QOMPREHENSIVE
`TEXTBOOK or
`PSYCHIATRYI III
`
`VOLUME 1
`FOURTH EDITION
`
`EDITORS
`
`Harold I. Kaplan, M.D.
`Professor of Psychiatry. New York University Schooi of Medicine
`Attending Psychiatrist. University Hospital of the New Yofl-r University Medical Center
`Attending Psychiatrist. Beilevue Hospital, New York. New York
`
`Benjamin J. Sadock, MD.
`
`Professor and Vice Chairman. Department of Psychiatry.
`New York University Schooi of Medicine.
`Kttending Psychiatrist. University Hospital of the New York University Medical Center:
`Attencflng Psychiatrist, Bellevue Hospital. New York, New York
`
`WILLIAMS & WILKINS
`Baltimore/ London
`
`1 of 80
`
`Alkermes, Ex. 1058
`
`

`
`Editor: Sara A. Finnegan
`Associate E'ditor.- Victoria M. Vaughn
`Design: Joanne Janowisk
`Development Editor.‘ Anne D. Craig
`Illustration Plannirzg: Lorraine Wrasse]:
`Production: Norvell E. Miller, III and Raymond E. Rater
`
`Copffisht o, 1935
`Williams & Wilkins
`4128 East Preston Street
`Baltimore. MD 21202, U.S.A.
`
`All rights reserved. This book is protected by copyright. No part of this book may be
`reproduced in any form or by any means. including photocopying, or utilized by any
`information storage and retrieval system without written permission from the copyright
`owner.
`
`The editors and the publisher of this textbook have made every effort to ensure that
`the drug dosage schedules herein are accurate and in accord with the standards accepted
`at the time of publication. Readers are advised, however. to check the product infor-
`mation sheet includsd in the package of each drug they plan to administer to be certain
`that changes have not been made in the recommended dose or in the indications and
`contraindications for administration and for adverse reactions. This recommendation
`is of particular importance in regard to new or infrequently used drugs.
`
`Mode in. the United States ofAmerico
`
`First Edition, 196'?
`Second Edition. 1975
`Reprinted 1976
`Third Edition, 1930
`Reprinted 1931, 1983
`
`Library of Congress Cataloging in Publication Data
`
`Main entry under title:
`
`Comprehensive textbook of psychiatry/IV.
`
`Rev. ad. of: Comprehensive textbook of psychiatry/III. 3rd ed. c1930.
`Bibliography: p.
`Includes index.
`. III. Com-
`ll. Sadoclr, Benjamin J ., 1933*
`I. Kaplan. Harold I.
`1. Psychiatry.
`prehensive textbook of psychiatry/III. IDNLM: 1. Mental disorders. 2. Psychiatry-
`I-Iistnry. WM 1130 C736]
`RC454.C637 1985
`616.89
`B3-25952
`ISBN 0-683-04510-5
`
`Composed and printed
`in the United States of America
`
`2 of 80
`
`Alkermes, Ex. 1058
`
`

`
`GHAPTER 1 7
`
`SOHIZOAFFECTIVE
`DISORDERS
`
`SAMUEL B. GUZE. }|-!.D.
`
`INTRODUCTION
`
`The third edition of the American Psychiatric Associatiorfs
`Diagnostic and Statistical Manual‘ ofMcrrtoi Disorders (DEM-
`Ill) provides no definition for schizoalfective disorders, nor
`does it provide diagnostic criteria. The category is included
`among Psychotic Disorders Not Elsewhere Classified to indi-
`cate strong reservations about its validity as a separate disor-
`der. Experienced clinicians recognize. however, that certain
`patients present with a mixture of‘ alfective and psychotic
`features, especially early in the course of their illnesses, that
`suggest either schizophrenia or a major affective disorder, but
`a confident differential diagnosis is not possible. Usually, the
`clinical course ultimately permits a diagnosis ofcither schizo-
`phrenia or affective disorder in these patients, but when first
`seen, a diagnosis ofschizoaliective disorder is frequently made
`to indicate uncertainty while defining the diagnostic problem.
`Obviously, implicit in any effort to distinguish among schiz-
`ophrenic, alfective, and schizoaffective disorders is the as-
`sumption that the distinction has validity; that is, that the
`classification is associated with some significant differences in
`clinical course, response to treatment. outcome. familial ill-
`ness patterns, cause, or pathogenesis.
`
`HISTORY AND DEFIBHTION Ever since K.raep_elm's work‘ on
`dementia pre-cox, debate about the concept and definition of schizo-
`phrenia has interested psychiatrists. For some psychiatrists, persuaded
`by Kraepelin. the diagnosis ofschizopbrenia should be reserved for a
`relatively narrow group of psychotic patients whose general Dfosllosls.
`both clinical and social, is poor. For other psychiatrists. who lbilcw
`Bleuler‘s views, the diagnosis of schizophrenia includes a wider range
`of patients with variable prognoses.
`It
`is somewhat paradoxical.
`however. to note that Kraepeiin claimed that about If} to [5 percent
`of his schizophrenic patients recovered completely, whereas Bleuler
`insisted that none of his patients ever returned fully to their prernorbld
`state.
`rspective, psychiatrists influ-
`As a result of these differences in
`diagnostic cnlena_aasocial.ed
`enced by Kine elin sought to identi
`with a gen
`y
`or
`rognosis and have defined schizophrenia
`accordingly. Emp SIS
`focused on the insidious onset of the
`disorder, the schizoid pretfisychotic personality. the absence ofobvious
`precipitating
`events.
`e restricted affect, the tendency to a cehbate
`life, the inability to establish ‘oneself in a career, and the increased
`familial prevalence of similar illnesses.
`As noted, ps chiatrists Influenced _by Bleuler adopted a much
`broader view o schizophrenia. The diagnosis of schizophrenia was
`made whenever patients showed a functional p_5ycl1ol.I_c 1ll_ness. Blenler
`emphasized certain _prirn.a.ry syrnptoms—autist1c thmloog. ambiva-
`lence, certain affective disturbances—that he belteyed were always
`present in schizophrenic patients. He assigned delusions and i1fl]ll.1C‘l-
`nations to a secondary -role, thus making it possible to make the
`dia
`osis of schizophrenia in patients showing Few. if any, unequiv-
`0
`psychotic features.
`_
`Psychoanalysts went one_ step further. By emphasizing a defective
`ego as the hallmark of schizophrenia. they were ready to include a
`soil broader range of psycho thology in
`e diagnostic category.
`It IS easy to understand
`ereforerthat major differences became
`evident in the way that the diagnosis of schizophrenia was made.
`Such opposing views even led to striking national differences: most
`Western European authorities used a narrow definition, in iteepin
`with Ki-aepelinian
`‘ces. whereas most Americans used a b
`dCi'lI1iiI1J0lII., in keeping with the Bieulenan and psychoanalytic ap-
`proac es.
`
`Attempts to clarify these opposing views have been reported during
`the course of the past 45 years. An early leader in these efforts was
`Langfeldt, who studied patients resembling more narrowly defined
`schizophrenics whose long-term course and prognosis, however, sug-
`ted that they were not typical Kraepelinianschizophrenics. Lang-
`eldt referred to such disorders as schizophremform and emphasized
`their relatively good firognosis and response to treatment. Since then,
`many investigators
`ave worked on the classification of psychotic
`patients according to their long-term course and prognosis. As a
`result, nondemented psychotic patients may be usefully divided into
`two broad groups, one with a relatively poor prognosis and the other
`with a relatively good prognosis. Such dla nosnc terms as chronic
`scbizophren:a,mErocras schizophrenia, no _car scluzo hrenia. and
`nonrernitting
`iaophrenla have men appliedto the ormer cases.
`and such terms as acute schizophrenia, remitting schizophrenia,
`reactive schizophrenia. schizophremforrn disorders, and schizoaffeo
`tive disorders have been applied to the latter cases. Some psychiatrists
`have argued that these prognostic di_lTerences, although V_3.il€I. do not
`represent fundamentally different Ci.l5OI'de'l’S; other psychiatrists have
`concluded that the differences reflect different basic conditions.
`lntercurrent affective syndromes develop in patients sutfering ii-om
`long-established schizophrenia, but such
`tients are excluded here
`fi'om the category of so izoaffective disc ers, because such atfective
`disturbances apparentl do not have the same significance as affective
`symptoms that p
`e or develop concurrently with a
`chotic
`syndrome or that a pear soon after the acute psychosis has su 'ded.
`‘ Schizoalfecuve isomers are defined here as syndromes _of depres-
`sive or manic features that develop before or concurrently with certain
`psychotic symptoms. such as it preoccupation with a mood-incon-
`gruent delusion or hallucination, or that
`immediately after the
`acute psychotic symptoms remit. The pa
`otic syn:
`toms are such
`as to be considered unusual in an uncomplicated a ective disorder.
`If the illness is due toany organic mental disorder, the diagnosis of
`schuzoatfechve illness Is not made.
`_
`Two kinds of
`ychotic symptoms are included in schizoalfective
`disorders. _The
`irst kind includes symptoms that are part of the
`criterion list for schizophrenia, such as delusions of control and
`certain types of auditory hallucinations, and that would suest
`schizophrenia, if there were no accompanying affective syndrome.
`The second kind includes symptoms that arise in the context cl’ on
`affective syndrome without an apparent relationship to depression or
`elation. Otherwise. the clinical features consist of various mixtures of
`affective and schizophrenia-like symptoms.
`
`EPIDEMIOLOGY
`
`Few data are available concerning the prevalence and epide-
`miological distribution of schizoaflecfive disorders. Most pop-
`ulation surveys of the incidence or prevalence of psychotic
`disorders have ignored the distinctions discussed here and
`have tended to include oondernented psychotic patients in
`the schizophrenia category. Those investigators who have
`included some psychotic persons in the affective disorder
`category hav_e generally done so on the basis of unspecified
`clinical judgment. rather than on the basis of explicit criteria.
`Certain observations are pertinent, however. and permit
`some tentative conclusions. Most patients with depression
`who consult psychiatrists do not report psychotic symptoms.
`Probably no more than one-quarter to one-third of such
`depressed patients experience hallucinations, delusions, or
`prominent ideas of reference. Such psychotic features proba-
`bly increase the likelihood of consulting a psychiatrist, so that
`the percentage of depressed persons with psychotic features
`included in the over-all group of depressed persons is most
`likely significantly less than the percentage seen by psychia-
`trists. At most, an estimated 5 to 10 percent of the persons
`seeking any professional help have both depressive and psy-
`
`3 of 80
`
`Alkermes, Ex. 1058
`
`

`
`chotic symptoms. The percentage is probably even lower,
`perhaps between 2 and 5 percent, among persons who never
`seek professional help, because this group includes many with
`mild and brief depressions.
`The lifetime general population risk for depression has been
`estimated to be between 5 and 20 percent, depending on the
`diagnostic criteria and sampling methods that are used. Tak-
`ing the above estimates for the frequency of psychotic features
`in depression, one may conclude that a maximum of some-
`where betwecn 0.1 percent and L0 percent of the population
`experience a depression with psychotic features.
`Combining the estimated prevalence of manic disorders-
`02 percent-—with the estimated percentage of manic patients
`who show psychotic features—about 50 to 70 p-ercent—tl1c
`population prevalence of mania with psychosis may be esti-
`mated at about 0.1 percent.
`_
`Most population studies place the prevalence of schizo-
`phrenia at less than I percent. Most schizophrenics experience
`affective syndromes sometime during the course of illness, so
`that an estimate of the association of schizophrenia and
`affective syndromes, usually depressive, is about 0.5 percent
`of the population.
`if the estimated frequencies of depression with psychotic
`features, mania with psychotic features, and schizophrenia
`with affective syndromes are combined, a total estimated
`frequency of between 0.7 and L6 percent is obtained. The
`estimate of 1.6 percent may be considered the approximate
`maximum frequency of schizoaffective conditions. The fre-
`quency of schizoatfective illness as defined in DSM-lll, how-
`ever, is almost certainly considerably less, because intercur-
`rent affective episodes during the course of schizophrenia are
`excluded, as are many patients whose psychotic features seem
`clearly part of an affective illness. Therefore, a reasonable
`estimate of the prevalence of schizoaffcctive disorders, as
`defined here, does not exceed 1 perccnL
`'
`A major justification for separating schizoalfective disorders
`from schizophrenia is the dilference in the associated familial
`illness patterns. Close relatives of patients with schizoalfective
`disorders tend to show a lower prevalence of schizophrenia
`than is seen in relatives of schizophrenics; instead, the relatives
`of patients with schizoaffective disorders tend to show a
`frequency of affective illness similar to that seen in the rela-
`tives of patients with affective disorders.
`Differential patterns of psychiatric illness in close relatives
`constitute one ofthe most important parameters for validating
`diagnostic categories. Regardless of the relative importance of
`genetic and environmental factors, nearly all psychiatric dis-
`orders have been found to be familial. Thus, Finding an
`increased prevalence of the same disorder among close rela-
`tives provides strong support for the validity of any particular
`diagnosis. When ill, most of the relatives of schizoaifective
`patients suffer from uncomplicated, straightforward alfective
`illnesses; however, an increased frequency of schizoaffective
`conditions may be seen among them. Some authors, especially
`authors reporting the latter increase, have argued that this
`findingjustifies considering schizoaflbctive disorders as a third
`functional psychosis, in addition to affective psychosis and
`schizophrenia. Other authors prefer to consider patients with
`schizoaffcctive disorders as a heterogeneous group with vary-
`ing proportions of depression, mania, and schizophrenia,
`depending on the method of selecting the samples. The ques-
`tion of a possible third psychosis is usually left unresolved.
`No striking sex differences in the frequency of schizoalfec-
`tive disorders have been reported.
`
`Gl'l'APTEH‘ 1'?
`
`;' SBHIZDAFFECTWE DISORDERS
`
`CAUSES
`
`little is known about the causes of all functional
`As yet,
`psychoses, including schizoaifective disorders. Evidence for
`some genetic predisposition to schizophrenic and affective
`disorders has been obtained from a wide range of pedigree,
`twin, and adoption studies. Unfortunately, as noted above,
`relatively little attention has been paid thus far to separating
`out schizoaifective conditions. It is hardly surprising that most
`speculation, whether psychodynamic or biological, concern-
`ing depressive, schizophrenic, and manic psychopathology
`has also been applied to schizoaffcctive conditions.
`
`CLINICAL FEATURES
`
`Patients present with a mixture of affective features, depres-
`sive or manic, and one or more hallucinations or delusions
`that are considered characteristic of schizophrenia or that,
`because they have no apparent relation to the disordered
`mood, are unusual in uncomplicated affective disorders.
`The psychosis typically begins abruptly, either coincident
`with an affective disturbance or after an affective syndrome
`has been present for days or even weeks. Often, it is ditlicult
`to be sure which feature was the first to begin. The psychotic
`and affective components may parallel each other in intensity
`throughout the illness, or one component may wax and wane
`while the other one holds steady.
`Generally, the psychotic and affective features begin more
`or less simultaneously; then the hallucinations or delusions
`subside, leaving the patient with a typical depression or mania.
`When depression follows,
`it
`is
`frequently described as
`“postpsychotic depression.“ The psychotic features are usually
`dramatic and overt, crting disturbances for relatives, neigh-
`‘bors, and friends.
`Episodes may be brief, but usually they last for either weeks
`or months. Some patients experience repeated episodes, sep-
`arated by months or years of apparently normal psychological
`fimctioning. Other patients have several similar episodes that
`are followed by other episodes oftypical depression or mania.
`Sometimes these episodes are supplanted by a persistent illness
`that is indistinguishable from typical chronic schizophrenia,
`with or without associated periods of disturbed mood.
`Suicidal thinking and completed suicide are common in
`these patients. It is not yet known what proportion of young
`schizophrenics who commit suicide were suliering from
`schizoaffective disorders, rather than from uncomplicated
`schizophrenia. As with the familial illness pattern, the suicide
`risk suggests to some psychiatrists that many, if not most,
`schizoaffective illnesses are, in fact, atypical cases of depres-
`sion or mania, ratherthan cases of schizophrenia.
`
`COURSE AND PFIOGNOSIS
`
`The long-term course and outcome of schizoaffective disor-
`ders cannot be discussed separately from the course and
`outcome of schizophrenia itself. The course of scltizoalfective
`disorders is quite variable, but on average, it seems to be
`significantly better than the course of schizophrenia. The
`better prognosis applies to the clinical course of the illness
`and to the social adjustment and appears to be true for
`untreated patients, as well as for treated ones
`Typically, the psychotic features develop acutely, and the
`patient comes for professional help within weeks of such
`onset, because the patient's family or the patient himself
`recognizes that a significant change in functioning has taken
`place. The relatively acute onset of the psychotic features has
`long been recognized as an important favorable prognostic
`factor. During the psychotic period, it may be difficult to
`
`4 of 80
`
`Alkermes, Ex. 1058
`
`

`
`758
`
`scHIzoAFl=Ec11vE otsonoens ; cameras 17
`
`asss adequately the pat.ient's affective state, although pa-
`tients usually discuss their moods freely. Sometimes the pa-
`tient is severely catatonic and is, therefore, inaccessible; but
`usually such periods are brief, and the patient communicates
`more freely afterward. Catatonic features may be as evident
`in schizoaffective disorders as in schizophrenic states.
`
`DlAGNO‘5lS
`
`The diagnosis of scliizoaffective disorders follows directly
`from their definition and the clinical picture.
`
`PSYCHIATRIC EXAMINATION The psychiatric examina-
`tion may reveal quite variable findings. In one patient, psy-
`chotic features may be more prominent than affective fea-
`tures; in another patient, the situation may be reversed. Yet
`again, in any single patient. the two types of features may
`fluctuate together or independently. Usually, the delusions or
`hallucinations are quite striking and are easy to recognize.
`Patients are grossly disturbed and create considerable diffi-
`culty for their families and friends. In general, the more
`floridly disturbed the patient, the more there is a likelihood
`that the illness is schizoaffective, rather than schizophrenic.
`The effective features are usually similar to the features seen
`in uncomplicated depression and mania.
`
`DIFFERENTIAL DIAGNOSIS The differential diagnosis in-
`cludes affective disorders, schizophrenia, organic mental dis-
`orders, and certain substance-abuse disorders, particularly
`those disorders associated with the abuse of lysergic acid
`diethylarnide (LSD), amphetamines, and other hallucinogens.
`Substance abuse should always be considered when an
`acutely psychotic patient is seen, including a patient with
`striking affective symptoms. Outside history, blood and urine
`screening for appropriate metabolites, and careful observation
`frequently permit the correct diagnosis. The majority of sub-
`stance-abuse illnesses usually subside a few days after discon-
`tinuing the drug, and such illnesses rarely last more than I0
`to 12 days after the drug has been discontinued.
`Some sclrizoaffective patients show clouding of conscious-
`ness early in an episode; therefore, an organic mental disorder
`must sometimes be seriously considered. Generally, however,
`the confusion and bewilderment are short-lived and leave the
`patient with a clear seusorium. despite the continuation of
`other symptoms. Mild confusion or disorientation may oc-
`casionally be evident throughout the illness; in such cases, it
`may be simply a matter of policy whether the patient receives
`a diagnosis of schizoaffective disorder or. alternatively, of
`organic mental disorder.
`The major differential diagnostic problems relate to schizo-
`phrenia and affective disorders. The history of the concept
`and the definition of schizoaffective disorders suggest that
`such patients are a heterogeneous group suffering from schizo-
`phrenia, affective disorders, and, possibly, a third functional
`psychosis. The relative proportions of the rniicturc probably
`vary with difierent circumstances and different diagnostic
`methods. Also, there is still disagreement as to whether re-
`mitting or good-prognosis cases of schizophrenia should be
`classified as schizophrenia or as affective disorders; to some
`extent, differential diagnosis is a matter of convention.
`Patients with these disorders vary greatly in course and
`outcome, and a major concern when such patients are first
`seen is that of estimating prognosis. Efforts to separate patients
`prospectively into two groups—patients with a relatively good
`prognosis and a remitting course and patients with a relatively
`poor outcome and a chronic course—have achieved varied
`SUCCESS.
`
`In general, successful efforts to discriminate good-prognosis
`and poor-prognosis cases have relied on the course of the
`illness up to the time of study, rather than relying on the
`clinical picture. A poor prepsychotic life adjustment-—-manh
`fested by a schizoid personality, few friends, a limited or
`absent sex life, and an insidious onset of illness, so that it is
`difficult to tell when the illnem began-—is the characteristic
`prognostic feature in poor-prognosis cases. The absence of
`schizoid personality features or lifestyle and an acutely de-
`veloping psychosis, which often seems to have been precipi-
`tated by some life event and is usually accompanied by
`prominent affective symptoms, are the important prognostic
`features in good-prognosis cases.
`Emphasizing the clinical picture, rather than the previous
`history, has been less successful. Prominent affective symp-
`toms seem to be significant in predicting a remitting course
`only when seen in the context of an acute psychosis with a
`good prenrorbid life history. In the past, when interest in
`psychiatric diagnosis was more limited, little effort was made
`to distinguish affective disorders from schizophrenia. so that
`any patient with psychotic features was simply called schizo-
`phrenic. This laclt of effort was particularly noted in the
`United States. As interest in this differential diagnosis has
`grown, however. patients have been less likely to receive a
`diagnosis of schizophrenia based simply on the presence of
`psychotic features. Most affective disorders with psychotic
`features are recognized as effective illnesses, and in the re-
`maining cases. the presence of affective features alone may
`not be as helpful in the differential diagnosis.
`
`PSYCHOLOCHCAL TESTS
`
`Psychological test results, not surprisingly, show a mixture of
`features associated with both schizophrenia and affective dis-
`orders. Few studies have dealt with schizoaifective disorders
`as a separate classification.
`
`TREATMENT
`
`Because their psychotic features, affective disturbances, or risk
`of suicide are generally striking, patients with schizoaffective
`disorders usually require hospitalization. Antipsychotic agents
`(such as the phenothiazines and butyrophenones), tricyclic
`antidepressants, antimanic drugs (such as lithium and the
`phcnothiazines), and electroconvulsivc therapy are the main-
`stays of treatment.
`The choice ofdrug or combination of drugs usually depends
`on the mixture of clinical features and on the relative severity
`of the various clinical elements. Patients usually do not re-
`spond as well to tricyclic antidepressants alone as they do to
`anlipsychotic dnlgs, with or without tricyclic antidepressants.
`Similarly, although lithiurn alone is sometimes effective, it
`generally is not as satisfactory as antipsychotic drugs, with or
`without lithium. Many patients do quite well with phan'na-
`cological treatment, but a significant number of patients
`respond so poorly or so slowly to such treatment that electro-
`convulsive therapy is recommended
`Most patients have a good response to electroconvulsive
`therapy. As yet, it is unclear whether such patients are further
`improved by concomitant drug administration, but many
`experienced clinicians believe that patients make better prog-
`ress if the antipsychotic or antirnood agent is continued after
`the electroconvulsive therapy.
`Most patients respond to the available treatments. For
`many, drugs or eiectroconvulsive therapy or a combination
`of the two results in prompt recovery and the ability to return
`to work, school, or home. To what extent the continuation of
`
`5 of 80
`
`Alkermes, Ex. 1058
`
`

`
`CHAPTER 1? I SGHIZOAFFEOTWE otsonosns
`
`759
`
`an antipsychotic or antimood drug prevents relapse is unclear,
`but evidence indicates that such a prophylactic effort may be
`helpful in certain cases. Unfortunately, some patients relapse
`after only a brief remission and must he treated vigorously to
`achieve a more lasting remission. A minority of patients show
`very little improvement. despite the application of all the
`above-mentioned treatments, and they progress to a chronic
`state of illness.
`
`SUGGESTED CROSS REFERENCES
`
`The schizophrenic disorders are discussed in Chapter 15, and
`the affective disorders are discussed in Chapter 18. Drug
`dependence is discussed in Chapter 22. Examination of the
`psychiatric patient is discussed in Chapter 12. The organic
`therapies are discussed in Chapter 30.
`
`REFERENCES
`
`Brpclgington I F. Leif J P: Scliizoafiective psychosis: Definitions and
`incidence. Psycho! Mod 9: 91. 1979.
`
`C1}: 8211 P J: Schizoaifective disorders. J Nerv Ment Dis J70: 64.5,
`Fowler R C. Liskow B I, Tnnria V L. Ly1.le I... Mezzich J: Schizophre-
`nia-primaty affective disorder discrirnioation. 1. Development ofa
`data-based diagnostic index. Arch Gen Psychiatry 37: B1 1, 1930.
`Fowler R C, Mezzich J. Liskow H 1. Van Valkenburg C: Schizophre-
`nia-priniary affective disorder discrimination. II. Where unclassi-
`fied psychosis stands. Arch Gen Psychiatry 37: E15. 1980.
`Goo-d_\vin 'D W. Guze S B: Psychiatric Diagriosls. ed 3, Oxford
`University Press. New York, 1934.
`Goplerud E. Depue Ft A: Affective symptoms. schizophrenia. and the
`garobiguity of postpsychotic depression. Schizophr Bull
`(‘nice 5 B. Cloninger C R. Martin R L, Clayton F J: A followup and
`family study of schizophrenia. Arch Gen Psychiatry 40: 1273. 1983.
`Johnson D A W: Studies of depressive symptoms in schizophrenia.
`I. The prevalence of depression and its possible cause. Br I Psy-
`chiatry 139: 89. I931.
`Langfeldt G: The prognosis in schizophrenia. Acta Psychiatr Neural
`Scaod{Si1ppl), 110. 1956.
`Pope H G, Jr. Lipinski J F, Cohen B M, Aitelrod D T: “schiaoalfective
`disorder“: An invalid diagnosis? A comparison of schizoaffoctive
`disoriglgr, slcgiétzfphrenia. and affective disorder. Am J Psychiatry
`37.’
`1,
`.
`
`6 of 80
`
`Alkermes, Ex. 1058
`
`

`
`CHAPTER 1 B
`
`AF FECTIVE DISORDERS
`
`18.1
`OVERVIEW OF AFFECTIVE DISORDERS
`
`ROBERT CANCRO, M.D., Meri.D.Sc.
`
`INTRODUCTION
`
`The affective disorders constitute a large group of illnesses
`characterized by alterations of mood. The vast majority of
`people suffering from affective disorders show an alteration
`of mood toward depression. Estimates of how many people
`are depressed in any particular year range widely. Conserva-
`tive estimates place t.he number of people who in any given
`year experience a depressive episode, which is potentially
`diagnosable, at between 10 and 20 million. In the United
`States 1
`in 20 persons is actually diagnosed as having a
`significant depression at least once in their lifetime.
`
`DEFINITION
`
`The very term "depression” is in many ways ambiguous. It is
`used to refer to a mood, a symptom, a syndrome, and possibly
`even a disease entity. Clearly, the Queen of Hearts did not
`restrict her authority to the world of Alice, but reigned in the
`world of clinical nosology as well. All human beings show
`fluctuations in mood as a reaction to life events. A depressed
`mood in this sense does not represent a disorder. Obviously,
`happiness is to be desired, but unhappiness—pa.rt.icularly as
`an appropriate response—does not constitute a diagnostic
`category. Unhappiness or normal sadness should not be con-
`fused with depression as a syndrome. It would be better in
`many ways if the mental status examination did not use the
`term “depression“ as a symptom, but replaced it with the
`term “sadness." Depression as a syndrome or disorder is the
`only clinically sound usage of the term, and its use should be
`so restricted.
`Just as the mood of an individual can be altered in the
`direction of depression, so can it be altered in the direction of
`elation. Elation is an important symptom in that larger con-
`stellation called mania. Mania should not be confused with
`good spirits and a high energy level. Most energetic people do
`not have a manic disorder, and most manic individuals ex-
`pend considerahle energy, but accomplish very little of value
`during their manic episodes.
`
`HISTORY Depressive disorders have been recognized and de-
`scribed for as long as history has been recorded. In ancient Egypt for
`over 3,000 years the depressive disorders were treated_by the priests
`who recognized that depression was often associated with_the expen-
`enoc of a psycholo ‘cal
`loss. King Soul
`is described in the Old
`Testament as mam estnig recurrent depressive episodes. These do
`scnptions of depression continue In classical Greek literature.
`It was notunnl approximately the 6th century a.c., however. that
`the observation of the mentally Ill began to enter the domain of the
`healer ratherjhan continuing to be a part of the theological tradition.
`Before this time madness generally was seen as somethin inllicted
`by the gods and, therefore, not subject to rational study.
`' move-
`ment away from theolo ‘cal and philosophical understanding to
`medical observation rear:
`its flowering in the thought of I-i.ipEfi-
`crates, who introduced the terms "mania" and “melancbolia.
`s
`
`descriptions of melancholia and mania are as clinically valid today
`as when written. He also attributed the origin of mental illness to
`natural rather than divine causes. Remarkably, it was Hippocrates
`who placed mental functions and malftlnctions in the brain. He
`It
`otheslzed that [It mental illness the brain was unhealthy as a result
`o imbalances in the internal hutnors.
`I
`The earl Roman physicians also made important contributions
`to our ‘u
`crstanding of the affective disorders Aretaeus made a
`distinction between exo enous and endogenous depressions,
`'ng
`thatalthough they S.l1fl.'l'
`‘asimilar symptomatology they had di erent
`t)l'i,gt1‘l5. He also recognized that mania and depression frequently
`ooexisted in the same individual. He, in fact,
`ued that mania and
`melancholia were part of a single disorder an that its origin was
`related more to the patient‘s emotional state than to internal hurnors.
`With the Renaissance there was again an emphasis on rational
`explanations and natural causes for
`e mental disorders including
`depression and mania. The role of witchcrafi and the influence ofthe
`stars became increasingly do-emphasized and was ultimately elimi-
`nated. The distinction between the mind and the soul was also helpful
`in giving natural science a domain se
`rate from that which belonged
`to theology. Finally, by the 16th an _I 'lth_ century there was general
`agreement that the brain was indeed unphcated in mental dlsorders.
`For the next 20_(} years there was an lncreastn emphasis onthe
`humane and enlightened treatment of the merit
`ly ill. The spirit of
`the French revolution and the age of enlightenment combined with
`an emphasis on moral treatment to lead increasingiy to a more useful
`apgroach to all mental disorders including depression and mania.
`y the end of the l9th century, Kraepeltn separated illogical
`psychoses without a tendency toward deterioration from illogical
`psychoses with a tendency toward deterioration. The former group
`was labeled the manic-depressive psychoses and constitutes the core
`of what is meant by the affective disorders today. Kraepelin‘-5 view
`was basically organic. but was complemented by the psychoanalytic
`theories of Freud, Abraham, Ratio, and others. The psychoanalytic
`writers emphasized the role of loss and the turning inward of anger
`against the