3- Elliot gt. 5}; (1950) md Crosslmd lid Herridc (195“). 61mm and Popou (1962) fomd the increm in aoetyldnlm following various dapmssants to bc proportional to the degree of depmssim of the central nervous system and the mduction in motor md Buck (196:4), turnover, studying 13min activity. My W lavas and sedation omeludod that some ”dating agents are associated with devoted brain aoetylomline, but that no dawns mlatimxshipo existed. In part, this may be mlated acetyld'xolina to the earlier obsorvatims of Wu: Elliott (1951) that acetylcholine synthesis unsound in mt brain slices, is accelerated by low dosages of mootic drugs, but inhibited by and him dosages. Pme autylcholim patimts with epilepsy was mported in the spinal fluid in (Cone, Tower and Wm, 19%; Tower an (7‘3 epileptic patients, Mom, domtmted free aoetylcholine in qumtities of 0.02 to 5.0 percent with an average of 1.0 gm percent. Acetylcholine and 191mb). 0f 56 gm lawla Hem related to the fmquonoﬁ of seizures, the extent of electmmplulogmphio abnomality, and to the time since the lam: soizum, but bore no relation to mdication, type of epilepsy or lawl of cholinesteme activity. Elliott at al. also noted that :1: fm acetyldmoline was dennnstmble in the spinal fluid in cmoentmtims up to 3 gm permnt after mmzoln convulsions. 7 .w .. "urn“... �.7.~w.. V. - V ,, “my",w 1...,"— 4~.vn,w—._._.m~,m raw-w": '— 0.. ”75v.. .— _‘ . ‘wwm‘ ,van... ..__.,.Wry.~.~ m-Zwm-V'I—r‘wn W.W ”-mw-w.w.mwr~m - n—r.~~—. >¢r:'l.irmv --"‘v-w-V‘MVSWVP -9Tower and McEachem (19'4933) viewed mm the increased acetylcholine of the seizure, and not causal. Studying the hypothesis that the acmlatim of acetylcholixm induced seizures, Tom (1953) masumd the level of acetyldxoline in brain tissue after mtmnolc convulsions. She noted a rise in the as a aoetyloholim content of bmin, before a soizum and a fall during the convulsion. Below certain levela of acetylcholine, cotwulsiona failed to occmr. that the fall in tissue aoctyldaolim during a convulsion was due to inhibition She suggested of aoatylcholim synthesis by increased concentmtims of metabolites such as mimn ions. Gianna!) and Pepeu also measured chmges in cantml nervous system acetylcholine follwing various stinmlanta. moholyl and 3, S—dimthylbutylcthylobarbiturate Chly was after them a significant chmgc in the amtylmolim level. may noted a decmase in association with induced convulsions. With other drug: which they classified as stimlmts iprmiazid 1: (LSD, hydroxytmyptophan and iprmiaxid a ipmniazid, DOPA) tum war: no changes in acetylcholine level. may omcluded that despite intense excitatim produced an by these coupomds, them in acetylomline levels unless trace mm by convulsims. (The differences in obscrvatims no changes Wand between these MomdemcgggléandTmranndEaduem muted to the differences in mthoda of biochemical monuments, for the latter measured chmges in spinal fluid my be mflocting the free acetyloholim. while Gimmn and Pepeu «way—.- —-—.\. �T- - w;—----w~~~.~ .7 um . r - xu ‘ r v,m__.mwa,mﬂmuwwr~pw m~'mvv'v—rﬂr vav-u—w. ---—w ~ ,~ .ﬁﬁr'A—HIwmmrrw‘(Wr-1Inr’mwmr"W'mv-w’ total acetyloholim reflecting band and free fame and Elliott, 1951]). of amtyloholim. The“ mom augguz that Apart/tango“ an. induced su'zwtu by moanpmécd in intercom 6n: mag/Maine an m abound 6m La bound {own which my be inﬂected in the (Laid. Cmbm activity and Auzwtu enhance magma” «lawman, awaiting wine Levels 05 Mots/Moan, Mule “up and muthuia my augment acetytchoune paoduotéan inc/away about mm. measured the [mm We W ’ (:3) Central Nervous sttem Cholinostemes: Tower and Worn (19%) also measured spinal fluid molinesterase activity. The typos of cholimatemnos are nomally found in the spinal fluid: mimestemoe-I (“tm,“ "opecifio," or macholyl—hydrolyzing), whim haaaa high specificity for aoetyldaoline; and cholinestemse—II ("psexido," "non-Specific," or banzoyloholine~hydrolyzing) . momds Both hydrolyze aoetyloholim but have different rates of hydrolysis for monolyl and benzoyldzoline . 'mis differential rate permits qualitative distinctions. By reporting the cholinestemsc activity as a ratio of the activity with a moholyl substrate and with a benzoyldioline substrate compared to a substrate of acetylcholim; two mtios are found: crolinestemse-L/aoetyldlolim and clnlimntemoolllaoetyldiolim. In such mtios normal oembmspinal fluid contains astemsea in the ratio of 33:17 for molimstome—I to dialinestcme‘ll . _ In patimts with head trauma, Twer and Mcanhom reported an inversion of tho cholinestemsea with an increase in the VHF-"147 �».———w ~. r... >qu . 'v—vv—W n» “W...“ mm xwwu-w_~ WY— . “-7 mrmm wnwW—u—mr- w...” maum—w—w—y w «W . unv'r“! "31A“ man-.wvvmw "w” w~:- -11.. dtolimtum—II fraction of the spinal fluid and a decrease in cholinesteme-I activity. Tho extent of the dualinssterass reversal was related to the severity of trauma and to the dogma of the electrocnccphalogmphic abnormality. In patients with elevated spinal fluid acetylchclins after $1)th seizures, however, no change in the ckmlimstomscs or total armlinestemse activty woof was found. in cholinestcms activity may be undamtood in relatim to ohmgcs in cell neutron: permsability. C'holixnsteme—I is fmmd in highest cmmntratim in the The charge cmtral mmus system whilc d'xolinsstemse-II pmdaninatss in othcr tissues, especially blood serum. With an incmm in acetylcmnnc levels in cerebral intcmellular fluids, vasodilatim md incmased cellular permeability may be predicted, with a dsgme of tmsudaticn of vascular fluids into the intemsllular spaces varying with the extent and duration of the vasodilatim and their (W g, 31:. 19%). Spiegsl, Spiegel-Adolf, oo-woﬂcem (19“1, 19M, 19““, 19148, 1953) demonstrated and: pemeability changes and inmassd conductivity of the titauos associated with the appearance of various ions (as pctassim and phosphate) in the Spinal fluid following electrically induced convulsims . Such nm~clcctrolytes as nucleic-acid splitting cellular psmability enzymes may also increased. in Changes thus provide the basis for the high concentrations of metylchclim and the increased concentmtims of duclinesteme-II in induced seizures or head trmma (Tcww V 4nd HcEcchem 19n9c). . persistence of acetylcmlim in spinal fluid after head dmlimstencsc dcspdte and trauma «fur seizma The imam . vmr Var" .muw ��rw ~—.r< —-._..'—v-w__ ‘- ,m Am w—w— WW 7- v nan—1"“ w—u-n w v mm mug; '- wmn—uw—v W v mm -- ,mmmm‘u—n w a"... mm -13- «mum m mm 5M nuvocu Mama 0‘ mbmu nmuimy «a WWW at «may. (a) Aceﬂldaolino, EEG 13mmmd‘wmy and Induced Oonvulsims: Alteration in the blood—brain permeability barrier by the cmtinuing action of acatylcholine may be a biochemical substrate for the postwlectmshoa hypemynchrmy of the electroencephalogram Sud: a possibility is evident in the damnation of an inmm in the mmtmtim of cocaine in brain tissues thme days after a series of 12 induced cmwlsims (Aird We g: .1332., 1956). The in emcentmtim of this large molecule, ordinarily absent in brain tissue, was associated with the appearance of syndimny delta bursts) in the electroencephalogm. We hove oonfimd the many hyper— pmvious reports that convulsive therapy induces electrogmphio hypersynchrmy (Pink and Karin, g 53;, 1961) . Despite a constant applicatim of treatments them is a great Variability in the time of appeanmce, 1956:, Pink the duration and the extent of the electrcgraphic slow wave activity as well as the sensitivity to modificatim by alerting, hyperventilation and barbiturates in pcytidaﬂxic populations. The early appearancn of dagroo hypersynchrony and high persistence thmugzout a prerequisite to mamnt cause has its been described as improvement following electmshodc (Roth, 1951; Roth, §£_g£;, 1957; Pink and Kahn, 1958). the differences in the dogma of induced It is EEG possible that hypersyndurmy mlated to differences in central clmlimrgic activity. The failure of certain patients to develop hypersynchrony may be associated with the absmce of fame aoetyldroline being related may be to him). changes in cumbml function and thus producing .a » “V.lvf"——Iw vu.- "a'v �WW. _. 7: .my- "“ .~..v.,W ”" . , . “V WW 7*MW--—- ‘-u :u wr—u ‘V-U-lw‘-um- WWWW‘,”._¢.~K—.wvﬂﬂ m”. ~"m--'~w , e ~ * .7 _,.,. , v ,7, , (lawn), in their study at” cmniocambml tmmna, included observations of six psychiatric patients undergoing cmvulsive trumpy. Studying the patients aftar 3~7 tmatmnts they reported free spinal fluid acetyldmline in two patients; and an increase in cholimstemse-II and a decrease in dwlinestemsesl with a reversal of the ratio of dialinestemses in five of the six patients. hm those obscrvatims they concluded that the spinal fluid changes in induced convulsions were more like those of amniocembml trump. than those of spmtmeous epilepsy. described the one patient in the series failed to show either fme mtylcmline or a dmlixnsterase ratio reversal in the. spinal fluid as: "It is interesting that this patient was the only one of the six to shrew no response to treatment." They If olectrogmphie hypersynchmny who is a mflectim of increased fme mtyldxolim, subjects who maintain hypersynchmny and those in whom it disappears rapidly may be exhibiting diffemnaes in the kinetics of the dwlinestamsawoatyldmoline hydrolysis systcns . Persistent hypemyndumy may result from a decreased rate of hyd‘olysis of wetylcholine , associated with low mntmtims of either- cholinestarase-I or cholinestemse—II . (Conversely, in patients with short-lived hypemymdurony, dmlimstnmse-I md -II in tissue md spinal fluid may be unusually high) . Fm thug chuwacéoM we would conclude demon; m mediated M an Mme in in W, mm enhancing 2th: MW“ that induczd {we acetyichouue Mg Momma. naming mutual 06 The and Lava as ﬁne 1:; . ru- » m. “mmvw-w' - , v- �"w aw-"m, wrrwnw“—5— mmrwmwm._ . mallow 426 Wad m wm—w—w w. "mm-v m-u—v—v— nw—wuw- gwmy"w_mw u- m. -55.. by muted induud autumn. EEG hwynchlwny a one. Reﬂection 05 abtmed {even 05 Managua and muted 05 01h“ momtym. It 11A pubabtz that that chaugu in movide the mam mngw mm“ pwibtwt 4mm: Mochwécaﬁ 50mm 56!: {nomad the bohemian“ changes mm“ . (f) malimstezm md the Classification of Psychoses: mesa studies have application to tho problem of autonomic reactivity and tho classificatim of the psychoses . Manstein, 91:. 31;. (19%, 1951, 1952) have demtmted a relationship betwaon the blood pmaaum maponse to injected mthacmoline (Macholyl) and the clinioal response of spydtiatric patients to convulsive therapy. is a potent cholimrgic agent which induces vasodilation, tamycardia, mating; and increased peristalsis . 11:53 rapidly Phﬂmacholinc hydmlyled by ermlimstemse-I and slowly by duelinesterase-II . mo blood pronouns of subjects falls after injected macholyl and returns to the baseline within five to whose blood pressure 20 Grow VI and VII have a 9 and a am recovery and Group VII mactom 1133;” 1952). patients in 20 89% to nﬁnutes. Patients 5 those whose blood Wine, Group II—III rate, respectively, while and 97% minutes have recovery mtes as reactors Group VI (Wotan GmupItoIII mactommybelohkeduponas whom while Grows v1 I, II, or III reactors; ormm minutes to motors. Group I and 35% than returns to the baseline within how classified as Gmup pronoun takes more the injected mdwlyl is rapidly hydrolyzed; ‘and VII have a slow hydrolysis rate. It is probable, themfom, that the blood and tissue oholimstemse activity levels of Grows I-III is high; while that of Groups - unr �.- n. .— . VI .wr-. .,m-w.w-,,. ..- - VII in low. A mwkwmr “or a mum: mviow, similar analysis systom levels of "'"ww—ﬁi-m may in mud: r—nmﬁm.mn-‘mrmrp.’ "nu—mu“wl'r-_'In. m Rose, 1962.] mgarding central nervous dwlimammo-I in the dcvelqmnt of EEG hypmyndnmy and spinal fluid levels of acetyldxoline, providing the built for a hypoﬂuais mgarding contra}. nervous cyst-m periptnral mt Inactivity to induocd convulsions and to momma agate. Arm �. ”V7“ :vn-r— www- 7.". New“- mu..~ “Av ‘:~vv-'me~'v xwmm~m.__en.sw—_. mm _.m immv—rmc "cw. .ww-‘rwwm-u-ﬁ—Wrw—_ml -17- see significant in the convulsive therapy ptccess. The published data indicates thlt induced convulsions ame.associated with an inczease in intercollulsr scetylcholinc to levels greater than can be destroyed by cholinsstensse—I activity. Vascdilstion and increased cellular permeability are fblloued by increased amounts cf cholineetersse—II electrolytes in inter» and other enzymes and cellular fluids. These changes are hypersynchwcny which reflected in the increased electrical is recorded as EEG slow wave activity in scalp electrodes, and which can be modified by a wide variety of enticholinerzic drugs. In these reasrds, induced convulsions are more similar to cerebral trance, than to spontaneous seizures. The changes in the onrebmel biochemical milieu alter cellular activities sufficiently to be associated with altered behavior of subjects. Failure to induce high and persistent concentrations of ecotylcholine and Illiuwe to induce concomitant fbilume to produce behavioral electrolyte changes results in a ‘ change. Difﬁerences in the rate of development of cerebral changes reflect differences in the dependence of subjects on cholinergic mechanisms or in their sensitivity to changes in acetylcholine 1mm. mm differences provide the basic for the classification of the mentally The the mode ill by Funkenstein and by Pink and Kahn (1961). observations provide a rational biochemical basis for of action of induced convulsions in altering the �m" 'A "VI-v Ww—vv—n—u—m—«rrm mum-mam mm with tho mm «truer mmmmwrmawm -13.. of pomtie subjactn. 'nnu mm view mwopmsiologie—adapﬂm (Fink, 1957, 1962). an mistmt wavy expressed �_.,. m...“ ... .4. .. .ﬁ-a v “3-..."- w..——_ww «av—m... ”VWFI-WquwLH-‘M‘AW‘K' w-v'lw . . "m." Inn—www-Iw‘m v. "uvw -wu v rays-y‘— :—.- me‘n—I'“m 32mm Aird, R. B... Strait, L. A., Pact, J. 91., muncff, H. K. and Witch, 8. C. Neurophysiologic effects of electrically indwed convulsims. M’ch. Newt. rum. scum, 1956, 75: 371-373. Pram and actim cf acatylchclinch experimntal Bomstuin, NJ). trauma. 1. Nuanpkyuatu 19166, 9: sue-355. min Horritt, H. B. Effect of certain choline dcrivatim clactrionl activity of the cortex. Auk. “want. (6%.). on Runner, C. and mm. Human, A. S. V. and NacIntosh, P. C. The physiOIOgical significant of acctylcholim. In K. A. C. Elliot, I. H. Page and J. H. Qustcl C. C. Thoma, Springficld, 111., 1955: 37I4~375. (Editors), uwmmuw. mtfield, on Dewy, cortical potentials. Mu. Cam, W. “Viv P. O. and Tm, in epil’psy. V., Worn, Jo‘oquo. 1&3, 73: D. B. Grassland, J. 1950, 162: “SQ—MW. E. w. Effects of prostimine md acetylcholine J. Pkg/«20L, 19142, 135: 633~6u0. and D. I. Acotylchcline and mammal 59.639 effect of anaesthesia on the matylchclim commit of the brain. J. Phydob, 195%, 125: 56~66. Dale, R. H. Th action of certain «tau and ether: of choline. and their relation to maxim, J. Plummet. Exp. Thu., 1913, 6: 1'47. Elliott, R. A. (3., Swank, R. L. and Henchman, N. Effects of mﬂmtics and cmvuhmts on acctylcholixn content of brain. W. J. Phgual... Pink, H. A and Merrick, A. Tm unified meaty of the cctim of psychodynmic therapies. Pink, H. Effect of anticholimrgic agent, diethazine, cn EEG and behavior: Iimificm for theory of convulsiva therapy. Mch. Newt. (cued, 1958, 80: 380-4587. was “ch. Fink, H. Effect of mticholinomic on pcat—cmvulsiw electromccplaogm md behavior of psychiatric patients. can. Humming 1%0, 12 (2): 359—369. Emeh. ’ Pink, view. m. of action of cmvulaivu therapy: the mm'ophysiolosic-adaptivc J. Nwaoplgcuazu 3: 231-233. M. Pbdo Pink, H. and Kahn, R. L. thtintive studies of slow wave activity following cloctmstnck. Bactuzuccph. can. "wuphyuotn 1956, 8: 158. Pink, 14., mm, R. I... Karp, 2., Pollack, M., Gm, H. A., Alan, B. and Lafkcwita, H. J. Inhalantuinducad convulsions. ma. Gen. mama, 1961, In 259-356. mm, A. PL, Bales, P. D., Willis, md Himwich, H. 8. Experimental pmdwtim of electrical major convulsive patterns. Amen. J. PhyuloL, 1&9, 1H6: 117—1218. Mkenstuin, D. H., Gmmblatt, H. and A. new Mutt. 0.3., 801mm, H. C. Autmmdc chins“ ramming electric shock Mutant. mm 19%, 108: #094122. J. New. �.- “ 'E'mr u-men... Mountain, wumW,mu“... 1~w‘mww.w“~-mmmern“—"~—IJ...- mm, amnesia H., paralleling peyoholoﬁo 1951, 11”: 1‘18. D. qvp- —..,. WW me‘w ”Va-WV“..— mwmmwmvmuww W3 mantally ill paﬂlnts. 1. How. m. 01.6., H. and Solomon, H. C. Autonoiuio Menuhin, D. it, emenbhtt, M. and 301m, H. C. Autammio nervous system out of prognostic simfioanoe in mlation to alactmskndc treatment. P‘ymm. Mo, 1952. 1“: 3“?“3620 Gianna, N. J. and Pepeu, G. Drug-induced charm in bmin aoetylcholim. W. J. Fitment” 1962, 1% W233. A. and Hiwich, H. E. Effects of Mam, J., 33313, C. P., Manley, di-iaopmpyl flmmptmplmto (DEF) on alectmanoephalogm and cholinastarase activity. ,Eumamcph. can. “Mphysutu 1950, 2: Mil—ha. Basis, C. F... C. F. Hampson, J. L. Balsa, P. D. and Effect of trimthadima (Tridima) and other drugs on Madam, oonwlaions caused by di-isqwmpyl flmmplmphata (OFF). Ame-A. J. mum. Himioh, H. 23., A. H. 1950, 106: 816-820. Jonkner, P. 1.. no ladmer, H. The effect of Dipamol on the olectmmoopmlogrm in tho normal subject and in time with canme tmuna. EWmuph. can. ”meto' 1955, 73 303’3050 6., Ulett, G. A., Johnson, H., Sﬂth, K. and Sines, J. 0. Eleotmomwlsive thrapy (with and without atmpim); affect on Johnsm, I... analyzed ahctmanoophalogmm. chemically 2: 32u-336. 1960, Melt. Gan. Paychiot” alum, M. and Knaub, V. Quantitative estimatim of the Kabat, E. A., albmin and gamma globulin in actual and paﬂmlogic oembmspinal fluid by nomads. MM. 1. Mad" 193:8, *3 (5): 653-662. Wm Kovada, A. G. 3., meo, A. and Halmagyi, M. hm Hamid"Wit Aoetyldiolina‘omtmt of the brain in traumatic smdc. Aotc Phyaiozaglca (HungJ, 13: fiber Lou-vi, 0. Meir. £. 4. gas. 14. our Hemmnwﬁkmg. 1921, 189: 239-»2u2. Haymrt, E. W. and Buck, E. 6. Effects of C.N.S. Dapmsmts on Brain Aoatyloholim. 19M, 6: 191. Wtagut, Heisman, H. and Elliott, K. A. C. Effects on omvulsmt and narcotic drug on aootyldxolim aynﬂnus. 1. PM. I Expat. Thump" 19513103: 35. mam. Wm, specificity of We in mm D. and Studies on cholimtama: on tissue. 1. Biol. (than, 191:5, 158: 653—666. M. A. Ridxtor, 1). mad Crossland, J. Variation in acetyloholim’oontmt of the brain with physiological stata. J. Phyatolu 19%, 159: 2h7-255. W. Rosa, J. '1'. 'me We; Menuhin hat in the ~ A mview of the literature. Add mdor barhitmte anaesthesia produced by twain-mt mad their simificmoa for the theory of M clam-awake actim. Enougmuph. can. Managua" 1951, 3: 261480. Roth, )4. EEG �Both, 15., Kay, D. W. K., Show, J. end (keen, J. Prognosis and pentothel induced electmnmplulogmphic changes in electm—omvuleive treatment. summaph. can. Nemphy‘iol” 1951, 9: 225-237. Spiegel, E. A. and Spiegel-Adolf, H. Permebility chmgee in the brain induced by tamed and insulin cannﬂaions. J. Nuv. Max. 91.5., 19‘31, 93: 750—3755. Spiegel, E. A. and Spiegel~AwlL H. mysiooodieuionl effects of electrimlly inclined cmvulsime (mmbmepinal fluid studies). Tum. Mu. mm. 1455., 19%, '70: 130-132. Spieaal, E. A. and Spinal-Adolf, H. Physiological and phyuicodwmicel mechanism in electroshock treatment. Conan. Newt” 1953, 13: 38-53. Spieael, E. A., Spinal-Adolf, H. and Hem'y, G. mysiooodxdical changes in the brain electrically induced convulsive discharges. marina Tm. m. Newt. Au" 19M, 68: 17h. Spinal-Adolf, M., Wilcox. P. H. and Spiegal, E. in electrmhodc treatment of psydxoees. Mae 19.48, 10“: 697-406. Stem, We Tom, H. E. 1. Pk”. The mole Me, A. Cerebmspiml fluid m. J. mama, of acetyldwbline in brain mtebolism and fmctim 1957, 36: 222'255. Effect of omwlsion inducing agents in the amtylcholine content of the brain. J. Phyeutn 1953, 173: 179—183. (2. m. Effects of single injection of corticotmpin (ACTH) on We, ion and emtyldxolim ambmt of bmin. Ana. 1. Miguel” mnim 1953, 173: 1764.78. C. Wm, and patterns wetyldmline in the oemhmspinal fluich 0011th a. Aoetylclmline ma neumml activity. I. ﬂower, D. B. and of patients with maimmbml mm. CW. 1. Quench, Tatar, Wehem, 27 lQuQa, (Seat. E): 105-119. D. B. and dnlimstemes in hm 1949b, 27 (Seat. 13): mutant and characterization of mmbmspiml fluids. Canad. J. Rum, D. 'Ihe 132-1'45. Acetyleholine and neuronal activity. Worn, II . Acetylmolim and dwlima‘hmsa activity in the Tuner, D. B. and D. fluids of patient: with epilepsy. szm'. J. (Sm. E): 120‘1310 Ulett, G. A. and mbmspiml RPAWA’?, 27 1mm, datum, M. W. Effect of atropine and soopolanﬁne upon eleetmenceplulogmphic charges induced by electm-oonvulsive therapy. Euwameph. can. Namaphguot" 1957, I: 2174224. Ward. A. A. Atropine in the treatment of closed head injury. J. Newsag” 1950, '7: 398-402. Ueeeoe, H. C., Green, R. Wm, of atropm md aoopolauim on the 3., B. P... and Kmp, S. central effects of DFP. Wt. The J. inﬂuence �DEPARTMENTAL CORRESPONDENCE DATE Julx 29z I965 SUBJECT Cholinergic Mechanisms in Convulsive Therapy To.“ Max Fink FROM George A, Ulettz MODo A most interesting paper, well put together and documented and with which I MoDo DEP'T DEP'T am in the main in agreemento There is one minor typographical error on page l2. GAUzlz �CFDLINBMC W315 WV!) IN Max W Fink, PM). mmmpmmotpmmnmmsmmmma Paydaiatzy, (immunity of Iii-semi. Sdml of Medicine SHOO Arsenal Street, St. Innis, Missouri. 63139. , Aided, in part, by usms grants ”44.921, 114-2715, ail-mus, md Iii-11380; ad the Psydiiatric March Fomdntion of Missouri. �VI: 7-17-65 WCWHWIVEW Despite mm application and study, the nod: of action ofﬂnccnwhivethmpmmnminsuﬁmic. Matudy mmmdtomumphysiological( paydwlogical( social ). clinical ( ), ( and aspects, elucidating me pmaent nam— ) phyaiological-«laptiw ). View of the process ). ( 'lha amply dnvalcpmnt and persimmon of signs of altered cerebral fmctiun mm mpomd to be requisite to (Pink md Kahn, 1956), with mess in behavior 0100*:ch slow wave activity as the mat significant index of altered brain function. Thu this Mien slow um that pmddcatim with ampina inhibited ‘Jormcn, 1957) and the report activity (Ulett and that antidxolimrgic a mm nursed these clinical ahatmgmphic alarms (Fink, 1958) 311mm that .me biodmnical basis for the convulsive therapy process the clnlimraic m as wall may be in of the central nervous system. This raviaw discusses the available data agarding acatylcholim ﬂ �and the dwlimstemes in the convulsive therapy process. Acetylcmline has been extermively studied m an active agent in the transmission of dowdptiom of Dale mm impulses since the It is (191A) and Loewi (1921). first a comtitmmt of mmm tissue, existing in a bound form which is liberated during the excitation process. It is rapidly hydmlyud thrwgh the specific action of duclinestarase and in rapidly momstituted by the ohcline~aoety1ase system (Rid'ater and Crosslmd, 19W) . In noml cembmspinal fluid, free acotylchclim is not present despite the mpid bound and breakdown of acetylomline during periom of activity and excitement (Tower Wm, 19u9a). The cambmspinal fluid does have measurable dwlinesteme activity, havever, principally of the "two" or mdwlyl hytvlyzing type (Madam and mm, 19%). In the absence of free aoetyldxomle and mdar the conditions described, electroencephalom fail to show abnormality. �(a) Grahame ﬂats of sootylcholim was found Crmiooembml Tram: Prue in the osmbrospinal fluid within a few minim after sxpsrimtsl Mad trauma in cats md persisted for varying periods up to “8 hours (Bomstein, 19%). The quantity of ﬂu the amtyldmlim varied W1: was (:th between 2.7 and 9.0 gm pennant, and related to the degree of induced mum. shotmsnoephalogmms amazes. me mooxds were demtmted pattmd first filled with activity, immuted as svidsnoo of high voltage fast an intense neuronal distant-3e. soon to be sumedsd by a short period of flattening of all recorded electrical activity. These phases wen then followed by pmlongod periods of high mlitude sharp waves- in ttwdcltafmqusnciss. 'msbehaviomlohmgsswsmmlatsdboﬂitothsdsgmsof mmmd to tho want of mmd fme amtyld‘nline. Vth highcr lovels of amtyldlolim, Bomstsin reported greater dogmas of EEG Why and water changes in consciousness. �31>th wt post-traumatic seizures ware also related to the of fme acetyldwlim appearing in the Spinal fluid. Bomstein applied amtylctnline to exposod cat cambml cortex. When the concentration of amtyldxolim percent or lass, higx amplitude slurp waves appomd in the electxmmaphalom. When was W6 t0 2 gm percent. was 1 gm of low frequency the concentration 01.0meth the 1000160 fashion the patetzmnatic flatumed in a parallal to Parallel investigatima in neurological patients by and Wm (mm dumtmtad free Tower acetylcholine in the cerebmspiml fluid only in patients with meant head tmuna, meant wand-ml seizures or after alectmcmvulsiye therapy. M0 amtychlim varied fluid spinal assaying from 0.2 to 0310111103001”: 100 gm peasant. In activity, they noted a sharp rise in the nonspecific dwlinesteme fraction (Mmoylcholim-splitting) and a dmp in the specific cholinesteme fzmtian (mohaiyl—eplitting) in patients with had tmma and sanguine convulsiva therapy. The cambmspinal fluid did not �exhibit such invemion, although after it contained free acetyldxolim, spontaneous seizums . They concluded fr“ mtyldzoline varied directly with the damage and that the level of degree of cerebral that reversal of the dualimeteraae fmetims was a mm sensitive indicator of cerebral dmgc. Electmencephalogrmna, taken at arming intervals fellowing minim between the dagme of tram, also indicated a EEG-Wt); md the appoamm of free amtylcmline in the cerebmspiml fluid. mm Wkwwm Tim «the, 4;me We! mm 0‘ due magma-u. may tame in the (cumming {m autgtchouu, abnombbty, and WW «the. Mg“ W“ W. «tam and the want chalk.“ and type 0‘ 4'.» 05 demomuphalogmpuc dialed mm); «ppm «6 �Antietam} (b) bahavioml and mutual m and trauma: mmlogio signs of mum The m electrogmphic, blocked by tbs awninistmtion of 0.5-1.0 Wkg ntmpim (Bernstein. I 1986). as was similar inmcistml clinical change” mowing after the additim of aestylchcline. Ward (1950) applied injtmida. those oboemtima to tbs tmatmnt of closed head In 20 of patients with varying dean-e3 trauma, ha administamd mopim WW1); immt in some and in doses of 0.1 m/kg, noting clinidal a mml effects in others. In a study of diethnxine. Jonkner and the W at the W forty patients with anticholimgic drug, altemtiaw in (1955) mportad post-mmtic aloctmcmophnlnm. dose in electroencephalographic W A sinﬂe intmvamus electroencepmlogrmm resulted in normalizing in twanty-tm and marked inpromnt in six otham. Similar observations have been Imported by Denisamco (1965) using mthyl‘bamctyzim and poat-atrmmtic mmtin in animal that and 03li em. ewinmta of �Truss obssmtims were assasssd in the convulsive therapy process by Ulstt and Jornsm (1957). These workers administersd dosages of atropine w to the patients waived that the mt: mm slsctmsm of slow wave per day during the weeks therapy. They downstmtsd activity prodmsd in those patisnts ms significantly less than tbs control group who had not received the atropine ministration. (In a 141th study these authors fdlsd to mplicats this study, suggssting that dosage factors or population changes have contributed to different msults [Jormsm These observations provided the basis g}. 31., 1960]). for studies with othsr imam anticholinsrgic mounds (Fink. 1958, 1960). hummus JB—336 arid Wins. the pipsridylbsnxilntss JB-329 (131mm). and WIN-.2299 induced dssmhrmiutim in psychiatric subjscts. These Hum The injection of smrimntally active anticmlinsrgic camels as disthssim. JB-ala, may EEG EEG changes associated with barnvioml darting, anxiety, tramm, illusions and hallucinatima. In patients also had mently - �mind elootmoonvcnsivs the achsinistmtion of throw, these Imomds was associated with a mduotion in slow awn, mm wave and 'eonnnion. activity and reversal of Aunpim was also examined in low doses, and in these administmtims, EEG dosynctumizstion ms obsomd nervousness sod tension. At highnr dosages, hypersynchrmous slow waves, followod by lower activity with menisci by tachycardia. mimosa wings. poorly organized delta bots activity melamine: by pmmssivo confusion and disorientation. Both in oleotrogmphic annual tum and indwed convulsions, the 0W8 may be mdified by the commont (hogs, administratioh of mticholinargio thus suggcoting that immaud smarts of aootylohlim or inorusod oholimrgic receptivity is sssoointod with the high voltage slow wave activity. (a) min and iomlino anticholimm gm m: SimilanEGorangesandtublookingthmmnobumd following the dinct application of mm systm. sootyloholixu to the mm]. �The aministmtim of a omlineeteme inhibitor- DP? (di-isopmpyl fluoroxmospheta) elicited high amplitude rapid frequency We 19mm, EEG patterns similar to status epileptious, as well as similm to those of post—hmtio states (Freeman 33 11., Hanson Egg, effects were blod<ed 1959; and Himioh by small doses 339;, 1950). These EEG of parenteral atropine. 'me great increase in aoetylcmoline after tetmtthyl pyrophosphete was (TBPP) manned and related to the toxic misfestetims and omvulaims induced (mm and u: thfield and Dempsey 1952; Stone, 1957;) (19%) prepared exposed animal cortex with pmstigmim md evoked electroencephalographic spike activity. The prior mistmtion of atropine blocked thio spiking, the almomality oould be eliminated present, by or if atropine. In contrast to those finding, Emma!" and Merritt (19%) applied topical aoetyldxolim in concentrutima of 2-412 to to the exposed cortex of cats, and noted no effect on 10% the electroencephalographic changes after intmwnous atropine (1 mg/kg.) 'lhe concentrations of acetyldtoline in these experiments, �10 however, were higher than the and the gm topical applications (l-‘t intrusistemal (0.2-10 gm percent) percent) injections of Bernstein (19%).. Burner and Merritt also made note of elem- encephalogmphic effects similar to acetylcholine from motion/1 (emtylhetmthylcmline) much lower than the and cloud (oerbanyldlolinﬂin mtyloholim concentrations. They cmoentmtims ascribed the increased effectivems of these diolinergic drugs to their lack of sensitivity to cerebral almlimstemses. These data are conflicting and further study is museum to qualify this issue . (c) Oembxnsgiml fluid Amtxlcholine and Seizures: of aoetyldiolim metabolism indicates that it is One View fomd in nervous tissues in an inactive band fem. hiring periods of activity, amtylcholim is liberated at the cell dsectivated rapidly by mm, dwlinestemse. The where wt it is of bum asetyldmolim is the resultmt of the continuous processes of synthesis, liberation and bredcdmm. It has been postulated that the level rises during sleep and falls during activity. (Richter and Cmssland, 19%; Elliott, Swank and Hendersm, 1950; Giaruun �Pepeu. 1962). By using liquid air quick freezing methods. Richter and Grassland measured the level of acetylcholine (micro- gem per brain tissue) during anaesthesia and sleep to be mg. 300‘ higher than post-“12m levels. The difference in tissue levels is tnansient. however, as the resynthesis rate for acetylcmline in net brain in high (1950) confirmed m1. the” owemtiom, also Pepeu (1962) fomd an increase 3 noting that after gm per cent. Gimmn md in wetylcholine named by a central nervous mum depressants to be roughly reduction in and no mm activity. acetyloholim we reported in the spinal fluid in patients withepllepey (Cone, and PbEeahem. 19149 1)). 0f 55 'Ibwer and mascara, 19%; epileptic patients. demetmted free acetylcholim in quantities of 5.0 M proportiml to the degree of depression of the central nervous system m :3in convulaims free wetylcholine me demustmble in the spinal fluid in concentrations w to 1;! gm/gm/minute). Elliot (7 with 1.0 of an cent average per gem gamma Tower an (77%) 0.02 to per cent. �12 Acetylchclim levels were related to the frequency of seizures, ﬂnextentofelectnnncemelogmphicmmlity,mdtothe the since the lat seizum, but bore no relation to medication, type of epilepsy or level of clnlinestense eotivity. Tower and Maﬁa-hem (1904912) vimd the increased acetyldwlim a by‘prodmt of the seiem, Studying the hypothesis that the and not camel . emetim of ecstylchcline indmed minutes, 'l‘orde (1953) measured the level of ecstylclwline in brain tissue netmmle convulsims. .‘ She noted a rise in the ,_ V V ecetylcholine content of brain, before a seizure and a the cmvuleion. Below fall (bring certain levels of ecstylcholine, convulsims failed to comm. Stu suggested that the fall in tissue acetylmolim during a oonvulsim was due to imibition of ecstylcholine synthesis by increased concentrations of metabolites such as mnium ions. Wmmmmumdohmgesmmmmm system acetyldmolim following various stimulmts . Only after �13 unholy]. and 3, S-dimthylbutylcthyl-barbitmte significant chmge in the acetylcholim level. damn. was They noted a in associatim with induced convulsions. drugs which ﬁrearm as stimlants Md mmmdumainmtyldmlim + other With 133mm, (LSD, hymoxytmyptaphm and iEprmiazid level. there a + DOPA) them WWW daspito inﬂame excitation produced by these commie. them wan no dung» in mtylcholim level unless than were accompanied by convulsions. (The differences in observations botmmmuwerkmmdmggglmdmmrmdﬂcﬁadmm my be in diffemnaas the to related mummnts, for thc latter methods of biochemical wand changes in spinal fluid w 61m and Pepeu mﬂecting the fun acctyldxolim,‘while 12; bound and reflecting acetyldwlim mumdntatal true form of aoetyldzoline.) Thu: Atuau wages: that on: Wed by an sputum Lame. in an. induced 1mm law 5n: awtytchaunc �”mm—“hr“ V» 3- ‘ v w» . m w 1-: “r. 0... ~ W "n , nr-r-w, ..-.p:..u<ﬂv.»rrw-¢.M “av—w. . .,. 4. ....“.,_. w... ,, 'zs-sznr-W"“air‘quvww'ﬁ'qmti'd‘u. w. » ,‘rv —.».‘ wm‘ , w - 1n abound 4m in bound (on which my wind. (Laid. Cmbm nativity Micheline dalmatian, manna. Lemming mum 15qu in #1: enhauu tame (cum 9‘ Me blew and Mama auguwut mallow: madam“ 42mm aunt (d) Comm]. Nervous Wm and be mm . Sgt” ('holinostemes: (19%) also uncured spinal Tower and ﬂuid cholimsturase activity. No types of dnlimstemes are normally found in the spinal fluid: dwolimstemad ”true," "Specific," or Molyl-hydmlyzing) . whim has a high specificity for acetylcholim; and dxolimtemacu-II ("pseudo," or bonmyld'uolim-hydmlyzing) . "mpacificﬂ Both oompomds hydrolyze acetylcholim but have diffmnt rates of hydrolysis for mcholyl and bonzoyloholine . 'mis differmtial mta permits qualitative diatimtiom. By reporting the cholinostemse activity as a ratio of the activity with a mocholyl substrate and with a homoyldmoline substrate compared to a substrate of acetyldmlim, two ratios are fomd: dzolimsteme-I/wetyldzoline . --- v r v , -- ‘ ~- a"; . ��rmw, 16 vasodilation and increased with a degree of cellular permeability may be pmdicted. amudetion of vascular fluids into the inter. the of duration md with extent the varying cellular spaces g: vaaodilxtutim (Rabat mad their comma pomability such 51;, 19%) . Spiegel, Spiegel-Arblf, (19%, 19W, 19%, 19%, 1953) chm demtmted and increased oonchwtivity of the ions (as various of with the associated appearance tissues potassium and phosphate) in the spinal ﬂuid following electrically indwed convulsions . Such non-electrolytes , as nucleic-edit: splitting mama , also increased. Ganges in cellular permeability @6011th may thus provide the basis for the high of aoetyldzoline and the increased concentratiom of aholimstemse-II in induced animus or head and We!“ The head 1989c.) . persistence of acetyldxolim in spinal fluid after tram activity tram (Taver- and may be after seizm'es despite increased cholinesteme related to the sensitivity of the acetyldxoline- dxolimsteme-I system to meantmim relationships (Nadmm W. , ~1— ~- A” .—,.- �17 and Wu, 1935; Tower and Wm, muse; Burger: and McIntosh, 1955) . At "physiologic" comantmticrns, hydrolysis of mtylcmlim is rapid (3-4 lunar com—um, MW) but at higher and the activity falls off quickly . In contrast, the dialinastemaun acutylchclim relatimship is map-cite and the rats of hydrolysis incimma with increased: ammunition. 0m view of these mktimhips suggests that while the usual concentrations of mtyldmolim a cell dostmyod by the specific activity of few Wounds, my «and the seizum are dnlimstomeJ in a m excessive concentration following excitation the mate of hydrolysis by coir-m Mahala mnbms may be itself cholimstcmeJ. m reached and a seizure inclined, with adding to the mum: of free amtylcholim. The immune! acctylcholine diffuses rapidly, affecting vascular and annular pumability and imam; the mntmticns of various iom and dmlinentemmn in the of molimateme-II , though of low 031". The activity efficiency and depending on ��in brain tissue, associated with the appearmoo of hyper- (delta bursts) in tho electroencephalogram. syndmrony We was have oonﬂmd the many pmvim reports that convulsive thumps: induces elootmgmphio hypomyndarony (Pink and Kahn, m 1956; 93. 93;, 1981) . mutants than is mom. slow by m Despite a constmt application of a great variability in the the W103! and the exam of the alcotmgmphio mitivity activity as well as the alerting. hypeantilatim synchrony and in psychiatric dew hyper- its persistence thmmlmt a treatmt has boon described as pmmquiaite to It is to mdifioatim and barbitumtes populations . 'lhe early appearance of high Week tins of (Roth, 1951; Both 93.2%, mm 19531;th possible that the £15.fome in EEG-hypemynduw my be of central oholimrgio following and @,1956) . induood the dogma of muted to differences in the activity ”Wm . patients to develop hypomyndmmy pnoluding a clinical me name me failure of certain may thus be associated to Wood convulsions. Tower �.. 7.7. wrunvx—u— 20 and Will“ (lauea), in ﬂair study of mommbml tram, included obaawations of six paydziatrio patients mdergoing convulsive therapy. Studying the patimts aftor 3.7 momenta aootyldaoline in two patients; may mpootod free spinal fluid and an imam in (momma—II mumstomod with and a demase in a reversal of tho mti-o of mono-stoma: in five of the six patients. hm those observations they minded that the spinal ﬂuid dmges in induced convulsions mmmliketmmofcmimmbmltrmmanﬂmoof spontaneous epilepsy. Boarding the one pttient in the series failed to who show either true wotyldmlim or a duolimoocmse ratio reversal in the spinal fluid, they wrote: patimt was Mt." "It is interesting that this the only one of the six to show no rospouso If electmgmphio hypemyndxrmy is of inommd {me acetylcholim , subjects whammy and those in whom it who to a reﬂection maintain hyperh disappears rapidly may be exhibiting diffemnoes in the kinetics of the d1011nestemse~ wm. w,- Nx‘vrpl .1 �-\ “ --~w an» .7 r'v-vww-‘ 1". -.r Ti'prp"-ﬂ-=Au‘n “-6.“..- ~-‘ ‘31 . W W . , “‘7.dvzw‘". V... mu. metw'w—mwmlv‘lu":.e.vrlvn—“Atm-‘mWW w-xm “m.- Y‘a""' 21 acutylctwlim hydrolysis system. 'Fhmistant hypemyndumy result dsmd {mm a may rate of hydrolysis of acetylemline, associated with low mnemtmtions of either molimatemsea-I with shortin patients '(Oonwmly, dlolimutcmc-II . or lived hypemynduw, dxommteme—I md -II in tissue and spinal fluid PM: be mmually him) . may that: anomalous was 0&0:va «wanted “W‘m, «shaming the We. an: WWW a EEG 51prwa 1.5 a; Lgtu at WWW paovtde We in We mwmum.‘ wumtuuu. Mad one WW W pubable that saw! an that induced Wag embmcpweabuétym and It a on would coucmde aw by The Level. 05 upcmd Mad .5qu . mama of pmabuéty Mud Law 05 exhale. ﬂzuc changes in 05 «anaemia. mm deem- m mama: 4mm (an m pmumx chugu foaming induced 0.0qu . w ..—-.w-w~.-w... �K. i [ ‘ v. ,7 W .. f m .l . V, ». V, ,,,,_V -. .o “:2 ....V ﬂu, ”w...“ - w-wﬂl’m'." ”no”. .7 ..n “w... amp-“mm- "...v'vmm. ._, f.v-w—«-—v~—— v0?" m—v‘ wkumu. , 3‘“ .7 a run ,. . -- 22 (6) Gaolimtemes Thus studies may and the Classifimtim of Paw: also have applicatim to the problem of ‘ automic Inactivity mum and the clansiﬁcatim of the psychoses . and athora ( a «Miami-nip between ) true blood haw ”castrated pmssum response to injected madmlyl an! the clinical mponae of psychiatric patients to ammlsiw whim ﬁlmy. lel is a potent cholimrgio agent mm, mama vasodilation, tadxyoardia, peristalsis. It is rapidly hydrolysed by and W6 diolinesteme-el and :11me by dzolimstemse-II . Tbs blood pronoun of subjects fall: after injected mohalyl within five to more than 20 md mtums to the basolina minutes. Patients whose blood E l I i plum returns to the baseline within classified as Group panama takes 20 Group VI and VII 5 minutes have boon I. II, or III mentors; those whose blood armors minutes to mtum to baseline, as rumors. Group I md Grow; IIoIII motors �23 have a 9 and a 35% recovery rota, respectively, while Group and Group VII reactors 9:92;, 1952). Group patients in whom 89% and 97% recovery rates I to III reactors may be VI (Menorah looked upon as the injected morolyl is rapidly hydrolyzed; while Groups VI and VII have a slow hydrolysis rate. We may predict, therefore, that the blood cholinestamsa activity levels of Groups I-III would be high; while the activity of Groups VI A - VII would be low. similar analysis may be made mgarding central nervous uysten levels of cholineatemmel in the development of Em hypersynolumy and spinal fluid levels of acetyloholim, providing a basis for a oongment hypothesis mgarding central nervous system reactivity to induced convulsions dmolimngio agents. and to peripheral �. ..— .—\..‘ .. .—Vw-~'. 7...... "any.” “.7 lmr.r"vv,~ .. ...~ y.. . _,_,‘ , ~~,.. m. .WWV mm. rm. ~ v-y ‘ WV W H .wa-ﬂq 2'4 CONCLUSION : Central oholinergic Insomniac: appear nah- W in!» in the convulsive therapy process. ‘ significant The published data [that induced convulsions are indicate associated with an increase: in interoelluler acetyloholme to levels greater thm can be destroyed activity.“ Veeodiletim and increased are followed by increased other enzymes and by cholinestemse-I cellular permeability wants of cholinesterese—II and electrolytes in intercellulsr ﬂuids. These chmges are reflected in the increased hypereynchrmy which can be modified by is electrical recorded in scalp electrodes, and which mticrnlimrgc drugs as atropine, benactyzine, and diethazine. The changes in the cerebral biochemical milieu alter cellular activities sufficiently to be associated with altered behavior of subjects. Failure to induce high and persistent cmcentrttions of acetylcholim and failure to induce concomitant electrolyte changes results in a failure to produce behavioral change. 4'u-L...» 1.x. —~- -- 7 �2S Diffcmnoos in the mates of development of reflect diffemnoea in mbml that ‘0me of subjects on ohangas cholinergic ruthenium or in their sensitivity to changos in aoetyloholixm levels. Then diffemoes provide the basis for the classifica‘ tion of the mntally “most: the mode ill by Pmkonstein and by Fink and Kahn (1961). observations pmvidu a rational biodnmical basis for of action of induced mnvulsicns in altering the buhavior of psychotic subjects. These views are consistent with the mom general neurophysiologio—adaptive theory expressed earlier (Fink , 1957) . �REFERENCES M, R. Bo, Stmit’ L. A0, PM, do We, “muff, Mo K. ma Bowditch, S . C. Nemphysiologic effects of electrically induced ccnvuleicm. Melt. Peyehiet. 1956, 75: 371-378. ”Wt. (cum, Bomstein, M.D. Presence and action of acetylcholine in experimental brain trauma. 1. Nwophyeutn 19%, 9: 3%«366. Bummer, C. md Merritt, H. H. Effect of certain choline derivatives on electrical activity of the cortex. Mch. Munoz. Psychmt. (cum, 19ﬂ2, H8: 382~395. Wu, of ecctylcholine. A. s. V. and Macintosh, 1-“. C. In K. A. C. Elliot, The I. physiological sigiificancc J. H. Springfield, Ill... H. Page and Queetel 1955: 37u-375. (Editors), Numchmmg. C. C Thomas, Omtfield, P. 0. and Way, E. W. Effects of proatigmine md acetylchcline on cortical potentials. Mu. J. P11544201... 1m, 135: 633~6H0. Cone, W. V., Toner, activity in Wm, D. Acetylcholine and neuronal and epilcpey. J.A.M.A., 19%, 73: 59-63. D. B. Dale, H. H. The action of certain esters and others of choline, and their relation to marine. J. thueol. Exp. Thu... lSlu, 6:1»7. Elliott, R. A. C., Snark, R. L. and Hmdemcn, N. Effects of mathetics end ccnvulsmts on acetyldmline content of brain. W. J. "15161.0(" 1950. 162: ass-hm. PM. M. A unified theory of the action of paydzodynmic therapies. J. Hill‘idl H06p., 1957, 6: 197-206. Pink, M. Effect of mtichclinergic agent, diethezine , on behavior: simﬂcance for theory of convulsive therapy. Adah. Mental. Paychiat. {Ch£c.). 1958, 80: 380‘387. EEG and Fink, H. Effect of mticholinergic compom$ on poet—convulsive olectmencephelogxm and berminr of psychiatric patients. Eummuph. cu... Nauphyuot" 1960, 12 (2): 359-369. Pink, H. and Kuhn, R. L. Qumtitati-ve studies of slow wave activity following electroshock. Eucmemph. can. ”canophyaiat” 1956, 8:158. Fisk, M... Kahn, R. 1..., Ken), 2., Pollack, H., Green, M. A.. Alan, and Iefhowits, H. J. Inhalmtoinduc-d convulsions. Mch. Gen. 1961, “:259-266. mm, ' m, Bales, P. p., Willis, A. md Hinwich, H. B. Experimtel production of electrical major convulsive patterns . W. A. J. ”twin-L" 1%9. 1%: 117.12“- B. hymn ��an'V-WI' -3Spicgol, E. A. and Spinal—Adolf, M. Physicochemical effects of electrically inclined convulsims (cambmspinal fluid studias) . Tm. MM. Newt. AAA” 19%, 70: 130-132. Spicgel, E. A. and Spinal-Adolf, H. Physiological and mysicochomical Marxism in tmatmnt. Conga. NewwL, 1953, 13: 38-63. 013::th Spiegol, E. A., Wm Spicgclmlf, changes in the brain H. and Benny, G. Physiococl'xcmical electrically induced convulsive discharges. Tum. ML. Haunt. MA... 19%, 68: 17a. Spinal—Adolf, 14., Wilcox, P. H. and Spiegel, E. A. Cembmspinal fluid menses in electroshock treatmnt of paydzoces. Mu. J. mm” Stone, H. E. The role of acatyldmolim in brain metabolism and “mm. Tom, m. J. M0 M9, Effect of convulsim content of the brain. Man. J. C. 1957, 36: 222“255c inning agents much, on the acetylcholim 1953, 173: 179.183. Tonia, C. Effects of single injection of corticotmpin (ACIH) on manium ion and acetylcholine (intent of bmin. MM. 1 . Myuol" 1953, 173: 176-178. Acctylcmline and murmal activity. I. Warm, Gnumtomso pattcrm and acutyldwlim in the cembmpinal fluids Tower, D. B. and D. of pationts with armiommbml trauma. 27 (seat. E): 105“].190 I cm. 1. Rucauh, 19u9a, cmtent and dmmcteriatim of cambmspiml fluids. Canad. J. Rumch, Tow-r. D. B. and McEachcm, D. The hm 27 (Sect. E): 132-1u5. dwiimatcmes in Rush, w Tower, D. B. and HcEaclnm, D. Amtylcholino and neurmal activity. II . Acetylcholim and cholinestcme activity in the cembmspinal fluids of patients with cpilnpay. Can“. J. Image, 27 (Seat. E): 120~131. Mum. “We Ulott, upon Rum, Effect of atropine md scopolminc changes indumd by electm—conwlsive G. A. and Johnson, H. w. can. MthyAioL., therapy. Ward, A. A. 1957, 9: 217-22u. Atropine in the treatment of closed head injuzy, J. Nwww., 1950, 7: 3984402. �cmLINElEIC WIﬂiS, AND BEHAVIOR CONWLSIVE TIERAPY Max hm tha Pink, M.D. Wt m1 of Psychiatry at the Miami. Institute of Psychiatry, University of Hisawm'. School of Hedicim, suoo Stmet, St. Louis, Missouri. 63139. Aided, in part, by USHiS grunts $1.009”, I‘m-2715, ”ii-07239, and Mil-11380; and thc Psychiatric Recent-h Poundaticn of Missmri. 'mismportispartofﬂnstudypmmminhmctimand Behavior" undertaken New York. Hillside at Hospital in �n -.v-..ww.nmipv~.. NJ, mi V: CHOLINERGIC MECHANISMS, CONVULSIVE THERAPY, AND BEHAVIOR Studies of induced convulsions have m that the early develommt and persistence of aims of altered colonel function are prerequisite to chmgee in behavior (Pink and Kenn, 1956). Electmemptmlogmphic slow new activity was found to be a significant index of altered bmin ftmction, and the dmnonetm- ticn that premdiceticn with atropine inhibited this slow activity (Ulett and Johnem, 195$) suggested a wave relation to cholimmio melamine. In the following review the mle of acetylcl'olixn and the axolineetemeee in convulsive therapy is diamond. Aoetylcholine he: been extensively studied as an active agent in the transmission of nervous iwulses since the descriptions of Dale (1911;) and loud. (1921). It is first a constituent of nervous tissue, existing in a bomd form mich is liberated during the excitation process. It is rapidly hydrolyzed through the specific ectim o rapidly reconstituted by gelimetemee and is the cholimﬂeoetyleee system (Richter s V 6~28~65 , �Croeslmd, 1909). In normal cerebroepinal fluid {me eoetylcholim is not present despite the rapid breekdom of bound ecetylcholine during periods of activity and excitement (Tour and HoEecMm, lease). The cerebrospinal fluid does have neasmble ctnlineetemee activity, beaver, principally of the "true" or mctwlyl hydrolyzing type (New and ibthenberg, m5). In the absence of free acetylcholine and under the conditions described, electroencephalogram fail to show abnormality. (e) Effect of ﬁrmiocerebral was Item: Free eoetylclnline fomd in the cembroepinal fluid within a few minutes after- experimntal heed periods up to '58 tram in cats and persisted for varying hours (Bernstein, 19“). The quantity of free ecetylcholim varied between 2.7 and 9.0 game percent, and the mount me related to the degree of induced Concurrent electmmoephelogrm The records were first filled he followed by e demetreted patterned changes. with high voltage fest interpreted as evidence of an intense to tram. nemel activity, discharge, only short period of flattening of all recorded �alactriaal activity. periods of high 'Iha These phases were than followed by prolonged mlituda sharp wam in the delta fmqmncies. behaviml chmgea wan nlatad both to the dame of amt of masmd trams and higher haul: of acatylcholine, of amornality and EEG to tha addition, spmtmaous to ﬂu matar With Bernstein uportad snatcr degrees (mange: poet-Me aunt of free fm aoatylcholim. in consciomnass. In aaixums «am also ralatad amtyldlolina app-axing in tha spinal ﬂuid. Bomatain also applied acatyld'zolim to exposed oat cambml cortex. ”Mt When 01‘ tho omeantmtion of mtg/lanolin. 1808. fraqmncy in the was inmasad to ht EX: vaporized high amplitude sharp waves electmphalogm. “man ’7 2 was 1 gm pamt, wam by Towar- and HoEaeham of law the oonoantratim the alactmonoaphalogrm flattened in a fashion parallel to the Pamllal studies ' post-Mic ram. can'iad out in mlogioal patients (19%”. Pm: acatylcholina was fomd in 7 1 {wéli 14?”! [6cm �«1—. . ;_.... 7,. rm. . ‘ 4‘1"“.7 .. run-- «m w, raw-"aw ~~.w.:-v-w—.--lam—www—nv-rwww - the cambmopinal fluid only in patients withmoent Mad wv .r'. r tram mount pond-m1 seizures or aftor convulsive trunpy. Free ...;—--°-"“' " aootyldioline varied from 0.2 to 100 gm __ ~ peroent. _,,./ Tour ~ v. m3...» Mom also assayed spinal fluid oholimtome activity, rating a sharp rise in the nonspecific cholinestemse fmctim (benzoylclwlimqmitting) and a drop in the specific oholinestemse the oeubmopiml fluid did not exhibit such invasion, although it “dined fm mtyloholim. of They concluded fm mtylcl'nlim varied directly with the damage huge. taken at varying intervals following Kantian batman the dome of {m EEG was a mo Electmmoephuomm, tram, also indicated a abnormlity and the appeazmoa aootylcholine in the umbmspinal fluid. Thu, ﬂu spinal dogma of oombml andhat reversal of the dwlinesteme fraction sensitive indicator of cerebral of that the level want as 549.: Micheline. my {mug in the (Mdéaltmiugmuocmbwmmmdmmuntaé Wt / W“ _4___._.._..-' follavdng oonvulaivo mommy. Pollovim spontaneous soizums 01W, 4a.: \ and fraction (mohalyl-splitting) in patients with had 12mm and , �.5and the degue acotylchoune, (no Wenuphdogmﬁic «type 06 abnambbty, and changu in clinical bellow»! my be {Wad phenom. (b) antioholm Am1m, o behavioral and neurologic aims of pamtenl m mm and The EEG were blocked by the Mimic»: of 0.5.1.0 lag/kg atropine (Bomtein, as were similar clinical charges counting addition of mtyloholim . to the tram: W1: Ward (1950) after the intmistenul applied these observations of closed head injuries. In varying dogmas of tame, he 20 patients ’with ministered atropine subcutmly indousof0.lnglkg,notingclinioelimrovmntinsommda Md reversal of the eloctxmoephalogmphic effects in others, In a study 09m, mower uﬁtmolinergio Inchner (1955) reported altemticns in the moephalogm. W A p‘tvtremtio electro- single intravenous dose in forty patients with aleotmpmlom resulted in normalizing in twenty- ), �F i H4 ~37». .V v . “WW. awn" V l -.—.p..r \':v';"'r~~ gw~-_.....—m .— ...r 1"" “v: n n‘ , , , m. ,- two and marked , . , .- ,,_ _ , , __.,,_3._.7,,_,._ “,1”, ‘4‘._,V , an- a www-ruymumrm-e ,, ., .F ‘7...arm'Hﬂ ,_ ya,V. a“W. .. ﬁauawﬂl.‘ .w-qﬂw’ uvwwwrvw-1': -r~)\w‘nw . . . I 5.1119th in six others. In subjects following convulsive therapy the (feet of atropine inblockingtheappeamceofelwwaveectbdtywaemported (mm 139 :Iohnsm, and 1956). (In a later study these authors failed replicate this study, suggesting that dosage factors or population changes [Johmcn gel“, “niece may have mntributed to different results 1980]). observations provided the basis for studies with other loom mticmolimrgic canpcunth (Pink, 1968, 1960). The intravenous injection of experimentally potent antidwolimrgic momds as dietlmine. bemctyzine, the piperidylbenzilates JB-Bls, and .— JB—329 (Ditm), Wution. VIN-2299 and pmcyclidine induced The EEG chmgea were alerting, anxiety, trauma. illusions and JB—336 EEG associated with behavioral hallucinaticna in peyduietric subjects . In patients with recent induced conwlsims these «awards resulted in a reduction in 31m useciated with a reversal of euphoria, denial wave and activity cmfmion. .3 “‘11 i a 5161,! . ﬁg?“ �“Rpm, .,,,,..( ,“_.,. ,.. , N" .37.. 7”,. v Atropine was also Md, . ”a“, N mined in y:~.uf..~r\v.“r - o—r- .. n «v low doses, maniac] by todnyouwdia, “any "n www-mur - voltage, poor-1y organized delta activity with activity was Mum.” ._..-t m... who .er ixﬂu’Joitor, I)?!” elicited high anplitude rapid 935;, post-tmmtic states 1950; andHiwidx 5.3;. m as (mm 1950). These 3: 2.1.2. m; offoats won block-d by small doses of parenteral atropine . Qutficld Tho - “law‘vpm-x- superimed beta patterns similar to atatm epileptious, as charges similar to those of with .-- slow waves . followed by lower mumatarau (di—isopmpyl flmmphooptute) Hanson .,.,, associated with pmgnssive confusion and disorientation. mo administmtimoof a 191:9; , nervousness and tension. At hyporsynolm £1qu ...,,.,..;. dosynohmnizatim was BEG higher dosages, BBC V and Dupscy (19“!) pmpamd exposed animal cortex prostim and evoked eleotmenoaphalogmphic spike prior aministmtion of otmpinc Hacked this spiking, or present, the abnormality could be olimiratcd In contrast to those findings, Mr activity. by and if atmpim. Darrin (19%), applied topical aoetylobolino in concentrations of 2~ll2 to to the exposed cortex of oats, and notedno effect on the 10% «- �ehatrmnaphlomxic The damages after intravenous atropine (1 mg/kg) . concantmtims of acetylcholim in those encperimants, however, were higher than the and thc topical gpplioatims (1-4 intraeistemal (0.2-10 gm gm pement) percent) injections of Bomstoin (19%) . Bmmmr and Merritt, also made note of electro- enceplnlognphic affects similar to aoetyldxolim from nacholyl (mtylbetmt‘m‘lmoline) much and doryl (carbmldlolim) in concentrations lower than the amtyldtolim concentrations . may ascribed the increased effectiveness of these dnlimrgic drugs to their lack of sensitivity to cambml dzolincsterases . 11qu nativity Mamie The“. W and war. 0‘ man, mama induced by autgzehaune 46 can be. backed out maﬁa, mama“, of mtyloholim antebellum indicates that an oak“ as Wed a imctiw bound by anti.- etc. (a) Cambrmghnl Fluid Anglcholine and tissue in that!» topical application, M lintuéowm. with chum-Amt activity 49M studio» tuggeat that it is 34513112.: Ono View fomdv in nervous fem. Wing periods of activity, mtyldxolinc is liberated at the cell membrane, where it is �.v. .mTr,--m.,—,w..‘_-w.. ”“51“,”, wwryw , . "a". 7.,“ -\‘-yuv;-vv—n—-,17'zr'~.m"--r mm.-- .ﬂ‘vv—‘r- - MW‘VW'v'bn-‘Imwx‘y ,. ..,,..‘v-_.v..—-u.-~, ,- -10.. rapidly deactivated by molmesteme. acetylcholim is the remnant of oontinm lihemtion and brim. rises dining sleep was amputee! and mmt The and It processes of synthsis, has been postulated that the level falls during activity. This hypothesis in miml experiments Elliott, Sunk of bomd by Richter and Crosslmd (19%) and Hmdemm (1950). By using liquid air quickffnezing methods, Richter and Grassland observed the level of aoetyldmolim during metathesis and sleep (unsound as W per levels. mg. The basin tissue) to be 300$ micro— higher thm post-seizure difference in tissue levels is tmsiont. however, as the msynthssis nuts for aoetyldaoline in net brain is high (7 gum/Walnuts). Elliott 939;, (1950) confirmed these observetims. After utmsole convulsions they also noted that free aoetyldaolim in concentrations m always demnstmble in the spinal fluid up to 3 gm per cent. In spine]. fluid studies in mm, Cme, Tower and (19%) and Tower and HcEsctnm (19am) reported Wm simificant �quantities of free eoetyldwline in patients with epilepsy. or 56 epileptic patients, an (77%) in quantities of 0.02 to 5.0 gm per cent. The gm mmted free acetyldxolixu per cent with at average of 1.0 eeetyldroline level was related to the frequency of seizures, the extent of electroenceplulogephic ehmlity,endtothetiusinoethelutseizm. Itboreno relation to mdioetian, type of epilepsy or level of dmlimstemse activity. Mather tr: ecetylcholine appearing in the spinal ﬂuid is e by~prudmt of the oonvuleim or Mather the increase in acetyl- cholim is e eeuee of the seizure is pmblemeticel. HeEeehem (19%») suggested Tower and that increased acetyleholine liberation ismtdutotheseizureitselfbuttothepmoese causingthe eeimre. In e study of the hypatrueis that the mmlation of mtyldtolim is causal for seizures. in urinals by mmzole m (1953) induced convulsion and determined the level of acetylcholine in brain tissue before and during convulsions. cmwleime are preceded by She noted that a rise in the acetylcholine content of �M- iv“... “.0". ,_ v Hr. “7 a.“ rm . . ~.— ,VT .m", ...,. ‘mr—v-,~7..‘..v.».. . , ..,_ 1mm- ’77.. ., w.‘ .5, 1. .w, 'TVV'WHP-‘ ‘(n'ry Humannnruu .. . ww'" v-vm ‘r‘ ~ , 1-v.‘.r—~-.- r---v um”... mam-awn” -12- tissuc, abut the content fills during the convulsion, below and that curtain Invals of acetylcholinn,‘eonvulsions failed to occur. She sugspstod that the fall in tissun aeotyldholine during a canvulsion was due to inhibition of acutylcholine oonc¥ntration incroaéed synthnsia by the of mutaholitns/ such as ammonium ions. Seizunzb nan aceompanizd by an lacke¢4¢ {act aettytchclluc libeaatld {Ann (:3 in inteacnllutan bound £03m, Amucmybeumuedinmwud (Md; and’liit this Mammal nativity and Atizultb cnhanct acatyteholluc debthuction, lawtning 125£u¢ (cvelt as aettytchalilc; ukilc Attcp W and ancsthetla acaywwm wanton Alumnus tune. mm . (d) Cuntral Nervous SystaEKCholinestcnanas: Oanoamitant with their~obaervarions of changpa in aestylcholine, waor and HhEaahorn (19kg) neasunod Tho spinal fluid cholinnstcraso activity. types of cholinnatexuscs are normally found in the spinal ,, -~a 1 Wm "F-Ir «rm-“r Tau—w �fluid: cholimter-ase-I which has a high Wm," ”specific,” or mdnlyl-hydrolyzing) , specificity for acetyldzolme; and cholinesteme-II ”punch," "um-specific," or bemoyldiolim—hydmlyzing). Bath mama-uh hydrolyze wetylclnlim but have different rates of » hymolysil form‘mdiolyl and hmmyldxolim . This differential rate permits qualitative distimticns . By reporting the cholinestemse activity In a ratio of the activity with a maholyl substrate with two on Walnut» substrate mated and to substrate of wetylcholim, ratios are found: dwlimstemso~1Iacetylcrwlim and oralinesteme-II/metyldaolim (with WM'IOO) . In Inch ratios noml cambmepinel fluid contains estemes in the ratio 33:17 of for dwlimtemee-I to eholimtemedl . In patients with head tram Tower md Wan reported an inversion of the cholimstemee, with an increase in the dxolimstemeI fraction of the spinal fluid and a decrease in cholinesteme-IL. (ctivity. me extent of the duelinestemee reversal was related ��u. wc- 15": w“: w—qggywww—mqw 'vwﬂvw‘r' w'w. ;~m«w usedatcd with the plum“) . we “c- ,‘ rm-“ ,n, mvmr "W_.,“-..‘w .ﬂ. appear-am: of variws isms (as potassium and in the spinal ﬂuid follwing electrically comm. than was electrolytes u cellular an. ._- ~———~> also a significant increase in such nan- music-acid splitting mama . Minty may aluminum-41 in md madam ‘13:. with the and the induced mixtures or hand km may be in cholimstem activity should of true mtyldxoline. be associated The persistence L a“? M man md after commas: relationships 1945; Tamar and Wm, mummtiom, microseconds) but Men (Nadmnsm and ”MA n5 and laser matmﬁms, contmt, the dzolimstemo-II— 5e 5 5744 (K biz k 4% 4: Mute-h, hydrolysis of mtyleholim at higher the activity falls off quidtly. In 19169; . é'dééﬂloéj“(.1 related to the sensitivity of me mtylahomu-v 1955) . At ”physiologic" (3—43 (Tamr- 54’2“” [w mid damnation Murmurs, is rapid than muse). dmlimstcmsed system to and in incmmd concentrations of mtyldaolim in spinal fluid after hand mum‘s Oranges thus provide the basis for th- high cone-stations of matyldxolim of inctuoed �. “N-r —~ n. 7., VFW..-” W _ a. .. vw—w-‘w— 7..- .—-..~,-— :7 tm'w“‘n‘.mm"\ "Va-"er-rwswrwnh‘ Inwr'n'ra'" ., "mu-wmu» m y'WWW—m. w~~vw-'VI"-’wr11‘xn—n‘ ~ .x v . .. ”rip-“73“‘miwl‘wuw1vv'1‘y; NV”; —,—-.-r~.. .nr w "WWW,— «.v “ «mu—v..."- ‘ . .15acctybholino rulaticnship is non-specific and the rate of hydrolysis inexact-a with cone-ntratian. Mi 1‘“ ; Aum£-‘£o’%}4i 4;; ‘T f? dnatrcyud by tho spocific activity of cholinnsteraseol in faw lasso-.aondn, an excessive concentration fallowing excitation may canned tho by cholinesterase-I. The L¢¢1¢4 A¢M4 ‘ acixurn thrushold nay be reached and a noifnnu indueen, with thc stizumi f i rats of hydrolysis Thu itself adding to the amount of free acetyldholine. innrnanod acutylcholins diffnoos rapidly, affecting vascular i and cnllulnr poxlnability and increasing the concentrations of various ions and cholinnstnrusc~11 in CSP. The activity of dholinnstoraao-II, though of law efficiency and depending th- mmmm kinetics, Mass on the mtylcholim in the tissuns in hours to days to lavels for tho physiologic action of cholinnatonuae.1. 422;“ 42351“ �‘vr , wwvw—M. . ‘ «ruuuv <t—V'1vwv “—w—ww wwwmwrwwnw. raw—em: un.mnv:.-.Wm "WW—.1» yrmlmx-N ltd-www'ﬁa'wmw'guw‘I‘v ~ 1.. —_ '~V"(—m'v M.Wr>‘\'m‘ .17- Choumtmu «ppm in nu mind We! as a acumen 05 their. 41mm: in Lu ceu. The mm: gammy ma m swam 6;;th (e) 5mm», muting 5m mentioned by changes 1,2:qu Midtown. momma; m pout of the eybmetéc mechanum awn-(muting the 604 Ante/Lem Me 05 «mama»: at was mainland: mu‘uy WW9. Mainline EEG! and Induced Ccmvulsiam: . Almmtion in the blood~brain pemability barrier by the cmtiming team of amtyldaolim may be the biodwmical substrate for the post-ehetmshod: hypcmyndmmy of the alectxmnmphalogrmn. Such a possibility is avid-at in the report by Aird «mutating an increase W 23; 3141955) in‘the concentration of cocaine in brain . tissues thme days after a series of 12 induced omvulsiom. His data Show the change in mnemtmtion of this large animals, ominarily abaerrgu: inbrain tissue to be mociated with the appeamnoa of hypnrsyndzmy (delta bursts) in the electm~ W. , �. inn-ha -'!SA‘-’-"—'r-.“ viva... ..».-~=v—-nn , wan-.wp» ‘ wn “-1....er ﬂ.” .7,» :w .r x» In studies of induced convuleime, many ﬂaw-u. we WW“ -; ‘v w "M”,Vrmm “ w... -wA.we--wﬁm~mvav" . _ ‘1 dump-.— have confirmed the pmvioue reports that convulsive therapy induces electmgraphic hypersyndxmny (Fiﬁ: and Kahn, 1956) . Despite a constant applica- tion of mutants, the time of appeamsoe, the dlmatim and the extent of the electromphic slow sensitivity to modificatim by wave activity as well as its alerting, hypemntilatim barbiturates vary greatly in paydxiatrk: populations . appear-awe of high degree hypereyndumy and Too and early its persistence through- out the txeatmnt name has been described as prerequisite to iapmvemnt following electmehodc (Fink md Kahn, 1956). The failm of certain patients to develop hypemyndmmny may be related to differences in the activity of central aeetylcholine and dwlineetemeee. with the absence of free acetyld'xolim beingmlatedtoninimalehangesincembmlfmctimmdﬂnm precluding a clinical response to induced convuleime. Tower and HeEaehem (mum, in their study of Madembml trmma, included observations of six peydmiatric patients mdergoing mleive therapy. Studying the patients after 3—7 treatments "- mpg-w“... �.ww pwzwrn . 7 .19... thay reported free two 41lede patients; and an 1mm activity in the spinal fluid in in duelimstemae-II md a dome in dummtomee-I with a mammal of the ratio of dwolixnstemes in five of thn six patients. ms that the spinal fluid like those of From mica-tubal these observations they concluded in induced convulsions m Ragar'dim the mo patient were mom than those found in epilepsy. in the series who failed to show cithcr me mtylaholim or a cholimstomc ratio reversal in the spinal fluid, thcy wmte: "It is interesting that this paticnt an the only can of the six to show no msponse It a pawn that induce! mama» £6 mmuu i/ t:”PM/1AA ﬂy ff-WLL AW by 1.6 3 0‘ JA mm, sums. Law 96 me EEG Fm «commune hypwyueMony mama“ and 1.6 mm on: mm ascenumcngm. uuuueehuguzazmouummm- AMM‘W was that plowidc ﬂu. biochemical. 60.be (on the pmaaut V WW) mamnt." mm mm pmabuuy m Mug the. mam a; mumamu. W W Wilma mm “#19” ( in Wt to bchaviom changes {allowing inland canmuiau. w;- �(f) Choline-tomes moss studies may and th- Classification of chosos: also have spplicatim to the problem of catatonic reactivity and the clmificntim of the psychoses . Mkonstoinsndotlwrs( )havsdsmxstmtedamlatiom ug ship botwun tin blood possum response to injectedﬂm) (dd‘é’ﬂﬂ and the clinical mpomo of psychiatric patients to convulsive W. lbchclyl is a potent molimrgic agont which induces vasoﬁmion, tachycardia, mating, It is and harassed peristalsis. mpidly hydrolyud by mournstoms-I and slowly by clmlinutcmc-II . M, injoctod m m blood pmssum of subjects falls aftor udulyl and 2‘th to the five to m bssclinc than 20 minutes. Patients Mobloodpmsmmtxmtothbaulimwiﬂﬁnsmutos are classificd as Groups blood possum takos 2O I, II, or III auctions; arm aszprIdeIImctims. imprcvomnt mactors a minutes to mum to baseline, mexoupIrssctorshawa9% rats with conwlsivs therapy, 35% those whose and the Group II—III memory mtc. In contrast, the Group VI �_.__.. ”(ya-v —— . h\'~rvhl."ll'F reactoreheveasstm'themupvnasﬂ recoveryme (human-1n 35;. Patients in an patiente in 1952). “main Groups I to III may be looked upon whm the injected maholyl is rapidly hydrolyzed; VI and VII patients heve the a slow hydrolysis rate. 41121311. 65‘ Weny predict, themfoze, that an blood ahalimateme activity levels of I-III would be high; while the activity of WV” y ’ ,-. u... V,._V.......,m--.-n—nw ’0 ﬂy” 6/” W W hypersynchxuny and spinal In studies of EEG fluid levels of acetylcholim. ahengee {uncaring induced omvuleicne subjects were identified in when e few seixme resulted in e greet of elm wave activity; mile other subjects exhibited mat few changes to my and to frequent seizures (Pink and Kuhn, 1956). If electmgrephic hyper-gum in e reflection of incremd (Conversely, in patients with short-lived hypereyndxrmy, dwiineetense-I be unusually and high). -II in tissue Thue and spinal ﬂuid these epeauletime provide may �-22a basis fcr a congruent hypothesis regarding central nervous system reactivity to clactroshock, and to peripheral éholinergic CONCLUSION: Ccntral dholincrzic nadhanismsqmpoar to be a significant flycﬂu«’g factor in the convulsive therapy process. ”Inc published data {unrinriznlmymnandhto indialté;that induced convulsions are associated with an incruasa in intarcallular acetylcholinn tn 4L¢¢4Eygd4£5414¢¢¢délAbiﬂ— lnvels greater than can be dustxoyed by choiéanoturuneéE— nativity. Vascdilatian follouod and and innnuasud callular'permnabilitylin«a4wc. 71L‘5@ﬁ¢.4;«xu> g aibcgérﬁyxapglugu‘542;;wmatvi byﬂincrnascd amounts of~ehoiinnaﬂcuuao~¥l~ other'enzymas clactrolytas in inturunllular fluids. ��n, w~. «v— ‘w—rr‘Y .r uy-nmvv—mwum-mn "vv'. rwzm—r w—uw-v-mw-wztwvm... a ~II'-v-'<w-:'W.\1v;w'rku'svmv‘mv'nvﬂwv wwww CEDLIWC WV}: mm. MD mum Max w;— .n»;_...v W... "on." ,vurw»; M Pink, H.D. W at th- Pﬂnmi Initiate of -Pmthanapmntof Psychiatry, admity of Miami School of Midas, 5800 Annual St. Louis, Missouri. 63139. attest, W, W mm. Wmismofthnwm"hinhnatimm York. Hillside Hospital in Ethnic!” at mm in part, 2:57 aunts iii-00927, iii-2715, W72“, md $11380; and the Paydaiatric- Renard! Fantastic: 0! New - - w—n mu, mung—.w an �CHOLINEMIC W, AND V: CONVUISIVE BHWIIOR 11W, StudiuofinMdmwldmhnwmmmuﬂy dwalopnntmdpmittmofsiguofutomdmwmmm mpnmquiaitetoahmguinbahavinr (Maximum, 1956). Wesleyanwmivitymfommm: aimificmtinduxoflltondbxuinfmctim,andﬂndemmticn that Mention activity (015th album-sic and Jdmm, W. mtylcmum and with atropine inhihimd tho 196’) this slow wave muted a minim to In the following review the dwlimmruas in mole of Waive ﬁnnpy is discussed. Mutyldnlimmwcmivelystudiedummive amtintrnmmuimofmmusimluusimsmﬂm It is a dcnmiptions of Dale (191k) and Load. (1921). mtitxmrtofmtium,uistinginaboundfommida illibnmtcdmmwiutimmm. )J and is action of culimmme specific hydrolyud m Itiarupidly W rapidly matitutcd by the cholimmtylau cystem (Richter 8 sum-55 �wan-r”... Grassland, 19%). In actual autumnal fluid has mtylclnlim Emmanpitemupidmmofmmmm (Town-mm, Magmaoaofactivitymdcmitmt 19%;). The activity. ”Mimi mm, fluid does but Inﬁnmoffm 19%). matylahonm md undnr the conditions than cholimatcraso principally of tho “tan” or medulla wdmlyzing typemmsmwibﬁmbcrg. fail to gamble Whoa, cleatrunmpimhgrm Witty. (a) Effcct of m Mint}: W hm: hm acetylctnlim mun-951151 ﬂuidwiﬁﬁnafwninuua after demmmtsmdpmiuedforvmina periods 2.» m as hours (Win, 1”). The qumtity of fun gm mtmmumdmthdumeofimmtrm. mtylcholim vanhd between 2.? did 9.0 The W accord. chcmewaphalogzu um first filled with percent. and th- mutated patterned W. high voltage fast activity, intorpmtad as alderman of an intern. mm). diam, only tobfoﬂmdbyadmtpexiodofﬂmingofmmcomod ﬂuv - v > .. �-- .vwru V.—.Ym'> electrical activity. Thou phuu wen then followed - 'u-uwuﬂxm n. ww- by pmlmgod mamamummmmmmmmms. mwmsmnmwmthtothedameof mmmmmtafmmdhumtyldnﬂm. highs:- levuln of mtyldnlim. Romania 911‘th "Modulator dew ofmcmntymdmmrctmpsinmcimu. In addiﬂm, apcntmn post-We aim wan also muted totbmmtoffmmtylebomnapparingintmspiml fluid. Wain also :13le acntyldxolim to expound out 03:11me W. Mthommmimofmtyldmlimmlgm pamtorhu,hnpwtodhighm11tudoshupwmoflm fmmncyinthocloctmmmplulogﬁm. mmmnoentmtim mimmdtoZmpcmt,ﬂnchctm-naplulogm Whafuhionpqﬂhlmﬂnpon—tmicm. Parallel studios m wr carried out in analogical patients byrmmunsmnumw. Pmautyldnnmmfmxdin - r-w» ' 'c . ' -' ' �- the Main]. mount grand-ml mtyldwlim 7...» 7w wn>wwv 'v'vcv’ ku- w. VII-"I'M‘WW ﬂuiﬂ mly in patients withncmt head 1""!t-W'J" \‘vv- "ram-V" tram 301nm or afar convulsive trnmpy. Fun vadedmeﬁtolOOgmpcmt. Tomrmd Wm also assayed spinal fluid cholimstcme activity, noting a map rise in the mpocific cholimtcme factim (WW-cpnttim) and a drop in the specific mailman” fmtim (metnlyl-splitting) in paticnts with had mm and following minim W. Followhu sputum calm the cornucopia-l fluid did not exhibit such it comma {no mtyldmlixn. inwaim, Thay cmcluded 11W that the lavel of {no mtylcmnm varied d1mct1y with the dame of comm}. Manama: mnnlofﬂnedlolimctem fmﬂmmam with» indicator of Gambia]. m. madam, talcmatvuyingintorvalsfonowingmm, mimic-med: mhtionbctmcntkmdcmeofﬁmmntymdtheappem of In: mtylcholim Thu. due in the annbmspinal fluid. want 0‘ We autylchounc my (me. in the ‘mmgoummwwmmmmmog ' 'v "F “'4‘“ �, 'V'lvw—‘U‘ w‘ war.- —',~3 nan—- u ,w--y_.n..-. u. ‘ ., .- ww,———w~.wm_w—w-q ‘1‘ wwm “- v-~.-W . a..“.~,~.-u . q. . WW -..' .m “Fwy-Fumwyv,‘ “15;.” .w, , .7 “mm .-.» 7w.v--m»w~uu-——. .3... 51m. “Wotan, abunuty, MW. (2)) «the «glue and type mmmmgupuc a; mmummmmamumw m, WWMO m and m: The EEG aim ofmmnmmodadhyﬂu behaviomlmdmmlogic (Bnmstein, pun-nun). examination of 0.5-1.0 ug/kg atropine mmmmcunimmmmmmmmum addition of mmmu. Ward (1950) applied mmmdmmmm. We m, Wand of varying ho m'obumum In20patiantswith ntmpim 3W1)? hduudOJq/kynothmdhﬁmliqmtinmmda mutual of the 013:!ch effects in om. In a smdw.muﬁamwm¢Jmm Loam (1955) meoph-‘logrn. m1 W am A single 5.an WW in the pit-atrmmatic ghetto— dose in forty patients with resulted in normalizing in twenty- ), was” w, �two and marked Wm: In subjects in 35.): mm. £011ng conwlsive therapy the affect of atropine inbloddmmappemotslmwmuﬁdtymmmd (um and Jdmsm, 1956). (In a Later smdy these mﬁm failed maplicmﬁxiastudy,suggastinsmatdouge facumuw popnlldmdwgauyhmmtdhumdtodiffemntmulta [Jemima $5, 1960]). Moumatimpmvidedtmmformwithm hum “idioms: Wad: (Pink, 1958, 1960). me hummus injection of Wm, and Wm “WW. durum, may, We mamas mum-yum. thn piperldylbmzilnm JB-318, (Dim), JB—329 pan-m: mticholinergic VIN-2299 and an JB-336 3% 1mm mendim MMWmm ammﬂﬁabduvioml truism, illusion whim. and mlminttims in In patients with mount induaad mnvulsium Mqultodinamdueﬁminslwm activity Wuiﬂzamdofmplmia,dmidmdommsim. ��-. _«.w...-.——~.m. w, .u . . r” v ﬂaw-v v "'wA“"‘f'N‘" . wrv-r-P electmncepiulogmphic The concentrations of were higher than Win W arbor _.. w-av. rwa-mvnw—wvm- v-.-~ TWZ'Awyvq-u'n‘Vtvmw‘T“ "Ann—w- 1::th th- topiml appliantims (1-4 (19%). atmpim (1 Myldlolim in these oxpeﬂmts, imiatnml and the , (—7.“ ~;—v—u~.~~.—.u—pv.—.—~nn:,+-ra.-w—u w... (0.2-3.0 gm pennant) gm '-‘a nag/kg) . however, parent) injectim of Exam md thud“, also made note of chat-.m- axmptulngmphic effects similar to amtyldwlim ﬁrm mcholyl mtmtiom (WWW) (mtylhetmﬂxxlmonne) ascribed mmh Mrthm tho amtyldnomn M Wm. in and duty). Wimqffmimwmwmmcmmm lack of mitivity to rumba]. duality-sums . ThuewmmmmmsuggutmuumWWWWWbyMWu/tmua man 9‘ aqua, tam Won, imam on. with WW¢Mmbebum¢ueummdbgma~ WWHMAn-gmnmmdmw «new (c) a mm, mm. etc. Onoviw «mlmuWMwa-smnnfomdiamm Winnimatiwbmfom. Wyﬁnchofactivity, WWhnmmdatthno-ummm.m1tia r umnnmv~wv yr.- -~ �“Hwy-v .7 m. » ._v .W”...w.— —...‘..r,.u...,...._...,-, Hm..."- va,unlum‘w‘hi‘wv'mvmwv;'QX.‘""“ W ~n-- v “w a”... ‘ ,7 ,v W---w mw_.-r—... Wt “‘1': run”... -- - ww» v" ‘7. "‘ ww.-,-_p.w.~.wmw. midlyduwtimdbydwlknmo. mamtofbomd mm is the resultant of continuum 1122mm lad mm. promotes of synthuis, It has bun pastuhtad that the rdmduuingslmmfnummuctivity. level Thishypaﬂmil mwmmwwmrmmammum) mm,mmmm(1asm. Byusing liquidair qumumm.mmmmmmmmm ofamtyldwlimdndngmﬂmiamdalup<mamdumim www.mmm)mhaocthigturthmpoum hurls. nudiffminmmmlaiatmsimt,hmm, uthnmthaismforamtyldacliminmbminism (7 gums/gallium). Elliott 539;, (1950) mnfimd than obsorvntima. Afﬁrm}. mum-ism Malacnated that {no mtyldxolim am always «washable in the spinal fluid mmwmagmparmnt. Insphulﬂuidstuﬁuinm,ﬂam,lbwnrmdmm (use) md fear and Wm (19m) “perm dwicam: ��m.uﬁumtfansmgﬁumnmdm,mdm balmeevuin lawn of mm, convulsions failed to om. Stunumudﬁntﬁnfanintium Winona: Wamwhimmdummiﬂmofmtﬂdmnm m‘md mm byst- anemia“. We! sud: mtabolim, Bummwwnmeumm mmmmwwwmmwm Wmuumam¢mm MW mmm;mmmuuyzmuummmn,zmmg rmumumzmum W MW WW madam» (d) §xg~ an MAMMWthuLa W (new: tutu. Lena. Cmocnitam: wimﬂnirohamtiam ofchmm inuntyldaolim, Wm (1939) Tutor-mt! name! spinal fluid dolimtcrm activity. Mtymofdnumemmmmnyfminﬁmspiml �» ‘am-V ”II-"Iv ."V'a. ~,.1- . u -;— V’V~-¥'U'~‘v‘<~u Tam—xv... mw—uL-ww-"wv Wanna-I ﬂuid: mich .V m ("pocudoﬁ W as nu-mq-wnwh-..“ .,.,ﬂ_. .. Um," sﬁociﬂcity for him "rm-amiﬂc,” ow two .,. ,... .. n. ..~-. - . ..- ’r .,.,_H. .\..v7,..,,..~—V.TM ,wv, .,.,.< V . a a ‘ , , v.“ .w: _v_ ”specific," or manlyl—hydmlyzing) , Micheline; and “museum-II WWHMWIM) . Both for udzolyl and bemoylduolim. This diffomtial me panda qualitatiw dintimtims . with 3 ”a.“ hydmlyu amtylcmmn but have diffmnt arm: of mm activity ,. By I: a ratio of the activity with MW!» ratios an found: sub-mu mind mpovting the dwlimstumsc a maholyl substrate and to mm of amtylcholim, mumm—I/amtyldxolim and Wm-II/mtylcmnm (with Adi/@8100). In much nudes 'mlm‘bmupimlﬂuidmuimuminttumioofﬂzu for Grantham-J to aluminum-II . mpnﬁmwimmmmmﬂcﬁadmmdm invasion of th- daolimumu, with an We in the cholimammac-II fmtim of tho spiral fluid and a dam in circumstance-I. iathity. m mam: of the WW maul was related �we: --r"vr— mr ww- ~r-r—vrm...‘ v .—-1«w‘ms¢—ae.—r ”"7.“ mgr-nus, r, mm, a." 'W nve- “w, -~. w n r...“ mwv “van" e w.— ‘1‘“ m‘r‘nvwvﬂﬁ‘l'v—vV-v ”Wuwx—m‘me - vuvax wmmrityofmmmdmmawofﬁuem- WWOWW. Inpatim with eleveudspimlﬂuid acetyldxolim other WW,Wr,mminmmioof dulimetemesortommlimtem wdvitymfomd. ‘meimmindxsmnetemeactivitymbemdentood mnmmmmmnmpemmmty. mW-Ihfmmhimmtmﬁminﬁn mud nervous system while duelineweme-II pram inwartiam,upooianyb1mdsem. Hiﬂamimas fin atyldnnne m1: in intemelluler mum fluia stimledm, communion: or hm, modiletim oellulmpemeabilitymybepmdiotod, Wﬁm and We! withedewof of wonder flunk into the inter-0011M spaces vuyingwdmthemmddm'etimofthevasodimion g g, 19:0). Spiml pun-Ability following W 1953). may cheer-val no Spinal-Molt in mm (Rabat m mm reports (19%, 19%. 19W, 19%. memo mndactivity of the tissm , ~~y-..‘.--~_~~.m-mm-v, �av“ y."— ww_"v-w.w . w «mum...»- a. 4 W cm van—n: . Wwmwum u wI-ww—t'h wmw—wmew-mw ..-,m.— w --u-- mumps—m mum-PV- Hw'ms a: w :w-n r- "rm usociatadwithﬂaappemofvuiwsm (apotmiummd W) in the spiral fluid follwing chemically inducad mm. Mmdmasimiﬁmthmminsmhm- electrolytes as madam-acid splitting cums. Chang-s in alluhrWilitywthmpmviwﬁabasisformhm demmmmmmmm ofdnumumeIinirmmdmoermmﬂw MWIMQGJ. mmmmmwuwmammm with the mid «instruction of hue mtyldxolim. me punctuation rammummspimnudmwmmm aims any be minted to the dxolixastuaso-J syntax m and Wm, 19%; mitivity of the mtyldzolinc- Widen mummy (um Tm adﬁcﬁadam, 19%; Burger: and martian, is rapid (3-H mama) but at high» and lunar 1955) . At ”physiologic” helm-h, hyckolyais of amtyldxonm the activity falls off quidcly. In contrast, the mm, chainsaw-II- �«.18.. “mum nhtimMpismn—spociﬁcmdﬁumof mmmwiﬁzmmim. mmammmsummmmm WWWOfac-tyldmmnnmnmm We hy the spadfin activity of him, an massiv- WW4 mﬁm in few billowing excitation mmmmdmmlmwmum-I. The uhmuthruhuldmhomadndnﬂamimindxmd,with mmimuwngmﬂnmtoffnomtyldnﬁm. n» and W murmur: durum 'mpidly, cellular pambﬂity and humming tho vmmmdwlimm-Ilmw. alum-II, W affecting vaswlar mmtim of 'nnactivityof of lowcfﬁcisxwy mt! chpcnding m ﬂammﬂgmkhnua.mmm1mmm dominhammdlyatohwhforﬁnphysiohgmmﬁm of <21»me . �“.1. -. _. n "w' .~. -»~ uv- r—r-wu. szﬂ‘”R—vu'w.vw w-W-wt mm- W-w—mwwswwmwwrrwmxmm’mv-mwmmun-m zmwm-Wm “W A. A. V. AW mmmuWuM¢mmuaumm _\_A_._V_-__‘__.__~V.A,__ ‘-_,__,A__________ 05mmc&W.W, Wad “WWWW m put“ ma Wm“ waning smut-Maya by The {named the waywam. Wade. madam-u ammmoguagmumauumw WW ‘MMWMAmMWW. (a) mymm. HE‘S MWintbblmd—bnin mm permeability and Induced 000mm: bmiwbytheconﬁmm actimofmtymnmmybaﬁlebiodmimmtmfwﬁn chphuogm. _m.mmwuommmmmbymgggy(ms} pout-electroshod: hypemymsm of 13m Wmmmmmumormmmm tummaysamrambfnmdmmm. mmmmmmimufthismmhm, ordinarilyabsmtinbnintissmtobemociamdwimm W orhyponyndm (delta bursts) in W. the electro- at: . �- Inmofﬁmmhm,whmcmﬁmdﬂn mpmimnpmﬂthﬂmwhiwwmchcmmuc Imp-W (Maxim, 1956). myimamtmt applica- www.mmaw,mmmm Wtdﬂunhmmdcslmmaadvityuwnuim sensitivity to mdiﬂwtim by muting. tamer-ventilation whim‘ vary my in manta: Wow. The and only memwmmmiupu‘ismmghmumthmmasMupmmmium W 1‘0le «loam-rm (Fink mm, 1955). m «land in diam {dimofamainptdmtodnvolaphymymhmxymybo Nahum. 1n th- activity of annual mtyldxonm withﬁnmoffmemtyldmlim mmmmeWMmmm mamammmemnmmmm. W (19‘8“), inmiz‘ttudyofcz‘iimbml Tmrmd trauma. imlududobumtimofdxpsyctﬂatricpaﬁm underpins mad“ W. Ming the patimts afar 3~7 mam-ms u I'vv: WW7 ~,-- a'ﬁr‘f �mwmmtymummutymmspmunudm mmmsmdmimmmmm-Hmdams in “11:33th with a mammal of the ratio of WW3 infiveofﬂnuixpatm. mmmWaﬂamﬂnyomclmed wmspimlﬂuiddminhumdmhimsmm mmwmmnbmmmmrmmcmy. wmmpatimtinmududnfdhdmm dmmmldnnmwacholimummmmalin thespimlfluid,ﬁuymz“1tisinmtingﬁutﬂﬁa WmmmlymnofﬂuaixtoﬂIwmmpm-emtm." Itammwzmwmuuuzm¢m mamgm,mmmm mmmWoammu. 1%...qu umbyupuudAumu. EEGhyme/uom umo‘mmwumgzmmmmmwxy at Mumwuqm. Radian muammmmmWMWWWWM‘MMMAM 6:!wa Mu 60W Mad «WM. ��-21- WanamaeﬂmtthmaSﬂmmrym 1952). 93a]. (Wain Patimtsinhmuinmltonlmybclmdupm when the in is injected rapidly hydmlyxed; putientl mdmlyl u uhiln ﬁn Groups VI and VII pctimts but a slow hydrolysis rate. V. my pndiat, theni‘on, that tha bleed dulimatem activity huhofWI-lemﬂdbohiﬂu mihﬂnaotivityof WAdlihrunlysiouyboudumaxdingmtnlm VI - VII walla be 1m. mmmhofdwmmm-Iinﬁummtofm Wynclumy and spinal ﬂuid hwls of amtyldnlim. Instadiosofﬁﬁﬂdumgu followingixducudmnvulsim subject-wan idlntifiodinmmafwsoimmultedin a mat mat of now an. activity; while othox- subjacts mind mammmymmMu-Muim (Pinkmdm, 1956). IfWWionntbctimofmd Inbjommuintainhypcnynm in: mm, inwmitdiupp-m them did mpidlynybccadﬁbitingdiffgmnccs in th- kimtim of the dwiimntm-mtylmolim hydrolysis mm. Panhtcnthypcnyndmyuymultfmamd Mcofhydmlysinotmtyldwlim. mociatcdwithlow I mutation of cithcr choline-tumult or mummy-II . (W13, in aheﬁrutcm-I In many paints and «II high). with m—livod hypnmyndmmny. in tissue and spinal fluid any Thus thou mutations provide �. ..‘-.,—r >17 ,...v v“ » , may .1 ~w ~ v....<~u-.~,nz‘y«.r.-~, w‘wrr' ,. ~_»w—-w-y- ash-:1" ~ want »-.1N" vmn www-z-‘w BMW-“‘1‘;- n ~wm~wvv qu-w-m-w- wrumrwS—V-‘a W-xmp‘rvww .22... amumamhmnmmmmm reactivity to W syntax: em, and to poripmm dwlimrgic WON: mmmmmmawmt _1’minﬁn mmiwﬁmupypmu. 1119me whimdmiﬂmomtimdmmmm Wummmmmmnmmmw MhWMmbodntmyodbydmlimmI nativity. Vuodilatimaﬂimuodmllulupmbﬂityis follmdbyimuodmxtsof diam-II, strut-am and electrolytes in int-”114mm ﬂuids. - "r' :1 Wyn-mu wr “unawa- "I“ �mwmminmmdumm mmmnmamswom.mwmm Mmeiduﬁuminbiodmicalnﬂiwwhidz alters cerebral «11.qu activities sufficient to Alter the 1m behavior of subjects. Failure to mountmim electrolyte dim. of acetylebalimi lid W, high md pmismm: {aim to 1m tht results in a failun to produce behavioral ”mummuofdowlmntofmw reflect differences in th- 63ch of subjects «1 dour-remit: admin”, or in their sensitivity to changes in acetylemlinc lawn. tim of M tho diffcmm ﬁnally in W by Mountain These observations provide a the mode the Win for the classificaand by Pink and Kuhn (1960). rational biochemical basis for of action of induced convulsions in altering the behavior of psychotic subjects. These views are consistent with the more general neurophysiologic—adaptive theory expressed earlier (Fink, 1957). �IFn->"'v'—-'—vnu—w— w—r—v-r—u ”ﬁt—W‘- ".9. ‘- -. u » V . WWII-.11“: CI-DUINEIBIC . , nv— rm mw- WIN, WWOR Wmvw—qmvmmpwmw'm x.xm~.;w~ww-ww mum—w". CONWLSIVB AND 13%”, Stalin of cerebral changes accounted with (Pink and Kain, 1956). convulsive trump}! In these studies, electroencephalographic slowing was the most siyzificant index of altered brain function. The dematmticn that premedicetim with prevented the appearmce of slow 1956) suggested a wave high doses of atropine activity (Ulett relatim to ctnlimrgic meﬁiims. and Johnson, The role of acetylcholine and the dmlineatemaes in convulsive therapy is mlified in the following review which summizes the published am. The role of acetylcmline in the tmsmissicn of nervous imulsea has been studied extensively since the first descriptions of Dale (1914) and Loewi (1921). Acetylcholine is a normal which form bamd is in a tissue existing of neurons cmstituent �.,, ~21- ' - "~va ":murmmrnur-v— «m . Ernie-'4 ‘ ,. v “War W'r’W-erd - 4wr‘; Wr' .w-nv 1'5“”uH-I'J. .1m- ,.w;uwv‘.m,w.‘. liberated mixing the excitation process. It is “m ...Y.,_.,. F“. -v-v—.ﬂ, ,. . t .. 7 m" ,..,nvrv.w._,,m_1w V,.w.,‘.,.,.,,v rapidly hydrolyzed thrmgh the specific action of eholinestemee and as rapidly reconstituted by the momﬁiaeetylase system (Richter 19“ 9) . No a Croeslmd, free ac}tylctoline has been reported in normal mmbnospinal fwd despite ﬂu rapid bmakdom of bound acetyl— eholine during perioa of activity and excitement (Tower and McEechem, 19u9e). The oembmpinal fluid normally has measurable cholinesterese activity, however, principally of the "true" or mcholyl hydmlyzing type (Neelmensm and Rothenberg, 19115). In the absence of free acetylcholine and under the conditions described, electroenceprnlogxms fail te show any consistent ehxornality. (a) Effect of Cranioeerebml Them: Free acetyleholine was found in the cambroepinel fluid within a few minutes after experimental head trauma in cats and persisted for varying periods up to #8 hours (Bomstein 19%). The quantity of free aeetylcholine varied between 2.7 and 9.0 gamma related to degree of induced percent, md the ammt was tram. N" ._., , . V.‘ ,.. . �F‘s—“ﬂ 4 w .iv-IJ'n-urr'wlv'i- \I'-w-v|n"r" ».v 21‘.- .IN w— rh- W Th! records were u. . - ~~w~mvww. a?“ : aux-rum W...“ m“- - ‘vv‘ w—a—E.ww~r_~w um... g‘vi- wn-rv-w mun» r: 1- K—‘Irw' «a...» ,. w... w” ‘quw u,- 1,- \w electroencephalogms demonstrated pattern-d changes. first filled with high an voltage fast activity, intense neuronal discharge, only to all short period of flattening of electrical activity. mesa recorded phases were men followed by prolonged periods of high amplitude sharp waves in the delta frequencies. The to the behavioral wt mrﬁzlated 13%:ng of clmges trauma and of seasoned free eoetylcholine. With higher levels of eontyloholine, Bernstein reported greater degrees of abnormality and greater charges in cmscicusmss. spmtanecus . -3- interpreted as evidence of be followed by a -~ post-tmmtic seizms were also EEG In additim. related to the want of free acetylcholine appearing in the spinal fluid. Bernstein $31- applied aoetylcholine to exposed cat cerebral cortex. men the concentration of acetyloholixm was or less, he observed high mlitude sharp the electroencephalogram. When waves 1 gm percent of low frequency in the concentration was increased to �-- <vw'x' >1:- 2 '.‘W',WWV\Wmm/'FP a». an gm . W v- .n ‘n'uv 7 ~m—w-w..». v m... .vvc'wTV-t or v'.‘.wwuwxnn_r'~u—l’v»wy wrv-suw‘ mw~wwn~w~mnpmmm .- »— -nnmmw—rr-muwawu nvre --u w percent, the electmenoephalogm flattened in a fashion parallel to the post-tramtic meant. 11.1% stndies wemWin neurological patients by Tour and Hohdmm (19am). Free aoatyloholine the oumbmspinal fluid only in mam, The 1.: patients was found in with recent head mount grand-ml seizures or after omvulsive therapy. free acetyloholinc varied from 0.2 to Tower and HoEachem of the spinal fluid. 100 gm percent. also assayed the molimsterase activity They noted a sharp rise in the nonspecific cholinesterase fraction (benzoyloholine-splitting) and a drop in the specific cholinesteme fmtim both in patients with head .trmma convulsive therapy. amd 'me oembroSpinal (moholyl—splitting) in those following fluid following spontaneous seizures containing free aoetylcholine did not exhibit such inversion. 3-2:. and-II: concluded that the level of free aoetylcholino varies directly with the dogma of cerebral damage - �that the reversal of the cholinestemse fraction sensitive indicator of cerebral (image. and was a more Electroencephalogrem, taken at varying intervals following mum in most of these subjects, indicated a degree of EEG relation between the abnormality and the appearance of free acetylcholine in the cerebrospinal fluid. ‘hecstmﬁu Watt. an to. mom 0‘ (no. aaetzﬂdwdne m1 incuae in #:24me {Md 4011ng Macadam tum and me a «wad: lactation my mwowa, duomug, (b) «in. degm and dumgo Effect of anathema“ ﬁe and type as in Am mount 05 ﬁne demamcmuagmic dialed bdrawloa. on ﬁb-traunatic EEG and Behavior: Bernstein aministered 0.5-1.0 lag/kg atropine parentually after head tram and denmstmted bloating of the EEG, behavioral and homologies signs of clinical tram. changes occurring Similar EEG and after the experimental addition of intruciaternal aoetylcholine were also blocked by atropine. �w. --r.-~r-v—~--ww- w-Im-vmm 'mm' "-W‘mmv'm" Ward (1980) 'memnmw applied tmse observations to the hum cases of closed dogmas of tram, head injury. In tremnt of patients with varying 20 he aaninistamd atropine subcutmzsly in doses immt in of 0.1 rug/kg. In saw‘oam he noted clinical and others a reversal of the eloctromoephalogmphic effects of the tmma. In a study of .1er and War diethﬁf’ mother mtidmlimrgic drug, (1955) reported sigmificmt alterations in the post-tmmtic elactmmoephalogm. dose in 1&0 patients with in normalizing in The same slow wave 22 A single 1:1th ahmal electroencephalogram subjects land marked «act of atropine in inmt msul’cad in six others. blocking the appearance of activity wm reported in subjects follwing convulsive therapy (Ulett and Johnson, 1956).. (In a later study thé‘authors failed to mplicate this study, suggesting that dosage factors or population mass” may have omtributed to the different results [Jdmm 559;, 19603). M... �8: These obeervatiom provided the basis for a series of studies with other Imam mtidlolinemic ooepomde (Pink, 1958, 1960). The intuvenom injection of experimental patent antidmolinergic «mantis es diethezim. (Dim). Maine, the pipeddylbemiletes, Jana, J8336, and pmoyclidine were shown to induce EEG illusions deeynotmiutim and behavioral alerting, mxiety. J8329 WIN 2299 end md helluoinetiom in nm—ehotmehodc subjects; and e reduction in allow new ectivity associated with e mvemal of the Wm; euphoria, dmiel ma omfmion in these with prior meant induced omvﬂsiom. In these studies, atropine was also emineddn low doses, EEG desynohrmizetion was observed, eoooepmied by considerable peripheral tachycardia, mmaenese and tension. At higher dosages, oonfmion and disorientation min! hypemyndzmm slow a mduction waves and of-hmmiutiea their replacement by lower voltage. poorly organized delta activity with superimposed beta activity. . �~. . a" ~~_,—vn~m«~p.-~W» A q ”We," W. _ ,_. 1..“ ., ,. w." .-—...n-r.. t ,, . u ,t. .( m...w-,V -—..~— _\|=V-\w:w.~a ~FVJH-ﬁ'u—p‘muwt »‘wb‘wﬂ- 7.;r._‘,.,v,wr _ﬁuv;a_n.‘--,,.p‘m .w-wunw... \ .,.—_,.....~ variety of experiments with a potent duolinesteme inhibitor, D}? (di—isopmpyl frequency EEG fluorophosphate) denmstmted high amplitude rapid patterns similar to status epilepticus, as well as lesser degrees of abnormality similar to that noted in post-tnunatic states (Munich 333;, 1950). 1950; Pmdman 3331., 19:49; md Hampson 93.51,. These electroencephalographic doses of effects were blocked pumteml atropine. Chetfield md Dempsey by small (19%) prepared exposed mimal cortex with pmtigmine and evoked electroencephalo- graphic spike activity. 'lha prior blocked this spiking, or ministration of atropine if present, the abnomality could be eliminated by atropine. In contmt to these findings, Brenner md Merritt (19%), applied topical aoatylcholine in cmcmtmtiom of 2-1/2 to to the exposed cortex of cats, and noted no 10% effect after intravenous atropine (1 rig/kg) on the electmmcephelogmphic changes. The montratims of acetylcholine in these experinmts , hmever, was significmtly higher than the topical applicatims (1-4 game percent) new v” rm— ‘7“ .wv-u- �and the intmcisteml (0.2-10 gamma percent) injections of Bernstein (191.6). Bmmer and hmzitt, also made note of electroencephalogmphio effects similar to soatylduoline from macholyl (aoetylbetmthuldsolinefmd Meryl (wbaxyldloline) in oonosntmtims moh lower thm the aoetylcholine cmomtmtims. inmd They ascribed the effectiveness of those oholinergic drug to their lack of sensitivity to oembml dualinsstemses. FM a waist; conduct: that and MAW“ Wencapdz Logaaﬁtic activity Mu a a “nu mu! upwwtaz 06 as deans tome. Manama agent induced by acwjzdwu'm, appuc'mon'og Mam, topical be. backed can it was; a (Lt/topaz, we may on. Magma Wand by humans, as. (c) Carebmsginal Fluid Amylcholine md Seizures: Aostyld'xolino bomd form. is nomally present in mrvous tissues in an inactive wring periods of activity, free acetylcholine is �. ; .m, . .. ..., , m .. .ﬂzwuwﬂurww—w 1.... y ..‘ , v ".4 .4 .. J, vV—I-N‘r W. . . ._... dwlimstorase. The v—- "’W\‘,a(')~\ro" >m»":qnaArv-n3l.!' 'r ~w.'vu.* '4.-:--wr~vr g~u~wr~a~~u~w> www.1-v-u mm it is libemted at the cell madame, by K." w- level of “mum rapidly deactivated bound aoetyloholine is thus the resultant of the prooosses of synthesis, liberation and It breakdom. may be rise during shop and pootulatod, therafom, that the level will fall during activity. lhis hypothesis was support“ in animal emunants and Elliott, by Richter md Cmasland (19%) Swank and Henderson (1950). By using liquid air quick-frosting mthods, Richter and Crosslmd observed the mtl'nsia and sleep gm per levels. mg. The level of aoatylcholim (masumd as brain tissua) to be 300$ higher than poet seizure difference in tissue levels is transient, however, as the “synthesis rate for aootyloholinc in (7 mimo— mulmlﬁnute). Elliott gt 5;, mt brain is high (1950) omfimnd these oheowatims. After- mtmzole oonwlsiom, they also noted that free mtylcholine was always fluid in concentrations up to 3 domtmble in the spinal gm per cent. v -.~~v~ , . .- �- .... nut, v-wwgg—w mauw-Vr‘ u-~0'iv-a—. n... mg. ._, -:Jpag-.'~vw1 4mv..l.‘N'-rv-~Vr‘-\ ﬁrm—um r“ nmww-r w WM- "— w—rw" .“ - -wmv~—-w--m.. -v.‘ F»; "-v-q .~ www-rwt:.v—.m.-v .10In spinal fluid studies in man, Cbne, waer and (lSMB) and waer and McEachern (laugh) reported McEanhern significant quantities of fro. acntyldholine in patients with epilepsy. 0f 56 apilnptic patients, an (77%) dnmnnstrated measurable acetylcholins in quantities of 0.02 to 5.0 «warns» of 1.0 gamma per cunt. The gamma free per cent with an acntylcholine level was directly related to the frequancy of seizures, the extent of olnctronnccphalogruphic abnonunlity, and the relation of the time of sampling to the last seizure. It home no relation to mndicatian, type of epilepsy or level of cholinesteruse activity. Whethcr>tho acutyldholino appearing in the spinal fluid is a byiproduet of the convulsion or whother the increase in acetyldholine is a Wu!!! cause is of the seizure prublamatical. (1939b) suggested Tower and that the increased wetyloholine liberation in not due to the seizura itself but is related to the procnss causing the seizuma. In a study of the hypothesis that �11 the acommlstim of acetylcholine is basic to the seizure process, Tonia (1953) induced convulsions in animals by mtmzolc and dotsmined the level of acatyloholine in brain tissue before and during comulsions. She noted that convulsions are pmcsded a rise in the acetyldmolim contsnt of tissue; Wily falls during the cmvulsion; levels, cmvulsims failed to occur. and an that the content that bolas curtain She suggested in tissue acotylctmline during a omwlsicn by was due that the fall to inhibition of aootyloholins synthesis by increase! concentrations of metabolites such as In. mim Likely ions. #:215de m mmwbg mm {m mam; ohm «:3;qu an wanted (m it inmate in bound tat t3 isms my be inﬂected in sum 5%; ands wanes «wanna: do 5m, and that cumbmt auction, taming and Leap nhuu an to in augment Minoan; tin no. touch as “mum“ pmduoaon imam ing “A as touch . �v......,.,.w.,. ., 7.“..- www. min-w: .~-.Twr-r.~a y: m nvmw-m ...v 'Nwwmu‘agnar' "n T“.1.,1~V;’§mm- ,M m..., . .u..." .“WWFV . m: or..‘m--.w-,.-W,‘_..< WW. m.ﬁwl... .V w‘~...oww»..wm-_v m_w,ﬁ WWW-A“ .12. central nervous slaten Cholineetoraaeez Concomitant with their observations or change: in ooetyioholine, Tower (d) fluid oholinoateraae end noanhern (1949) mnaeured epinel activity. Two types or oholinoetorenoe ere normally found in the epinnl fluid: oholinoetereee—I ('true," "specific,” or neoholyl hydrolysing), whioh has e high specificity for aoetyloholine: til oholineetereee—II ('peeudo.””non~epeoitio,” or bensoylcholineohydrolyging). Both compounds hydrolyze eoetyioholine but have dirforont rate: of hydrolyeie for This meoholyi and tensoyoholine. qualitative dietinotione. activity as a By differential rate permit: reporting the oholinootoraee ratio of the nativity with meohdvl end with bonzoyioholine outstrnten compared to an noetyloholine lubetrete two ratios are round: oholineeteresoai/aoetyicholine and cholineoterooo-II/aootyioholine (with retﬂoa Initials! norMul 08F th/th: 100). In such contains eeteroeeo in the ratio of 53.17 for oholineatoreno-I to oholineotoroee-II. Thus. normal 08? consist: , ,»-.- .- �_.w.W—-« “mu-wow. arr-u- ﬁmwmmm "WW?“ me-‘Ww‘wmvjrimwmmrm )5 s: mainly of "specific" estomes with a small mn~specific ostemse want. In patients with head tram Tower and McEnchem report and inversim of the dualinestsmos with a simificant increase in tbs daolhnsts'mse-II fraction of the spinal ﬂuid dualimstems-I activity. They and a «mass in also observed a relation batman the extant of the momentous” manual with the severity of trans and with the dogma of the olcctmmceprmlompie In patients with 5.an spinal fluid acetyldzoline as a result of spmtmom saizms. howswr. of cholincstsmss or total Why. no change in the ratio duelinsstss-ase activity was found. Certain usunptions my be mad. mgmding changes in cell mm psmability as explaining the humans in duelinsstcmse contamination in found in highest is Gaolinsstcmse-I activity. the antral mm systm mile molinestemse-II in atlas:- tissues, especially blood sewn. pmdminates With an increase in �,7. ,.~.n_..._..‘..,.q—. 7. v . ...,~ “NW... . «g..- Wv-slv'n-nrrh w-rw-muwwwmmmwwvaWmn-mmmmmv‘wvwrvhmv w -w~'r v- acutyloholim levels in interoellular cerebral fluids following stimulation, convulsions or trauma, vaaodilatim md increased cellular pomability may be pmdiotad, with a degree of transudatim of vascular fluids into the inter cellular Spaces dependant on the extent and duration of tha vmodilation (Kabat 33:. 9;, 19%). Spiegal and SpiogebAdolf dummtmted such pamability ohmgas in nmorma "ports 1953). Thay reported inmmd (19141. 19%, 198%, 19148, oomhzctivity of the tissues associated with tho appearance of various ions as potassium and phosphate in the spinal fluid following convulsions. more was also a significant as nucleic-acid nm-clactmlytes cellular pamability mtmims electrically inmoed may imam in such splitting mzyms. Chases in thus provide the basis for the high of acetyldxolino and the managed omoantmtions of dwlinostorasaJIﬂTmr and Hoanhem muse) . '5 �— m‘ w «'7'- M-mrwrvva-mmmw.mw m The increase in ammnstcme activity should be associated with the rapid «stamina of free mtylcholim. Its persistence in spinal fluid afar tram ad 931m related to the sensitivity may be mtmim of the amtyldwlim—dmﬂmstm-I system to ships 5mm (mam md Rathmbarg, and lowar Midtown Mauritius, ad mo mnemtmtims, tha nativity falls off quickly. In contact, of hydrolysis mm minimip «sciatica mm who in few isdestroyedbythe udlliuomds. where bmoentmtim of mtyldwlim in tiasun. tbs mm of hydrolysis by dwlixnstome-I is W. com. m WWW—I to an is nut—specific with concentration. Thus, the mlhwnbfmtyldxonmatmnmbm specific activity of Wm, 19kg; is mpid (3-3 mimeoonds) but at higher th- dnlimanmc—II-m‘tylcholino the m and At "physiologc" and HacIntoah, 1955). hydrolysis of 19445; mktim~ mmmMMMmybemadndmdaseizm me disaoaiatim in ship nouns in a pemiatm amtylmoummﬁneamml relationof mldwline. The seizure may �16 itself in add wt to the of free acetyloholine. 'lhe increased mtylctnlim diffuses rapidly, affecting vascular and cellular permeability and increasing the cmocntmticns of various ions and dmolincstemse—II (SF. activity of cholinsstemsc—II, though of The on the concentration runs to days to efficiency and dependant kinetics, reduces the acetylcholine in the tissues in in! levels mm” 1c»: for the physiologic action of cholinescemse-I. #:1st am Manuela manta 5M, «may 5m «ppm in {Add dowsmaa someway in. «was {on mm 05 ma past a a gestation dzangm “mad Mwouﬂne. Mme. madman; om «toned by (named in 06 «he :1ij (ﬂ 05 in cut 'hc mechanism mun-um at sou moms nausea; system sanctioning. (c) Agglchclinc a EEG WNW and Induced Convulsicns: Altamtion in the blood brain permeability barrier by the continuing action of acotyloholine may be the biochemical substrate for the post- olectmsbock hypemynchrmy of the electroencephalogram. Such a possibility is oviduct in the upon an increase days by Aird 93 9_1_, 1956, W denmstmting in the cmocntmtion of cocaine in brain tissues three afar a series of 12 induood convulsions. His data shows the change in �-17concentration of this large molecule, ordinarily absent in brein tissue to be seeocieted with the eppearence of hypereynchrony (delts'burets) in the electroencephalogren. In studies of induced convulsions. we have confirmed the neny previous reports that convulsive therapy induces electrcgrephic hypersynchrony (Pink and a constant Kuhn, 1956). Despite time the or however, or treetncnts. epplicetion slow the and of extent electrosrsphic duration eppearence. wave activity; its sensitivity to modification by alerting, hyperventilation and barbiturates psychiatric populations. degree hypersynchrcny. end The - s11 vary greatly in early appearsnce of high its persistence throughout the treatment course, hes been described as prerequisite to improvement following electroshock (Pink and Kuhn, 1956). The failure of certain patients to develcp hypersynchrony may be relatedto differences in activity of central seetylehcline and cholineeteraees. may reflect The degree of hypereynchrcny the level of tree ecetylchcline and should follow s decay rate eqael to the rate of ccetylcholine destruction. �vuzvnc—v-w: —. Since previous studies demonstrated thnt ens prerequisite to the it may be EEG hypersynchrony clinical response in convulsive therapy, suggested that the absence of free soetylcholine suggests minimal changes in cerebral function and thus precludes s clinicsl response to induced convulsions.Touer snd their study of creniocerebrsl trauma, hoEedhern (1949s), in included observstions of six psychistric pstients undergoing convulsive therspy. Studying the pstients after 3.7 trestu meats. they reported free soetylcholine activity in the spinal fluid in ten pstients; and en increase in cholinestersse-II and a decrease in cholinestersse~l with a reversal of the ratio or cholinestersses in five of the six patients. From these observations they concluded that the spinsl fluid changes in induced convulsions were more like those of creniooerebral trsume than those found Regsrding the one show in. ilepsyu pstient in the series who thiled to either free ocetylcholine or e cholinesterese ratio reverssl in the spinal fluid, they wrote: that this patient was the only one "It is interesting of the six to show no _.,. �7‘ response to treatment." It is I probably that induced convulsions increase free acetylcholine and enhancing cerebral perniability altering fluids. in intereellular the appearance of cholinesterases. Free acetylcholine by JMAco repeated seizures. EEG hypersynchrony is one is maintained reflection of altered of other electrolytes. and altered permiebility of acetylcholine levels It is these changes in intercellulor electrolytes that provide behavioral changes the for substrate biochemical persistent the following induced convulsions. L/ (f) Cholineatersaes and the Classification of Pezchoses: These studies may also have autonomic reactivity and the Funkenstein and others ( application to the problem of classification of the psychoses. ) have demonstrated a relationship between the blood pressure response of patients -“.:')l\w - w—w - Fry-w M7.“ �rm, w.» v—v-v- ya—_ -7. -. v'*a‘ 1——.r an ad“): , v-u n.7,. y ~. 7' V .. - r—*yx:'\r‘~'7—‘ —..vwr rhw- revues—WWI: a-m-x) v aw. 'IIMIN'.WP1L _,.. wr—Mrn 'w .n-u- u ...- nun-mun—u-wwwsrx— I‘d 'fllr-nr-F-qlf r".:'m~ — - —» ~ to injected meoholyl and their clinical response to convulsive therapy. which induce! Neoholyl is e potent oholinergie agent Vlsodiletion, tachycardia, sweating, and It is inoreesed peristelsis. rapidly hydrolysed by cholinesterese-I and slowly by eholinestsrese-II. blood pressure or subjects tells etter injected The meeholyl end returns to the baseline in a variable length of time, 2‘2;, five to pressure returns to the hgaeline in as Groups Pstients more than an minutes. I. II, or III reactions: 5 whose blood minutes ere olessitied those whose blood pressure takes so or more minutes to return to baseline, as Group and VIII reactions. The Group I reactors here s 9% improvement reactors s rate with convulsive therepy, and the 35% recovery rate. In contrast, the reactors heve s 89% (Punkenstein 35 3;, 1952). petients In whom IInIII Group VI and the Group VII 3 9'71 recovery Patients in Funkenstein Groups I to III upon as Group VI may be rate looked the injected meeholyl 1s rqpidly ~ �. . ”(Inni- rwlv‘v -. v -hr ~r. ‘r Wﬂm‘r;vz.z ~~w~ ‘ vmvrmm-mwvnvmwurr . . . . -.n- . ~v-cv rwwmvrrw-r ’Hm . , . warm-n'ku-w—w-vwvu-r‘mwm ’W'I-W‘WW . , ., . ‘23.. Groups VII v1 and the while hydrolyzed; slow hydrolysis rste. we may patients have a. the therefore. that predict, would 1.1!! Groups of blood oholinestersse nativity levels be high; while the setivity of Groups A VI-u-VII would be low. central odds nervous be rsgsrding similsr analysis msy devsIOpeent of the in system levels or oholinsstersse~l EEG of soetyloholine. levels and fluid spinal hypersyndhrony In studies of EEG changes following indueed eonvulsions resolted in seizures subjects were identified in whom a few a great amount or slow save activity; while other subjects (Pink seizures and to frequent exhibited few changes to many and Kuhn. 1956). If electrogrsphio hypersynehrony is s that probable is refleetion of inoressed tree soetyloholine, it subjeets who rapidly (the usintain hypersynehrony end those in whom it differences be exhibiting hours) disappears nsy hydrolysis oholinestsrsseoseetyloholine the of in the kinetics systems. Persistent hypersynehreny may be seen to result from associated of soetyloholins. s decreased rate of hydrolysis with low or oholinestersse-I either oonomntrstions of z - w mv as ‘— e �nw—w—uurw—u-A ~ «wv-u . "Hp; v-r w: w-ws-u—mxw —» al’im'rw‘imﬂl'wnnmmﬁ.rww-‘wmm' cholinesterasemII. Conversely, in patients with hyperaynchrony. cholinestoruaoul and fluid may be a basin fbr :yutom 1110111 : unusually high). wwwvvnwa >vv'wwa-uww «VII-MWI—w-W short~IIth .1: in tissue and spinal Thus these speculations providn congruent hypothesis rognrdlng central norvnua ruaativity to electroshock, and parephoral ahelinergio 09‘. �‘‘ r— v» -v «'1: -w:. . ~v~wr 1.». —.vn.~n—u nvw .w is w,“ . V m .,._v you-um: v...“ .uw m...” w. i. (“Hwy . , . V . v—wr\wl~;r‘-V‘va"vwg . 7-..,emu.,_,._c w‘,_pwmi,,”.w.'w.ww rtr‘ ., 1”,.“ M y OOHGLUSIONI be to e neehsnisns appear Gentrel eholinergie The convulsive the therspy process. dignifiesnt teeter in induced that to indioste be date interpreted any published Leonvulsione ere ssseeisted with en increase in intereelluler be by destroyed than esn to levels greeter seetyleholine eholinestersseal activity. Vhsodilstion and increased oellulsr pernisbility is relieved by increased amounts of eholineetsreeeoII, other and electrolytes in inter- celluler fluids. It is these changes that ere reflected in the increased electrical hypersynehreny which is recorded in scalp electrodes, and which esn be modified by sntieholinergie drugs. as stropine, beneotysine, dietheeine, proeyelidine, etc. It in these changes. else. thst provide the change in biochemical milieu which to slter alters cellular ectivities eufﬂ.eient the behsvior of subjects. Fhilure to induce high and failure of aoetyicholine, concentrations and persistent ( . . 'W—vnww �- —-——--p~rm- ,v-vln’ .-. ‘w-m-w --v< w u-wv «m ”uru-ewmmw‘ vat—rm,“ W'WV -. - . wwwm mmnmnuw—wm "wrrm,w— "-1. Wm, chengpe, concomitant results in a failure to induce electrolyte to produce behavioral change. Difference: in the rate 0! development of cerebral chengee may on reflect differences in subjects in their reliance cholinergic mechaniene, or in their sensitivity to changes in acetylcholine levele. These differences provide the basic fer the claeeificcticn cf the menilly by my: and Kuhn (1960). 111 by Funkenetein and �.4 w . .._u~mv — \w"wxww ~ wlxmw-mwmmwwrlmmrrw IV: 6-6-65 CI‘DIINEmIC WISE, CWVULSIVE AND BBMVIOR W, Studies of cerebral changes associated with convulsive therapy have indicated that the development of early and persistent signs of altered coronal fmctim are prerequisite to oranges in behavior (Pink and Kern, 1956). In these studies, electroencephalographic slowing was the most sigmificent index of altered brain function. Th demonstratim that premedication with high doses of atropine and Johnson, (Ulett slow of mve the activity prevented appearance 1956) suggested a relation to cholinergio nechnisms. The role of eoetylcholine and ﬂu cholinestemses in convulsive therapy is amplified in the following review which smrizes the published data. The mle of acetylcholine in the tmsmis sion of nervous impulses has been studies extensively since the of Dale (19136) and Loewi (1921). Acetylcholine constituent of nervous tissue existing in a first descriptions is bound .21 normal fans which is �. -~»-.- cwlwx—Wm.m~mn mmmvwvx 'w'w-m‘ w'dnuev—Wn —-'-v.":'-v-yvl~<-wmv -‘-w'-W"’mnrm"u'm’mmp '«ai-lu'vwv'w»; umpnw-so w-wm'n It is liberated driving the excitatim process. W the specific action of ctnlimstemse and as rapidly recmstituted 19:59). mpidly hydrolyzed by the dwlimacetylase system (Richter 8 Welland, free ac etylcmline has been reported in normal No cemhmspinal ﬂuid despite the rapid breakdom of bound acetyl— choline during pariah of activity and excitement (Tower and HcEechem, muse). The cembmspinel fluid normlly has resemble chclinesteme activity, homver, principally of the "true" or mechclyl hydrolyzing type (Nectmensm and Rcthmberg, 19u5). In the absence of free acetyldxoline and under the cmditims described, electroencephalogram fail to shm: any mietent abmmelity. (1:) was fmmd Effect of Wiccambml Mm: Pme acetyldioline in the cerebrmpirml fluid within a experimtel heed tram varied between 2.7 and 9.0 dew after in cats and persisted for varying periods (Bernstein 19%). an hours to m related to few minutes gamma The qumtity of free acetylchclim percent, and the amount was of induced trmrne. -n way-a ---1-m'— «mu-w v;- �v ‘ .v-vuwv—‘uwuwaI—r'm mm ‘lh'une‘ “an”, . - 1W um van-mar ammw— mmmx($—‘Wv~ ~-;Www Ww-v' .wma a..- ‘nv‘w I'u Commitmt electmemephalogme Th records were first filhd with mmted patterned dwxges. high voltage fast activity, interpreted as evidmoe of m intense manual disclmze, mly to befollmdbyasrwrtperiodofﬂettmingofallmcomed electrical activity. 'Ihese planes were then followed by pmlmged periods of high amplitude sharp waves in the delta frequencies. The to the beheviml enemas were mutant of measured fme related to degree of acetylcmlim. tram and With higmer greater of acetylcholine, Bernstein reported degrees of abnormality and greater- changes in moiwmss. levels EEG In addition, spmtaneous poct~tmunatic seizures were also related to the mt of free eontylcholine appearing in the spinal fluid. aoetylcholine Bunstein later applied to expomd out cerebral cortex. mm the cmmtmtim of acetyldaoline was 1 gm pement orless, Mowemdhimmlitude sharpwavesoflwfmquencyin the electmenoephalm. When the concentration was inmd to w... wal‘r-vunu .,.. u ��min-u .41. - v... and :— » -1~—— “Va-x v,m..,».«n—n ww'Al'wr‘w'nx‘xa'r .. ”-p- vwrn 'iwrylvv.-ws“ «ﬁrm-mu». tr'r'r—I‘lumm$1~I'm’w-VWW-Iv‘rn'wwu .~ that the reversal of the dwlinestemse fractim sensitive indicator of cerebral BMW tram Jag-Anny... ”a.“ r‘np‘woyppﬂ" v—y- x w— v—w-1,msw»: v. was a more damage. were takan at varying intervals following in most of these subjects. me authors reported the relation homunmofﬁmahmmntymdtheappeammoffrm mtyldwlim in the w‘bmspinal fluid. Thu: AW my We and that a «the mount 05 (m acdytcholxiuc 5mm summing Weenebmdtﬂawm batman the mount 05 mayuuz Won W Memory, main wind In the Micheline, (1)) M indicate m dcgm and changes Effect of and typc 05 in AM mm on unﬁnisnmd 0.5-1.0 awomuphatogmmc bchawéoa. at-«mmtic nag/kg (an. atropine EEG and Behavior: pmtually after mmummdmmmmdbmmofmeme. behaviomland anatomic aims of tmuna. Atropine also blocked the clinical changes similar to head mum EEG md seen following the experi— mtal additim of intracisterml aoetyldnline. n-w �.r .nwm-nuw v m, 1‘ x—~.wwrv-—um—mw“n-«WW«-Waqm v Ward (1950) . mm dawn c." m xwwuv— m ‘- um ,r—m—xw applied thase observations to the treatment of hmm cases of closed head injury. In of a: patients with varying be administered atropine subcutaneously in doses tram, of 0.1 mg/kg. In 20 some cam he noted clinical immanent and in others a reversal of the electmphalogruphic effects of the tram. In a study of dietlmint. another antidmolimrgic dmg, Janknor and “dancer (1958) reported significant alterations in the post~trmmntic olectmenoephalogzm. dose in #0 slow single intravenom patients with ahmml electroencephalogram resulted in normalizing in The A 22 subjects and marked immvemnt in six others. sum elect of atropine in blocking the appearance of um activity convulsive following in subjects reported was 1956); (In a therapy (Ulett md Johnson, later study then authors failed to mplioate this study, suggesting that or population changes may have [Johnson 93.51., 1960]). dosage factors cmtributed to the different results .u-wmwm �"rm—W .7, . .\.—.~ v‘ u. w wr— w' w --=»—-.--«-v- 'w' nu.- "I 1- nun.“ mm-‘Ivm’lwuu‘twr "uvmq-WIWVWW. “HM-:rv‘lwr." 1— x—A 'i‘w'wwuvuwrwwn uvvmw": «rung-w unmoun- . aw awn:v-v—nnJ—m variety of experimta with a potent dzolinestomo inhibitor, A DI? (di—iaopmpyl ﬂmmophosphatc) fmqumcy EEG mutated hiya mpﬂttxde rapid éimilar pat-hams to status epilepticus. as well as dam status (Md: 5331.. of abnormality similar to that noted in pmt—trmtic looser m 1950). doses of mad 1950; W ﬁg, 19139; aid Won 95%, eleotmonoeptulomphic effects were blocked by small pmteral atropine. Chatﬂald md miml com»: with proatignine Way (19142) pmpamd and evoked electmmoamalo- graphic spike activity. The prior uninistmtion of atmpim blodmd this spiking, 'cuminatod by wif mat, the abnomlity could be mine. what to these findings, Banner md Harri.“ (19152), applied topical mimome in Momma of 2-1/2 to In 10% to tho awed cortex of cats, and noted no effect after intravmous WClm/kg)mﬂne1¢otmumphalommicdmges. 'Iho mtmtims of acetyldnlim in those experimts , mm, was significantly higher than the topical application: (1—1; gm meant) m "nm‘lV‘I-"WPX' mm» �.9— intmiﬁuml and the Bormtdn (19%). (0.2—1.0 W gm percent) injections of and Pbrz'itt, also made mate of elmwuhgrmic effects similar to aoetydxolim from ucholyl 1n (mummyldwline) commenting: dam. '33); m and dozyl (carbmayldloline) later than the acutyldnlim concentrau ”W th- inmmd offeetivomss of these momma. drum to their mitivity to animal lack of durum. FmavWa‘WandWaMu my I mama that Waupiwgwm «may mm by «wane, uau we. on a a mutt 0‘ mm. Magnum: with chaunutume blocked M (:3) We): Waxed bg We. Role mm away applied.- can be ‘ of Oanbmsgg ﬂuid @951me in Saizums: Amtyldzolim is normally present in mrvous tissm in an inactive bound fem. Daring periods of activity, free amtyld'aoline is ��. N...- ~mv nun-7‘ «mamwmw-nrwu-W-ww-m—mmw Yum—U" v2»: 'lwwvv Wx-uwww- vv'r‘wr-I w-ww ‘t‘I—L :\ mean-v1- avast-Lo— nary-row: .10... Inspimlﬂuidstudiesinm, (19%) and Tower md Warn Cone. TmrmndEadnm (mush) reported significant qumtitios of fun mtyldwlim in patients with epilepsy. 0f 56 cpilaptic patients, an (77%) demastmted ﬂammable free Michelin in quantities of 0.02 mm of 1.0 gm to 5.0 gm per cent with m per cunt. The acetylcholine 11.3ch. was dinctlymlaudmﬂmfmqmcyofaeizm, theemntof 0W0 dun-normality, and the minim oflthe It‘bom lagt seizure. tha to angling tingof no mmim to of Ila-dictum. type epilepsy or lewd of dwlimtemse activity. WW a W 61011110 Michelin: appearinginﬁn of the awn. is a (mm of the Madam arlwhetha-r the aim fluid is spinal W is pmblmtical. (mush) suggested that the in acety1~ Tower md' inmd acetyldwline mlat§d liberation is not due to the seizum itself but is to the process casing the seizum. In a study of the hypothesis that v w. �' “W "m’ W“"‘W*P"W‘ TW""-'“'M'rmz‘m-ww' : ~<I w'l-w' uzm-w-wwnw-rmr wrmnsa-mmrw “my; —nwu—n-»mrw—u-—r w-w w n—w- wan-m .mmw- n- -_w.—..——,aw—. mw'hmmrmw m «w -11. the accumulation of acctylcholine is basic to the seizure process, and animals metrazole convulsions induced in (1953) by Tcrda dctcrnined the level of aoetyldmlinc in bmin tissue befom and during convulsions. She noted that convulsions are pmocoded by tissue; of content that the content in the acotylcholinc a rise gradually falls during the convulsion; and that below certain lcvols, convulsions foilod to occur. fall in tissue acctyldholinc She suggested that the during a convulsion was due to inhibition of acctylcholinc synthesis by increased concentrations of notabolitcs such as alumniumicns. Tho passagp of electric current through brain substances induces a change in callular activity with an increase in free aoatylcholinc to lnvcls sufficient to induce a grand mal soizumc. Tho prosenco of free aoctylcholinc in the interocllular fluids is associated with electrical hyperoynchrcny, reflected the EEG as dolta slowing. (d) Effcct of Electroahock on Acctxlcholinc and Cholin~ saturates: Tower and McEachern (lShQa), in their study of cnanioocrcbnnl trauma, includcd obscrvations of six psychiatrin �, .— “7 hin""'-"""""’n w—xwwr‘W'wv-Wsmuwvw ”‘1.meer!. ., . A a .m "Jaw-«v 7 wmr- mm- vmm:wwwq~mw‘m¢7~w 1"‘3-0! w ~12-- patients attu- 3-7 Linda-going mmrulsive therapy} Studying the patients mam-atmﬂay upwind fm Micheline activity an.incseaae .ad rxuia in.two in in th. Spinal patients; dwlimsteWII rawnrsal a: a damase in and mum-I with a the ratio of cholinesteruses in five of the six obsewatims time has paints. W they concluded that'the spinal new; convuisions were 11kg those tunic ahansps in induced mm a! than those found in epilepsy. Ragarding the ma patimt in‘the series who failed to show 01th» I’m mtylolnline or a dwlirastemao ratio reversal in this intsmsting the spinal fluid, thoy smote: "It is that pstimtmﬂamlyaaoftrasistosmwnompameto mamt." WM than. a show: in «1mm, cons/Lamb“ augment about ﬂu. note 1,: 1.6 05 “chaste that 7W!- acaytchaune mwmgaammwmmuwsm <1“ch 4:.qu and Adm/Lu enhance. autyb Ls that «sorghum damnation, �“mu-w. v— vaw >W—Wrﬁww.vwam—.m .‘w'wwrr Mr“!!! wrwwumm'm WV - W9 augment wmm 1WW"WYI3"W'FVI'W‘VW wwmmww-zw (”wan-vim -13- Lawn. tww 05 “Midtown whiz: “up and auuthau wetytchauu puduocéou inc/mum about. (was. (2) Central Nervous Sygtem Cholinesterases: Cbneumitant with their observatims of W (1939) muasumnd spinal in acetycholine, Towor md Hcﬁadxem fluid cholinesterase activity. The types of'dholinostoruscs art normally found in the spinal fluid: momentum—I ("trm,” "specific," which has a <92" mdmolyl hydrolyzing) . big: specificity for amtylcholim; and duolinestemseoﬂ ("peeudo,” "um-specific,” or bonnoyldwlinc-hydmlyzing) . wands hydrolyze mtylmolim but have different Both rates of hydrolysis {bu-ulcholyl and banzaylcholine. This diffcrantial rate permits gamma distinctions. By ram-ting the cholimsternse activity as a ratio of the activity with macholyl bonaoyidaonm substrates two mama and with acetyldmbline an to- substrate ratios am fomd: momentum-Ilacetyldnlim md alwlimstcmeII/amtylmolim (with ratios normal CS? Ach/Aeh a 100) . omtains ostemses in the. ratio of cholimstcme—I to dmlincsteme-II. Thus, normal In such 33: 17 CS? for consist. �-.v rmvs 'mm l-F'W'WW wmmmm .mpr—w— rm . . may of "specific" caucuses with a small now-spedfic estemae coupon-mt. In pathmts with hand inmim of tho cm the fluid fraction of the spinal activity. dam the and 'mey also observed a of tha dwlhmstomse with ad mm Wm report and daclizmtomes with a simifioant increase in the “Wm-II Wanna-I mm Tower and of the W a decrease in relation batman with the severity of cummpmlogmpic mun. In patients with increased spinal fluid amtyldxolim as a multofspmm of Wm warm seizmu.‘hdnvor. or total dwlinestcmo activity in the made was found. metimmybomﬂomgamﬂngdmgeainmn mm activity. tha pemability as explaining the WWW-I m1 mm: syatcm is fomd 1n imam Wt in dulimstemse mnomtmtim in mile dwlixmtemesﬂ pmdmimtes in 0th:- tissuaa. especially blood scrum. With an increase in �,- xw- m-mmwm m anatylmolina lawla in intercollular cambml fluids following atimlatim, convulaima or tram, vasodilaticn md cellular pamability my be ﬁlmed pndictod, with a dogma of mmudaﬁm of vascular fluid: into the inter gallular spams mtmmmtmdamimofmvmodimm(mt g; g, 19%). Spiagal and Spiegal~Adolf mutated such pamabmty W 1953). marred inmaaad omchctivity of the tissues Thay associated with W than in mm reports (19%; 19u2, 1m, 19%. appaarmca of various ions as potassim and in the spinal fluid following electrically indumd commie». Thom was also a simificmt-imm in such nm-aloctrolytaa as manic-acid splitting anzymas. (images in of circumstance-11 (Tower and Wm lSth). _ �wwlv mun-am.- V‘r‘ww.\\.sm uwrvvu‘x' ..- me—wwmvmvwn .q-zwuwm pawn-w ., cannwmuw v-Mr-ru-m‘ovr WWWWW «um—a. -.--< www.mm -15.. The increase in dwlinsstsms activity should be associated Its persistence with the rapid dostmctim of free asstyldxolins. ' in spinal fluid after trauma and seizure of the amtyldxolins—dxolixnstsmsvl may be system related to the sensitivity to concentration relation- ships (Nsdmsnsm and Bothsnbsrg, 19%; Tower and 3mm and MscIntosh. 1955). At “physiologic" Wm, 19%; oonosntmtims, hydrolysis of aostyloholins is rapid (3-H mimosaoonds) but at higher and mosntmtims, the activity falls off quickly. In lomr W, the cl'nolimstsms-II-sestylohomm relationship is naiospscific and the rats of hydrolysis increases with concentration. usual levels of sootyldxolim stosll sambmms is specific activity of cimlinsstemss-I in Thus, the destroyed by the few milliseconds. Wm omosntmtion of soatyldioline in emsssivs excitation leads to an mm tissue, the mm of hydrolysis sxosedsd. com. The ssizm threshold may by cholinsstemss—I is be roamed and a seizure me dissociation in mstylduolinwdxolinestemseul relation- ship results in s psrsistsnos of aostyldaolﬁne. The seizure may �mm “a." "W.— .mﬂmpw txm mm Wm-mmwmm—mwm m "m . amtyldiolixn diffunes rapidly, affecting vascular md cellular pamability and and Wins catamaran-II W of in the concentrations of various ions CSP. The nativity of dwlinostamse—II, cfficimw md depuuhnt low on the oonomtmtim kinetics, mmmldnwninmetissmsinhwmtodaystolewls for the physiologic action of dwlinostemse-I. (I) mo md Classificatim of mmm, gmmm . mamas: Altemtion in the blood brain pemability barrier by the continuing actim of mtyldmolim may be the biomenﬁcal sub- strata for the post-3W hypemyndumy of the electro- mmpmom. Such mag, 1956 is possibility o mom in the report by Wmtingm 5.11m intha concentration of‘ miminbmintissmsmmdaysafteraserieaofuinduoed Gambian. this His dun 1m mlccmln, aim the change in momtmion of mutually absent in brain tissue to be ��mm. WV wwwm'wmmww’rr‘v m (memwmw“'m'ww .19- my be mama“ in the. mum nub/mug ad the. dwuuuthu— hypmymmuy Awwu. my mama Whom 1’th be. oﬁ acetyl— dummzd hyd/wtyau to as a mt: {m mm an Law ma mammom wowed mun, u Cthénutcmc-II. Comma (Ly, in and Wmmv! WW, my be muddy 06, mm ~11 ewwc with 5h0u~uv¢d in Mac, to the Wainwmmk Mammy. WW and spinal (laid high) . stat-ﬂea ’meae may also have application 3 chaunutmvr MM}: between the blood problem of )have pmsum mponse of patients to initiated médblyl and their (minim). response to I convulsive mm tram. which is cholinorgic a potent hamlyl amt vaodilatim. tachycardia, mating, axomestemeq hydrolyzed by is It midly astemo—II. "me blood and hemmed peristalsis. and slowly by moun- pmssm of subjects’fans after injgcted manlylmdmtmmtoﬁnbmeuminavariablplmgﬁmofﬁm, �-m. “...u. “v ,,.. ‘mw you ,,, d . ”are". ‘V‘ -- m, mus-www- I vm‘ five to W rm www.- w. m 1 ”3.... v- .-r'l w - way-vr—v- .m-MWWWW. “gnaw-why , Patients more than 20 minutos. Mums to the baseline in 5 an minutes ,,.mu(._“‘,_,m,“ . whose blood classified as present. Groups I, II,’ arm mmmmbaaoline, amHdeIImactions. MW]: or III mactima; ﬁnes mean blood rams hm a 9i Wt the aroup II~III reactors a 35% rate pmsm takes minutes 20 and convulsiva'thompy. with. unwary rate. In umtmst, the MHmmmmmaast'mddnGmupsvnath-wverymu (main 5; g, 1952). Patimtsinmﬂcmaminmltolnmaybelmdm as patimts in whiu the We may the injactgd mdaolyl is rapidly hydrolyzed; Group Hand VII predict, hvels of W when: Won, W H~Vii a slaw hydrolysis rate. that tha blood Esolimstemo activity -I~III would be him; whim the activity of ma be low. regarding the data for eatcmenl, in patina hm We recall hem a similarpmdictim mntmlm which the domiopumt syntax: levels of cholin— of early and sustaimd EEG lypamynclumy and elevated spinal fluid levels of aoetyldlolirm was minted to a low level of dwiineaterase activity. mus, w-n —. wu- �,-.n I ‘ -21- the data of paripiuml stimulation by dwlimrgic agents is wt to the hypothesis regarding mutual “activity to electroshodc. mm system m1? m'.mrrw-uww gum �CIDLINBMIC PECHANISIS IN WV}: m m M, NJ). From PM the Departunt of at the Missouri Institute of Paydziatry. Lhimity of ransom School of Medicine, 5WD Arsenal Stunt, St. Louis, Missouri 63139. Aided, in part, by usms grunts 1914-927, 11-1—2715, mmzus, and Iii-11380; and the Psychiatric Renard: Fomdation of Missouri . �VI: 7-17-65 GIOLINERGIC MICHANISI‘B IN CONVULSIVE W Despite extensive application and study, the mode of the oonwlaive therapy process “mains enigmatic. has been devoted to neurophysiological social ) aspects , ( Much study l, ( ), clinical psychologice1( . of action ), ( elucidating the present neuro- ). physiologioal-edeptive View of the process ( 'me wly development and persistence of signs of {motions were reported to be (Pink and m, activity es the The this and muisite to changes altered cerebral in behavior 1956), with electroencephalogramic slow wave most significant index of altered brain function. demtmtion that pmdicetim with atropine inhibited slow wave activity (Ulett and Johnson, 1957) and the report that mtidaolinergic «wounds reversed these clinical as well as electrogrephic menses (Fink, 1958) suggests that the biochemical basis for the mvulaive therapy process may be in the cholinergic mdmmisms of the central nervous system. This review discusses the available data mending acetyldxoline and �and the dualineetemsw in the convulsive therapy process . Acetylcmlim has been extensively studied w an active agent in the transmissim of nervous impulses since the deecziptiom of Dale (191») and Ioewi (1921). It is first a constituent of nervous tissue, existing in a bound form which is liberated during the excitation pmoess . It is rapidly hydrolyzed through the specific action of molimaterase and is rapidly reconstituted by the choline-acetylase system (Ricmer and Crosslend, 19%). In normal cerebmspinal fluid, free acetylcholine is not present despite the rapid breakdown of bcmd acetylmolim during periow of activity and excitement (Tower and Hailed-tern, wheel). The cerebmepinel dwiimnteme activity, however, medxclyl hylmlyzing type fluid does have maurnble principally of the "true" or (Madman md Rothenberg, 19%) . In the absence of free acetyldmline and under the conditions described, electmenceplumgm fail to show elmozmlity. �(a) Cholinemc Aspects of (kmiooembml Trams: Free eontylcholine was found in the oerebmspinsl fluid within a few minutes after experimental head tmuma in cats and persisted for varying periods up to “8 hours (Bernstein, 191:6). The quantity of gm free acetyldloline varied between 2.7 and 9.0 the wt was Wt related to the degree of induced electroencephalogram menses. The records were percent, and tram. demtmted pet-rm first filled with high voltage fast activity, interpreted as evidence of an intense neuronal disdurge, soon to short period of ﬂattening of all recorded he succeeded by e electrical activity. These phases were then followed by prolonged periods of high saplitude sharp waves in the delta frequencies . Ihe behavioral changes were related both to the degree of tum and to the want of measured free aoetyldwline. 9th higher- levels of aoetylcholine. Bernstein imported greater- degrees of EEG abnormality and greater damages in consciousness . �Spmtanccm post-traumatic seizures mm also related to the mmt of free acetylcholine appearing in the spinal fluid. Bernstein applied ccatylcholine to exposed cat cerebral cortex. M the cmccntmtim of acutyldrolinc WM 1 gm low frequency of waves unplitudc sharp high percent or loss, appeared in the electroencephalogram. men the cmcantmticn was Wed to 2 gm percent, the electroencephalogram: flattened in a fashim parallel to the pcatétmumatic records. Pmllel investigations in neurological patients by and Madam (191ml) Tower dammtmted free acctyldrcline in the ccmbmspiml fluid only in patients with meant head trauma, recent grmdoml seizures or after clactmconvulsivc therapy. Free acetylchclim varied from assaying spinal fluid 0 .2 to 100 gm percent. In drclimstemc activity, they noted a sharp rise in the nonopecific cholincsterasc fraction (benzoylcholimnsplitting) and a drop in the specific cholinestemse fraction (maholyl-splitting) in patients with head trauma and ﬁll-owing convulsive therapy. The cerebrcspinal fluid did not �exhibit such inversion, althougz lit command free acetyldxolim. after Spontaneous seams . that the lavel of They comluded two watylcholim varied directly with the dame of cerebral damage and that reversal of the dzolimsteme fructims a more sensitive indicator of mmbral dmaga. taken at varying intervals following mlntim batman the W EEG 935;, Ehcﬂmmaphalom, also indicated a abnormality and the of fme mtg/10mm in [Add 1 Kovach Thu dogma of mm. was ﬁne cerebmspiﬁal fluid. 1957] mmummmuummcam maumuuam WWWMdﬂwmo‘ (an Widow, the ham and. type. 0‘ WWch abmmutg, mmuummuuaappmu Mandated pm. �Fwy-.. W, .,- V l .7..— (wt‘ mm- M 1-... WWW“ 'mw .. :‘w ,v- a. , , m1. vv vv-uw-u-,o-vw-w.w.w ‘V'I-V-t.mNrIV-WI AntiohoMc (b) wry-urn "I“ wv-mvww—w-wuam—run-mnw—uu—wxw m and tram: ”myr—w—vm—wwwq wrivlwmwwr-wﬂw v: ,«w- me electmmphic, beluvioml md nemlogic Sign of trauma were blocked by the mutual ministration of 0. 5~1.0 ag/kg atropine (Bomatein, 19%). as were similar olinmel oranges occurring after the inmatemel additim of acetylcmline. Word (1950) applied these observations to the Moment of closed head injuries. In 20 patients with varying degrees of amine tram, ministered subcutaneously in done: of 0.1 ng/kg, mating clinical improvamt in some and a reversal of the electmenoepmlogmphic effeots in others. In a study of dictum, mm mticmlinergic drug, Jenkner and warmer (1955) mpwted electmmphalogxm. the postnmtmtic done he in forty patimts with A altemtims in single intmvemua em}. electroenceprulogrmne resulted in normalizing in twenty—m and muted imminent in six others. Similar observations have been reported by Denisenko (1965) using methylbmectyzim and ‘ meantin in poet-trumatic ﬂock and cerebral edem. animal experimts of ‘ . u—v. . .mmrrmm �- .v -'4In v'nvwr»vr Anew—Wt nv -V “war w rr v. I1wurwuu‘wv gm" w'twv‘z' 'or‘ Ila-3 », ~.,r-.mwm-w-—~ v.“ ,1,“ .‘ .v-y m twinw-vp "Ivy" .m.‘ war. .r my rnm ~; . "mam—q .74- ..w w. .... , Thee duet-mums wen eeueeed in the omwleive therapy process by Ulett and Jornem (1957). Then workers eduiniotemd doeegeaofatmpineupto the patients received that the was mt: mper'daydm‘ingthemeke «mm of slow wave therapy. They Wed activity produced in these patients significantly has then the omtrol m who had not mind the atropine ministration. (In a. later study these eutm failed to replicate this etuiy, suggesting that douse factors or populatim changes have Wed may to different results [Jomem 3:311; 1960]). These observations provided the basis otlur 1cm mtieMlinergic W for studies with (Fink. 1958, 1960). The intmmue injection of emerimentally active antiomlimrgid comma es diethedm, benectyzine. the piperidylbenziletes JB-318, JB-336 and JB—329 (Dim). and wan-2299 induced deemmmiution in psychiatric eubjects. These were associated with bernvioml ﬂirting, anxiety. EEG EEG clmges tram, illusions and hallminetima. In patients um had recently �,__.,,__,,.. . V... 7)... W- w -— ....,... . .V-r—w, .wx-7'Uwiwt ~s| '1‘ u u a...” ,.. w‘mmjwlm‘vwnmu‘m . "0...an ”mi—W- .thwuww. ‘ m.,.m-.-.,,, M_ "H". H," ., ,.. .w-.m.1, , a“, r .neqy..-mw—-; - .r» vr'." received eleotmoonwnoive therapy. the eduinietmtim of theseoomomdemeeaooietedwithemdmtioninslowmve activity and meme]. of euphoria, denial Atropine was also EEG emined in desmlumiutim WI m and tension. and confusion. low doses. and obeemd in these administratims, mind At higher superimposed beta tachycardia, We, hyper-8mm slow waves, followed by lower voltage, poorly activity with by activity mined delta “mind by progressive confueim and disorimtatim. Both in oenbral mm and indumd omvulsime, the ehotmﬁmphio clauses my be modified by the comm-rent administmtim of micmmemic drugs, thus Weed mt: of aoetyloholine or- mating that incmeeed cholimrgic receptivity is eeeooieted with the high voltage slou’ wave activity. (o) 13min mmnm and m! mmm : SimilarEBGohmgeemdthblookingthmfheshenobmmd following the direct application: of aoetyloholim to the centre). mam. - .rml... ww—wu-uuwy w— “WY—r! �'lho anninismticn of a chainsaw. inhibitor DP? (di-isopmpyl fluomphocptute) elicited high maplitudo rapid frequency W EEG patterns similar to status cpilcptiws, as well as similar to those of post~tzmmtic states amen 23%, 19%, 1950; and ma: gag, (W We 1950). effocts'wom blodcad by small doses of pmntaral atropine. mat was 91; 5}; EEG The inmaso in acetyldaoline after tetmrdxyl pymphosphate named indumd and routed to the toxic mmisfostatims (Wand 3m, PM: 1952; ('11???) and convulsims 1957;) Chatfiold and Dummy (19h?) pmpamd exposed animal cortex with Tho pmtimim and ma chmmlomic spike activity. prior administmtim of atmpino blodcod this spiking, or pment, the mutuality could he oliminatcd by if atropine. In contrast to those findings, Bram” and Merritt (19%) applied topics-.1 acctyloholim in to the expound cortex mania-ts of 2~1l2 to 10$ of cats. md mted no effect on the electroencephalographic changes after intravenous atmpim (1 Wits.) 'me concanmtims of acatyldnlim in ﬁxes: cxperimanta, �10 harem, wan higher than the topical applications and the inmoistomal (0.2-4.0 Bernstein (19%). Exam» and gm (1-14 gamma percent) pennant) injections of hwitt also made note of electro- m unholy]. onooplulogmphio effects similar to Midtown (nostylhotmﬁayloholine) and doryl (Wlmlinoﬁn mantmtims moh lowor than the acutyloholim oonoonmtiom. 'Ihoy ascribed tho imaged effoctivomos of look of sensitivity duolingio those drugs to thoir to oembml olnlimstemes. Thou data one conflicting and furthr study is masonry to qualify this issue . Gummyiml Fluid mglmlinc (o) of aoetyloholim mtabolism and inﬂates that it is Selma: found in One View mm tissuns in an inactivo band form, wring periods of activity, mtyloholim is liberated at the call midly mum, Mum it is deactiva‘ood by dzolimstomso. 'Iho mount of bomd mtyloboline is the resultant of tho oontinumas pmoosses of synthesis, liberation and broakcbm. It the level has been postulated that rim timing sleep and falls during activity. and Czomland, 19%; Elliott, (Richter Sam): and Hmdorson, 1950; Gianna: �,7... ,r‘ w .w..,» "gun-w WW, _ w w" Rpm. 1962). .1,‘ A. 4w- By ....- a. m brain mg. higher than 3005 tissue levels is mw. 1...,” wr'w".‘— wan mama basin .v—w tho love]. of during :- "w m:a..»=-v~<wmu «we» u-m—v .fr'um-g v.~'mrw-"n—u'w .r‘xm is high mtylcmlim (micro- munch and sleep to b- mm, mini-It. \‘w‘ , air quick freezing Minds. post-ulna! levels. (7 Thu diffm in as the msyntlnais mm for gm/m/ndnuta). Elliot $3; omfimd these observations. also toting that after nan-uncle aonwlaims spinal "Wu-1 tim) wotylcmm in rat (1950) , using liquid Richter and Cmoclmd per ‘v-‘w‘m fm acetylcmlim m «ﬂammable ﬂuidinmncmtmtimamtoagampermm. Pepeu (1962) fomd an qt central mm 11mm in mtylclnlim Wan depressants to in the mm caused by a group be roughly proportional totindamoofdepmasimoftheemmlmmusmummm‘ mdmtim in Prue mm activity. mtylcrolim m 'fluid in mportad in‘tha spinal patients with epilepsy (Cone, Tum“ md and mum. mmud 5.0 m 19149 b). or 56 fm amtylcmlim percent with McEncMm, 19%; epileptic patients, an (77%) in quantities of 0.02 to an average of 1.0 TM:- mm cont. �v— v w. «...v..v,v .-A—W. ,_.1,._,...V,. -v-.»-m—wv —-.~ ammm‘ «wwwm 'y'vvx'v u—wu.uw,n-w.-w.~:.wmw.1». mu '1 “a“. - .vwruw—Nv- l2 Maryldnlim levels wan related to the froqmncy of seizures, mmdcmmmhmiomlﬂy,mdtoﬁm 1b zinc. the lat column, but bore no mlation to medication, type of cpilopsy or level of Tadcr and Wm ($0th (Hugh) Vimd tbs increased acetyldmclim a lay-product of the Stwying the hypothuis that the inducod aim. m activity. (1953) 301m, and not causal. mum We! of acotylcholine the level of acatyldiolim inbmintissucmotmaoh convulsion. Stumtcdarisoinﬂae acetyldaolim content of brain, baton a sebum and a fall during tho convulsion. Below curtain levels of acetyldmolino, convulsion hind-to comm. She smeared that the fall in tissue can due acetylcholim during a cmvulsim acetylcmlim synthesis sue): on by Wed to inhibition of concentrations of natabolites amnim 10m. Wendhpoualsommdclmgosincenmlmm systcn acetylcholim follauins “rims stinulmts . Only after �13 SMDutyhthyIMimte was there a mcholyl and 3, W significant dam in the acutylcholim level. they noted a in association with inmost! omvulsions. drugs which may qumtifiad as atiwlmts 1:me maninaoetyldwlim impmniazid 4» and no W mind + 1309A) comma, them in mtyleholim lava]. muss these by convulsions. (The than WWW duspite int-mo excitation produced by those mu imam. (LSD. mpmma level. other With were diffemnms in observations mmmmmggmrmrmdmm may be related mutants. to the differences in fm‘ methods th: Lunar unwind of biochemical changes in spinal fluid nflcatingttnfmeaoetylmolim,whilnsiamamandhpeu‘ manna tatal Myldwlim in tissue uncaring bound fm form Thu: an and of acetyldmlim.) AW W Auggut ﬂux Apontaum by an u induced We 1mm in law (no. acotyzchouue �-, .4.‘ . rum- .1:.--—.-. -. ‘T r. .l ~,w ':.»"-rx\~\I--«-~-v~’ ‘mw"‘ m~.r...v.w—.m...~»-. . .«m-n vyr -. . 1-.“ , —;..- r...» ,.r;« “a v.—~ 1n tummy-1 La 5pc“: (mid. mmwe bound (on which my Wag dalmatian, “up and mduaﬁon immune mane (d) Oantml Nervous activity. (19%) also ‘mo Austen/ted 6mm «cavity and Aazuu mm:., m Wm be. tum . Sgt” mama enhance Mae. Lama masthead in the W 06 acetytdtoum (holimstomaa: Tour and spinal fluid diolimstema typas of duolimstarms we normally fund in thc spinal fluid: dmlimstume-I ("tr-m," “specific," or Molyl—hydmlyzing) , which has a high specificity for acetyldiolim; and daonmstemo-II <"imudo," "mspadfic," com or benzeyldxolim-hydmlyzing) . Both mtyloholim but rates of hydrolysis for have diffamnt hydrolym diffcmtial rate Molyl and bomoyldmolim . This qualitatiw distinctions. reporting the duolimstemse By permits activity as a ratio of the activity with a maholyl substrate with a bemoyldxolim aubstmtc mud and to a substrate of mtyldmolim, ten mtios are found: dualﬁnatemeJ/mtyldmlim �-- ~ :4: 7r>m\‘-Vrmwu~<hvuwrr. n >--'rw. aw, ww H'VJ’IW'W‘VCu-‘rm'"‘l ~w:wa-w-._,.rm unr— w .vumma .w. "- urﬁ ,. .... 0-» ‘wV.M-a>vﬁ “Tr-aw -r-.-~,:-. 1m.” ~ m 15 and Mm-II/mtyldmlim. comm fluid :30an censuses for “must-men! to In such ratios mall in tho ratio of 33:17 dawn . Inpatimtswithhadtmm.mrmmmmmd mimmimofﬂndnﬂmtmwiﬁ'minmeinm W41 Mum-I fraction of th- spinal fluid and a activity. ‘11:. W in what of tho cholimtomso Wmmuudmtmmtyofmmmdmm m at the In :13qu WW. mints with owned spinal fluid acetyldxolino m:mm,mvar,mm1nﬁnmioof dwlimtm or total mun-statue activity was fomd._ mmmannmmmymmmamm mumimmminanmpombiuty. WWW-Ii: antral mm system while Manama-II pmdminms 1’ththth in other tissue. specially blood scum. in mtyldmlim hula With an inmue in mnbml intcmauular fluids, up“ .7. 7" .- » -~ ..,_, , u �A , . ,_ =...V........ w...” ..l.._, nv'rvxw w." .7 "Myw-IlI-Irwwaur- ‘7 ""Fvwmm“ v raw-4‘7“-” ”Val n”,_~ -17 . "A «rum—u ﬂ,” "mum—.1,“ NW... , 16 vasodilation and Wei with a degree of umudatim of vascular fluids into the inter» cellular permeability cellular spaces varying with the extent vaaodﬂataticn (Kabat and their Wm 35. _a_1_, 19%). and may be pmdicted, dmtion of the 81313301, Spiegel—Adolf, (1981. 19%, 19%, 1938, 1953) WWed sud: permeability changes md maimed mndmtivity of the tissue associated with the appearance of various ions (as potassium and prosphate) in the epiml fluid {alluring electrically induoud convulsions . Such nucleicaoid splitting cellular permeability WWW of aims, may nm-elactmlytes, as also ixmaaed. Changes thus pmvida the basis for the high acetylde and the inmased mntratims of cholimsteme-II in induced animus or head tmuma and Wm 'Ihe in ' (Tamar- 1939c) . persistm of mtyldwlim in spinal fluid after head trauma and after aims daspita increased dwlinastemse activity related to the sensitivity of the aoetyldiolin'e- may be dwlimstarmd system to Wmtim relationships (Nadmansm �,wn‘ww’ ,.. i . ..-.. _‘ “a... n”. “ ‘,,_ .3», .1. m, .Vq‘r‘. am-rw , ~,--‘V~rwtrm—Ww ..~.-—-~—..-w wr".v\-4I"\9-rr"x““w-myrvwrmmwn'v .(-,.‘v.,..._..-..‘_w,,,,rn.—.y~.—_-.r~,- 3“ .~.-. 17 and Withers, 19'65; Towcr and Wm, HacIntosh, 1955) . At ”physiologic” 1909c; Burger: and comtmticns, hydrolysis of acatylcholinc is rapid (34 micxmocondn) but at higher and lower concentratims, the activity what, falls off quickly. In the dmlincatnmo-II acctyldmolim mlatimship is ad ﬁn mn-cpociic m 01’ hydrolysis cmccntmtioc. W witl': increased. anvimcfﬁnscmlatimhipc suggestsﬂmtwhilem usual commtrwticns of acetyldmoline t cell m: are dcstmyud by tbs specific activity of cholimsteme-J. in a fut micro-cm, an emaive concentration following cxcitaticn may exceed the rate of hydrolysis by cholimstemso-I. seizure mmmm the uixum may be mmd and a seizure itself adding to the mm: The induced, with of free amtylcmline. 1110 increased acetylcholinc diffuses rapidly, affacting vascular and cellular minty and increasing the various ism and circumstance-II in the of dialimtcmc-II , mums CSF. The of activity thaugh of low efficiency and depending on �the mien kimtics, mamas tho watyldxolim in the tissuns in hours to days to levols for the physiologic actim of dwlimstame-I... Chaumtemu «ppm is ﬂu. camamemmmm In The. am 5M cu a. gamma gum, mating 5m a“ when pmabuug “mined by imucd changu mm. Wed mm“ me put “the hmmtéc Wm “mucus the ants (n ma agate»: 05 Wu manually «mum. (a) Amgzleholine, Alumina in MW at cm EEG the. blood-brain Mum and Indumd Oomvulsiaw: pemnbility barrier winning action of mtyldwlim may be the by the biodmmioal substrate for tha poatwlectmahock hypemyndmy of the eloctmanmpinlom. 3% a possibility is evident in the Mommim of an immense in the concentration of cocaine in brain tissms thme a series of 12 induced convulsions (Aird army in concentration of this days after 5331., 1956). The 1m mlecmle, ordinarily absent �mnpr- rug—m.» r m «7 r.~L,-»---.--,V-...Ww.‘n - v v '.>T4wmw‘m .mw—z , ru71.,‘ mu mr‘m—D'J.lr>aw' yawn-vanquas,‘ ‘w. - p". yr. -., “wharf” . WV. ”us-apt..." 1.. .19- in brain tissue, was asaociatad with the appoarunoe of hyper» synchrony (delta bursts) We hIVD in the electroencephalogram. confirmed tbs many pruvious reports thut convulsive thaxapy induces olectnngnlphic hyporuynchrcny (Pink and Kahn. 1956; Pink 33.3;, 1961). Duspite a constant application of mmmmuammmty'mmtmo: appoarunnn, the duration and tho cxmnnx of the electrogruphic slow Haws by activity as wall as the sensitivity to modification alnrting, hyporvuntilatian and barbiturates in psychiatric (papulntians. Tho early appoarnnnn of high degxan hyper~ syndhmuny and its puraistnncn throughout a truatmant course has been dnscribod an pmuruqnisite M (Roth, 1951; Roth It is possible that EEG to £11., impruwument ﬁollcwing 1933; Pink md M111, 1956). the diffirnnces in tho degree of indncod hyporuynchrcnv may bc related to differances in the activity or auntrul cholinnrgic mechanisms. patients to davalop hyporsynahruny The may failure of certain thus be associatad precluding a clinical rlsponse to induced convulsions. Tbuer .. l . V , ”.17 v ,, n �w, ._‘_,._..._‘,|,,, r. Wm. ;.,,,,.__ m. ,. ~ "v.0... . (T W . r r, -_ "u . rw.par.-‘W-.~ .erz. .7.” , .1 . _ y . ., 4.1-. . -- n v-uvnwwwv-wm‘uv “wave-«W.www—ur-p—, w-n—w—w M-ru- "n" .,-v , . _ _ , ‘ v—av-um . . woun- 7 -w v-_. .- m 20 and Wm (19%.), in ﬂair study of W231 tmm, hcludcd observaﬁm of six psydtiatric patients mder'going omwlsive mampy. Studying the patients after 3-7 tiny upon“! {me spinal fluid and an inmm mutants Minimum in two patients; in mournstcmvn and a dam in .mvemal pith of the ratio of dxonmatorms a dwiimstame-I in five of the six patients. From mludad that the spinal fluid these obscwations ﬂwy We: in ma commlsiom mmﬁmmoofmioambmltmﬁmmof sputum epilepsy. WWMpntientinﬂwmﬂaawhofanedtom oither {no acetylomnm or a dmlimsteme ratio reversal in iﬁtemsting that this the spinal ﬂuid, tiny. wrote: "It is patimtwaaﬂnonlymafﬂnsixmshwmmsmoto Wt." ‘ at If alectmgraptdc hyporsyndmrmy increased free acetyldmolim, subjects who is a mﬂectim maintain hyper- syndmymdttmeinﬁmitdisappemmidlymybc waiting diffemnoas in the kinetim of the dmolimstemsw » , _ v—-— w . 7 v vamp-omen“ W . p ,. . V... , ‘ �22 “I (21011th 'mooo studios and the Classificatim of a : malochm applioatimtotmpmblanof atomic mootivity and the classification of the Mountain Po mm and ( ) mlatimhip boom the psychoses. how dumstmted blood possum response to injected ndxolyl and the clinical mpomo of psychiatric patients to convulsive ﬁxaapy. Homolyl which W is a percent cholinorgio agent vaoodilation, taduyoudia, sweating, and peristalsis. It is rapidly hydrolyzed dxonmotorm-II . slowly by The blood falls after injoctod Immolyl within five to more than 9mm and takes Group 20 Group VI and VII oholimstemeel md pussum of subjects mtums to the baseline minutes. Patients whose blood {within baseline the returns to classiﬁed as prawn 20 by W 5 ndnutes have been I, II, or III reactors; those whose blood ormminums tomtumto baseline, reactors. M I and thp III—III as mam �.. pr 7: . -r WW..." . . .r. . n .. 7.. .- -. mm». . 1 unw- u . “val ~ « - ....._. v .. wiv'r—z-v .?-'a‘.v~'uV.—T{=n‘)("\ﬁlr- - ,r., "saw-- wry-WW...» N. mv—ﬁ m—m ‘»-y-_I-sﬁ-vvvvx , 23 have a 9 and a 35% recovery and Grow VII mentors 91; gl__. 1952). patients in Group whom while Groups VI 89% rate, mspectivuly, while and 97‘ recovery I to III mactom the injected mornlyl Group VI rates (Funkeastein may he looked upon as is rapidly hydrolymd; md VII have a slow hydrolysis rate. We may pmdiot, thcmfore, that the blood dxolinesteme activity levels of Grow): I-III would Groups VI A uystcm - bu high; while the activity of VII would be low. similar analysis may be mad: regarding central nervous levels of dwlinectemse—I in the duvelownnt of EEG hypersynchrmy and spinal fluid levels of aoetylcholim, providing a basis for a omgment hypothesis regarding centml nervous syntax: reactivity to induced oonvulsims cholinergic agents. and to peripheral �- ~—-~vw=rr'u. . ~ . “,_ w-vvww (“vwxx mu, .- v*'ul""‘v‘“""w“1-c-»w‘mlh-rtr"'4<-Ia‘.—-vuz‘ --— (—1 m-wry_._ 7...," .V, 7 ,_, . ‘ my — . w". ,.c_..,.. .. u... w. Flaw—w. v3. ‘~.,..,,‘w,-." 2‘4 CONCUISION: Central cholinergic mechanism appear to be a significmt factor in the convulsive therapy process. may The published data interpreted to indicate that induced convulsion: are be associated with on increased- in intercellular acetylcholine to levels greater than can be destroyed activity. Vaeodilatim and increased by dmlimsterese—I cellular pemability are followed by increased ammte of clnlinestemee—II and other enzymes and electrolytes in intercellular fluids. These chmgea are hypemynclu'my which can be mdified by reflected in the increased electrical is recorded in scalp electrodes, and which mticholinergic drugs as atropine, benactyzine, and ydieﬁuazine. The changes in the cerebral biochemical milieu alter cellular activities sufficiently to be associated with altered behavior of subjects. Failure to induce high and persistent cmoentrttions of aoetylcmline and failure to induce concomitmt electrolyte changes results in a failure to produce behavioml change. n: M ...1,.“‘..w. “,4 _. ...... ._ �25 Differences in the rates of development of mm reflect differences in their lependance of cubjects mechanism- changes on chom'cergic or in their sensitivity to chmges in acetylcholine levels. mean differences provide the basis for the classification of the mentally ill by kaenstein and by Pink md Kuhn These observations provide the mode a Miami (1961). Mechanical basis for of action of indmed nmvcﬂsims in altering the behavior of psychotic subjects. These views are consistent with the more earlier general neurophysiclcgic-«iaptive theory expressed (Rink, 1957) . �" -v~1r'-W4'VY—,‘V.'Z"V‘."-‘ w "- ---'~-' REFERENCES Aim, R. 8., Strait, I... 1‘... Pace, J. W., Hmnofi', M. K. md S . C. Nemphysiclogic effects of electrically loaned deitch, convulsions. Aach. ucuxoz. Izyahtat. (catc.). 1956, 75: 37l~378. Pmmoe and actim of coetyldwline in oxporinnntal Box-cumin, M.D. brain trauma. 1. Nounaphga£o£., 1986, 9: 3%9-366. Brannon, C. and Merritt, H. H. Effect of certain choline derivatives on electrical activity of the cortex. Moh. Newt. Pageant. (ChicJ. 19H2, M8: 382-395. W, of amtylcholim. S. A. (Editors), V. and Hoolntcsh, F. C. ‘lhc physiological Biglificmoe In I. K. A. C. Elliot, C. C limos, ummag. H. Page and J. H. Quutcl Springfield, 111., 1955: 378-375. Omtfiald, P. O. and Dagny, E. W. Effects of proatigmine and acetylcholim on cortical potentials. Mn. 3. Phyaialu 1982, 135: 633-630. Wm, D. Acetylchclino and murmal Corn, w. V.,-'l'cwcr, D. B. and activity in cpilcpsy. J.A.M.A., lane. 73: 59-63. Dab, H. H. thoiz- The action of certain caters md others of choline, and nlctim to maxim. J. Hamel. Elliott, Exp. The)!" 19114, 6:187. C., Swank, R. L. and Henderson, N. Effects of mostlutico and cmvulamts on acetylcholine content of brain. MM. 1. Phytiol... 1950, 162: 888-1371;. Pink, H. R. A. A mified theory of the cation of psychodynmic therapies. Pink, H. Effect of mticholimrgic agent, dietmzinc, on behavior: simificmcc for theory of convulsiw ﬂxcmpy. Melt. Pogohiat. (Chic). 1858, 88: 380487. BBQ and mm. Effect of mtichclimrgic compomdc on pat-mullahs cloctmcnocphalom and bobcvior of pcydaiatric patimts. Eltethoenctph. Cliu. Neukophg6£a£., 1960, 12 (2): 359-369. Firm, M. Fink, H. and Kahn, R. L. Quantitative studies of slow wave activity following electroshodc. Electuuceph. can. Newman!” 1958, 8:158. Pink, 14., Kuhn, R. L., Karp, 3., Pallcck, M., Green, M. A., Alma, B. and Infkowits, H. J. haunt—induced convulsions. Molt. Gen. Paychiatn 1961, “:259-266. W, m. ' 8 A. 14., Bales, P. 1)., Willie, Hiwich, H. E. Exporimtcl production of electrical major omwlsivc patterns. 1. MM” 19kg, 1.35: 117’12“. A. and �'"WW.'I<-.~;—-- -, -‘—-'-a . .. r! _‘,',.."_'__m, ,- . ‘1).m. u ‘P. - ..~—.—.-a..nuu.~.~ . ‘~»~..ww*m‘m—. - v w W .-w-rvu.wm.m .w, ”mu “.3 w-w WW..."— xw-mv-vrv at K Ib‘mwv": “nun-ms?” u mmic mutt, of in mlation pmgnoatic system sigxifiomoa to test mm Maintain, D. H., 013011031106: truatmant. Payclwaom. “ad” 1952, lb: 3u7~362. .Giaman, N. J. wtyld‘tolim. H. and Solomon, R. C. ML, F., Md Pepau, G. W. 1. Drug—inclined changes in brain 1962, 19: 226-23“. A. and Hiwich, H. E. Macaulay, J., amen, Effects of diwinopmpyl flmmplmsm (DE?) on ahatmenoepbalognm and dwlimtama activity. methamph. can. ”Mphgunl., 1950, 2: “1-48. Basis, C. Wm, W,mm" H. 3.. Basia, C. In, J. I... Bales, P. D. and A. H. Effect of trimathadiono (Tridimo) and other drugs on mvulsims named by di~ioopmpyl fluorophosph'ata (DFP). 1950, 106: 816-820. mu. 1. Pﬁwidl, Jamar-r. F. L. and bachnar, H. The effect of Dipamol on the ehatmwmphalogminmmmlaubjcctminﬁmewith Gambia]. 7: um. 303‘3050 Ehctaouuph. can. Namephgalatu 1955, Jansen, L. C., Ulatt, G. A.. Johnson, 24., Smith, K. 31:! Sims, J. 0. thanpy (with md wiﬂmt atmpim); affact on alantrmioany Julyzad electroencephalogram. Malt. Gan. WWW! mm" 1960, 2: 323—336. 61mm, M. and Knaub, V. Quantitative estimation ofﬁnalbminandgmglnbulininnomlmdpaﬁmlogic cembmspinal fluid by imxmehamiml methods. Mu. J. Meet, Kabat, E. A... 1938, k (5): 653-862. Loud, 0. Fiber hwmrale {Ibertmgbarkait den Hennammiﬂnmg. Mali. 5. d. an. ”quiet" 1921, 189: 239~2u2. Wm, mm, spadficity mm in new on D. and Studies on dualinestame: tissue. J. Biol. (than, H. A. of 19%, 158: 653-666. Richter. D. and unwind. J. Vaziatim in acetyleholim content of the brain with physiological state. MM. 1 . Phyaiatu 19139, 189: 2157-455. W in the EEG mdar bubimmte Mmesia pmdwad by alactm-omvulsiva tumult and thair significance ECT of the action. Manuphguol.” can. Eumuuph. may to? 19 1, 3: 261-280. Roth, H. ‘ W mt. WW. Ruth. 14.. Kay, D. Pmtothal omwlsiva 1957, 9: 225-437. J. md amen, J. Prognosis and ahetmphalogmphic changes in electroW. K... Shae, can. Memphyauln Spiagel, E. A. and Spiagal-Adolf, H. Permability changes in the brain induced by mm). and insulin convulsions. J. New. Matt. v.3... 19M, 93: 750-755. �F ” rum" , ,7“... T9,“ wm.~n..wr.”“.,.,r,.w ..;._‘.,..,_,Vk,»,mqr,..r. 14."... _.-..,.4,. r...“ ‘. ”um-um..." :w-"CRIWJEFIMI-‘wf‘t . .,»;r-,W—;.—‘m'w"Ir-E'WAn-‘n-vu-I 1”“7(IAHV«——l ._ - n -.--~ 7»-v—-———~r-—-n~—w-v-—. -3Spicgol, E. A. and Spinal-Adolf, H. Physioochemiml effects of ohctrically 1mm oonvulsiam (oembxospinal fluid studies) . Tm. Mu. Haunt. AM” 19%, 70: 130-132. Spiogel, E. A. and Spinal-Molt, M. Physiological and physioochemioal mohanim in electroshock tmatmnt. Conga. Newt” 1953, 13: 38-63. Wm Spiegol, E. A., Spinal—Adolf, We dinning“. in the brain Tm. Mu. and Kenny, G. Haysiooodmﬁoal electrically indumd omvulsiw Nunez. AM" 19342, 68: M. m. Wt Spiegcl-Adolf. 21., Wilcox. P. H. and Spiegel, B. A. Oambmpinal fluid in elnctmehodc of psychoses. J. 19%, 10”: 697-706. chm W. 3ch” Stem, W. E. The min of acetyldxolim in bmin metabolism and ﬁmction. Man. J. ”13‘. “£41., 1957, 36: 222-455. Torda. C. Effect of omwlaion ﬂaming agents on the acetyldmlim content of the brain. J. Phyaiol., Amen. 1953, 173: 179—183. Tom, C. Effects of single injection of oortiootrvpin (ACE!) ion and acetyloholim content of brain. on I. “watch, 1953, 173: 175-178. mum W. and nauronal mtyldmline activity. I. Mr. Wm. Cholimterm patterns ma motyldwolim in the oambmspiml fluids of patients with Canad. J. Hum, 19mm, tram. 27 (Seat. E): 105-419. D. a. and Wm the omtmt md WMim of W323, in human cerebmcpinal fluids. Cam. 1. Tower, D. B. and cholimatcmes 191.9», 27 D. D. mm, (Seat. E): 132-435. Tower, D. B. and unis-clam, D. Mutyldxolima md mama]. activity. Motylcholine md daclimteme activity in the In”! osmbmspinal II. fluids of patients with epilepsy. Canal. J. 3.914%, 27 (Scat. E): 120-131. mm, Ulett, G. A. and Johnsm, H. w. Effect of atropine and soopolaminc upm chotmonoeptnhgmphic changes induced by electm—oonwlsive therapy. Eamomuph. can. Monophyunzn 1957, 9: 217—22u. Hard, A. A. Atropine in the tmatmnt of closed hand injury, J. Meano.ung., 1950,‘7: ass-noz. .V. .- - �(July 2, 1965) Jan. 3, 1958 EDIE 0!" ACTION OF TheCNS BIWCAL ms IN EHAVIOR indopendcntupmanmrofenzyne for systems proper mtabolism and functim, including cholimstemae- aoctylcholine, glucose-phosphatase, etc. The bahavior variety of is large, in either direction wt: that affect CNS ﬁmcticn and, thereby, since processes in equilibriun by increasing may be shifted or damaging the available quantity of a metabolite. A. For drug action, thanfom, tho following are cmsideraticns in potency: ‘ (a)mescdrngaffectmmzymsyste1nina reliable my? it (1:) Can (c) What get to CNS to affect the system? defenses does organism process to block or limit drug's actim mac in CNS? metabolism the affect directly amt of a specific system, to that extmt is the CNS dependent upon the system? Is the dafoct thm induced sigiificmt for the metabolism B. of CNS Secondly, while an may mderlying behavior? Rut Menace can body call into play when system has, is affected to substitute other may system? the variatim in drug effects in behavior depend upon: (a) Beluvior at onset; and pmdispositim (personality) to response; (b) mug dosage - availability to has on m mzym system; CNS and the effect it �W'wv‘mw n—m—.n-u.r:~wvmr .v 4-:- \I.’—:r~"!lwwmi‘ mama v; M'er‘ui'v-V-‘P 1‘2'.~vr1v-'wv— (c) Depmdence of war "-3;*..)I(7'4<~<'I‘R,IWT~’:~.~HV~’V~W ~, - an.» :uru.r-owr:< , .. mm? a. mum cvw V:""\ 1 < =- 1 w - -—-v. again on specific enzyme ommimic defenses (Le. substitutim for affected system). (d) Whether effect was gradual (allowing for system -— defenses, and ,r'ia Le. , enema metabolic system) or acute (not allowing defense). Individual differemes in meme may be due, thus, to differences in: (a) Dosage, ratio 8 mute of mainiatmtim (b) dependence on the affected system (c) adaptive ability to biochemical changes. To these changes, EEG is a me approximation and indicator, reflecting the homeostatic balance in various the CNS. enzyme systems of ��21 mtylcholim hydrolysis system. Persistent malt from a damned rate of hydrolysis of aoetylomlme. associated with low mmantmtim of either or Grantham-11 . livcd W, hypemyndmany my (immunised (Oonvamly. in patients with shortcircumstance—I md «II in tissue and spinal fluid my be mustang! high). Fmthuc obawa‘ioumwouldcsuaudetmmduud MW ”mam m «wanted We. and in cmbut pmabuoty 5m. Wag MW mm (at. EEG «the hypwymmny Wow nu 06 wumwmu. Mad a WW and 426 in 6m with as on. attend by amazon 9‘ WM W behauiuat dung“ the blockade“ 50M um 06 muted Mud bum. pubabLgtMtuu the“. dungu Lgtu that The We! men 06 ethyl. 05 campus“. ammummamm- mm 60!: the. attuned wavubiana. mam � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Research Files and Unpublished Works Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Files: Acetylcholine and Cholinesterase, 1956-1966 (folder title 3/4). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-003-0-003 Date A point or period of time associated with an event in the lifecycle of the resource 1956-1968 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research http://exhibits.library.stonybrook.edu/mfp/files/original/023fc3470d6cfddf7614342c86456639.pdf b07bb6498b31f3e58fe2ba4d191c8c0f PDF Text Text l+/26/57 To: Dr. Max Fink From: Dr. H. Goldenberg are contemplating a change in our cholinesterase incubation system which would cause significant differences (5-15% increase) in the reported values for true and pseudocholinesterase. This is the primary reason we haven't fOrwarded your spinal fluid values as well as the more recent serum analyses. We cholinesterase method (like all methods) comprises 2 steps: (1) incubation of enzyme with substrate under fixed Our conditions , and (2) analysis of the reaction products, from which enzyme activity is calculated. The second step employs our new and efficient color procedure. Step 1 is essentially that of earlier workers. On reinvestigating step 1 we find objections to the large amount of salt used by others in their system and may eliminate this ingredient. an apparent As salt is inhibitory, this increase in enzyme would cause concentration. All our past analyses can be corrected for this change by using appropriate factors, but the ultimate decision whether we are to shift our medium will be about 10 days in the making. are naturally anxious to get some idea of the relative changes in spinal fluid values following EST, I will forward figures based on the original salt system on Tuesday. However, as you will start running benzoylcholine as well as the butyryl susbstrate to determine whether there are 2 pseudocholinesterases in spinal fluid. This should resolve our uncertainties on this point and just might possibly lead to new findings. Next Friday we �February u , 1966 Dr. Harvey Robinson WW thimsity of The Baltim, Bur Dr. Institute Maryland Maryland 21201 lbbimm: In mid-October. I submitted the muncript ”0101111132310 Marxism in vaulsiw 'mempy" for ymr mitigation for publication in thc Jam 05 Havana and Mental Dame. I Max MP : jmh Fink. NJ). Promoter of Payduatry �L45 SOL.‘NAL OF /" .Nervour and Mental Diyemc ‘ Harvey A. Robinson} Managing Edi'oy' f Psychiatric Instihne u iv r re “’ofM—u‘ Ia d The \ 82mm”, ,, M0250; OCtOber 19, 1965 "’"-”‘\.:;,_. n—~L"""”"W‘m“‘“'°-—ﬂ _ ..._.. of receipt your acknowledge to This is Mechanisms "Cholinergic entitled manuscript " in Convulsive Therapy. �Max Fink, M. D. Department of Psychiatry Missouri Institute of Psychiatry 5400 Arsenal Street St. Louis, Missouri 63139 �Wm' ~ - .m ﬂ 9 .. w w' ‘5w; Hug-«m- - ‘ nun—v- w-pr. W 4mm‘w-q-w—I-sm . . w wwwmvwmm w “a - . m . , , an(rum October 15, 1965 Dr. Harvey Robinam Psychiatric Institute adversity of Huylmd The Baltimn. Maryland 21901 Dear Dr. Robinson: mm Pbdwﬁm in Convulsiw at. publication in the two copios The Joanne 05 of the manuscript " "010111101310 for your midnmtim for mm and W Dame. style of ﬂu citations follow those of this imtitutim, we will aubdt copies following your stylc if the article mots your approval. While the mead Sincumly yours , MIX HF: jun Pink, M.D. Professor of Psychiatry .wW '- 7k "-7“. m."- �THE N JOURNAL 67/92/011 I OF 6111 d M611 ta l lcwrence DifEdje S. Kubie, Editor-in-Chief Harvey A. Robinson, Managing Editor Eugene B. Brody, Consulting Editor The Psychiatric Institute F 0 U N D E D | N 1 University of Maryland Baltimore, Md. 21201 3 7 4 February 10, 1966 Dr. Max Fink Department of Psychiatry Missouri Institute of Psychiatry University of Missouri 5400 Arsenal Street St. Louis, Missouri 63139 Dear Doctor Fink: I am very sorry to have to tell you that your manuscript is still under editorial consideration. I do hope to be able to be able to write to you about it very soon. Sincerely our 8, 9V 5 W H. A.‘ Robinson HAR/sa »' �’4 THE JOURNAL OF New/0m and Mei/Ital Diieme lawrence S. Kubie, ZZZ:23:3,”;3.327.315?" The Psychiatric F 0 U N D E D | N 1 8 7 4 Editor-in-Chief Institute University of Maryland Baltimore, Md. 21201 February 1 1, 1966 Dr. Max Fink Missouri Institute of Psychiatry 5400 Arsenal Street St. Louis, Missouri 63139 Dear Doctor Fink: The Editorial Board has carefully considered your manu" Convulsive in entitled Mechanisms "Cholinergic Therapy. script Subject to your willingness to meet a number of minor criticisms and to make some changes that have been suggested by our readers, we should be very pleased to publish this article. This, then, is in the nature of a provisional acceptance. This consideration of brain cholinergic mechanisms and their significance in convulsive therapy represents an interesting and valuable point of view. Of course, other chemical changes have been demonstrated after seizures and have been assigned equally as important roles as acetylcholine. However, this position is clearly dated, developed forcefully, and the argument is pertinently documented. We feel that the manuscript makes a definite contribution. Nonetheless the Editors are of the opinion that the report embodies some weaknesses which if dealt with would significantly improve the quality of the paper. No one doubts that acetylcholine is important in neural function and that changes in acetylcholine and cholinesterase occur with induced seizures. The assumption that the handling of acetylcholine is fundamentally related to the amount A of hypersynchrony of the EEG is, we feel, an oversimplification. Q) in}. The thesis that the results of treatment by induced convulsions is related to the sensitivity to changes in acetylcholine levels (pp. 18—19).] has no information to substantiate it. Although you describe a "rational biochemical theory" for the mode of action of induced con- �Dr. Max Fink February 11, 1966 2. vulsions, you state only what is already known, that acetylcholine decreases in the tissues and increases in the spinal fluid with induced seizure and that the slow waves can be modified by anticholinergic drugs. Although you cite your own work for the effects ”I of atropine in counteracting the acetylcholine effects of induced seizures, you do not give evidence that the use of atropine changes 1 the therapeutic results in any confirmed study. There is no con— w “7 of evidence in for differences the vincing reactivity or sensitivity (3) central nervous system between psychotics and normals to r" acetylcholine or cholinesterase. ‘ recommend that you consider the following ideas for inclusion in the summary: We There is as yet no consistent evidence for differences in anticholinesterase or acetylcholine senstivity or levels between the psychotic and the normal brain. 1) \/" as yet no reproducible evidence that anticholinesterases given before, during or after electroconvulsive therapy change the results of the treatment. 2) There is 3) Cholinesterase and acetylcholine levels change in response to electroconvulsive treatment and in response to trauma may be a result of other biochemical changes resulting in vasodilation and increased cellular permeability which affect the level of consciousness, EEG, and behavior as well as acetylcholine distribution. At a more superficial level, we should also recommend that the manuscript be carefully scrutinized so as to ensure consistency in drug terminology. We would recommend that the generic names be used throughout the manuscript and that the capitalized trade name be included in parentheses, e. g. , methacholine (Mecholyl). We have indicated a few of these changes on p. 7, p. 9, and p. 10. I regret to note that the references do not follow the style we prefer to use. I am enclosing an information sheet, which may be of some help. Please note that the references should be alphabetized, then numbered, and cited by number in parentheses in the y / �Dr. Max Fink February 11, 1966 3. text. Please note, too, that the references should be typed double-spaced. This enormously facilitates preparing copy for the printer. On the hopeful assumption that you will be of a mind to undertake the recommended changes, I am returning one COpy of the manuscript, and will retain the other for purposes of reference. Please let me know how you feel about all of this. Very sincerely, H. A. Robinson HAR/sa Enclosures �February 16, 1966 mwmmwm Mm Manny mm Dmﬂuvoybmum Psychiatric of mm. Maryland 21201 M 3:321th Myoum andingm W"ﬂwmﬂcmin0mwlsiwnunpyﬂ MWWWmmWW Ivdﬁuﬂacmaffwttompem mum-mm. including meanwmmmmmmnwd. ﬁndtatian following tin style: whidnmmmmud. mmmmmmumamymwimmw mks. 11'. Rabin-cm ’nunkyou formant-aim. Stanlyymm, ﬂux Pink. NJ). Professor of Paydﬁatry fokp �Harsh n, 1986 Hr. Haw-y A. Roux-won, Hanging Editor 1?. Journal a! Havana and Hmtal Dim Psychiatric Institute m Lhimdty of Maryland Baltim'e. Manama new it. Robina: 21201 My" "(2le Wthunofgmdcma,mdmdﬂiedmcitatima toftttlnstyloottmjoumu. than Follovdngymmuwsﬂmn,1hvomdmfmdpmdmsuof in Oanvulsiw hernia: apart Mmemmhth meunincludad,udngayomlmm. Ihawdmdﬂntiﬂewdnhmdmmtimaddoh wanemtmdiatm. Ihopethntthiadmft.michI11hnmmttor,m dthyumappzovnl. M you for your mu. Stanly yams, Fink, NJ). Manor of Psychiatry Max 31‘? �‘5: i THE N JiOURNAL or I 67.120“ 5‘ 3' Men ta ﬂyld lawrence 1 D1336“? Harvey A. Robinson, Managing Editor Eugene B. Brody, Consulting Editor The Psychiatric F O U N D E D | N 1 Editor-in-Chief S. Kubie, Institute University of Maryland Baltimore, Md. 21201 3 7 4 March 9, 1966 Dr. Max Fink Missouri Institute of Psychiatry 5400 Arsenal Street St. Louis, Missouri 63139 Dear Doctor Fink: revision of your manuscript, for which many thanks. This now looks perfectly fine in all respects, and we shall be pleased to schedule it for publication. We have the best guess is that this material should get to the printer in five weeks' time or so. Galley proof, then, should come to you some time late in April. My When you receive the galley proof, I hope you will be able to correct it and to return it to me promptly. Very sincerely, H. A. HAR/sa Robinson 02,9 8“! �THE JOURNAL OF NERVOUS AND MENTAL DISEASE Copyright © 1965 by The Williams & Wilkins Co. Vol. 140, No. 2 Printed in U.S.A. Information for Authors Manuscripts and correspondence pertaining thereto should be addressed to the Managing Editor: DR. H. A. ROBINSON, The Psychiatric Institute, University of Maryland, Baltimore, Maryland 21201. Manuscripts should be typed double spaced on one side only of 8% x original and one clearly legible carbon copy should be submitted. 11 paper. The It is helpful if the author supplies a short title for use as a running head. This should be typed on a separate sheet and be the ﬁrst page of manuscript. Type the complete title of the article on a second sheet, and the authors’ names and afﬁliations on a third sheet. Type double-spaced on separate sheets: tabular matter, case histories, quotations, formulas, and other subsidiary matter in the text, footnotes, bibliographies, and legends for illustrations. Legends must not be attached to or written on the illustration copy. Positions for tables and ﬁgures in the text should be indicated in the margin of the text page. Manuscripts should be accompanied by two copies of an abstract of 300 words or less. Illustrations should be drawn in India ink on white paper with clear lettering. Photographs should be glossy prints. The title Of the article, name of author, and number of the ﬁgure should be written with a soft pencil on the back of each illustration, and the top designated. References should be designated in the text by number in parentheses, e.g., (7). The list headed REFERENCES at the end of the paper should be arranged in alphabetical order and numbered. Abbreviations should follow the style of the Index Medicus. Examples: Book reference: 3. Critchley, M. The Parietal Lobes, pp. 171—181. Arnold, London, 1953. Journal reference: E., Mirsky, A. F. and Pribram, K. H. Inﬂuence of amygdalectomy on social behavior in monkeys. J. Comp. Physiol. Psychol., 47: 173—178, 1954. 11. Rosvold, H. Costs of author’s alterations of type or cuts, in excess of $1.00 per page, will be charged to the author. Corrections of printer’s errors are not charged to the author. Also the author will be charged with the cost of engravings in excess of $50.00. One invoice will be sent covering cost of reprints, alterations and engravings. The editorial ofﬁce should be notiﬁed promptly of any change of address. Galley proofs are sent to the author, and should be returned with manuscript to the editorial ofﬁce. A table of cost of reprints with an order slip. is sent with galley proof. �runs-“mm” w'u‘. \ q. WJ~F'WWWWMW'W rerI-Iw-um w-mrwmwwz—mr urn—rm—v- mmrﬂrvmuu (HOMO ASPECTS NIX 0? rim, mm W HJ). "mt—amt“: �....‘.;v- I-‘mm ..r.-- .. ... v t . .. .... -- . 71-17”W‘ m .wn -.-»r.-n---» 1'- ~ 1* ~- the Department of Psychiatry, Washingtm University School and the Dapummt of Psychiatry at the of [ﬂasmri Institute of Paydmiatry, University of Missouri Sdhool of Madicino, SHOO Arsenal St., St. Louis, Missouri 63139. mam Aidad, in by usms grants m—sm, m—2715, menus, and PEI-11380; and thc Psychiatric Ibsen-cm medatim of Missouri. Ix: 65-8 part, 2—25-66 Ravisod for the Iowa 05 Nuvoua and Mental Dame. �GiOLIhEIRGIC ASPECTS OF CONVULSIVE 'DiERAPY While the mode of action of convulsive therapies remains enigmatic, one theory holds that the early development and persistence of changes in brain function are rﬁquisite to change in behavior (17, 20, 22). A useful index of murophysioloﬁical changes is the appearance of high voltage electroencephalographic slow wave activity (22, 23). While the biochemistry of this activity is poorly understood, damstretims that it may be inhibited by atropine premedicaticn (3k,66) or blocked by anticholiner-gic coepomds (18, 19) suggest that crolinergic system may play an active part. 'lhe EEG patterns and the response to anticholinergic drugs issimilar-inexperdmntalmdclinicalheadtrmmamdtoa lesser extent, in spontaneous seizures to that seen with convulsive trerepy. 'Ihe activity and changes in concentration of cholinesterases in brain and spinal fluid in head trams, spontaneous seizures and convulsive therapy also slow many similarities . This review discusses these observations to provide the basis for a hypothesis of the role of oholinergic changes in the convulsive therapy process . Acetylcholine has been extensively studied as an agent in the trensmissim of nervous impulses since tion by Dale (12) and Load (38). in a bound form, acetylcholine process . It is A its early identifica— constituent of nervous tissue is liberated during the excitaticm rapidly hydrolyzed through the radiation of acetylcholnesterase and is rapidly reconstituted by the cholineacetylase systemMS) . Free acetylcholine has not been measurable �in normal oerebmspinal ﬂuid despite the rapid bound aoetylcholine during periods But breakdown of of activity and excitementms) . tl'e normal cerebrospinal fluid does have mamble oholimstemse activity, principally of the "tune" of mcholyl hydrolyzing type ChoLéuuch Mpew 05 Wombat Tum. Free acetylcholim was fomd in the oerebrospinal fluid of cats (I41) . within a few minutes after experimtal heed trauma and persisted forvaryingperiodsuptouam. 'Ihequantityoffree eostylomline varied between 2.7 and 9.0 game percent, and the mmt was related to the degree of indmed trams (6). Conctmnt electroencephalogram first denmstrated high voltage fest activity, interpreted as evidence of an intense mutualdismarge,whichwassomsumededbyasmmperiod of flattening of all recorded electrical activity. 'Ihese phases were followed by prolonged periods of high mlitude sharp waves in the delta mquencies. 'Ihe behavioral changes related to the degree of induced of manned free aoetylcholine . With to the aunt higher levels of acetylcholine, Bernstein reported greater degrees of EEG abmvrmlity and greater changes in mciousness. trams and Spontaneous post~trmnnetic seizures were also related to the emunt of free acetylcholim appearing in the oerebrospmal ﬂuid. �em the concentration of ccctylcholim Bomstcin applicd acetyloholinc to cortex. When out oercbrul m l gonna porcentcrlcss,hizhmlitudosharpwavosof1wfmqucn¢m appeared in tho doctmmceptulcgrm. was mm in flattened to 2 gm: When tho concontmtim percent, the cloctromcapmlogmm a fashion parallel to the post-mtic records . Investigatiom in neurological patients by Tower and in the free ccctylcholinc com-Wmtod Wm spinal fluid only in patients with meant head trauma, meant seizures or after olectroconvulsivc thwapy (63). Mal Fun acctylcholim varied from 0.2 to 100 gm pcrctmt. In assaying spinal fluid circumstance activity, they noted a rise in the mpccifio oholimstcmsc fructim (bcnzoyloholinc— splitting) and a drop in tin swcific circumstance {motion (unﬁmdnlim-splitting) in patimts with head tram and sharp following convulsive tmmpy. Artur spontmoms seizures, fluid did not exhibit such inversim contained free acctylcholim. They concluded that however. the ccmbmapiml although it with the varied of free directly acotyloholim m1 and that mammal of the oholinestcmse dome of cerebral functions was a more mitivc indicator of ocmbml damage. the W Bloctmencophalom. talent at varying intervals following also indicated a relation betwum the degree of EEG m. abmmlitymdtmappwmocoffmcmtyldnlincintm combmapinal fluid. �-7- 1......» um"... —— u r. mﬁ" 57—..- .. -- 1"...” y-w.-u~m-v»- vows-r r, wlma-«w- ”a: u . ...v - -. mmased aoetylolnlim in net brain after trumatic also reported by Kovach, activity was inhibited in was to the muscle preparation. 9:5}; m ., n '- e . 71‘ —_.... - "MW“, shock (36). This aoetylcholine by the adninistmtion of atropine eleotrogruphic, behavioral and mmrologic signs of head me trauma were blocked by the parenteral administrvatim of O.5-—1.0 tug/kg atmpins, asweresimilar'clinicaldmgesooomringaftertm inhmisterml additim of anetyloholine (6). observations to the mamnt of closed head Ward applied these injtmies (67) . In 20 patients with varying degrees of trauma, he administered atropine subcutamxsly in doses of 0.1 rug/kg, mting clinical inpmvemnt in scan and a reversal of the electrogrephic effects in others. ‘Ihe some oranges in the post-trumtic electroencephalogrm were mporhsdbyJemmerandDednmrinastmyofdieﬂnazim, another mtidmolinergic drug (33). A single intravenous dose in forty patients resulted in normalizing the abtmal electroencephalogram in twenty—two and marksdnpmvementin six others. of post-Wtic shock and Similarly, in Wm oembraledemainminals, Denisenkorepor'tedablodcingofme clinical changes and trunntin by such (13) . Thu, the mount Aptnat (no. mticholinergio ounpomds as mthylbenaltyzim 05 (up. acetytdwune my thymus 4'1: the mum and the amount as 5w (cumming Wombat “Layman, the dzgue and type abnalmauty, and changu in demomcephatoguphtc W mm“ Md behavtm appm pheuauena, which may be udueed by the «Mugs. 05 «A 05 antéchounugtc _, t , �Bmu'n eeetytchoune and Mahounugic dkugA . The effects of the direct application of acetylcmline to the central nervous systemmyalsobeblookedbymtidmlinergic drugs. The aaninietntion of the clmlineeteme hmibitor diuisopmpyl flmrophoaphate (DFP) elicited high amplitude mpid frequency EEG patterns similar to status epileptiws and ecu post-traumatic states (2!, 31, 32, 68). These EEG effects were blocked by small doses of parenteral atropine and sccpolamine. The great increase in acetylcholim after tetmethyl pyrophosphate ('13P?) was measumd and related to the toxic effects and the induced cmwlsions (29, 59). Wield and Denpsey prepared exposed animal cortex with pmstignﬁne and evoked electroencephalographic spike activity. prior ministration of atropine blocked the appeamoe of spiking, or if present. this electrical activity could be 'Ihe eliminated by atropine (9) . In contrast to these findings, Brenner and Merritt applied topical acetyloholirm in concentrations of exposed cortex of cats , and noted no encephalogmphic chmges The 2—1/3 to 10% to the effect an the electro- after intravemm atropine (1 tug/kg) (7). concentrations of coats/lemme in these experimnts, however, were higher than the topical applicatims (1-H gamma percent) and the intmcietemal (0.240 game percent) injections of Bernstein (6). Brenmr and Merritt also noted electroencePMJogr'aplﬁc effects similar to acetyloholine after meﬁuolnline (rbctwlyl) and car‘bmxyldlolim (Daryl) in concentrations mob lower than the acetylcholine cmcentmticns . They asmibed the increased �effectiveness of these choliner-gic drugs to their lack of sensitivity to cerebral cholinasterases . These data are conﬂicting and to qualify this issue. Cmbnaepémc Fluid View Mar study is necessary Amman of aoetyloholine mtsbolism finds and it Su'wuu. One in nervous tissues in an bustive and bomd form. wring periods of activity, sootyloholixnis libemtedattheoellmmbmwl'nmit is rapidly deactivated by dnlinestemses . The mom“: of bound acetyloholine is the resultant of the oontimnous processes of syntl'nsis, liberation and It has been postulated mm. that the level rises during sleep and falls during waking activity (15, 29, #5, 60). Tobias egg};mported increased free and total sootyldmoline after chloroform and nonbutal (ck) anesthesia in net and frog brinui but no changes after strychnine or piorotoxic oawulsims (60). Richter and levels in transient, however, as the msynthesis rate for aoetyloholim in rat brain is high (7 ganm/gm/minute) (as). mass observations were confirmed by Elliot 51:. 514. (15) and Ckossland and Merrick (ll). Giarm and Pepeu found the increase in acetylolwline following various depressants to be rwghtypr'oportimltomedogmeofdopmsimofthe central mus system mad the redaction in motor Rayner-t and Buck, activity (29). however, studying brain acetylcholine levels �during sedation cone-1m that some sedatives were associated with elevated bmin acetylcholine, but that no rigorous mletimships existed (39). In part, this may be related to the earlier observations of and Elliot that acetyldwline synthesis assured in rat brain slices is accelerated by low dosages of mm narcotic drugs, but irhibited by high dosages (140). Free acetyldaoline was reported in the spinal ﬂuid in patients with epilepsy (10, 63). 0f 56 epileptic patients , m; demxsmtod free acetyldlolinc in qumtiﬁes of 0.02 to 5.0 with an average of 1.0:bgannn percent. Acetyldaoline percent gm levels were related to the fmqmncy of seizms, the extent of electroencephalographic abtmmlity, and to the time since the last seizure, but bore no relation to medication, type of epilepsy or level of cholinesterase activity. Elliot 9}; 114 also noted fme aoetylcholine in the spiral fluid in mundane up to 3 gm percent after pentylene tetremol (Mammal) convulsions (15) . Mechem vimd the increased acetyloholine as a by—pmchct of the seizure, and not came]. (63). Studying the hypothesis that seizures were imhced by the commution of mtyloholine, ’lbrde measured the level of acetylcholine in hm tissue after pontylenetetmzcl convulsions. She noted a Tower and �rise in the acetylcholina content of the conwlsion. failed . to occur. hash before and a fall during certain levels of aoetyldwline, convulsions suggested that the fall in tissue aoetylcholine Below She during a convulsim was due to the inhibitim of acetylcholine syntresie by increased concenmtions of metabolites such as ammonium ions (61, 62). GiummmdPepeualsomeasmdclmges incenmlnewous system acetylcholine following various after mﬂadmlﬂle stimlatts (29) . Only and 3, 5-dimthylbutylethyl-baxbitm'ete was there a significant changein the acetyldmolim level . They noted a decrease in association with induced convulsions . With other drugs which they classified as ipmniazid + stimnam ipmiazid, (LSD, hydrmcytryptophan, and iprcniazid + DOPA) there in acetylcholine level . they concluded that despite intense excitation produced by these conpomda, them were no changes in acetylcholine hols unless these were observations ('lhe in convulsions. differemes by awarded were no changes betwentheseobservemandOomgtglﬁimdlbmrmdeadmem related to the differences in mthods of biochemical masummnts, for the latter measured chmges mflecting free may be acetylcholine only, while Siam and Pepeu measured the total acetylcholim. including forms of These AW“ bound and m acetylcrmlineluol). suggest that spontaneous an induced mm 4;qu in 5m. acetylehoLéne an abound 5m m bound 50m which my be Reﬂected in the enhance and Auzuau Cmbxal acetylchoune (Laid. activity spud deemed“, teaming tum Levels 06 acexyzehoune, whue deep and anesthesia augment Wicca“ plwduduon taming tame Levels . accompanied by an inc/Lease �t ~ .wr, ~ also Two ,7 w“ in... gym. m.“ cm u , . .......w....w,,.,_ .7... , , .7 , ,...,. “ﬂu..." ......._ , ». __‘ -7, N-... .. n"... -..—.. - .u»...——..r.n Wm m -gNuvom 3mm Chounutwuu. m:- and Wm maid spiral fluid momesternae activity (63, types of dumnstemes 614, 65). whioh hydrolyze acetylcholine are mutually found in the spixml fluid: ctnlimstemse~1 ("trm," "amcific," or mom—hydrolyzing) which has a high specificiw for anatyldnlino; and cholinestemse—II ("pseudo," "mnapccific," or bamyldmolimahydmlyzing) . The diffemt rates of hydmlysis for nothao‘noline and benaoyloholim permits qualitative distimtiom . By reporting tho dwlinestemse activity as a ratio of the activity with mtrudloline and huuoyldmlim substrates empamd to an acetyldxolim substrate dnlimstomseJ/aoatylcholﬁxe and armlimstemse—II/ aoetyldnlim ratios are derived. Normal oembxospinal fluid contains estemses in the ratio of 33:17 for dnlixxestemsa-I to dmlimstemse-II . In patients with head mum. 'lbwer and McEac-Mm reported m inwnion of the oholhnstemses with an shamans in the okxolia‘IIstomean fraction of the spinal fluid and a decrease in dxolimstemao-I activity. 11» extent of the oholimstemse malwasmlttadtoﬂmsewrityofmmmdtothedagzu of the elootmumphalomphio abnormality. In patients with elevated spinal fluid aoetyloholim after ratio of dolineatemoes or total oknlixmstemse activity was fomd. spontaneous seizures, mwever, no chmge in the �Following the recent denmstratims that neurol stinmlation produces changes in brain weight and acetylcholinesterase (37, ), Pryor M9, induced swims in and Otis studied the activity effects of repeated Wistar rats ('43). After as little as u weeks, they observed increases in brain weight and in acetylcholinestemse activity, related to decrements in behavioral performance. in cholinestemse activity may be related to which was Changes changes in cell membrane permeability. Qualinesterese-I is found in highest concentration in the central nervous system while cholinestemse—II predominates in other tissues, especially cerebral acetylcholine, vesclilaticn blood serum. With immersed and increased cellular permeability may be predicted, with a vucﬂai‘}uitrgnswatim varying with the extent and duration degree of of the vasodilation (35). Spiegel, Spiegel-Adolf, and their coworkers demtrated such permeability changes and increased conductivity of the tissues associated with the appearance of various ions (as potassimn and phosphate) in the spinal fluid following electrically induced convulsions (Bu-58) . Such non- electrolytes as nucleic—acid splitting enzymes also increased. Changes in cellular permeability may be the basis for the high concentrations of acetylcholine and increased concentrations of cholinesterase-II after induced seizures or head trauma (65). The persistence of acetylcholine in spinal fluid after trams and after seizures despite increased cholinestemse activity may be related to the sensitivity of the acetylcholine— head cholinesterase-l system to concentration relationships (8, #1, 85) . �.At "physiologic" concentrations , hydrolysis of acetylcholine is rapid (34+ microseconds) but at higher. and lower comentrations, the activity falls off quickly. In contrast, the cholinestemse-II acetylchcline relationship is non-specific and the rate of hydrolysis increases with increased concentratim. ' relationships are related to the induction of seizures. the usual concentrations of ecetylchcline at cell membranes These While are destroyed by the specific activity of clmlimsterese-I in a few microseconds, an excessive concentmtim following excitation may exceed the rate of hydrolysis by dualinesterase-I. is seizmre threshold seizure reached and a seizure induced, with the wt scetylcholine affects vascular itself adding to the increased The of free scetylcholine. and The cellular pemeebility, altering the concentrations of various ions, including dialinestemse-II, in tissues and in the derebrospinel fluid. The activity of dwlinestemse-II, though the low efficiency and depending on cmcentmtion kinetics, remces the acetylcholine in the tissues in hours to days to levels for the physiologic action of chcljnestemse-I. Chawutuase theta ins/wade in appeals. in the spinal (ﬂuid as a uéueaon 06 ﬂuids, mulling (Item chaugu in mm sea numb/tans pumeaway occasioned by teamed aeetylehoune. The teamed ehounutuasu Me paint 06 the homeostatic mechanism canWLung the Leveu 6M. nmuoub system 06 acetyzchaune at can mmbmu necessary datum. �-12.. t-!ypeluync/wny and Induced EC?! Canvuuiom. The significance activity for the convulsive therapy process has been repeatedly stated (22, 23, SO, 51). The early appearance of high degree hypersynchrony and its persisof the deVelopment of high voltage slow wave tence throughout a treatment course has been described as pre- requisite to inpmvennnt. Both the electrograﬁiic and the behavioral clunges of inde cmvulsions were transiently reversed by the acute aministmtion of experimntal anticholimx‘gic alnpomds (18, 19). The intmvernus injection of diethazine, benactyzine, the piperidylbenzilatea and WIN-2299 induced These EEG JB—318, JB-336 and JB-329 BBQ (Ditran), deayncruonizatim in psychiatric subjects. changes were associated with behavioral aka: alerting, anxiety, tremors, illusions , and railucinatims. In patients who had recently received electromnvulsive therapy, them was a reduction in slow wave activity and a reversal of euphoria, dnnial and oonfmion. Atropim in low doses was associated with EEG desynolmnizatim accompanied by tachycardia, nervousness and tension. At higher dosages, hypersynchrmws slow anes, followed by lower voltage, poorly organized delta activity with activity fusion and diswientatim. superimposed beta was associated with progressive con- effect of anticholinergic drugs on slow wave activity was also assessed in convulsive therapy by the chronic adminis— tration of atropine (5 mam per day) and scapalomine (1 - 3 mg) The of-WW during the weeks of tmatmmt. The �-13.. mm of group who alwing was significantly less than in a cmtrol had not moiived the amine adminietretim (66). EEG The sasnples were too small for clinictl correlation, but the date is maistent with a definite blocking of the clinical effect. Marked improvement was seen of 5 in 2 of '7 atropine treated, none scapolmnine treated and in four of the six waiving mmdified authors may have Ad who ECT. cmtmls this study we not replicated by the suggest that dosage factors or population changes contributed to the different results (34). in mam Mam, the demoguphic changed induced continuum my be modiﬁed by the 06 muchounugic 06 acctywzounz ad anou’ated 9W1. dlmgd, dugguzéng inc/Lead ed that WWO): anemia inc/Lead ed chaunctgic adaptivity the high wattage Mow wave 05 x16 activity. AcetyMaune and Induced Couvwionc. Despite a constant application of mm , however, there is a greet variability in the time of eppeardnce, the duration and the exxent of the electmgrephic slow ween activity as well as the sensitivity of to modification by alerting, hyperventilation and barbiturates in psychiatric populations(30). The differences in the demo. of induced EEG hypersyncmrcny may related to differences in central duelinergic activity. The failure of certain patients to develop hypersynchmny be may be associated with the absence of free acetylcholine and with minimal clmxges in cerebral function, thus precluding a clinical response to induced convulsions. Tower and HcEachem, �-33.. in their study of omniooerebml tram, included observations of six psychiatric patients undergoing convulsive therapy (63). after 3-? treatments they reported free spinal fluid acetylcholine in two patients; and an increase in clnlinestemseull and a decrease in cholinestemse-I with a reversal of the ratio of oholinestemses in five of the six Studying the patients patients. the one patient in the series who failed to show either free aoetyloholine or a oholinestemoe ratio reversal in the spinal fluid was described as: "It is interesting that this patient was tmtmt.“ From the only one of the six to show no response to these observations they omeluded that the spinal fluid changes in induced convulsions were more like those of cmniooerebml trams than those of spontaneous epilepsy. Other evidence of altemtimas in the pemability barrier seen in the damstmtions of an increased cmoentmtim ofoooaineinbmintissues threedays aftersseriesole induced omvulsions (l). The change in concentration of this large molecule, ordinarily absent in briin tissue, was associated may be with the appearance of hypersynohmny (delta btmsts) in the elect'oenoephslogram. Fm thus obsmvauam we would conducts that induced command, Like mucouebmﬁ Mama and spontaneoua balm/ms, an associated with an inc/Laue in ﬁne. acetyzchoune in am, mey enhancing the. «:2qu as chaunutmuu. The Level. 05 ﬁne Macadam sawing «mm and �a hypUuynchlwny a one mama 06 mend Leveu 05 magichouue maintained by upewted induced Aazwlu. acetytchaune and the. melted mey including chewable/(Mu. 05 The momma», changu in Lym, including acetytchoune (that Aubamue 504 the. pwutent EEG and 04‘.th Aubetancu, mmummm elect/w- H movide the behavioml. changu and EEG hypn- the. Maﬁa Aynchhong ﬁauomlng induced convulsions. An 05 application the medic/tan Medication 06 05 05 «than couoquonA 424 (men in the convuuive zhmpy aupome and the paychoeu (21.). Chounuteluuu and the Medication 05 Peychaeu. Funkenetein g_t_ g}: demnstr‘ated a relationship between the blood pressure response to methocholine, an active cholinergic agent, the and the clinical response to omvuleive therapy (25-27). Inmdiately after the injection of methaoholine, blood pressure falls, usually returning to the baseline within 5-20 minutes. A return within 5 minutes places in the patients in Groups I, II or III; while a return after 20 minutes places the patient in Groups VI and VII. Group I and Group II-III have a 9 and a 35% recovery 89% VI VII and while Group Group respectively, motors rate, and 97% recovery rates to induced convulsions (27). Group I to III reactors may be looked upon as patients in whom methecholine is rapidly hydrolyzed; while Groups VI and VII have a slow hydrolysis rate. (The response to injected epinephrine was suggested as a second criteria in the �-16.. While (H8). value of limited but discriminating is classificatim, we have no biochemical explanation of the differences metabolism of nethachcline in these psychiatric in the it M8, is possible that the blood and tissue cholinestemse activity levels of Groups I-III is high, while that of Groups VIJII is to genera psychiatric populations. differences in blood oholinestemse levels in normal and low ccnpared The ill subjects have been extensively titled studied. Despite differences in methods ('4, 5) , elevated cholinesterase levels mntally ccupared to normal populations have been reported for depressive subjects (W, #6, H7, 52), schizOphrenic subjects (1“, 28, 53) and a mixed psychiatric population (#2) . Alpem reported lowered cholinestemse levels in schizophrenic subjects (2). mile these studies appear inconclusive, they provide data that the variations in blood cholinesterase levels are generally greater and frequently elevated in the mntally ill. Negative reports include the failure by Bllman and Callaway (16) to confirm Rubin's study; and Altschule's review of the data suggesting no abnormality of cholinesterase Conclusion. levels in the mentally ill (3). This review stunnerizes sane of the available data suggesting that cholinergic mechanism may be central to the convulsive therapy process. Induced convulsions are associated with vasodilation and increased cellular permeability, followed by the pppeamnce of increased amomts of enzymes and electrolytes in �intercellular and cerebrospinal fluids. Amng the changes are immase in intercellular acetylcholine to levels greater than can be destroyed by aoetylcholinestemse activity, and enhanced amounts of butyrylcholinestemse. The increase in an acetylcholine, vasodilation, and increased cellular permeability appear as interrelated phenomena associated with trauma, seizures and induced convulsions. These biochemical changes are associated with increased electrical hypersynohmny which is recorded as EEG slow wave activity in scalp electrodes, and which can be modified by acute and chronic ediﬁnistmtims of many anticholinergic dmgs, including atropine. benactyzine, diethazine, pmcyclidine and various piperidylbenzilatus. In these regards, induced convulsions are more similar to cerebral trauma. than to spontaneous seizures. in cerebral biochemistry alter cellular activity sufficiently to affect consciousness and the behavior of subjects. Failure to induce persistent biochemical changes , including the concentration of acetyloholine, results in failure to produce The changes behavioral change. Thin! is, as yet , no consistent evidence for differences in the sensitivity or dependence of populations on cholinergic medianisms; the differences in the rate of development of cerebral changes to the same number and frequency of induced convulsions and the classification based on the blood pressure response to mthacholim suggest, however, that such differences may be important in the pathogenesis of different psychoses. ��E' U ‘6 :6 _J! U m 3: = g 0 D. YOUR :3 I) Ta. 41: E O ° 8 : z a £3 'u E as. WITH .- g o 5 .— ‘E 3 e “ n:<3 0? DESK £5 :a: “1’" = 0 0)|.um :3? 1:5a o ‘ﬂ :1: III z....a) co n— .I I) o- '. ”-0 c: :3 0 >~ 3: 5 ” 9 '23: :2 a - c: 1.: U an 3.. 0>§ E "E g0 " L D. a; 0w a0 £5 z13 (g i: (U .—l ._ \— 3 13 U! w e 13 U < .g 23 at- 3 0 o - ac il ,~ 3" :2 '3 E PRESENT ea " ‘- 2'5o AT o 5" a»5 °E n.—O mi 1:8 m “ Ex a Illa REGISTRATION “" ”'7 a: c c q, u:3 32:) «n- m '0 C m >‘ 3: Q h” o: a: 0< c E 5‘: h o55 ON Eucu 0 1 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIII|IIIIIIIIIIII|IIIIIIIIIIIIIIIIlllllIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII 122nd ANNUAL MEETING AMERICAN PSYCHIATRIC ASSOCIATION ATLANTIC CITY, N. J.—MAY 9-13, 1966 HIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIHIL_ IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII First Name City state Last Name �CHOLINERGIC ASPECTS OF CONVULSIVE THERAPY Max Read M.D. at the May Now, Fink, l22nd ﬂeeting of the American Psychiatric Association, 12, 1966, Atlantic City. Proféssor of Psychiatry, 5-9-66. New York Medical College, New York City. �The mode of action of induced convulsions is still puzzling. Various theories have been proposed, including those best described as wholly psychological in scope, and those wholly biological or Neither extreme point of view is consistent organic - structural. with the available facts, and the neurophysiological - adaptive models — combining, as they do, both the biological data and the personality historical facts - are the most satisfactory today. One of the neurophysiological - adaptive theories suggests that persistent alterations in brain fUnction are a necessary condition fOr behavioral change and inprovement in the convulsive therapies. While many measures of altered brain function have been studied, similar relationship of change in measure to behavioral change, the appearance of high voltage slow wave and each has shown a activity in the scalp recorded electroencephalogram.has been the The induced delta activity most useful index in these studies. is readily observed, easily quantified and the amount, distribution over the scalp, amplitude and persistence are each directly related the frequency of the induced seizures and are independent of the mode of induction of the seizure. to the number and While the biochemical basis for these EEG changesgii=3 poorly understood, observations that the induced slow wave activity was inhibited by the intravenous administration of anticholinergic that cholinergic mechanisms may play an active part not only in the EEG activity but in the therapeutic compounds, suggested process as well. �patterns and the response to anticholinergic drugs M. in convulsive therapy were—seen to be similar to the EEG and The EEG behavioral changes in experimental and clinical head trauma and to a lesser extent, in spontaneous seizures. This was clearly reflected in measures of the cholinesterases in brain and spinal fluid in these conditions. These observations led to a review of the neurological and biochemical data in induced convulsions, head trauma and spontaneous seizures, to attempt to relate the available observations to the neurophysiological and therapeutic changes observed in the convulsive therapy process. The activity of acetylcholine in the transmission of nervous impulses has been extensively sutdied since the early descriptions by Dale and Loewi.in 1914 and 1921. A constituent of nervous tissue in a bound ﬁorm, acetylcholine is liberated during the excitation process. It is rapidly hydrolyzed through the mediation of acetylcholinesterase and is rapidly reconstituted by cholineacetylase. Free acetylcholine has not been measurable in normal breakdown of bound the fluid despite cerebrospinal rapid acetylcholine during periods of activity and excitement. But the normal cerebrospinal fluid does have measurable cholinesterase activity. �In_exparimenta&—trauma—ie—eaes, free acetylcholine was found in the cerebrospinal fluid within a few minutes after head trauma lk.(4T$ and persisted for varying periods up to #8 hours. The quantity of free acetylcholine varied between 2.7 and 9.0 and the amount was gamma percent directly related to the degree of induced trauma - the greater the induced head trauma, the higher the amount of neasured acetylcholine. Concurrent electroencephalograms first demonstrated high voltage fast activity, interpreted as evidence of an intense neuronal discharge, which was soon succeeded by short periods of flattening of all recorded electrical activity. were fbllowed by prolonged and These phases persistent periods of high amplitude sharp waves in the delta frequencies. The degree to which the animal's behavior was disorganized related both to the degree of induced trauma and to the amount of measured free acetylcholine. The higher the observed levels- was of acetylcholine, the greater the degree of EEG abnormality and the greater the changes in consciousness. The development and the persistence of spontaneous post—traumatic seizures were also related to the amount of free acetylcholine measured in the cerebrospinal fluid. In a parallel study, acetylcholine was applied directly to the exposed cat cerebral cortex. acetylcholine was 1 gamma When the concentration of percent or less, high amplitude sharp �waves of low frequency appeared in the electroencephalogram. the concentration was increased to 2 gamma When percent, the electro- encephalogram flattened in a fashion parallel to the post-traumatic a relationship between the EEG changes records, thus again showing and the concentration of free acetylcholine. Investigations in neurological patients by in 1948 demonstrated Tower and McEachern free acetylcholine in the cerebrospinal fluid only in patients with recent head trauma and recent grand-mal seizures, but also after electroconvulsive therapy. Free acetylcholine varied fron10.2 to 100 gamma percent. In parallel studies they measured the spinal fluid cholinesterase a sharp rise in the butyrylcholinesterase (non-specific) fraction and a fall in the acetylcholinesterase activity. They noted (specific) fraction both in the patients with head trauma and in those fbllowing convulsive therapy. After spontaneous seizures, however, the cerebrospinal of cholinesterases although fluid did not exhibit such it an inversion did contain free acetylcholine. They that the level of free acetylcholine varied directly with the degree of cerebral damage and that the reversal of cholinesterase fractions was a more sensitive indicator of cerebral damage. concluded Electroencephalograms taken at varying intervals following trauma also indicated a relation between the degree of EEG abnormality and the appearance of free acetylcholine in the cerebrospinal fluid. �Continuing a review of head trauma, we note behavioral and neurologic signs of head trauma that the may be EEG, blocked by the parenteral administration of atropine. ward applied these observations to the treatment of closed head injuries. In 20 degrees with of trauma, the subcutaneous varying patients administration of atropine in some and was a reversal of the associated with clinical improvement EEG effects in others. The same changes in the post—traumatic electroencephalogram.were reported by Jenkner and Lechner cholinergic drug. A in a study of diethazine, another anti— single intravenous dose in forty patients resulted in normalizing the abnormal electroencephalogram in twenty-two and marked improvement in six others. That, the amount 06 ghee acetylchouhe may the/LeaAe tn the Aptnat ﬁhee Mia/Cd 5031.0th Wicca/Lewd Mama and the amount acetytchotthe, the deg/Lee and abrzolunaLity, ahd‘changeé type 05 etect/Loeneephaﬂog/Laphéc tn euntcat behautot phenomena, whtch may be ILeduced by the 05 appea/L a4 ammmmon 06 ate/mutated anti- ehotéhejtgtc d/mgb. 3W acetytchoune and antéehouhugtc d/LugA. While the data is not as clear, the effects of the direct application of acetylcholine to the central nervous system by anticholinergic drugs. The may also be blocked administration of cholinesterase inhibitor di-isopropyl fluorophysphate (DFP) elicits high amplitude �patterns similar to status epilepticus and posttraumatic states. These EEG effects have been blocked by small rapid frequency EEG doses of parenteral atropine and scopolamine. Chatfield and Dempsey prepared exposed animal cortex with prostigmine and evoked electroencephalographic spike activity. prior adndnistration of atropine blocked the appearance of spiking, or if present, thes electrical activity could be eliminated by atropine. The Bornstein also reported that the parenteral administration of atropine to modify the behavioral and neurological signs observed after the intracisternal addition of acetylcholine. seemed In contrast to these findings, Brenner and Merritt applied topical acetylcholine in concentrations of 2-1/2 to 10% to the exposed cortex of cats and noted no effect on the electro- after intravenous atropine. not deﬁthtte, the obeehvattone éuggebt that atnoptne encephalographic changes White may bzoch the behautotat and EEG eﬁﬁecté 06 ghee tntaoduced acetytchottne tn the Aptnat glutd. CehebhOAptnat Ftutd Acetytchotthe and Setzuheb. to free acetylcholine and spontaneous seizures ship. One view we of acetylcholine metabolism finds tissues in an inactive and bound fornn Turning again note a relation- it in nervous During periods of activity, �acetylcholine is said to be liberated at cell membranes where it is rapidly hydrolyzed The amount and deactivated by cholinesterases. of bound acetylcholine is thus the resultant of the continuous processes of synthesis, liberation and breakdown. It has been postulated falls during waking that the level rises during sleep and activity. Free ace: Icholine was reported in the spinal fluid in patients with epilepsy. Of 56 epileptic patients, HM denonstrated free acetylcholine in quantities of 0.02 to 5.0 gamma percent with an average of 1.0 gamma percent. Acetylcholine levels were related to the frequency of siezures, the extent of electroencephalographic abnormality, and to the time since the last seizure but bore no relation to medication, type of epilepsy or level of cholinesterase activity. Elliott at aﬁ. also noted free acetylcholine in the spinal fluid in concentrations up to 3 gamma percent after pentylenetetrazol (Metrazol) convulsions. the increased acetylcholine as a by-producifof the seizure and not causal. Studying Tower and MCEachern viewed the hypothesis that seizures were induced by the accumulation of acetylcholine, Torda noted a rise in the acetylcholine content of brain before and a fall during pentylenetetrazol convulsions. certain levels of acetylcholine, convulsions failed to occur. She suggested that the fall in tissue acetylcholine during a convulsion was due to the inhibition of acetylcholine Below synthesis by increased concentrations of metabolites such as ammonium ions. �that AponianeOuA on induced Aeizunei incneaie in inieiceiiuian ﬁnee aceiyichoiine Theee etudicb AuggeAi ane accompanied by an iibenaied 5iuid. gnom iii Ceaebnai bound 50am which may be neﬁiecied activity in the Apinai and Aeizuneé enhance aceiyichoiine deeinuciion, iowening iiAAue ieueiA 05 aceiyichoiine, whiie bicep and anebihebia augment aceiyichoiine pnoduciion incneaAing iibéue £evw . EEG Hypenbynchnong and Induced ConuuiAionA. of high voltage EEG slow wave The significance activity for the convulsive therapy process has been repeatedly described, with numerous observers indicating that increased slowing is associated with behavioral In the usual course of convulSive therapy, inter- improvement. treatment electroencephalogram record progressive increases in amplitude and in theta activity and a reduction in beta activity. As treatment continues, delta activity appears in bursts and is the dominant activity in all leads. These changes eventually are directly related to the number and rate of induced convulsions, and is not specific ﬁor a method ofinduction. While some relationships to type of electrical current has been observed, all _ seizure inducing methods or inhalant —— —- exhibit the electrical, intravenous same type of EEG chemical pattern changes. �early appearance of high degree hypersynchrony and its persistence throughout a tre-tment course has—bean—éeuné4834xr The «Milan... prerequisite to inprovement. Both the electrographic and the betavioral changes ofincuced conVulsions are transiently reversed by the acute administration of experimental anticholinergic compounds. The intravenous injection of diethazine, benactyzine, the piperidylbenzilates JB—318,JB—336 and JB- 329 (Ditran), WIN-2299 These EEG induced EEG desynchronization in psychiatric subjects. changes were associated with behavioral alerting, anxiety, tremors, 'llusions and hallucinations. In patients had recently received electroconvulsive therapy there was a reduction in slow wave activity and a reversal of euphoria, who denial and constion. Adztpine, in low doses, was also associated with EEG desynchronization accompanied by tachycardia, nervousness and tension. At higher dosages, hypersynchronous slow waves followed by lower voltage, pooly organized delta activity with superimposed beta activity was accompanied by progressive constion and disorientation. effect of anticholinergic dimugs on the slow wave convulsive of activity therLapy was also assessed by the chronic administration of atropine (5 mgm per day) and scopolamine (1-3 The during the weeks of treatment. The amount of EEG slowing was significantly less than in a control group. The samples were too small fora dinical correlation but the data is consistent mg) �-10with blocking of the clinical effects of electroconvulsive therapy. treated, Marked improvement was none of 5 scopolamine-treated and in controls receiving unnodified replicated ECT. of 2 u atropine- 7 of the 6 This study was not that dosage factors have contributed to the different by the authors who suggest or population changes may results in a second study. A6 reported in tn eeaebaat thauma, the eteetnognaphtc changeb 05 thduced convutttont may be modtﬁted by the adhthtbthatton 06 anttchottnehgte dnugt buggeétthg that tncheabed 05 acetytehottne on amountb tncneated chottnehgte necepttvtty t4 abboctated with the htgh wattage atow wave aettuttg. Convutttonb. Aeetytchottne and INduced Despite a constant application of treatments, however, there is great variability in the time of appearance, the duration, amount, and sensitivity to modification by alerting, hyperventilation and barbiturates activity in psychiatric populations. we would suggest that these differences may relate to differences in central cholinergic activity. The failure of of the electrographic 81 w wave certain patients to develop hypersynchrony may be associated with the failure to liberate excessive amounts of free acetylcholine, and with the minimal changes in cerebral fUnction ��-11a clinical response to induced convulsions is precluded. in their study of patients with head trauma, included observations of six psychiatric patients undergoing Tower and MCEachern after to 7 treatments they reported free spinal fluid acetylcholine in two convulsive therapy. Studying the patients 3 patients; and a reversal of the ratio of cholinesterase ratio reversal in the spinal fluid, the authors stated: "It is interesting that this patient was the only one of the six to show no response to treatment." From these observations they concluded that the spinal fluid changes in induced convulsions were more like those of craniocerebral trauma than those of spontaneous epilepsy. Fnom thete obtenvattont we woutd conctude that induced convutétont, tthe chantocenebnat tnauma and Apontaneout tetzuneé, ate attoctated wtth an tncneate tn ﬁnee acetytchottne tn tnten- cettutun gtutdb, attentng cehebnat penmeabttttg and enhanctng the appeanance 05 chottnettenateb. The tevet t4 matntatned by nepeated tnduced tetzunet. tA one ncétectton 05 attened penmeabtttty attened tevett 05 06 06 ghee EEG acetytchottne hypenégnchhony acetytchottne and the etectnotgtet and othen Aubttanceb; tnctudtng ehottnebtehabet. The changeé tn tntencettutan etectno- tyte4,'tnctudtng acetytchottne, ptoutde the btochemtcat Aubttnate ﬂat the penttbtent behautonat changeA and EEG hypeneynchhony ﬂottawtng induced convutetont. ��-12- CONCLUSIONS This review summarizes some of the available data suggesting that cholinergic central to the convulsive have observed that induced convulsions are mechanisms may be therapy process. We associated with cerebral vasodilation and increased cellular perneability, fbllowed of by the appearance of increased amounts electrolytes in intercellular and cerebrospinal increase in acetylcholine, vasodilation and increased enzymes and fluids. The permeability appear as interrelated phenomena associated with trauma, seizures and induced convulsions. These biochemical changes accompany increased hypersynchrony which is recorded as EEG slow wave electrical activity in scalp electrodes and which can be modified by the acute and chronic administration of anticholinergic drugs as atropine, benactyzine, diethazine, procyclidine and various piperidyl- benzilates. In these regards, induced convulsions are more similar to cerebral trauma than to spontaneous seizures. The changes in cerebral biochemistry alter cellular activity sufficiently to affect consciousness and the behavior of subjects. Failure to induce persistent biochemical changes, including the concentration of acetleholine, results in failure to produce behavioral change. �-13There is, as yet, no consistent evidence for differences in the sensitivity or dependence of the cerebral mechanisms underlying interpersonal behavior of populations on Cholinergic mechanisms. Differences in the rate of development of cerebral changes to the sane number and frequency of induced convulsions and of the mentally ill classifications based on the blodo pressure response to methacholine suggest, however, that such differences may exist and may be related to the pathogenesis of different types of psychoses, as well as the success or failure of our present varieties of biologiCal treatments . �CHOLINERGIC ASPECTS OF CONVULSIVE THERAPY max Read at the Now, Professor of Psychiatry, Fink, M.D. 122nd meeting of the American may 12, 1966, Atlantic City. 5—9~66. New York Psychiatric Association, Medical College, New York City. �of action of induced convulsions is still puzzling. Various theories have been proposed, including those best described The mode - as wholly psychological in scope, and those wholly biological or Neither organic - structural. extreme point of view is consistent with the available facts, and the neurophysiological models — — adaptive combining, as they do, both the biological data and the personality historical facts - are the most satisfactory today. One of the neurophysiological - adaptive theories suggests that persistent alterations in brain fUnction are a necessary condition fbr behavioral change and improvement in the convulsive therapies. While many measures of altered brain fUnction have been studied, and each has shown a similar relationship of change in measure to behavioral change, the appearance of high voltage slow wave activity in the scalp recorded electroencephalogram has been the useful index in these studies. delta activity is readily observed, easily quantified and the amount, distribution most The induced over the scalp, amplitude and persistence are each directly related to the number and the frequency of the induced seizures and are independent of the mode of induction of the seizure. While the biochemical basis for these EEG changes were poorly understood, observations that the induced slow wave activity was inhibited by the intravenous administration of anticholinergic that cholinergic mechanisms may play an active part not only in the EEG activity but in the therapeutic compounds, suggested process as well. �patterns and the response to anticholinergic drugs in convulsive therapy were seen to be similar to the EEG and The EEG behavioral changes in experimental and clinical head trauma and to a lesser extent, in spontaneous seizures. This was clearly reflected in measures of the cholinesterases in brain and spinal fluid in these conditions. These observations led to a review of the neurological and biochemical data in induced convulsions, head trauma and spontaneous seizures, to attempt to relate the available observations to the neurophysiological and therapeutic changes observed in the convulsive therapy process. The activity of acetylcholine in the transmission of nervous impulses has been extensively sutdied since the early descriptions by Dale and Loewi,in 191” and 1921. A constituent of nervous tissue in a bound form, acetylcholine is liberated during the excitation process. It is rapidly hydrolyzed through the mediation of acetylcholinesterase and is rapidly reconstituted by cholineacetylase. Free acetylcholine has not been measurable in normal breakdown fluid the of bound cerebrospinal despite rapid acetylcholine during periods of activity and excitement. But the normal cerebrospinal fluid does have measurable cholinesterase activity. �In experimental trauma in cats, free acetylcholine was found in the cerebrospinal fluid within a few minutes after head trauma persisted for varying periods up to H8 hours. The quantity of free acetylcholine varied between 2.7 and 9.0 gamma percent and and the amount was directly related to the degree of induced trauma the greater the induced head trauma, the higher the amount of measured acetylcholine. Concurrent electroencephalograms first demonstrated high voltage fast activity, interpreted as evidence of an intense neuronal discharge, which was soon succeeded by short periods of flattening of all recorded electrical activity. These phases were fbllowed by prolonged and persistent periods of high amplitude sharp waves in the delta frequencies. The degree to Which the animal's behavior was disorganized related both to the degree of induced trauma and to the amount of measured free acetylcholine. The higher the observed levels was of acetylcholine, the greater the degree of EEG abnormality and the greater the changes in consciousness. The development and the persistence of spontaneous post-traumatic seizures were also related to the amount of free acetyldholine measured in the cerebrospinal fluid. In a parallel study, acetylcholine was applied directly to the exposed cat cerebral cortex. acetylcholine was 1 gamma When the concentration of percent or less, high amplitude sharp �waves of low frequency appeared in the electroencephalogram. the concentration was increased to 2 gamma When percent, the electro- encephalogram flattened in a fashion records, thus again showing parallel to the post—traumatic a relationship between the EEG changes and the concentration of free acetylcholine. Investigations in neurological patients by in 19H8 Tower and MeEachern demonstrated free acetylcholine in the cerebrospinal fluid only in patients with recent head trauma and recent grand-mal seizures, but also after electroconvulsive therapy. Free acetylcholine varied from.0.2 to 100 gamma percent. In parallel studies they measured the spinal fluid cholinesterase activity. They noted a sharp (non—specific) fraction and a rise in the butyrylcholinesterase fall in the aeetyldholinesterase (specific) fraction both in the patients with head trauma and in those fellowing convulsive therapy. After spontaneous seizures, however, the cerebrospinal of cholinesterases although fluid did not exhibit such it an inversion did contain free acetylcholine. They that the level of free acetylcholine varied directly with the degree of cerebral damage and that the reversal of cholinesterase fractions was a more sensitive indicator of cerebral damage. concluded Electroencephalograms taken at varying intervals following trauma also indicated a relation between the degree of EEG abnormality and the appearance of free acetylcholine in the cerebrospinal fluid. �Continuing a review of head trauma, we note that the behavioral and neurologic signs of head trauma may be EEG, blocked by the parenteral administration of atropine. ward applied these observations to the treatment of closed head injuries. In 20 patients with varying degrees of trauma, the subcutaneous administration of atropine was associated with clinical improvement in some and a reversal of the EEG effects in others. The sane changes in the post-traumatic electroencephalogram were reported by Jenkner and Lechner cholinergic drug. in a study of diethazine, another anti— single intravenous dose in fbrty patients resulted in normalizing the abnormal electroencephalogram in A twenty-two and marked improvement in six others. That, the amount 06 ﬁnee acetytchottne may tncneabe tn the Aptnat ﬁtutd ﬁottownng enatnoeenebaat thauma and the amount 06 ghee aeetytchottne, the degnee and type 06 eteetaoencephatogaaphte abnoamattty, and changeA tn cttnteat behavton appeah ab tnteanetated phenomena, which may be deduced by the athntAtnatton 06 anti- ehottnengte dnugb. Baatn acetytchottne and antichottnengtc daugA. While the data is not as clear, the effects of the direct application of acetylcholine to the central nervous system by anticholinergic drugs. The may also be blocked administration of cholinesterase inhibitor di-isopropyl fluorophysphate (DFP) elicits high amplitude �patterns similar to status epilepticus and post— traumatic states. These EEG effects have been blocked by small rapid frequency EEG doses of parenteral atropine and scopolamine. Chatfield and Dempsey prepared exposed animal cortex with prostigmine and evoked electroencephalographic spike activity. prior administration of atropine blocked the appearance of spiking, or if present, thes electrical activity could be The eliminated by atropine. Bornstein also reported that the parenteral administration of atropine seemed to modify the behavioral and neurological signs observed after the intracisternal addition of acetylcholine. In contrast to these findings, Brenner and Merritt applied topical acetylcholine in concentrations of 2-1/2 to 10% to the exposed cortex of cats and noted no effect on the electro— after intravenous atropine. not deﬁtntte, the obbchvat£0n4 tuggebt that ataoptne encephalographic changes White may btoch the behautoaat and EEG eﬁﬁeeté 06 ﬁaee tntaodueed aeetytehottne tn the Aptnat ﬁtutd. CeaebaaAptnat Ftuid Aeetytchottne and Setzuaea. Turning to free acetylcholine and spontaneous seizures we again note a relationship. One view of acetylcholine metabolism finds it in nervous tissues in an inactive and bound fbrnn During periods of activity, �acetylcholine is said to be liberated at cell membranes where it is rapidly hydrolyzed The amount and deactivated by cholinesterases. of bound acetylcholine is thus the resultant of the continuous processes of synthesis, liberation and breakdown. It that the level rises during sleep and falls during waking activity. Free acetylcholine was reported in the spinal fluid in has been postulated patients with epilepsy. epileptic patients, denonstrated free acetylcholine in quantities of 0.02 to 5.0 gamma percent with an average of 1.0 gamma percent. Acetylcholine Of 56 HM levels were related to the frequency of siezures, the extent of electroencephalographic abnormality, and to the time since the last seizure but bore no relation to medication, type of epilepsy or level of cholinesterase activity. Elliott et al. also noted free acetylcholine in the spinal fluid in concentra— tions up to 3 gamma percent after pentylenetetrazol (Metrazol) convulsions. Tower and MCEachern viewed the increased acetylcholine as a by-produce of the seizure and not causal. Studying the hypothesis that seizures were induced by the accumulation of acetylcholine, Tbrda noted a rise in the acetylcholine content of brain befbre and a fall during pentylenetetrazol convulsions. certain levels of acetylcholine, convulsions failed to occur. She suggested that the fall in tissue acetylcholine Below during a convulsion was due to the inhibition of acetylcholine synthesis by increased concentrations of metabolites such as anmonium ions. �ane accompanied by an tibenated ﬁiuid. that Apontaneoub an induced Aeizuneé incneaAe in intetceiiuian ﬁnee acetyichoiine Atudiei buggeét TheAe iib gnom Cenebnai in the Apinai bound 60km which may be neﬁiected activity and Aeizunei enhance acetyichoiine duuuctéon, tom/ting tame Lewis and aneatnebia augment acetytchome, white deep acetyichoiine pnoduction incneaeing tiibue 06 ieveii. EEG Hypenaynchnony and Induced Convuiiioni. of high voltage EEG slow wave The significance activity for the convulsive therapy process has been repeatedly described, with numerous observers indicating that increased slowing is associated with behavioral In the usual course of convulsive therapy, improvement. inter- treatment electroencephalograms record progressive increases in amplitude and in theta activity and a reduction in beta activity. As treatment continues, delta activity appears in bursts and eventually is the dominant activity in all leads. These changes are directly related to the number and rate of induced convulsions, and is not specific fbr a method ofinduction. While some relation— ships to type of electrical current has been observed, seizure inducing methods or inhalant -— -— electrical, intravenous eXhibit the same type of EEG all chemical pattern changes. �early appearance of high degree hypersynchrony and The its persistence throughout a treatment course has been fbund to be prerequisite to inprovement. Both the electrographic and the behavioral changes of hduced convulsions are transiently reversed by the acute administration of experimental anticholinergic compounds. The intravenous injection of diethazine, benactyzine, the piperidylbenzilates JB-318, induced WIN—2299 These EEG EEG JB—336 and JB-329 (Ditran), and desynchronization in psychiatric subjects. changes were associated with behavioral anxiety, tremors, illusions and hallucinations. alerting, In patients who recently received electroconvulsive therapy there was a reduction in slow wave activity and a reversal of euphoria, had denial and confusion. Atropine, in low doses, with EEG was also associated desynchronization accompanied by tachycardia, nervous- ness and tension. At higher dosages, hypersynchronous slow waves fbllowed by lower voltage, poorly organized delta activity with superimposed beta activity was accompanied by progressive constion The and disorientation. effect of anticholinergic drugs activity of convulsive therapy administration of atropine (5 was mgm on the slow wave also assessed by the chronic per day) and scopolamine during the weeks of treatment. The amount of EEG (1—3 mg) slowing was significantly less than in a control group. The samples were too small fbr a clinical correlation but the data is consistent �-10with blocking of the clinical effects of electroconvulsive therapy. Marked improvement treated, none of 5 was of 2 scopolamine-treated and in controls receiving unmodified replicated reported in of the 6 This study was not ECT. by the authors who suggest or population changes u atropine- 7 that dosage factors contributed to the different may have results in a second study. A4 tn cehebhat thauma, the eteetnoghaphte changeb 06 tnduced eonkutows may be modiﬁed by the achntnatjwtéon 06 anttchottnehgtc 06 acetytchottne dhugA Auggebttng on tnmeazsed that tncneabed amountA choltnetgtc heceptéw’ty t6 aAAoctated with the htgh voltage Atow wave activity. Acetytchotthe and INduced Convutbtoné. Despite a constant application of treatuents, however, there is great variability in the time of appearance, the duration, amount, and sensitivity to modification by alerting, hyperventilation of the electrographic slow and barbiturates activity in psydhiatric populations. we would suggest that these differences may relate to differences in central cholinergic activity. The failure of certain patients to develop hypersynchrony may be associated with the failure to liberate excessive amounts of free wave acetyldholine, and with the minimal changes in cerebral function �-11a clinical response to induced convulsions is precluded. in their study of patients with head trauma, included observations of six psychiatric patients undergoing Tower and MCEachern convulsive therapy. Studying the patients after 3 to 7 treat- ments they reported free spinal fluid acetylcholine in two patients; and a reversal of the ratio of cholinesterase ratio reversal in the spinal fluid, the authors stated: "It is interesting that this patient was the only one of the six to show no response to treatnent." From these observations they concluded that the spinal fluid changes in induced convulsions were more like those of craniocerebral trauma than those of spontaneous epilepsy. Fnom theée obAenvationA convuibionc, we wouid tihe cnaniocenebnai ane aAAociated with an inn/Lease eonctude that induced tnauma and Apontaneoui beizuneb, in ﬁnee acetytchotine in inten- cettuian ﬁtuidb, ditching cenebnat penmeubiiity and enhancing the appeanance 06 choiinebtenabei. The tevet 06 ﬁnee acetyichotine i2: maintained by nepeated induced bunt/(.66. i6 one neﬁiection 06 attened penmeabiiity ditched ieveté 05 06 EEG hypeuynchnony acetyichotine and the eiectnoiytea and othen iabAt‘ance/s, inciuding choiineAtenaAeA. The changeA in intencetiuian etectno- iyteb, inciuding acetyichoiine, pnouide the biochemicat bubbtnate 50h the penAiAtent behavionai changeé and EEG hypenaynchnony ﬁattowing induced canvutbionb. �-12- CONCLUSIONS This review summarizes some of the available data suggesting that cholinergic medhanisms may be central to the convulsive that induced convulsions are associated with cerebral vasodilation and increased cellular therapy process. we have observed perneability, followed of by the appearance of increased amounts electrolytes in intercellular and cerebrospinal increase in acetylcholine, vasodilation and increased enzymes and fluids. The permeability appear as interrelated phenomena associated with trauma, seizures and induced convulsions. These biochemical changes accompany increased hypersynchrony which is recorded as EEG slow wave electrical activity in scalp electrodes and which can be modified by the acute and Chronic administration of anticholinergic drugs as atropine, benactyzine, diethazine, procyclidine and various piperidyl— benzilates. In these regards, induced convulsions are more sinilar to cerebral trauma than to spontaneous seizures. The changes in cerebral biochemistry alter cellular activity sufficiently to affect consciousness and the behavior of subjects. Failure to induce persistent biochemical changes, including the concentration of acetylcholine, results in failure to produce behavioral change. �-13‘5 There is, as yet, no consistent evidence for differences in the sensitivity or dependence of the cerebral mechanisms underlying interpersonal behavior of populations on cholinergic mechanisms. Differences in the rate of development of cerebral Changes to the sane number and frequency of induced convulsions and of the mentally ill based on the classifications blodo pressure response to methacholine suggest, however, that such differences may exist and may be related to the pathogenesis of different types of psychoses, as well as the success or failure of our present varieties of biological treatnents. �CHOLINERGIC MECHANISMS IN CONVULSIVE THERAPY MAX FINK, M.D. DEPARTMENT OF PSYCHIATRY AT THE MISSOURI INSTITUTE OF PSYCHIATRY UNIVERSITY OF MISSOURI SCHOOL OF MEDICINE 54-00 Arsenal Street St. Louis, Missouri 63139 PSYCHIATRIC RESEARCH FOUNDATION OF MISSOURI Pulilicntion No. 65 - 8 �CHOLINERGIC MECHANISMS IN CONVULSIVE THERAPY Max Fink, M.D. Psychiatric Research Foundation Publication 65—8 September, 1965 �From the Department of Psychiatry, washington University School of Medicine and the Department of Psychiatry at the Missouri Institute of Psychiatry, university of Missouri School of Medicine, 5400 Arsenal Street, St. Louis, Missouri 63139 Aided, in part, by USPHS grants MEI—927, NIH-2715, MH-o72u9, and MH—ll380; and the Psychiatric Research Foundation of Missouri. VIII: 8/21/65 65-8 �CHOLINERGIC MECHANISMS IN CONVULSIVE THERAPY Despite extensive use, the mode of action of the convulsive therapy process remains enigmatic. The neurophysiologicalradaptive theory attempts an assimalation of neurophysiological, psychological, clinical, social aspects of the process (Fink, 1957, 1962)° In this View, the early development*and persistence of signs of altered cerebral function are and requisite to changes in behavior (Pink and Kahn, 1956), with electroc encephalographic slow wave activity as the most significant index of altered brain function, Demonstrations that premedication with atropine inhibited this slow activity (Ulett and Johnson, 1957) and that-anticholinergic compounds reversed clinical as well as electrographic changes (Fink, 1958) suggests that the biochemical basis fbr wave “the convulsive therapy process may be of the central nervous system. The in the cholinergic mechanisms role of acetylcholine and the cholinesterases in the convulsiVe therapy process is discussed in this review, Acetylcholine has been extensively studied as an active agent in the transmission of nervous impulses since the first descriptions by Dale (191%) and Loewi (1921); It is a constituent of nervous tissue. existing in a processa bound form Which It is rapidly is liberated during the excitation hydrolyzed through the specific action of cholinesterase and is rapidly reconstituted by the choline— acetylase system<Richter andessland. 191:9)w In normal. �cerebrospinal fluid, free aoetylcholine is not present despite the rapid breakdown of bound acetylcholine during periods of activity and excitement (Tower and McEachern, 19u9a)° The cerebrospinal fluid does have measurable cholinesterase activity, principally of the "true" or mecholyl hydrolyzing type (Nachmanson In the absence of free acetylcholine and Rothenberg, 19MB), under’resting conditions, electroencephalograms fail to (a) Cholinergic Aspects of Craniocerebral Trauma: acetylcholine was found after experimental up to H8 show and abnormality. Free in the cerebrospinal fluid within a few minutes head trauma in cats and persisted for varying periods hours (Bornstein, 1946)o varied between 2,7 and 9,0 gamma The quantity of free acetylcholine percent, and the amount was related to the degree of induced trauma, Concurrent electroencephalograms demonstrated records first filled with high voltage fast activity, interpreted as evidence of an intense neuronal discharge,which was soon succeeded by a short period of flattening of all recorded electrical activity, by prolonged periods These phases were then fOIlowed of high amplitude sharp waves in the delta frequencies, The behavioral changes were related both to the degree of trauma and to the amount of measured free acetylcholine, With higher of acetylcholine, Bornstein reported greater degrees of EEG levels abnormality greater changes in consciousness, Spontaneous post-traumatic seizures were also related to the amount of free acetylcholine and �appearing in the spinal fluid. Bornstein applied acetylcholine to exposed cat cerebral cortex, the concentration of acetylcholine When was 1 gamma percent or less, high amplitude sharp waves of low frequency appeared in the electroencephalogramo When the concentration increased to 2 gamma was percent, the electroencephalogram flattened in a fashion parallel to the post-traumatic records° Investigations in neurological patients McEachern (19M9a) demonstrated by Tower and free acetylcholine in the cerebro— spinal fluid only in patients with recent head trauma, recent grand—mal seizures or after electroconvulsive therapy° Free acetylcholine varied from 0,2 to 100 gamma percent, In assaying spinal fluid cholinesterase activity, they noted a sharp rise in the nonSpecific cholinesterase fraction (benzoylcholine—splitting) and a drop in the specific cholinesterase fraction (mecholyl—splitting) in patients with head trauma and following convulsive therapy. After spontaneous seizures, however, the cerebrospinal fluid did not exhibit such inversion although it contained free acetylcholine. that the level of free acetylcholine varied directly with the degree of cerebral damage and that reversal of the cholinesterase fractions was a more sensitive indicator of cerebral damage. ElectroThey concluded encephalograms, taken at varying intervals following trauma, also indicated a relation between the degree of EEG abnormality and the appearance of free acetylcholine in the cerebrospinal fluid. �These observations were recently confirmed by Kovach, Who recorded increased acetylcholine in rat brain inhibition of this activity and an by gt_§l. (1957) after traumatic shock the administration of atropine to the muscle preparationo ThuA the amount 06 ﬁnee acetytchottne may tncneaAe tn the Aptnat ﬁtutd ﬂattening chantacehebnat tnauma and the amount 06 ﬁnee aeetytchottne, the degnee and type changed tn cttnteat behavton appean (b) 06 a4 eteetnaencephatognaphtc abnonmattty, and tntennetated Anticholinergic drugs and trauma: The phenomena° electrographic, behavioral and neurologic signs of head trauma were blocked by the parenteral administration of 095-100 mg/kg atropine (Bornstein, 19u6), as were similar clinical changes occurring after the intracisternal addition of acetylcholine. Ward (1950) applied these observations to the treatment of closed head injurieso In 20 patients with varying degrees of trauma, he administered atropine subcutaneously in doses of 001 mg/kg, noting clinical improvement in some and a reversal of the electrographic effects in otherso Similar alterations in the post—traumatic electroencephalogram were reported by Jenkner and Lechner (1955) in a study of diethazine, another anticholinergic drugl A single intravenous dose in forty patients resulted in nornalizing the abnormal electroencephalogram in twenty~two and marked improvement in six otherso �Similar observations have been reported with methylbenactyzine and trasentin in animal experiments of post—traumatic shock cerebral The and edema (Denisenko, 1965), effect of atropine was assessed in the convulsive therapy process by Ulett and Johnson (1957), With the administration of to per day during the weeks the patients received electroshock therapy, the amount of slow wave activity atropine was up 5 mgm significantly less than in a control group received the atropine administration. who had not (These authors failed to replicate this study, suggesting that dosage factors or population changes may have contributed to different results [Johnson et_al., 1960])o Both the electrographic and the behavioral changes of induced convulsions were also reversed by the administration of experimental anticholinergic compounds (Fink, 1958, 1960), The intravenous injection of diethazine, benactyzine, the piperidylbenzilates JB-336 and JB-329 (Ditran), and in psychiatric subjects, These WIN—2299 EEG induced EEG JB—3l8, desynchronization changes were associated with behavioral alerting, anxiety, tremors, illusions, and hallucinations. recently received electroconvulsive therapy, a reduction in slow wave activity and a reversal of euphoria, In patients there was who had denial and confusion, Atropine in low doses, was associated with BEG desynchronization accompanied by tachycardia, nervousness and tension. �At higher dosages, hypersynchronous slow waves, followed by lower voltage, poorly organized delta activity with superimposed beta activity was associated with progressive confusion and disorientation, Both in eenebhat eteethoghaphte changeA 06 thauma and induced convutétOhA, the may be modtﬁted by the adhinttthatton anttchottnehgte dnugb, buggebtthg that tncheabed amountb aeetgtehottne on thcaeabed ehottnehgtc heeepttvtty t5 aMoctated with the high wattage stow wave aetéuttg, 06 Brain acetylcholine and anticholinergic drugs: (c) Similar EEG changes and similar blocking by anticholinergic drugs has been observed following the direct application of acetylcholine to the central nervous system, The administration of a cholinesterase inhibitor DFP (di-isopropyl fluorophosphate) elicited high amplitude patterns similar to status epilepticus, as well as changes similar to those of post—traumatic states (Freedman et_al., 19H93 rapid frequency EEG et_alf, EEG effects Himwich Hampson 1950; These were blocked by small doses of scopolamineo The 3:.Els’ 1950; and Wescoe et_al,, 1948). parenteral atropine and great increase in acetylcholine after tetraethyl pyrophosphate (TEPP) was measured and related to the toxic and convulsions induced (Giarman and Pepeu, 1952; Stone, 1957). Chatfield and Dempsey (1942) prepared exposed animal cortex with prostigmine and evoked electroencephalographic spike activity. The prior administration of atropine blocked this spiking, or the abnormality could be eliminated by atropine. if present, �In contrast to these findings, Brenner and Merritt (19u2) applied topical acetylcholine in concentrations of 2-1/2 to to the exposed cortex of cats, and noted no effect 10% on the electroencephalographic changes after intravenous atropine (l mg/kg)o The concentrations of acetylcholine in these experiments, however, were higher than the topical applications percent) and the intracisternal (002—10 gamma (l—M gamma percent) injections of Bornstein (19%)° Brenner and Merritt also made note of electroencephalographic effects similar to acetylcholine from mecholyl Cacetylbetamethylcholine) and doryl (carbamylcholine) in concentrations They much lower than the acetylcholine concentrations. ascribed the increased effectiveness of these cholinergic their lack of sensitivity to cerebral cholinesterases. These data are conflicting and further study is necessary to qualify this issue° drugs to (d) View Cerebrospinal Fluid Acetylcholine and Seizures: of acetylcholine metabolism indicates that nervous tissues in an inactive bound fornn it is One found in During periods of activity, acetylcholine is liberated at the cell membrane where it is rapidly deactivated by cholinesterasea The amount of bound acetylcholine is the resultant of the continuous processes of synthesis, liberation and breakdown. that the level rises during sleep (Tobias gt_al., 19u6; Richter and It has been postulated falls during activity. Crossland, 19u9; Elliot, Swankt and and Henderson, 1950; Giarman and Pepeu, 1962). Tobias et_al. found �8 increased free and total acetylcholine after chloroform and nembutal anesthesia in rat and frog brain, but no significant changes after strychnine or picrotoxin convulsions. Richter and Crossland measured the level of acetylcholine (micro-gamma per anesthesia and sleep in rat brain to be seizure levels, The brain tissue) during higher than postdifference in tissue levels is transient, however, as the resynthesis high (7 gamma/gm/minute)o Elliot et_§1f mg, 300% rate for acetylcholine in rat brain is These observations were confirmed by (1950) and Crossland and Merrick (195M). Pepeu (1962) found the increase Giarman and in acetylcholine following various depressants to be roughly proportional to the degree of depression of the central nervous system and the reduction in motor activity. Maynert and Buck (196”), however, studying brain acetylcholine and sedation concluded that some levels sedating agents are associated with elevated brain acetylcholine, but that no rigorous relationships existed. In part, this may be related to the earlier observations of Melennan and Elliot (1951) that acetylcholine synthesis measured in rat brain slices is accelerated by low dosages of narcotic drugs, but inhibited by high dosageso Free acetylcholine was reported in the spinal patients with epilepsy (Cone, fluid in Tower and McEachern, 19MB; Tower epileptic patinets, nu demonstrated free acetylcholine in quantities of 0.02 to 5.0 gamma percent with and McEachern, 19u9b), an average of 1,0 gamma Of 56 percent. Acetylcholine levels were related �to the frequency of seizures, the extent of electroencephalographic abnormality, and to the time since the last seizure, but bore no relation to medication, type of epilepsy or level of cholinesterase activityo Elliot §t_al3 (1950) also noted free acetylcholine in the spinal fluid in concentrations up to 3 gamma percent after metrazole convulsions, Tower and McEachern (19u9b) viewed the increased acetylcholine as a by—produce of the seizure, and not causal, Studying the hypothesis that seizures were induced by the accumulation of acetylcholine, Torda (1953) measured the level of acetylcholine in brain tissue after metrazole convulsions, She noted a rise in the acetylcholine content of brain befbre a seizure and a fall during the convulsion° Below certain levels of acetylcholine, convulsions failed to occur° that the fall in tissue acetylcholine to inhibition of acetylcholine synthesis She suggested during a convulsion was due by increased concentrations of metabolites such as ammonium ions. Giarnen and Pepeu also measured changes in central nervous system acetylcholine following various stimulants. Only after mecholyl and 3, 5-dimethylbutylethyl-barbiturate was there a significant change in theacetylcholinelevel° They noted a decrease in association with induced convulsions. With other drugs which they iproniazid + classified as stimulants iproniazid, hydroxytryptoghan, and iproniazid + DOPA) there were no changes in acetylcholine level. (LSD, They concluded that �10 despite intense excitation produced by these compounds, there were no changes in acetylcholine levels unless these were accompanied differences in observations between these by convulsions, (The workers and Cone gt ale and Tower and McEachern may be related to the differences in methods of biodhemical measurements, for the latter measured changes reflecting free acetylcholine only, while total acetylcholine reflecting bound and free forms of acetylcholine, [McLennan and Elliot, 1951]). TheAe AiudieA Auggebi that Aponianeoui an induced beizuheb ane accompanied by an incheaAe in inienceiiuian ﬁnee aceiyichoiine iibenaied ﬁnom ii» bound 60am which may be neglected in the Apinai ﬁiuido Cehebnai aciiviiy and Aeizuneb enhance aceiyichoiine Giarman and Pepeu measured the debtnuction, iowehing iiAAue ieveii 06 acetyichoiine, whiie Aieep and aneéiheéia may augment aceiyichoiine pnoduciion incneaiing iiiéue ieueiie (e) Central Nervous System Cholinesterases: Tower and McEachern also measured spinal fluid cholinesterase activity. TWO types of cholinesterases are normally found in the spinal fluid: (19H9) cholinesterase—I ("true," "specific," 0r mecholyl-hydrolyzing), which has a high specificity for acetylcholine; and cholinesterase-II ("pseudo," "non—specific," or benzoyldholine—hydrolyzing)o compounds hydrolyze Both acetylcholine but have different rates of hydrolysis for mecholyl and benzoylcholine. This differential rate perndts qualitative distinctions. By reporting the cholinesterase �11 activity as a ratio of the activity with a mecholyl substrate and with a benzoylcholine substrate compared to a substrate of acetylcholine, two ratios are found: cholinesterase—I/acetylcholine and cholinesterase-IIlacetylcholineo In sudh ratios normal cerebrospinal fluid contains esterases in the ratio of 33:17 for cholinesterase-I to eholinesterase—IIo with In patients head trauma, Tower and McEachern reported an inversion of the cholinesterases with a increase in the cholinesterase-II fraction of the spinal fluid and a decrease in cholinesterase-I activity. The extent of the cholinesterase reversal was related to the severity of trauma and to the degree of the electroencephalographic abnormality. In patients with elevated spinal fluid acetylcholine spontaneous seizures, however, no change in the cholinesterases or total cholinesterase activity in cholinesterase activity after ratio of was found. related to changes in cell membrane perneability. Cholinesterase-I is found in highest concentration in the central nervous system while cholinesterase-II predominates in other tissues, especially The change may be blood serumo With an increase in acetylcholine levels in cerebral intercellular fluids, vasodilation cellular permeability may be predicted, with a degree of transudation of vascular fluids into the intercellular spaces varying with the extent and duration and increased of the vasodilation (Kabat et_alo, 19u8). Spiegel, Spiegel—Adolf, �12 and their co-workers (19u1, 19u2, lguu, 19H8, 1953) demonstrated such perneability changes and increased conductivity of the tissues associated with the appearance of various ions (as potassium and phosphate) in the spinal fluid following convulsions° electrically induced Such non—electrolytes as nucleic—acid also increased, Changes in cellular perneability Splitting enzynes may thus provide the basis for the high concentrations of acetylcholine and the increased concentrations of cholinesterase-II in induced seizures or head trauma (Tower and MCEachern, 19H9c)o The persistance of acetylcholine in spinal fluid after head trauma and after seizures despite increased Cholinesterase activity may be related to the sensitivity of the acetylcholinecholinesterase-I system to concentration relationships (Nachmanson and Rothenberg, lQHS; Tower and McEachern, 19u90; Burgen and MacIntosh, 1955)o At "physiologic" is rapid concentrations, hydrolysis of acetylcholine (3-H microseconds) but the activity falls off quicklyc at higher and lower concentrations, In contrast, the cholinesterase—II acetylcholine relationship is non-specific and the rate of hydrolysis increases with increased concentration; These relationships are related to the induction of seizures. at cell membranes are destroyed by the specific activity of cholinesterase-I in a few microseconds, an excessive concentration following excitation While the usual concentrations of acetylcholine may exceed the rate of hydrolysis by cholinesterase-I. The seizure �13 threshold is reached and a seizure induced, with the seizure itself adding to the amount of free acetylcholine. The increased acetylcholine diffuses rapidly, affecting vascular and cellular perneability and increasing the concentrations of various ions, including cholinesterase—II, in tissues and in the cerebrospinal fluid, The activity of cholinesterase-II, though of low efficiency and depending on concentration the acetylcholine in the tissues in hours to days kinetics, reduces to levels fbr the physiologic action of cholinesterase—I. Chounutemu appeal: in the meme Maid Iheih anheaee in Lhzeheeﬂluiah ﬁﬁuidb, hebuﬁting in cell memblume The Una/Leaded a4 a heﬁKeetéon 05 ghom changee pumeabLU/ty oeeaAioned by incheaeed aeetyZehoLéne. emanate/wees connotahg the [evea 50h rte/wow byAtem 05 ahe pant 06 the homeozstauc mechahbsm acetyzehouhe at eeu membhahu heme/54mg activity, (f) Acetylcholine, EEG Hypersynchrony and Induced Convulsions: Alteration in the blood-brain perneability barrier by the continuing action of acetylcholine may be a biochemical substrate for the postelectroshock hypersyndhrony of the electroencephalogram, Such a possi- bility is evident in the demonstration of an increase in the concen- tration of cocaine in brain tissues threeidays after a series of 12 induced convulsions (Aird et_§lo, 1956)o The change in concentration of this large molecule, ordinarily absent in brain tissue, was associated with the appearance of hypersynchrony(delta bursts) in the electroencephalogram° �11+ We have confirmed the many previous reports that convulsive thrapy induces electrographic hypersynchrony (Pink and Kahn, 1956; Fink 1951)° Despite a constant application of treatments there is §t_al., a great variability in the time of appearance, the duration and the extent of the electrographic slow wave activity as well as the sensitivity to modification by alerting, hyperventilation and barbiturates in psychiatric populations (Green, 1957). degree hypersynchrony and has been described as (Roth, 1951; Roth its persistence prerequisite to stain, in the degree of induced The early appearance of high throughout a treatment course improvement following electroshock 1957; Pink and Kahn, 1956)o EEG The differences hypersynchrony may be related to differences in central cholinergic activity, The failure of certain patients to develop hypersynchrony may be associated with the absence of free acetylcholine and with minimal changes in cerebral function, thus precluding a clinical response to induced convulsions° Tower and McEachern (19H9a), in their study of craniocerebral trauma, included observations of six psychiatric patients undergoing convulsive therapy. Studying the patients after 3—7 treatments they reported free Spinal fluid acetylcholine in two patients; and an increase in cholinesterase—II and a decrease in cholinesterase-I with a reversal of the ratio of cholinesterases in five of the six patients, The one patient in the series Who failed to show either free acetylcholine or a cholinesterase ratio reversal in the spinal fluid was described as: "It is interesting that this patient was the only one of the six to show no response to treatment." �15 From these observations they concluded that the spinal fluid changes in induced convulsions were more like those of creniocerebral trauma than those of spontaneous epilepsy° If electrographic hypersynchrony free acetylcholine, subjects whom it disappears rapidly who may be is a reflection of increased maintain hypersynchrony and those in exhibiting differences in the kinetics of the cholinesterase~acetylcholine hydrolysis systems. Persistent hypersynchrony may result from.a decreased rate of hydrolysis of acetylcholine, associated with low concentrations of either cholinesterase—I or cholinesterase—II. (Conversely, in patients with short—lived hypersynchrony, cholinesterase—I and in tissue and spinal fluid may be unusually higho) Fnom —II these obaehvationi uh uuuid conciude that induced convuiiionb ahe accociated with an incheaie in ghee acetyichotine in intehceiiuian ﬁiuidt, aitehing cehebhai pehmeabiiity enhancing the appeahance 05 choiinettehatei. The ieuei and 06 ﬁnee it maintained by nepeated induced beizuneb. EEG hypencynchhony it one heﬁiection 06 aiteaed ieveii 06 acetyichoiine acetyichoiine and attehed penmeabiiity 06 otheh eiectnoiyteb° that theAe changec It i4 phobabie in intenceiiuiah eiectnoigteb phovide the biochemicai Aubcthate ﬂan the penAiAtent behavionai changei ﬁoiiowing induced convuitionia �16 t.‘ Cg) wfi 0. as. oses= studies have application to the problem of autonomic reactivity and the classification of the psychoseso Funkenstein These between 1952) have demonstrated 1951, a relationship E£;,(19”89 g: the blood pressure response to injected methacholine (Mecholyl) and the clinical response of psychiatric patients to convulsive therapy. is a potent cholinergic agent which induces vasodilation, tachycardia9 sweating, and increased peristalsiso It is rapidly Methacholine hydrolyzed by cholinesterasedI and slowly by cholinesterase-IIo falls after injected blood pressure of subjects to the baseline within five to 20 minuteso returns to the baseline within 5 II, or III reactors; and Group have a VI and Group VII (Funkenstein EE.E£;9 1952)o upon as patients in while Groups VI Patients whom 9 and a reactors Group VI 89% 20 or and VII reactorso 35% pressure Group I, more Group I recovery rate, respectively, and 97% recovery rates I to III reactors mecholyl the injected may be looked is rapidly hydrolyzed; and VII have a slow hydrolysis rateo It is possible that the cholinesterase activity levels of Groups I-III is review, see Rose9 19620] whose blood classified as those whose blood pressure takes IIuIII reactors while Group mecholyl and returns minutes have been minutes to return to baseline, as Group The [For a recent blood and tissue high, while that of Groups VI-VII is low compared to general psychiatric populations° The mentally differences in blood cholinesterase levels in normal and ill subjects have been extensively studiedo Despite differences �17 in methods (Augustinsson, 1955, 1957) elevated cholinesterase levels compared to normal populations have been reported for depressive subjects (Richter and Lee, 1942; Rowntree e£_al;, 1950; Ravin and Altshule9 1952)? schizophrenic subjects (Early 33 Gal9 1963) and a mixed iii, psychiatric population (Plum, 1999; Rubin, 1958; 1960)o Alpern (1956) reported lowered cholinesterase levels in schizophrenic subjectso studies appear inconclusive, they provide data that the variations in blood cholinesterase levels are generally greater While these and frequently elevated in the mentally illo Negative reports include the failure by Ellman and Callaway (1961) to confirm Rubin's study; and Altschule“s (1953) review of the data suggesting no abnormality of cholinesterase levels in the mentally illo A similar analysis may be made regarding the relation of central nervous system levels of cholinesterase in the development of EEG hyper- fluid levels of acetylcholine, thus providing a congruent hypothesis regarding central nervous system reactivity to induced convulsions and to peripheral cholinergic agents° synchrony and spinal �Dig- CONCLUSION: This review indicates that central cholinergic mechanisms are significant in the convulsive therapy processo Induced convulsions are associated with an increase in intercellular acetylcholine to levels greater than can be destroyed by acetylcholinesterase activityo Vasodilation and increased cellular permeability are followed by the appearance of increased amounts of butyrylcholinesterase and other enzymes and electrolytes in intercellular fluidso These biochemical changes are associated with increased hypersynchrony which is recorded as EEG electrodess and which can be modified by slow wave many electrical activity in scalp anticholinergic drugs, including atropine9 benactyzine, diethazine, procyclidine and piperidylbenzilateso In these regards, induced convulsions are more similar to cerebral trauma than to spontaneous seizures° in cerebral biochemistry alter cellular recovery and firing rates sufficiently to alter the behavior of subjectso Failure to induce high and persistent concentrations of acetylcholine These changes or failure to induce concomitant electrolyte changes.does not alter cerebral cellular activities and results in a failure to produce behavioral changeo Differences in the rate of development of cerebral changes to the same number and frequency of induced convulsions may reflect differences in the dependence of subjects on cholinergic mechanisms or �:19- in.their sensitivity to changes in acetylcholine levelso These differences provide the basis for the classifications of the mentally ill based on neurophysiological responsitivity by Funkenstein and by Pink and Kahno These data on cholinergic mechanisms provide a theory for the mode rational biochemical of action of induced convulsions in altering the behavior of psychotic subjects9 and are consistent with the more general neurophysiologicmadaptive theory of the convulsive therapy process expressed earliero �REFERENCES J W9, Hrenoff, M9 K9 and BowditchLS. C9 Aird, R9 139, Striit’ L A9, Pace, of electrically induced convulsions ﬁnch. Neel/1.0L effects Neurophys1ologg§§ (1959. )19: 371— 378 ”WW I Aktivnost kholinesterasy 99999 Alpern, D90 i kholinergicheskaya reaktsiya krovi pri shizofrenii9 [Cholinesterase activity and choliner 10 reaction of the blood in schizophrenia ”J; Fizzéoh 2%{719575 .57 87- Pg\ 9 3%; J 1/9 .9 Vitamins, enzyme systems, and trace elements9 Bodéﬂy Phyzsioﬁogy in Mental. and Emotional Duoadefvs) Grune 8 Stratton, New York, It 1953! .1 Altschule, ‘ W M9 W Augustinsson, V D9 New 913$“. f\ M for cholinesterases9 In WGlick 05 Biochemical Ana/Emu) Interscience Publishers, 3‘,We 5’ 1‘1” [103 Presence and action of acetylcholine in experimental 5% Method/s Bornstein, M9 D9 brain trauma9 J; NewLophyAwL, Wig: J 399— 399 Merritt, H9 H9 Effect of certain choline derivatives ctrical acti ity of the cortex. Aach9 Neww£9 PAychia/t. 99: 382 395, Brenner, 91942. #4.. ' Assay methods K9-B9 York, 1957, f” ________ Augustinsson K '-B9 The normal variation of human blood cholinesterase activity9 A1199 PhyALOL Scand9,\l955 \3__5_: 90——52}/ '/ arr” C9 and ' ‘ M physiological significance of acetylcholine9 In K9 A9 C9 Elliot, I9 H9 Page and J9 H Quastel)116(/y) Thomas, Springfield, 4-1-12, 1955],) NeuaochenuADLy) jam-939911 27s“. M99949», 309 my, and acetyl;2 Chatfield, P909 and Dempsey, E9 W9~ Effects of prostig%ne choline on cortical potentials, (Ame/L9 .79 PhyAzéofw', 1992 135: 633-6M0. )9] Burgen, Cone, ., 9 ,1 99, W9 A9 S9 V9 and MacIntosh, F9 C9 The W V9, Toner, D9 B9 and McEachern, D9 Acetylcholine and neuronal {j activity in epilepsy9 (.79A9 M9A9,119u8 73: 59 63 A9 and Merrick, Crossland, The effect of anaesthesia on the acetylcholine content of the brain9 .79 Phybioh ,\¥l95lt.9125 56- 66 9,! .11 1. (/JJ’j) Dale, H9 H9 The action of certain esters and ethers of choline, and their relation to muscarine. V] Phwunacoh Exp9 Them, 1911+, 1195/ Denisenko, P P9 Pharmacological blocking of central cholinoreactive systems and the possibilities of its therapeutic applicatiom In G B , Koelle, w W. Douglas and A9 Carlssogffzheereﬁ Phamnacoﬂogy 06 ChoLLneJLgnc V” and Adaeneagxec Mammmwn. Vol 3 o Glen» J J , J _6_: 9 pj’ 9 Paoceed/cngb 05 W Rascovaﬁenm I‘M" ' and Investigations the Second Inxunaﬁonaz’ Pha/unacoﬁogicaf. Meetcngjgjgb New York, 1965/ Macmillan)9% D9 F9 ,Hemphill, Early, 9 R9 E9 ,Reiss, M9 Brummel, E9 2499199 into cholinesterase levels in serum and cerebrospinal fluid of psychotic patients (Biochem. ”Li/V“) / .7 ,Fl—E9, M5: 556 -552- DJ a” , I 9. �Elliott, K ‘A Co, Swank, Ro L and convulsants on acetylcholine content of {@93sz brain JiwﬂhgéLQ£»¢T//’”//JK (AMeagl 1469—44781 _....—_,—.— A . 1 Ellman, G be and Cal.laway,E E1 throcyte cholinesterase—levels in mental patie.nts Natuhe (Land )@961.J192: l2l§)j w'v-xﬂ 8. rI/J>-~/ Effects of anesthetics and Henderson,_Ng -/7 unifiedtheory of the ac.tion of physiodynamic therapies° HstLde 6: 197 (J 206 H08p)(i1967 (116., “37" “m1 F1nk, Mo Effect of anticholinergic agent, diethazine, on EEG and behavior: significance for theory of convulsive therapy (AﬁkM (Neon/L01: PbyWaL—WH‘J’IQFM3803875J F1nk M A W F1nk,M Effect of anticholinergic compounds on post onvulsive electro: encephalogram and behavior of psydhiatric patients Lectaoenceph CLLn.-~~ NeuhuphyéLOL Jl§66;JlEW(2); 359— 369 convulsive The M mode of action of Fink, therapy: the neurophysiologicadaptive View (9: NeuhopAychLato,J1962Jc3: 231—~233)\ \ )J [AK—y... 7! um: 17% A, m "lat/"M1- Fink, Mo and Kahn, Ru L Quantitative studies of slow wave activity following electroshock ELecLLoenceph CLLn NeuaophyALOLO, @ﬁﬁﬁiq:_;;l58?J Fink, Mo, Kahn, Lefkowits, H 1961,u: R0 J 259 266 Le, Karp,E o, Pollack, Mo, Green, M AC, Alan, B and Inhalant-induced convulsions (:Ahch Geno PAychLa§>((3K; . Freedman, A Mo, Bales, P D, Willis, AG production of electrical major convulsive 117— 121% fIgﬁé'Jﬁ—J: “£11-“.V./ FUnkenstein,D and Himwich, Ho Ea J. ,Ameao patterns — Experimental,€$§£;7 PhgoLoLo, ,. , ”kw—.-Wn J Greenblatt, M and Solomon, H C Autonomic nervous Nehvo MenM 0L6 system changes following electric shock treatment :yatt77M Ho, [1988,L108: 1109422, FUnkenstein, DOH a, J Greenblatt, Solomon, M and paralleling psychologic changes in mentally 1 ill H C Autonomic changes patients 5:T Neav Mani.”’ﬁ . 1951. 011%“ 18,.I Funkenstein, DQH o, Greenblatt, Mo and Solomon, Ho Co Autonomic nervous system test of prognostic si ificance in relation to electroshock Made, {Pbychozsomo treatmento 13: 1952, 3u7—3629” {as 1__1___~u Gal, E0 M8 Cholinesterase activity of who blood from healthy and Sohizophrenic individuals° (Natune" 1963. 19821118-1119> WW (M) ) \9=*" , 5 6%-,“ V �and Pepeu, Go Drug-induced changes in brain acetylcholineo Jo Phanmac0£o," [meg/1&1: 226—2311, 5 Qiarman, (But, J M, o Signi ficance of individual variability in Home, :19574 ﬁg, 229-21104; electroshocko NJ, Green, A, MD Hampscn, w Jo wae " Essig, Co 1:1, ((muuw; and McCauley, f luorophosphate Himwich, A0 EEG response to Effects of H9 Ea electroencephalogram and cholinesterase asvivityo_(Ekectaoencepho Ciino Neuhophybio£0,f1950, g; ulgug> / div-isop‘ropyl (DFP) on Hinwich, Ho E0, Essig, Co Po, X-Iampson, Jo Lo, Bales, Po Do and Freedman, AU Mo Effect of trimetnadione (Tridione) and other drugs on convulsions caused by di—isopropyl fluorophosphate (DFP) Amen. J. R\“”” ““1950,‘1062 816-829) o * fM W . ” ”rm Lo and Lechner, Ho The effect of Diparcol on the electroencephalogram Jenkner, and in those with cerebral trauma, E£eot2wenceph. can. in the normal 1E"o ﬂax iwx subject /”Neun0phy4£o£o,{1955,LZE 303-6053 1M, Johnson, Ulett, Co, Lu J “3 '7 - A0, Johnson, Go Smith, MD, K0 and Sines, Jo Electroconvulsive therapy (with and without atropine); effect on electronically analyzed electroencephalogram Allah, Geno Pbychj. 1/ WM"' Kabat, E0 A0, Glusman, 0%., 0/ > and Knaub, V0 Quantitative estimation of the albumin and gamma globulin in normal and atholo ic cerebrospinal fluid by immunochemical methodso Wells 10 Mada, [194845;E 653—66253 ‘ “NW Mo / brain of the content Acetylcholine ’ Hung, if E53,: 13; 1—H >J 1;::11 t I44wéhjié. humorale Ubertragbarkeit der Herznervenwirkungo Fonyo, A0 and Halmagyi' in traumatic shocko (Aota Pkg/31.0 Kovach, A, Ga Bo , Mo ,1 ‘\ ’ ‘ _ , §’ Loewi, Anch, O.) 55 Maynert, Ube ﬁts, E0 W; Ho and Buck, 1319: 239-292, Effects of Eo Go onacetylcholine synthesﬁgofjo Phwumcoz, Nachmansohn, specificity Plum, (cum /. f; I, iﬂw 0‘ depressants on brain . convuls and narcotic drugd/ Expo ThULo, 1951, 103:_ 35,5433 { and Rothenberg, M, A, Studies on cholinesterase: on of enzymes in nerve tissueo (J. Mob Chmo,ffgu5.} _]_._5_8: 653—666“; Do Study of cholinesterase Chemo, 1960; pg: 332-390, Co Mo activity in nervous Serum cholinesterase activity in mental >M195 , } and mental disorders. R Ravin, H, A, and Altschule, Mo Do diseaseo /AItho Newwﬁc Pbychiaxo a CDNIOSO thacolagi£t,, 1961+, g; 191, and Elliott, K A 9C, Effects; "adetylcholineo Mcbennan, Phybiozo, 1921, . §§: 616-650) �1 Richter, D and Cmssland, J Variation in acetylcho ine content of the Phybioio, 19891159: 2887— 255 a, brain with physiological stateo /Ame8)L88 J 0 M Richter, D and Mo leeI 838 £882,188821 than yfI8828188 ,J’ "T“. <72: D and Lee, 1- Rose , MD 835~83gfj The , W. Ment. 306,8“, 0/1,” 0\ Serum choline esterase and depresmon. 13° Mani. Soc.) f“‘p‘. . 7, Punkenstein est-57K review of the &;8§dand P3ym ,j19625138 , o esterase and anxietyc J. Serum choline (,4 128—153, / ”W i literature. Aota ». in the EEG under barbiturate anaesthesia produced by electroa-convulsive treatment and their significance for the theory of Roth, M Changes C228. action fEZectaoenceph ECT Roth, Ma, Kay, D W Ko , Shaw, ) W28” NeuhophyéLOKO,[1951,[__w261—280 J J and Green, Prognosis and ﬁPentothal induced electroencephalographic changes in electroyzonvulsive treatment .. Eﬁemoenceph can NewzophyA/ZOLO, 8f‘1957.;___9: 225- 237 7’ A S [/80 ofd1d1opmpyl——° i and Wilson, A, The effects aﬂcorophosphonate in schizophrenic-1and manic depre sive psychosis. Newwz NQMOAU/tgo Paychiwto, 1950.313: 87-62, Romtree, D J Rubln, ° We, Nev1n, ° ° WW“ Acetylcholine hydrolysis in psychiatric patients Lo So /.1958,,Ll2___8258-25858) 7 7; /1881, ‘~‘ : 8 .x' )1 Spiegel, E A and Spiegel—Adolf, M Physioochemical effects of electrically induced convulsions (cerebrospinal fluid studies) K Titan/.5 Ame/r.° NewwL AM., 81888.70: 130132 @1111): Spiegel, E A and Spiegel-Adolf, M Physiological and physicochemical mechanisms in electroshock treatment Canéin Weuhoz [195’‘13, 38-63/ A changes Go M and Spiegel—Adolf, Spiegel, E Physicochemical Henry, in the brain accompanying electrically induced convulsive discharges W/TW Spiegel-Adolf, Arnuo ,____ Newwz MAM/Tmﬁﬁﬁ: 81783811 ,Wilcox, P H and Spiegel, E changes in electroshock treatment of psychoses 1988, gg_; 697 706); Stwone W E 90] Pkg/8 Amm M A. Cerebrospinal fluid Amen. J Paych/éaio, o role of acetylcholine in brain metabolism and functiom Med ,f19'7'; 3‘6: 222——255>/ The m._._ . ’1qu ,,,,, ~ '~'" - if! Suence, Spiegel, E A and Spiegel—Adolf, M Permeability changes in the brain induced by Metrazol and insulin convulsions (Jo NULU. Manx. 0125:, 83; 750 755 /0 %% . y“ ,2. ' �Lipton, Tobias, J and convulsants on brain acetylcholine contento *, Med“; ’7 (KS Me MW 0 1:. 51—515 and IJepinat, A, A0 A, Effect of anesthetics Phone Soco Expo BLO£./;~“ ' "I" 1 “t” "‘1’ r7 _ and McEachern, Do Acetylcholine and neuronal activity. I. Cholinesterase patterns and acetylcholine in the cerebrospinal fluids of— patients with craniocerebral traumao x/“Ctinado J Ru ea/Lch m cm 5,, Towem 7. {ﬁn/x”, ' CO ‘ Wm. _, Wk Effect of convulsion inducing a ents on the acetylcholine Ame/Lo Jo Pkg/Maze; 1953, ;l73: 179—183, brain; of the content (ACTH) on of Cc corticotropin Effects of single injection Torda, Jo PhyMLoL, braim,gj'ArrIe/Lo of content and ion acetylcholine ammonium 1953, ll}: 175—178j / Torda, - ,3- a Do Bo Q:W105=1195 W Towem Do Ba 191M313o 2],: and McEachern, molinesterases in jettg ) content and characterization of ., human Do The cerebrospinal fluidso (f'fCanado l32=~ll+53j a «QC/t; Ruea/Lch, J. é)' Do and neuronal and activity. II. Acetylcholine McEachem, B Acetylcholme and cholinesterase activity in the cerebrospinal fluids C’a‘nado p] of patients with epilepsy», \_’\ Tower, D; < 120~l3l> IVWL a Ruem&9?%27“m $0 ’5) and Wo M, of Effect scopolamine upon Johnson, atropine Ulett, electroencephalographic changes induced by electro-ccnvulsive therapy. Ezecthoencepm Cum Neu/Lophyaiozo,fI§S’7‘g"ig_: 217-221;} Go A, and ’/wt" 1 WardiAu AU, tropine (1950, E3 3984020) 1 ‘ in the treatment of closed head injuryoﬁJo Co, Green, RC _ V :1: r7?“ , . V___“,_,,_-..._. W0 1 Neu/LOAu/Lg., E0, McNamara, Bo Po and Krop, So The influence J. -7“~Phalmmroi. Exp. (”of atropine and scopolamine on the central effects of DFP°_ "»»».N..r lgu8'5‘_9_‘2;: 63-720 We‘oea ' /’ (“L-9““ The/Lo , �.l mI ,l I II, .I Al. _I ”I .l .I ,l 'l I JI I _l �SET DuPQCAaTE MAY 24 1966 (m (FINAL EG—J 68 HR �(mm (FINAL EG—J 68 EG—J 68 (CL oE-NMD-Mar 5-20-5D (COG 6131 MAX FINK MAX FINK MAX FINK MAX FINK MAX FINK (READ 660 BY PROVE!) MAX FINK THERAPY CONVULSIVE OF ASPECTS CHOLINERGIC THERAPY CONVULSIVE OF ASPECTS CHOLINERGIC THERAPY CONVULSIVE OF ASPECTS CHOLINERGIC THERAPY CONVULSIVE OF ASPECTS CHOLINERGIC THERAPY CHOLINERGIC ASPECTS OF CONVULSIVE THERAPY CONVULSIVE OF ASPECTS CHOLINERGIC THERAPY CONVULSIVE OF CHOLINERGIC ASPECTS MAX FINK, MD.1 �ﬁUPLECﬁzTE SILT MAY 24 1966 EG—J 71 W Ward-BMW Gal 2 %E-NMD-Mar 5/20-5Gx 6131 P. 15 5/19/66 722(3) 'E]li“l" 1Department of Psychiatry, ... . ’ - H' i I I .o E u - This study was aided, in part, by USPHS grants MH-927, MH—2715, MH-07249 and MH-11380; and by the Psychiatric Research Foundation of Missouri. While the mode of action of convulsive therapies remains enigmatic, one theory holds that the early development and persistence of changes in brain function are requisite to changes in behavior (18, 21, 22). A useful index of neurophysiological change is the appearance of high voltage electroencephalographic slow wave activ— ity (22, 23). While the biochemistry of this activity is poorly understood, demonstrations that it is inhibited by anticholinergic compounds (19, 20, 34, 66) suggest that cholinergic systems may play an active part. (m (FINAL The EEG patterns and the response to anticholinergic drugs in convulsive therapy are similar to experimental and clinical head trauma and, to a lesser extent, spontaneous seizures. Changes in concentration of cholinesterases in brain and spinal ﬂuid also show many similarities in these conditions. This review discusses these observations to provide a hypothesis for the role of cholinergic changes in convulsive therapy. The activity of acetylcholine in the transmission of nervous impulses has been extensively studied since the early descriptions by Dale (12) and Loewi (38). A constituent of nervous tissue in a bound form, acetylcholine, is liberated during the excitation process. It is rapidly hydrolyzed through the mediation of acetylcholinesterase and is rapidly reconstituted by the choline-acetylase system (45). Free ace— tylcholine has not been measurable in normal cerebrospinal ﬂuid despite the rapid breakdown of bound acetylcholine during periods of activity and excitement (63). ///"L.i//>{{ I "'4 1/. ,1/ :J Waéff?.__ �part. mm (FINAL (CL (GOG The EEG patterns and the response to anticholinergic drugs in convulsive therapy are similar to experimental and clinical head trauma and, to a lesser extent, spontaneous seizures. Changes in concentration of cholinesterases in brain and spinal ﬂuid also show many similarities in these conditions. This review discusses these observations to provide a hypothesis for the role of cholinergic changes in convulsive therapy. The activity of acetylcholine in the transmission of nervous impulses has been extensively studied since the early descriptions by Dale (12) and Loewi (38). A constituent of nervous tissue in a bound form, acetylcholine, is liberated during the excitation process. It is rapidly hydrolyzed through the mediation of acetylcholinesterase and is rapidly reconstituted by the choline-acetylase system (45). Free acetylcholine has not been measurable in normal cerebrospinal ﬂuid despite the rapid breakdown of bound acetylcholine during periods of activity and excitement (63). But the normal cerebrospinal ﬂuid does have measurable cholinesterase activity (41). CHOLINERGIC ASPECTS OF CRANIOCEREBRAL TRAUMA (READ 660 BY PROVE!) Free acetylcholine was found in the cerebrospinal ﬂuid of cats within a few minutes after experimental head trauma and persisted for varying periods up to 48 hours. The quantity of free acetylcholine varied between 2.7 and 9.0 ga /100 cc, and the amount was related to t e degree of induced trauma (6). Concurrent electroencephalograms ﬁrst demonstrated high voltage fast activity, interpreted as evidence of an intense neuronal discharge, which was succeeded by a short period of ﬂattening of all recorded electrical activity. These phases were followed by prolonged periods of �f.’u ”1: $3.: .gsi 1:..n‘1' 24 1955 EG—J 71 %E-NMD-Mar 5/20-5Fx 6131 P. 15 5/19/66 722(1) Gal 3 high amplitude sharp waves in the delta frequencies. The behavioral changes related to the degree of induced trauma and to the amount of measured free acetylcholine. With higher levels of acetylcholine, Bornstein (6) reported greater degrees of EEG abnormality and greater changes in consciousness. Spontaneous post-traumatic seizures were also related to the amount of free acetylcholine measured in the cerebrospinal ﬂuid. Bornstein applied acetylcholine to exposed cat cerebral cortex. When the concentration of acetylcholine was one gamma/100 cc or less, high amplitude sharp waves of low frequency appeared in the electroencephalogram. When the concentration was increased to two 100 gamma/ cc, the electroencephalogram ﬂattened in a fashion parallel to the post-traumatic records. by Tower and McEachern (63) demonstrated free acetylcholine in the cerebrospinal ﬂuid only in patients with recent head trauma, recent grand-mal seizures or after electroconvulsive therapy. Free acetylcholine varied from 0.2 to 100 gamma/ 100 cc. In assaying spinal ﬂuid cholinesterase activity, they noted a sharp rise in the butyrylcholinesterase fraction and a fall in the acetylcholinesterase fraction in patients with head trauma and following convulsive therapy. After spontaneous seizures, however, the cerebrospinal ﬂuid did not exhibit such inversion although it contained free acetylcholine. They concluded that the leve 0f free acetVlChnll‘np (FINAL ((1 �Bornstein applied acetylcholine to exposed cat cerebral cortex. When the concentration of acetylcholine was one gamma/100 cc or less, high amplitude sharp waves of low frequency appeared in the electroencephalogram. When the concentration was increased to two 100 gamma/ cc, the electroencephalogram ﬂattened in a fashion parallel to the post-traumatic records. Investigations in neurological patients by Tower and McEachern (63) demonstrated free acetylcholine in the cerebrospinal ﬂuid only in patients with recent head trauma, recent grand-mal seizures or after electroconvulsive therapy. Free acetylcholine varied from 0.2 to 100 gamma/ 100 cc. In assaying spinal ﬂuid cholinesterase activity, they noted a sharp rise in the butyrylcholinesterase fraction and a fall in the acetylcholinesterase fraction in patients with head trauma and following convulsive therapy. After spontaneous seizures, however, the cerebrospinal ﬂuid did not exhibit such inversion although it contained free acetylcholine. They concluded that the level of free acetylcholine varied directly with the degree of cerebral damage and that reversal of cholinesterase fractions was a more sensitive indicator of cerebral damage. Electroencephalograms taken at varying intervals following trauma also indicated a relation between the degree of EEG abnormality and the appearance of free acetylcholine in the cerebrospinal ﬂuid. Increased acetylcholine in rat brain after traumatic shock was also reported by Kovach et al. (36). This acetylcholine activity was inhibited by the administration of atropine in vitro. The electrographic, behavioral and neurologic signs of head trauma were blocked by the parenteral administration of 0.5— 1.0 mg/kg atropine, as were similar clinical changes occurring after the intracisternal addition of acetylcholine (6). Ward applied these observations to the treatment of closed head injuries. In 20 patients with varying degrees of trauma, he administered atropine subcutaneously in doses of 0.1 mg/kg, noting clinical improvement in some and a reversal of the electrographic effects in others (67). The same changes in the post-traumatic electroencephalogram were reported by Jenkner and Lechner in a study of diethazine, another anticholinergic drug. A single intravenous dose in 40 patients resulted in normalizing the abnormal electroencephalogram in 22 and marked improvement in six others (33). (READ “660 mom �2' on I'-.-..AY 24 '“ 1965 EG—J 84 OE-NMD-Mar 5/20-5E GAL 4 6131 P. 18 5/19/66 722(1) Similarly, in experiments of post-trauma- tic shock and cerebral edema in animals, Denisenko (13) reported a blocking of the clinical changes by such anticholinergic compounds as methylbenactyzine and adiphenine (Trasentin). Thus, the amount of free acetylcholine ma increase in the spinal ﬂuid following craﬁicerebral trauma and the amount of free acetylcholine, the degree and type of electroencephalographic abnormality, and changes in clinical behavior appear as interrelated phenomena, which may be reduced by the administration of anticholinergic drugs. BRAIN ACETYLCHOLINE AND ANTICHOLINERGIC DRUGS (REV (FINAL (CL (00G (READ 660 BY PIOVID The effects of the direct application of acetylcholine to the central nervous system may also be blocked by anticholinergic drugs. The administration of the cholinesterase inhibitor di-isopropyl ﬂuoroph sphate (DFP) elicited high amplitude rapid frequency EEG patterns similar to status epilepticus and some post-traumatic states (24, 31, 32, 68). These EEG eﬂ'ects were blocked by small doses of parenteral atropine and scopolamine. The great increase in acetylcholine after tetraethyl pyrophosphate (TEPP) was measured and related to the toxic effects and the induced convulsions (29, 59). Chatﬁeld and Dempsey (9) prepared exposed animal cortex with prostigmine and evoked electroencephalographic spike activity. The prior administration of atropine blocked the appearance of spiking, or if present, this electrical activity could be eliminated by atropine. In contrast to these ﬁndings, Brenner and Merritt (7) applied topical acetylcholine in concentrations of two and onehalf to ten per cent to the exposed cortex of cats and noted no effect on the electroencephalographic changes after intravenous atropine (one mg/kg). The concentrations of acetylcholine in these experiments, however, were higher than the topical applications (one to four gamma/100 cc) and the intracisternal (0.2—10 gamma/100 cc) injections of Bornstein (6). Brenner and Merritt (7) also noted electroencephalographic effects similar to acetylcholine after methacholine (Mecholyl) and carbamylcholine (Doryl) in concentrations much lower than the acetylcholine concentrations. They ascribed the increased effectiveness of these cholinergic drugs to their lack of sensitivity to cerebral cholinesterases. These data are conﬂicting and further study is necessary to qualify this issue. , 0 �(FINA! (CL (COG (READ 660 BY PROVE!) atropine blocked the appearance of spiking, or if present, this electrical activity could be eliminated by atropine. In contrast to these ﬁndings, Brenner and Merritt (7) applied topical acetylcholine in concentrations of two and onehalf to ten per cent to the exposed cortex of cats and noted no effect on the electroencephalographic changes after intravenous atropine (one mg/kg). The concentrations of acetylcholine in these experiments, however, were higher than the topical applications (one to four gamma/100 cc) and the intracisternal (0.2—10 gamma/100 cc) injections of Bornstein (6). Brenner and Merritt (7) also noted electroenceph— alographic effects similar to acetylcholine after methacholine (Mecholyl) and carbamylcholine (Doryl) in concentrations much lower than the acetylcholine concentrations. They ascribed the increased effectiveness of these cholinergic drugs to their lack of sensitivity to cerebral ch0linesterases. These data are conﬂicting and further study is necessary to qualify this issue. CEREBROSPINAL FLUID ACETYLCHOLINE AND SEIZURES One View of acetylcholine metabolism ﬁnds it in nervous tissues in an inactive and bound form. During periods of activity, acetylcholine is liberated at the cell membrane where it is rapidly deactivated by cholinesterases. The amount of bound acetylcholine is the resultant of the continuous processes of synthesis, liberation and breakdown (15). It has been postulated that the level rises during sleep and falls during waking activity (16, 29, 45, 60). Tobias et al. (60) reported increased free and total acetylcholine after chloroform and pentobarbital anesthesia in rat and frog brain but no changes after strychnine or pictrotoxin convulsions. Richter and Crossland (45) measured the level of acetylcholine (microgamma per mg brain tis— sue) during anesthesia and sleep in rat brain to be 300 per cent higher than postseizure levels. The difference in tissue levels is transient, however, as the resynthesis rate for acetylcholine in rat brain is high (seven gamma/gm/minute). These observations were conﬁrmed by Elliott et al. (16) and Crossland and Merrick (11). Giarman and Pepeu reported the increase in acetylcholine following various depressants to be roughly proportional to the degree of depression of the central nervous system and the reduction in motor activity (29). Maynert and Buck, however, studying brain acetylcholine levels during sedation concluded that some sedatives were associated with elevated brain acetylcholine but that no rigorous relationships existed (39). In part, this may be related to the earlier observations of McLennan and Elliott (40) that acetylcholine synthesis measured in rat brain slices is accelerated by low dosages of narcotic drugs, but inhibited by high dosages. �£.;__1 -C£HTE rJdJl “‘ . 2-59—11! RAY 24 l966 EG—J 84 OE—NMD-Mar 5/20-5E 6131 P. 21 5/19/66 722(3) A) GAL 5 Free acetylcholine was reported in the spinal ﬂuid in patients with epilepsy (10, 63). Of 56 epileptic patients, 44 demonstrated free acetylcholine in quantities of 0.02 to 5.0 gamma/ 100 cc with an average of 1.0 gamma/ 100 cc. Acetylcholine levels were related to the frequency of seizures, the extent of electoencephalographic abmality, and to the time since the last sféizlmre but bore no relation to medication, type of epilepsy or level of cholinesterase activity Elliott et al. (16) also noted free acetylcholine in the spinal ﬂuid in concentrations up to three gamma/100 cc after pentylenetetrazol (Metrazol) convulsions. Tower and McEachern (63) viewed the increased acetylcholine as a by-product of the seizure and not causal. Studying the hypothesis that seizures were induced by the accumulation of acetylcholine, Torda (61, 62) measured the level of acetylcholine in brain tissue after pentylenetetrazol convulsions. She noted a rise in the acetylcholine content of brain before and a fall during the convulsion. Below certain levels of acetylcholine, convulsions failed to occur. She suggested that the fall in tissue acetylcholine during a convulsion was due to the inhibition of acetylcholine synthesis by increased concentrations of metabolites such as ammonium ions. Giarman and Pepeu also measured changes in central nervous system acetylcholine following various stimulants (29). Only after methacholine and 3,5dimethylbutylethyl-barbiturate was there a signiﬁcant change in the acetylcholine level. They noted a decrease in association with induced convulsions. With other drugs which they classiﬁed as stimulants (LSD, iproniazid, iproniazid plus hydroxytryptophan, and iproniazid plus DOPA) there were no changes in the acetylcholine level. They concluded that despite intense excitation produced by these compounds, there were no changes in acetylcholine levels unless these were accompanied by convulsions. (The differences in observations between these observers and Gone et al. (10) and Tower and McEachern ( may be related to the differences in methods of biochemical measurements, for the latter measured changes reﬂecting free only, While Giarman and ) measured total acetylcholine Pepeu includin_ bound and free forms of acetyl- K ya .7; Mageline ”ﬁl- These studies suggest that spontaneous or induced seizures are accompanied by an increase in intercellular free acetyl choline liberated from its bound form which may be reﬂected in the spinal ﬂuid. Cerebral activity and seizures enhance acetylcholine destruction, lowering tissue levels of acetylcholine, while sleep and anesthesia augment acetylcholine production increasing tissue levels. (REV (FINAL 206((1 CENTRAL NERVOUS SYSTEM �bllUl‘U l/oi ’/—\, C/ were LlU Guanges 111 we acetylcnoune level. They concluded that despite intense excitation produced by these compounds, there were no changes in acetylcholine levels unless these were accompanied by convulsions. (The differences in observations between these observers and Cone et all. (10) and Tower and McEachern ( may be related to the differences in methods of biochemical measurements, for the latter measured changes reﬂecting free holine only, while Giarman and ce ) measured total acetylcholine includin bound and free forms of acetyl- K m “Tho («3 in). These studies suggest that spontaneous or induced seizures are accompanied by an increase in intercellular free acetyl choline liberated from its bound form which may be reﬂected in the spinal ﬂuid. Cerebral activity and seizures enhance acetylcholine destruction, lowering tissue levels of acetylcholine, while sleep and anesthesia augment acetylcholine production increasing tissue levels. (REV (FINAL (CL CENTRAL NERVOUS SYSTEM CHOLINESTERASES Tower and McEachern (63, 64, 65) also measured spinal ﬂuid cholinesterase activity. By reporting cholinesterase activity as a ratio of the rate of hydrolysis with two substrates compared to an acetylcholine substrate, acetylcholinesterase/acetylcholine and butyrylcholinesterase/acetylcholine ratios are derived. Normal cerebrospinal ﬂuid contains these esterases in the ratio of 33:17. In patients with head trauma, Tower and McEachern reported an inversion of the cholinesterases with an increase in the butyrylcholinesterase of the spinal ﬂuid and a decrease in acetylcholinesterase activity. The extent of the cholinesterase reversal was related to the severity of trauma and to the degree of EEG abnormality. A similar reversal was observed in patients undergoing convulsive therapy. In patients with elevated spinal ﬂuid acetylcholine after spontaneous seizures, however, no change in the ratio of cholinesterases or total cholinesterase activity was found. Changes in cholinesterase activity may be related to changes in cell membrane permeability. Acetylcholinesterase is found in highest concentration in the central nervous system. while butyrylcholinesterase predominates in other tissues, especially blood serum. With increased cerebral acetylcholine, vasodilation and increased cellular permeability may be predicted, with vascular ﬂuid transudation varying with the extent and duration of the vasodilation (35). Spiegel, Spiegel-Adolf and their coworkers (54—58) demonstrated such permeability changes and increased conductivity of the tissues associated with the appearance of various ions (as potassium and phosphate) in the spinal ﬂuid following electrically induced convulsions. Such non-electrolytes as nucleic-acid splitting enzymes also increased. Changes in cellular permeability may be the basis for the high (ooc (nun 660 8! mom �..._.l!_ﬁ$ .0"de " ;CF;TE MAY 24 55-12%”? 1965 That changes in cholinesterases may be large and measurable is suggested by the acetylcholinesterase activity which was related to decrements in be havioral perform- ance. The persistance‘ of acetylcholine in spinal ﬂuid after head trauma and after seizures despite increased cholinesterase activity may be related to the sensitivity of the acetylcholine~acetylcholinesterase ip is non-speciﬁc, and (m the rate of hydrolysis increases with increased concentration. These relationships relate to theories of the induction of seizures. While the usual concentrations of acetylcholine at cell destroyed by the speciﬁc activity of acetylcholinesterase in a few microseconds, an excessive concentration following excitation may exceed its rate of hydrolysis. The seizure threshold may be (FINAL altering the concentr including butyrylcholinesterase in tissues and in the cerebrospinal ﬂuid. Through the activity of this esterase, though of low efﬁciency and depending on concentration kinetics, acetylchol' ' J (CL (GOG ”J (nun 660 BY mom acetylcholinesterase. Cholinesterases appear in the spinal ﬂuid as a reﬂection of their increase in intercellular ﬂuids resulting fr om changes in cell membrane permeabilit y accompanying increased acetylcholine. EEG HYPERSYN CHRON Y AND INDUCED CON VULSIONS onvulsive therapy process has been repeatedly described (22, 23, 50, 51). In the usual course of convulsive therapy, inter-treatment electro~ encephalograms record progressive increases in amplitude and in theta activity and a reduction in beta activity. As treatment �(FINAL (CL (GOG (READ 660 BY PROVE!) Name wscu adding to the amount of free acetylcholine. Increased acetylcholine affects vascular and cellular permeability altering the concentrations of various ions, including butyrylcholinesterase in tissues and in the cerebrospinal ﬂuid. Through the activity of this esterase, though of low efﬁciency and depending on concentration kinetics, acetylcholine is reduced in tis- acetylcholinesterase. "" ”My Cholinesterases appear ﬂuid as a reﬂection of their ' tercellular ﬂuids resulting fr om changes in cell membrane permeabilit y accompanying increased acetylcholine. EEG HYPERSYN CHRON Y AND INDUCED CON VULSIONS onvulsive therapy process has been (22, 23, 50, 51). In the repeatedly described usual course of convulsive therapy, inter-treatment electroencephalograms record progressive increases in amplitude and in theta activity and a reduction in beta activity. As treatelta activity appears in methods~electrical, intravenous chemical or inhalant—exhibit the same type of EEG pattern changes (21, 22, 23, 30). The early appearance of high degree hypersynchrony and its persistence throughout a treatment course has been found to be prerequisite to improvement. Both the electrographic and th e behavioral changes of induced convulsio us are transiently reversed by the acute administration of experimental anticholinergic compounds 19 20). The intravenou injec ion 0 diethazine, benactyzine, t e piperidylbenzilates JB—318, JB—336 and JB—329 (Ditran), and WIN—2299 induced EEG desynchronization in psychiatric subjects. These EEG changes were associated with behavioral alerting, anxiety, tremors, illusions and hallucinations. In patients cently received electroconvu lsive therapy there was a reduction in slow and a reversal of ' euphoria, d fusion. Atropine, in low doses, was also associated with EEG desynchronization accompanied by tachycardia, nervousness and tension. At higher dosages, hypersynchronous slow waves followed by lower voltage, poorly organized delta activity with superimposed beta activity companied by progressive confusion and disorientation. The effect of anticholinergic drugs on the slow wave activity of convulsive therapy was also assessed by the chronic administration of atropine (ﬁve mgm per day) and scopolamine (one to three mg) during the Weeks of treatment. The amount of EEG slowing was signiﬁcantly less than S �J anaema WKY ,— 24 ("f “" -' 1965 EG—J 85 OE-NMD-Mar 5—20-5Fx Gal. 7 6131 P. 28 5/19/66 722(3) Marked improvement was reported in two of seven atropine-treated, norx of ﬁve scopolamine-treated and in four of the six controls receiving unmodiﬁed ECT. This study was not replicated by the authors who suggest that dosage factors or population changes may have contributed to the different results in a second study (34). As in cerebral trauma, the electrographic changes of induced convulsions be may modiﬁed by the administration of anticholinergic drugs suggesting that increased amounts of acetylcholine or increased cholinergic receptivity is associated with the high voltage slow wave activity. ACETYLC‘HOLINE AND INDUCED CON VULSIONS Despite a constant application of treatments, however, there is great variability in the time of appearance, the duration, amount, and sensitivity to modiﬁcation by alerting, hyperventilation and barbiturates of the electrographic slow wave activity in psychiatric populations (30). These differences relate to differences in central cholinergic activity. The failure of certain patients to develop hypersynchrony may be associated with the absence of free acetylcholine and with minimal changes in cerebral function, thus precluding a clinical response to induced convulsions. Tower and McEachern (63), in their study of craniocerebral trauma, included observations of six psychiatric patients undergoing convulsive therapy. Studying the patients after three to seven treatments they reported free spinal ﬂuid acetylcholine in two patients, and an increase in butyrylcholinesterase and a decrease in acetylcholinesterase with a reversal of the ratio of cholinesterases in ﬁve of the six patients. Only one patient in the series failed to show either free acetylcholine or a cholinesterase ratio reversal in the spinal ﬂui They concluded that the spinal ﬂuid anges in induced convulsions were more like those of craniocerebral trauma than those of spontaneous epilepsy. Other evidence of alterations in the permeability barrier may be seen in the demonstrations of an increased concentration of cocaine in brain tissues three days after a series of 12 induced convulsions ( 1). The change in concentration of this large molecule, ordinarily absent in brain tissue, was associated with the appearance of hypersynchrony (delta bursts) in the electroencephalogram. From these observations we would conclude that induced convulsions, like craniocerebral trauma and spontaneous seizures, are associated with an increase in free acetylcholine in intercellular ﬂuids, altering cerebral permeability and enhancing the ‘ (FINAL 06((1 �”renown; m cm; patients, and an increase in butyrylcholinesterase and a decrease in acetylcholinesterase with a reversal of the ratio of cholinesterases in ﬁve of the six patients. Only one patient in the series failed to show either free acetylcholine or a cholinesterase ratio reversal in the spinal ﬂui They concluded that the spinal ﬂuid anges in induced convulsions were more like those of craniocerebral trauma than those of spontaneous epilepsy. Other evidence of alterations in the permeability barrier may be seen in the demonstrations of an increased concentration of cocaine in brain tissues three days after a series of 12 induced convulsions (1). The change in concentration of this large molecule, ordinarily absent in brain tissue, was associated with the appearance of hypersynchrony (delta bursts) in the electroencephalogram. From these observations we would conclude that induced convulsions, like craniocerebral trauma and spontaneous seizures, are associated with an increase in free acetylcholine in intercellular ﬂuids, altering cerebral permeability and enhancing the appearance of cholinesterases. The level of free acetylcholine is maintained by repeated induced seizures. EEG hypersyn— chrony is one reﬂection of altered levels of acetylcholine and the altered permeability of electrolytes and other substances, including cholinesterases. The changes in intercellular electrolytes, including acetylcholine, provide the biochemical substrate for the persistent behavioral changes and EEG hypersynchrony following induced conv onsM. An application WM““WWWM‘MMMK of these conclusions is seen in the studies of the prediction of the convulsive therapy response and the claspsychoses. I ., / l \\ W CHOLINESTERASES AND THE CLASSIFICATION OF PSYCHOSES 69‘ / Funkenstein et al. (25—27) reported a relationship between the blood pressure response to methacholine and the clinical response to convulsive therapy. Immediately after the injection of methacholine the blood pressure falls, usually returning to the baseline within ﬁve to 20 minutes. A return within ﬁve minutes places the patients in Groups I, II or III; while a return after 20 minutes place the patients in roups VI and VII. Group I and Group II have a nine per cent and a 35 per ent recovery rate, respectively, while Group VI and Group VII subjects have 89 per cent and 97 per cent recovery rates to induced convulsions (27). Group I, II and III reactors may be looked upon as patients in whom methacholine is rapidly hydrolyzed; while Groups VI and VII have a slow hydrolysis rate. (The response to injected epinephrine was suggested as a second criteria in the classiﬁcation, but is of limited discriminating value [48].) While we have no biochemical explanation for the differences in the metabolism of methacholine in these psychiatric groups, it is possible that the blood and tissue choline— sterase activity levels of Groups I—III is I/ high while that of Groups VI—VII is low compared to general psychiatric populations. (m (FINAL (CL (COG �1»:er 24 1966 EG—K 5 %E-NMD-(March) 5/20-5FX 6131 P. 31 5/19/66 722(1) a» (mm /’ ' J (run. , (CL (GOG (READ 660 BY PROVE!) Gal. 8 The differences in blood cholinesterase levels in normal and mentally ill subjects have been extensively studied. Despite differences in methods (4, 5), elevated cholinesterase levels compared to normal populations have been reported for depressive subjects (44, 46, 47, 52), schizophrenic subjects (14, 28, 53) and a mixed psychiatric population (42). Alpern reported lowered cholinesterase levels in schizophrenic subjects (2). While these studies appear inconclusive, they provide data that the variations in blood cholinesterase levels are generally greater and frequently elevated in the mentally ill. Negative reports include the failure by Ellman and Callaway (17) to conﬁrm Rubin’s study; and Altchule’s review of the data suggesting no abnormality of cholinesterase levels in the mentally ill (3). -. ..-_-- _ HeSe studies suggest that cholinergic measures may play a signiﬁcant role in the therapeutic response to convulsive therapy and in the pathogenesis of psychoses. ., ' , 7 CONCLUSION This review summarizes some of the available data suggesting that cholinergic mechanisms may be central to the convulsive therapy process. Induced convulsions are associated with cerebral vasodilation and increased cellular permeability, followed by the appearance of increased amounts of enzymes and electrolytes in intercellular and cerebrospinal ﬂuids. The increase in acetylcholine, vasodilation and increased permeability appear as interrelated phenomena associated with trauma, seizures and induced convulsions. These biochemical changes accompany increased electrical hypersynchrony which is recorded as EEG slow wave activity in scalp electrodes and which can be modiﬁed by the acute and chronic administration of anticholinergic drugs as atropine, benactyzine, diethazine, procyclidine and various DineridVI-hﬂnzilnqu �“lose stuures suggesr, that cholinergic measures may play a signiﬁcant role in / ( (CL ((IJG (READ 660 BY PROVE!) the therapeutic response to convulsive therapy and in the pathogenesis of psy- { choses. , ,- ' ’ CONCLUSION This review summarizes some of the available data suggesting that cholinergic mechanisms may be central to the convul— sive therapy process. Induced convulsions are associated with cerebral vasodilation and increased cellular permeability, followed by the appearance of increased amounts of enzymes and electrolytes in intercellular and cerebrospinal ﬂuids. The increase in acetylcholine, vasodilation and increased permeability appear as interrelated phenomena associated with trauma, seizures and induced convulsions. These biochemical changes accompany increased electrical hypersynchrony which is recorded as EEG slow wave activity in scalp electrodes and which can be modiﬁed by the acute and chronic administration of anticholinergic drugs as atropine, benactyzine, diethazine, procyclidine and various piperidyl-benzilates. In these regards, induced convulsions are more similar to cerebral trauma than to spontaneous seizures. The changes in cerebral biochemistry alter cellular activity sufﬁciently to affect consciousness and the behavior of subjects. Failure to induce persistent biochemical changes, including the concentration of acetylcholine, results in failure to produce behavioral change. There is, as yet, no consistent evidence for differences in the sensitivity or dependence of populations on cholinergic mechanisms. Differences in the rate of develop— ment of cerebral changes to the same number and frequency of induced convulsions and classiﬁcations of the mentally ill based on the blood pressure response to methacholine suggest, however, that such differences may be signiﬁcant in the pathogenesis of different psychoses. 1. REFERENCES Aird, R. B., Strait, L. A., Pace, J. W., HrenoH, M. K. and Bowditch, S. C. Neurophysiological effect of electrically induced A.M.A. Arch. Neurol. Psychiat.,convulsions. 75: 371— 2. 378, 1956. Alpern, D. O. Aktivnost kholinesterasy i kho— linergicheskaya reaktsiya krovi pri shizofrenii. (Cholinesterase activity and choliner— gic reaction of the blood in schizophrenia.) Fiziol. Zh. (Kiev), 4: 87—90, 1956. 3. Altschule, M. D., Bodily Physiology in Mental and Emotional Disorders, pp. 169—172. Grune & Stratton, New York, 1953. 4. Augustinsson, K.-B. The normal variation of human blood cholinesterase activity. Acta Physiol. Scand., 35: 40—52, 1955. 5. Augustinsson, K.—B. Assay methods for cholinesterase. In Glick, D., ed. Methods Bioof Chemical Analysis, vol. 5, 1—63. Interpp. science Publishers, New York, 1957. 6. Bernstein, M. D. Presence and action of acetylcholine in experimental brain trauma. J. neurophysiol., 9: 349—366, 1946. 7. BFe'hner, C. and Merritt, H. H. Effect of certain choline derivatives on electrical of the cortex. A.M.A. Arch. Neurol. activity Psychiat., 48: 382—395, 1942. 8. Burgen, A. S. V. and MacIntosh, F. C. The physiological signiﬁcance of acetylcholine. In Elliot, K. A. C., Page, I. H. and Quastel, J. H., eds. Nem‘ochemistry, pp. 374—375. Thomas, Springﬁeld, Illinois, 1955. l l l | �SET aumscmi-Z MAY 24 1966 EG—K 5 %E-NMD-Mar 5/20-5Fx Gal 6131 p. 7 5-20-66 640 9. Chatﬂeld, P. O. 9 (4) and Dempsey, E. W. Effects of prostigmine and acetylcholine potentials. Amer. J. Physiol., 135:on cortical 633—640, 1942. 10. Cone, W. V., Tower, D. B. and Acetylcholine and neuronal McEachern, D. activity in epilepsy. J.A.M.A., 73: 59—63, 1948. 11. Crossland, J. and Merrick, A. J. The effect of anaesthesia on the acetylcholine content of the brain. J. Physiol. (London), 125: 56—66, 1954. 12. carine. J. Parmacol. Exp. Ther., 6: 147, 1914. Denisenko, P. P. Pharmacological blocking of central cholinoreactive systems and the possibilities of its therapeutic application. In 13. 14. Early, D. F., Hemphill, R. E., Reiss, M. and Brummel, Investigations into cholinesterase levels in serum and cerebrospinal ﬂuid of psychotic patients. Biochem. J 45: 552—556, . ., 1949. 15. Eccles, J. C. The Physiology Academic Press, New York, 1964.of Synapses. 16. Elliott, K. A. C., Swank, R. L. and Henderson, N. Effects of anesthetics and convulsants on acetylcholine content of brain. Amer. J. Physiol., 162: 469—474, 1950. 17. Ellman, G. L. and Callaway, E. Erythrocyte cholinesterase-levels in mental patients. Na- ture (London), 1.92: 1216, 1961. 18. Fink, M. A uniﬁed theory of the action of physiodynamic therapies. J. Hillside Hosp. (Glen Oaks), 6: 197—206, 1957. 19. Fink, M. Eﬁ‘ect of anticholinergic ethazine, on EEG and behavior: agent, diSigniﬁcance for theory of convulsive Arch. Neurol. Psychiat., 80:therapy. A.M.A. 380—387, 1958. 20. Fink, M. Effect of anticholinergic compounds on post convulsive electroencephalogram and behavior of psychiatric patients. Electroenceph. Clin. Neurophysiol., 12: 359—369, 1960. 21. Fink, M. The mode of action of convulsive therapy: The neurophysiologic-adaptive View. J. Neuropsychiat., 3: 231—233, 1962. 22. Fink, M. and Kahn, R. L. Quantitative studies of slow wave activity following electroshock. 23. 1956. ' ' i ’ Fink, M., Kahn, R. L., Karp, E., Pollack, M., Green, M. A., Alan, B. and Lefkowits, H. J. Inhalant-induced convulsions. Arch. Gen. Psychiat. (ChicagO), 4: 259—266, 1961. 24. Freedman, A. M., Bales, P. D., Willis, A. and Himwich, H. E. Experimental production of electrical major convulsive J. Physiol., 156‘: 117—124, 1949.patterns. Amer. 25. Funkenstein, D. H., Greenblatt, M. and Solo26. mon, H. C. Autonomic changes psychologic changes in mentally illparalleling J. Nerv. Ment. Dis, 114: 1—18, 1951. patients. 27. Funkenstein, D. H., Greenblatt, M. and Solomon, H. C. Autonomic nervous system test of prognostic signiﬁcance in relation to electroshock treatment. Psychosom. Med., 14: 347—362, 1952. 28. Gal, E. M. Cholinesterase blood from healthy and activity of whole schizophrenic individuals. Nature (London), 198: 29. 1963. 1118—1119, Giarman, M. J. and Pepeu, G. Drug-induced changes in brain acetylcholine. Brit. J. Pharmacol., 19: 226—234, 1962. 30. Green, M. A. Signiﬁcance of individual variability in EEG response to electroshock. J. Hillside Hosp. (Glen Oaks), 6‘: 229—240, 1957. 31. Hampson, J. L., Essig, C. F., McCauley, A. and Himwich, H. E. Effects of di-isopropyl ﬂuorophosphate (DFP) on electroencephalogram and cholinesterase activity. Electroenceph. Clin. Neurophysiol., 2: 41—48, 1950. 32. Himwich, H. E., Essig, C. F., Hampson, J. L., Bales, P. D. and Freedman, A. M. Effect of trimethadione (Tridinmn) A—--~— (REV (FINAL :OG(CL �“““““““ vuuvululULlS. Arch. Gen. Psychiat. (Chicago), 4: 259—266, 1961. 24. Freedman, A. M., Bales, P. D., Willis, A. and Himwich, H. E. Experimental production of electrical major convulsive J. Physiol., 156': 117—124, 1949.patterns. Amer. 25. Funkenstein, D. H., Greenblatt, M. and Solo— 347—362, 1952. 28. Gal, E. M. Cholinesterase blood from healthy and activity of whole schizophrenic individuals. Nature (London), 198: 29. 1118—1119, 1963. Giarman, M. J. and Pepeu, G. Drug-induced changes in brain acetylcholine. Brit. J. Pharmacol, 19: 226—234, 1962. 30. Green, M. A. Signiﬁcance of individual variability in EEG response to electroshock. J. Hillside Hosp. (Glen Oaks), 6: 229-240, 1957. 31. Hampson, J. L., Essig, C. F., McCauley, A. and Himwich, H. E. Effects of di-isopropyl ﬂuorophosphate (DFP) on electroencephalogram and cholinesterase activity. Electroenceph. Clin. 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Ravin, H. A. and Altschule, M. D. Serum cholinesterase activity in mental disease. A.M.A. Arch. Neurol. Psychiat., 58: 645—650, 1952. 45. 46. Richter, D. and Crossland, J. Variation in acetylcholine content of the brain with physiological state. Amer. J. Physiol., 159: 247—255, 1949. Richter, D. and Lee, M. Serum choline esterase and anxiety. J. Ment. Sci. (London), 88: 428—434, 1942. PROVE!) �Dupucmr. MAY SET 241966 EG—K 6 EG~K 6 %E-NMD6131 p. 12 5-20-66 640 (4) 47.R h M. ee, Serum choline and depression. esterase J Ment. Sci. 435—439, 1942. (London), 88: extension. J. 429—437, 1962. 50. Roth M. , Changes in the EEG under barbiturate anaesthesia vulsive treatment pro duced by electro-conand their signiﬁcance the theory of ECT for a ction. Electroenceph. Clin. N 51. Roth, M.,europhysiol., 3: 261—280, 1951. K physiol., .9: 225—237, 195 . 52. R owntree, D. W., Nevin, :I‘he eifects 53. Rub' 54. (REV 55. Spiegel. E. (FINAL (CL �J. , .,Kay, ' .W.K SI 52. Rowntree, D. 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Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-03-01-003-0-004 Date A point or period of time associated with an event in the lifecycle of the resource 1956-1969 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource <a href="http://id.loc.gov/authorities/subjects/sh85113021">Research Files</a> and Unpublished Works -- Hillside Hospital, Glen Oaks, NY, 1953-1965 Relation A related resource The Max Fink Collection Description An account of the resource Research papers, files, and related correspondence Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Research