COMPREHENSIVE
`TEXTBOOK OF
`PSYCHIATRY/V
`
`VOLUME 1
`FIFTH EDITION
`
`EDITORS
`
`Harold I. Kaplan, M.D.
`Professor of Psychiatry, New York University School of Medicine
`Attending Psychiatrist, University Hospital of the New York University Medical Center
`Attending Psychiatrist, Bellevue Hospital
`New York, New York
`
`Benjamin J. Sadock, M.D.
`
`Professor and Vice Chairman, Department of Psychiatry,
`New York University School of Medicine,
`Attending Psychiatrist, University Hospital of the New York University Medical Center
`Attending Psychiatrist, Bellevue Hospital
`New York, New York
`
`SANS WILLIAMS & WILKINS
`
`—
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`Baltimore ' Hong Kong ' London ° Sydney
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`Editor: Michael G. Fisher
`Associate Editor: Victoria M. Vaughn
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`Design: JoAnne Janowiak
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`
`Copyright © 1989
`Williams & Wilkins
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`
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`duced in any form or by any means, including photocopying, or utilized by any information
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`
`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 information sheet included in
`the package of each drug they plan to administer to be certain that changes have not been made
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`adverse reactions. This recommendation is of particular importance in regard to new or in—
`frequently used drugs.
`
`Printed in the United States of America
`
`First Edition 1967
`Second Edition 1975
`Third Edition 1980
`Fourth Edition 1985
`
`Library of Congress Cataloging in Publication Data
`
`Main entry under title:
`
`Comprehensive textbook of psychiatry/V.
`
`III. Com-
`.
`II. Sadock, Benjamin J.
`[DNLM:
`l. Mental disorders. 2. Psychiatry-
`
`Rev. ed. of: comprehensive textbook of psychiatry/IV. 4th ed. c1985.
`Bibliography: p.
`Includes index.
`I. Kaplan, Harold I.
`1. Psychiatry.
`prehensive textbook of psychiatry/IV.
`History. WM 100 C736]
`RC454.C637 1985
`
`616.89
`
`83-25952
`
`8.9909192
`
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`CHAPTER 1 6
`
`PSYCHOTIC DISORDERS)
`NOT ELSEWHERE
`CLASSIFIED
`
`16.]
`
`SCHIZOAFFECTIVE DISORDER,
`SCHIZOPHRENIFORM DISORDER, AND
`BRIEF REACTIVE PSYCHOSIS
`
`WARREN R. PROCCI, M.D., Ph.D.
`
`INTRODUCTION
`
`Naturally ‘occurring disease processes often have the perverse
`habit of not conforming to diagnostic criteria. The admirable
`and more rigorous diagnostic criteria for schizophrenia, mood
`disorders, and delusional (paranoid) disorders specified in the
`third edition and revised third edition of the Diagnostic and
`Statistical Manual of Mental Disorders (DSM—III and DSM-
`III-R) do not cover all patients with psychotic conditions. As
`a result, DSM—III and DSM-III—R have established a section
`entitled psychotic disorders not elsewhere classified. Included
`in this section of DSM-III—R are the three disorders discussed
`in this section, namely, schizoaffective disorder, schizophre-
`niform disorder, and brief reactive psychosis. This section of
`DSM-III—R also includes a fourth disorder, atypical psychosis,
`a residual category for psychotic disorders that do not meet
`the criteria for any specific psychotic disorder. Atypical psy-
`chosis is discussed in Section 16.2, which follows. DSM—III-
`R has added a fifth disorder to the above four, induced psy-
`chotic disorder. This disorder is discussed in Chapter 15,
`Delusional (Paranoid) Disorders.
`There has long been considerable confusion concerning the
`nosology, classification, and etiology of schizoaffective dis-
`order, schizophreniform disorder, and brief reactive psy-
`chosis. Various diagnostic labels,
`including Bell’s mania,
`catatonic syndrome applied to manic—depressive insanity, be-
`nign stupor, schizoaffective psychosis, schizophreniform psy-
`chosis, recoveredschizophrenia, cycloid psychoses, remitting
`schizophrenia, good prognosis schizophrenia, and reactive
`psychoses all have been used to describe a disorder—-or, more
`correctly perhaps, a heterogeneous group of disorders_—
`characterized by some or all of the following: positive B1eu—
`lerian signs, acute onset, presence of precipitants, good pre-
`morbid adjustment, affective symptoms, heredity positive for
`mood disorder, psychomotor excitation, and remission. There
`has been no universal agreement concerning the definitions of
`these various conditions or their relationship to one another.
`Because of this diagnostic and classificatory confusion, any
`discussion of schizoaffective disorder, schizophreniform dis-
`order, and brief reactive psychosis must be qualified regard-
`ing the clinical and research applicability of these terms. Both
`the second edition of the Diagnostic and Statistical Manual of
`Mental Disorders (DSM—H) and the ninth revision of the In-
`
`830
`
`ternational Classification of Diseases (ICD-9) handle these
`concepts differently from DSM-III—R. Subsequent editions of
`DSM, aided by a continued flow of sound empirical data, will
`no doubt offer further alterations in the understanding of these
`disorders. DSM-III—R brought new and specific defining
`criteria for schizophreniform disorder and brief reactive
`pyschosis, criteria that take these concepts somewhat afield
`from what their founding authors described.
`Schizoaffective disorder is considered first and in greatest
`detail, as it has generated the most empirical research. Para-
`doxically, DSM—III provides no specific criteria for schizoaf-
`fective disorder, although it does for schizophreniform dis-
`order and brief reactive pyschosis.
`
`SCHIZOAFFECTIVE DISORDER
`
`DEFINITION Schizoaffective disorder is not specifically
`defined in DSM—III. Rather, the category is to be used for
`those cases in which the clinician is unable to make a differ-
`
`ential diagnosis between affective (mood) disorder and either
`schizophreniform disorder or schizophrenia. DSM—III sug-
`gests the following defining criteria: conditions with a full
`affective syndrome accompanied by prominent mood-incon-
`gruent delusions and hallucinations that occur when affective
`symptoms are not present. This definition implies that schizo-
`affective disorder is probably a variant of mood disorder, as a
`full affective syndrome should be present, but a full schizo-
`phrenic syndrome should not; DSM-III—R does provide specif-
`ic defining criteria for schizoaffective disorder: an illness
`marked by a full major depressive or manic syndrome with
`concurrent symptoms from the “A” diagnostic criterion of
`schizophrenia. During an episode of the illness, delusions or
`hallucinations are present for a period of at least 2 weeks in
`the absence of affective symptoms. The condition does not,
`however, meet all the criteria for schizophrenia. Organic fac-
`tors must not be implicated in initiating ‘and maintaining the
`condition. Finally, the illness must be specified as bipolar or
`depressive.
`
`.
`
`COMPARATIVE NOSOLOGY The term “schizoaffec-
`tive” has caused a great deal of diagnostic confusion since it
`was first coined in 1933 by Jacob Kasanin. Historically, it has
`been considered as a form of schizophrenia, and DSM-II
`accordingly categorized schizoaffective disorder asa subtype
`of schizophrenia. DSM—III moved this condition to the cate-
`gory of psychotic disorders not elsewhere classified. It is now
`labeled simply schizoaffective disorder.
`DSM—III encourages using this diagnostic label in only rela-
`tively rare circumstances in which the diagnosis cannot dif-
`ferentiate between mood disorder and either schizophreniform
`disorder or schizophrenia. Major mood disorders with psycho-
`tic features, especially major depression or bipolar disorder
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`SECTION 16.1
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`/ SCHIZOAFFECTIVE DISORDER, SCHIZOPHRENIFORM DISORDER, AND BRIEF REACTIVE PSYCHOSIS
`
`831
`
`with mood-congruent or mood-incongruent psychotic fea-
`tures, must also be ruled out.
`DSM-IH aims toward a careful and accurate differential
`
`implying that the schizoaffective diagnosis rarely
`diagnosis,
`needs to be used if an adequate differential diagnosis is possi-
`ble. When the schizoaffective diagnosis is appropriate, DSM-
`HI seems to assume that the disorder is probably a mood-
`disorder variant with the addition of persistent mood—incon—
`gruent psychotic features that are present for at least some
`time when the affective features are not.
`
`DSM-III-R improves on this by presenting specific criteria
`for making the diagnosis of schizoaffective disorder; that is, it
`is no longer primarily a diagnosis of exclusion. These criteria
`are clearly delineated in Table ‘l6.1-1. DSM-III-R also re-
`quires specifying the disturbance as either bipolar or de-
`pressive. Because DSM-III-R replaces the term “affective dis-
`order” with the term “mood disorder,” this disorder should
`really be called “schizomood disorder.” DSM-III-R, however,
`retains the schizoaffective designation for historical con-
`tinuity.
`The Research Diagnostic Criteria (RDC) definition for
`schizoaffective disorder is similar to that of DSM-III-R, but
`the RDC diagnostic criteria are more detailed. The criteria
`also divide the disorder into schizoaffective disorder, manic
`type, and schizoaffective disorder, depressed type. These two
`types are further subdivided according to duration (i.e., acute,
`subacute, subchronic, or chronic). The RDC also makes an-
`other subdivision,
`into a mainly schizophrenic subtype, a
`mainly affective subtype, or another subtype based on the
`temporal relationship of the affective and schizophrenic fea-
`tures during the current episode. The RDC, like DSM-III-R,
`emphasizes an illness that fulfills the criteria for an affective
`syndrome but also presents at least one major schizophrenic
`symptom. But the RDC differs from DSM-III-R in the follow-
`ing way: The RDC defines the mainly affective subtype by
`the absence of the schizophrenic symptoms for at least 1 week
`during the absence of the affective symptoms, whereas DSM-
`HI—R requires that the schizophrenic symptoms (delusions or
`hallucinations) be present for at least 2 weeks in the absence
`of the prominent affective symptoms. The RDC’s mainly
`affective subtype may well define an illness even more close-
`ly allied to mood disorder than that described in DSM-III-R,
`whose definition itself leans toward mood disorder.
`The ICD—9 classification of schizoaffective disorder is sim-
`ilar to that of DSM—II. Schizoaffective type is listed as a
`specific subtype of schizophrenic disorders. In its glossary,
`however,
`ICD—9 describes the schizoaffective type as char-
`
`TABLE 16.1-1
`Diagnostic Criteria for Schizoaffective Disorder
`
`A. A disturbance during which, at some time, there is either a major
`depressive or a manic syndrome concurrent with symptoms that
`meet the A criterion of schizophrenia.
`B. During an episode of the disturbance, there have been delusions
`or hallucinations for at least 2 weeks, but no prominent mood
`symptoms.
`_
`C. Schizophrenia has been ruled out (i.e., the duration of all epi-
`sodes of a mood syndrome has notvbeen brief relative to the total
`duration of the psychotic disturbance).
`It cannot be established that an organic factor initiated and main-
`tained the disturbance.
`Specify: bipolar type (current or previous manic syndrome)
`or
`I
`
`depressive type (no current or previous manic syndrome)
`
`D.
`
`Table from DSM-III-R Diagnostic and Statistical Manual of Mental
`Disorders, ed 3, revised. Copyright American Psychiatric Associa-
`tion, Washington, DC, 1987. Used with permission.
`
`acterized by. both affective and schizophrenic symptoms, and
`both of these groups of symptoms must be pronounced. The
`illness also tends. to remit without permanent defect, but it is
`prone torecur.-Therefore, although it is classified as a sub-
`type of schizophrenia in ICD—9, schizoaffective disorder is
`seen as having a numberof characteristics more akin to mood
`disorder than to schizophrenia.
`
`EPIDEMIOLOGY ‘ Because -schizoaffective disorder has
`been variously definedthrough. the years, precise data con-
`cerning its incidence are limited. Some ‘information is avail-
`able, however, that indicates the, frequency of occurrence of
`schizoaffective disorder. In onerecent study, the incidence
`per year of schizoaffective disorder (0.-3 to;5..7 per 100,000)
`was compared with the incidence per year ofgschizophrenia
`(7.3 to 15.0 per 100,000) and mania (1.7 to.3.3 per 100,000).
`Thus, it was about one-quarter as commonas schizophrenia
`and roughly as common as mania. These data show. that
`schizoaffective disorder is far more common than onewould
`expect were it to represent the combination of both schizo-
`phrenia and mood disorder (calculated by multiplying the.»in-
`cidence of schizophrenia by the incidence of manic-depressive
`disorder, yielding a miniscule figure), as a handful of in-
`vestigators have speculated.
`
`ETIOLOGY It is naive to speak of an etiology of schizoaf-
`fective disorder at this point, as the issue is still clouded by
`the chronic confusion concerning the nature of the illness. Is
`it a variant of mood disorder or schizophrenia, or is it yet
`another psychotic disorder? These questions have puzzled
`several generations of investigators, even before Kasanin in-
`troduced the term in 1933. Emil -Kraep'e1in’s classification
`system is partly responsible for this diagnostic confusion, as
`he conceptualized psychotic illness as composed of two major
`groups:
`the deteriorating illness, which he called dementia
`precox, and the remitting illness, or manic-depressive disease.
`The best data currently available suggest that most of what
`is now diagnosed as schizoaffective disorder is probably the
`result of factors»-similar to those predisposing to mood dis-
`order. The psychotic symptoms, those resembling or mimick-
`ing schizophrenia, remainesomething of an enigma, but it has
`been suggested that
`they are independent of the affective
`symptoms and are evoked only when the affective symptoms
`become sufficiently intense. This should not be taken, howev-
`er, to imply that schizoaffective disorder is necessarily a more
`serious version of mood disorder, with a more problematic
`course and negative outcome. Furthermore, at
`least some
`patients with the schizoaffective diagnosis probably have an
`illness more closely related to schizophrenia,‘ and a few may
`have an unrelated disease. Clearly, determining the etiology
`of schizoaffective disorder
`is
`a task that will keep in-
`vestigators occupied for some time to come.
`
`PATHOLOGY DSM-III sparked psychiatrists’ long-stand-
`ing desire to identify specific pathologies for specific ill-
`nesses. Current psychiatric knowledge is sufficiently ad-
`vanced so that such correlation may be available in the near
`future. But at present, no known specific’ neuropathological
`process correlates reliably with schizoaffective disorder.
`The biological-marker approach to understanding psychiat-
`ric illness has yielded some relatively promising suggestions
`concerning possible physiologicalcorrelates for schizoaffec-
`tive disorder. A beneficial side effect of biological-marker
`research is that it has enabled investigators to speculate about
`the etiology of schizoaffective disorder. For example,
`if a
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`PSYCHOTIC DISORDERS NOT ELSEWHERE CLASSIFIED / EHAPTER 16
`
`,
`
`biological marker found in schizoaffective disorder is closely
`related to a biological marker also associated with schizophre-
`nia but not with mood disorder, then schizoaffective disorder
`may be hypothesized as being a subtype or variant of schizo-
`phrenia. Similar logic would apply if the biological marker
`closely corresponded to a marker known to identify a mood _
`disorder.
`Various studies have measured the urinary excretion of 3-
`methoxy-4-hydroxyphenylglycol
`(MHPG)
`to
`establish
`a
`biochemical classification for serious mood disorders. One
`study examined schizoaffective patients and found that they
`had mean urinary MHPG values very similar to those of bipo-
`lar manic depressives and quite different from subjects with
`schizophrenia and also some signs of depression. Elec-
`troencephalogram (EEG) records provide another biological
`marker. One study compared the all-night sleep records of
`schizoaffective and psychotic depressive patients, but no sig-
`nificant differences were found. Brain ventricular size has
`also been used to classify psychotically ill patients, and some
`of the current findings,
`though inconsistent and still con-
`troversial, are of interest. In general, schizoaffective patients,
`in contrast to schizophrenics, have relatively normal ventricu-
`lar/brain ratios (VBRs).
`Biological-marker studies thus have failed to identify a
`specific pathophysiological identifier of schizoaffective illness
`nor have they identified a specific etiological origin. Consid-
`ered together, however,
`these few studies support a closer
`relationship between schizoaffective disorder and mood dis-
`order
`than between schizoaffective disorder and schizo-
`phrenia.
`
`CLINICAL SIGNS AND SYMPTOMS A precise clinical
`description of schizoaffective disorder depends on one’s defi-
`nition of the disorder. Since Kasanin introduced the term-
`
`primarily to describe atypical psychotic patients with a mix-
`ture of schizophrenic and affective symptoms—severa1 in-
`vestigators have described similar clinical syndromes. But
`most of these descriptions have not been precise enough to
`allow comparative research. Some of these conditions are
`described in the introduction to this section. A careful reading
`of the original papers reporting these conditions reveals that
`these descriptions have much in common, and they may well
`refer to the same condition or a similar group of conditions.
`Among the factors common to at least several of these de-
`scriptions are the following:
`
`1. Relatively early age of onset (i.e., between ages 20 and
`40), perhaps with a subclinical episode during adolescence.
`2. Acute onset, often in the face of a precipitating environ-
`mental stress.
`\
`3. Marked emotional turmoil.
`
`4. Good premorbid functioning, with good social and voca-
`tional adjustment.
`5. No evidence of emotional withdrawal.
`6. Brief duration of the psychotic illness.
`7. No family history of schizophrenia.
`8. Presence of a family" history of mood disorder.
`9. Good outcome, with preservation of social and vocation-
`al functioning.
`
`Although not all of these features are present in all of these
`clinical descriptions, these signs and symptoms do merit be-
`ing grouped together and are considered as important charac-
`teristics of schizoaffective disorder.
`
`To be more specific, schizoaffective disorder consists of an
`acute episode of a floridly psychotic illness characterized by a
`
`mix of classical manic or depressive features with prominent-
`mood-incongruent psychotic symptoms, especially mood-
`incongruent delusions or hallucinations. For at least some of
`the time during the acute episode, the affective symptoms are
`not present, and the mood—incongruent psychotic features per-'
`sist.
`
`Often, there have been earlier episodes of the illness, which
`may have been more typically affective or schizophrenic in
`nature. If this is so, the clinician should be wary of making a
`diagnosis of schizoaffective disorder.
`By definition, the cross-sectional presentation of the illness ~
`varies considerably. If the patient is seen when the mood-
`incongruent psychotic features are prominent and the affective
`features are absent, the patient may well be indistinguishable
`from a schizophrenic. Conversely, there are periods of time
`when the affective symptoms are florid and the mood-
`incongruent psychotic features are relatively quiescent.
`The outcome of this illness also varies. Incomplete recov-
`ery with functional deterioration is possible. But this does not
`necessarily indicate that the illness is really schizophrenic in
`nature, as some patients with an apparently pure mood dis-
`order go on to exhibit impaired vocational, social, and in-
`terpersonal functioning. More typically, the outcome is rea-
`sonably benign, with the resolution of the acute episode fol-
`lowed by a substantial recapture of premorbid psychosocial
`and vocational functioning. A recurrence, however, is likely:
`DSM—III—R emphasizes a tendency toward chronicity in this
`disorder.
`.
`
`As suggested above, DSM-III was disappointing because it
`did not precisely define schizoaffective disorder but made it a
`residual diagnostic category characterized by a mixture of
`schizophrenic and affective symptoms. Later, the RDC and
`then DSM-III-R called for the presence of a full mood dis-
`order syndrome and then the addition of mood—incongruent
`psychotic features in order to make the schizoaffective di-
`agnosis. This attempt at codifying the diagnosis has indeed
`helped narrow the competing clinical descriptions, but it by
`no means solves the problem of accurate description. Even
`according to the more precise clinical descriptions of the RDC
`.- or DSM-III—R, patients may display in cross-sectional‘ view
`any one or more of the wide array of symptoms characteristic
`of either schizophrenia or mood disorder. Still, the RDC and
`DSM-III—R are a vast improvement over prior efforts and are
`more amenable to comparative research. Because" both the
`, RDC’s and DSM—III—R’s descriptions require the presence of
`a full affective syndrome, there is the danger of circularity in
`the definition. If an affective syndrome is necessary for the
`diagnosis, then it is more likely that schizoaffective disorder,
`so defined, is either a subtype or a variant of mood disorder
`than of schizophrenia. If only it were that clear. Indeed, one
`study specified that both a full mood disorder syndrome and a
`full schizophrenic syndrome, as defined by DSM-III, were
`required for the schizoaffective diagnosis. When subjected to
`a 15-year follow-up, these patients exhibited an outcome quite ’
`similar to that of rigorously diagnosed schizophrenic patient.
`A reasonable implication of this data is that the presence of a
`full schizophrenic syndrome carries a poor prognosis, even
`when a full affective syndrome coexists. Thus, schizophrenic
`symptoms in the presence of a full affective syndrome may
`not be associated with a poor prognosis, but if the schizo-
`phrenic symptoms evolve into a full schizophrenic syndrome,
`- then even the presence of a full affective syndrome will not
`protect against a poor prognosis. Prognostic precedence
`should be given to a full schizophrenic syndrome over a full
`affective syndrome.
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`SECTION 16.1
`
`/ SCHIZOAFFECTIVE DISORDER, SCHIZOPHRENIFORM DISORDER, AND BRIEF REACTIVE PSYCHOSIS
`
`833
`
`THE NATURE OF SCHIZOAFFECTIVE DISORDER
`
`Through the years, there have been three major possibilities
`regarding the nature of schizoaffective disorder. The first
`possibility, which prevailed at the time of DSM—II and which
`is suggested by DSM-III-R, is that schizoaffective disorder is
`a variant of schizophrenia. The second possibility, as ex—'
`emplified in the RDC and DSM—III,
`is that schizoaffective
`disorder is a variant of mood disorder. The third possibility is
`that schizoaffective disorder is truly an independent category,
`a “third” psychotic disorder that defies the long-standing
`Kraepelinian dichotomy.
`Some researchers have attempted to combine all three of
`these possibilities by suggesting that schizoaffective disorder
`itself is not a single disorder but is heterogeneous and com-
`posed of at least three subtypes: first, a mood-disorder sub-
`type, which is probably the most common; second, a schizo-
`phrenic subtype; and finally, a mixed subtype. This approach
`is probably the wisest one to adopt given the current available
`data and vague definitions.
`-
`Until recently,
`little attention was paid to possible differ-
`ences between the manic and depressive subtypes of schizoaf-
`fective disorder. The development of the RDC criteria has
`provided an incentive to pursue this, as the RDC does specify
`criteria for these subtypes. DSM-III-R insists that the schizo-
`affective diagnosis be subtyped into one of thesetwo catego-
`ries. These two subtypes may,
`in fact, not be subtypes but
`two distinct disease processes.
`
`Variant of schizophrenia In many respects, the DSM—II
`criteria for schizophrenia were an outgrowth of Manfred
`Bleuler’s criteria, which lacked precision and defied reliable
`operational definition. However, Bleuler’s criteria held sway
`in the United States for a considerable time, and as a result,
`schizophrenia was undoubtedly overdiagnosed. Bleuler’s
`criteria considered the presence of the so—called fundamental
`signs, the four A’s, to be pathognomonic for schizophrenia. If
`these were present, the diagnosis was schizophrenia, regard-
`less of whether prominent affective symptoms were also
`present. Many investigators view the introduction of lithium
`as a landmark in reconsidering the importance of affective
`symptoms, perhaps because a relatively specific and highly
`effective treatment became available for mood disorder.
`Following the introduction of lithium, the concept of schizo-
`affective disorder was
`reexamined by a number of
`in-
`vestigators who, while studying patients with mixed schizo-
`phrenic and affective features, chose to consider the illness as
`affective in nature and elected to treat
`the patients with
`lithium. Because many patients responded favorably, some
`researchers began to view schizoaffective disorder as a mood
`disorder variant.
`»
`»
`V
`.
`
`Recently, however, a few contrary studies have challenged
`this assumption and have lent new life to the idea that schizo-
`affective disorder is a variant of schizophrenia. DSM—IH—R
`subtly suggests this. Several studies have found that the pres-
`ence of affective symptoms within the framework of marked
`schizophrenic symptoms do not necessarily predict a good
`outcome. The criteria used to determine schizoaffective dis-
`
`order in at least one of these studies did include the presence
`of a persistent thought disorder during the time period be-
`tween the acute episodes. In another study, a full schizo-
`phrenic syndrome was required for a schizoaffective di-
`agnosis. Clearly,
`then,
`these criteria may have been biased
`toward selecting patients with an illness more akin to schizo-
`phrenia, analogous to the manner in which RDC and DSM—III
`criteria may bias diagnosis toward mood disorder. This again
`
`demonstrates clinicians’ dependence on various investigators.’
`diagnostic criteria and thus the importance of standardized
`diagnostic criteria.
`'
`-
`=
`
`Variant of mood disorder One approach to» diagnosing
`schizoaffective disorder is to examine the longitudinal course
`of schizoaffective illness via either retrospective or pro-
`spective follow-up studies and compare this with the longitu-
`dinal course of patients with schizophrenia and patients with
`mood disorder. This approach is a tried and tested one. Some
`investigators have found that Bleulerian—positive schizophren-
`ic patients whose psychosis remitted were often characterized
`by the presence of prominent affective symptoms. One pro-
`spective study associated the presence of depressive symp-
`toms in Bleulerian-diagnosed schizophrenic patients with a
`positive outcome. Another. investigator, perhaps overly op-
`timistically, asserted that the evidence was sufficiently con-
`clusive that the presence or absence of affective symptoms
`alone could differentiate recovered patients from chronic
`patients. A consistent finding is that thetpresence of the so-
`called first-rank symptoms of Kurt Schneider do not augur a
`poor prognosis as long as affective symptoms are present.
`Some researchers feel strongly that the presence of affective
`symptoms, and not schizophrenic symptoms, should be ac-
`corded diagnostic precedence.
`’
`Patients with schizoaffective disorder have a better long-
`term course than that of schizophrenia but probably not as
`good as that in pure mood disorder.
`Schizoaffective patients have also been subcategorized as
`schizomanic or schizodepressive. Six studies compared the
`course of illness in schizomanics with bipolar mania, and four
`of these six studies also included comparisons with schizo-
`phrenic patients. The twostudies that compared schizomanics
`only with manics found that the outcome was at least as good
`in schizomanics as in bipolar manic patients. In each of the
`other four studies,
`the schizomanics had an outcome in-
`termediate between that of the schizophrenics and that of the
`bipolar manics. Six studies compared schizodepressive pa-
`tients with patients with major mood disorder, depressed type,
`and five of these six studies also made comparisons with
`schizophrenic patients. The pattern is similar to that found for
`schizomanics. In four of the five studies in which schizo-
`
`depressives were compared with affectively depressed patients
`and with schizophrenics,
`the outcome was intermediate. In
`one study, however, schizodepressives did no better than
`schizophrenics.
`In the study comparing schizodepressives
`with depressed patients with mood disorder,
`the schizo-
`depressives had a less favorable course.
`Although the more ‘recent studies ‘have more similar di-
`agnosticcriteria than the earlier studies, in part because of the
`increasing use of the RDC, the later studies still disagree on
`what is meant by the term “outcome.” Certainly, the presence
`of schizophrenic symptoms in an otherwise typically affective
`illness generally lowers the prognosis. But it is also clear that
`the presence of affective symptoms in an otherwise typically
`schizophrenic presentation improves the prognosis, although
`one recent study found no improvement in prognosis even if a
`full affective syndrome coexisted with a full schizophrenic
`syndrome.
`In the future,
`this type of investigation should
`result in a higher yield as- more uniform and more objective
`outcome criteria are developed to match the currently more
`precise diagnostic criteria.
`to the investigation of
`Family history is also important
`schizoaffective disorder, because if schizoaffective disorder is
`a variant of schizophrenia, there should be more schizophreni-
`
`60f3‘|
`
`Alkermes, Ex. 1059
`
`6 of 31
`
`Alkermes, Ex. 1059
`
`

`
`834
`
`PSYCHOTIC DISORDERS NOT ELSEWHERE CLASSIFIED / CHAPTER .16
`
`cally ill relatives in the families of probands. Similarly, the
`children of such individuals should be at increased risk for
`schizophrenia. Analogous considerations apply if schizoaffec-
`tive disorder is a variant of mood disorder. If schizoaffective
`disorder is a third psychosis, an “independent” disease cate-
`gory, the relatives of index cases should exhibit a schizoaffec-
`tive picture, and the children of such patients should be at
`increased risk for schizoaffective disorder.
`Early studies noted that schizoaffective patients with a good
`outcome had many more relatives with a mood disorder.
`Several more recent studies, however, have found that the
`relatives of schizoaffective probands were more likely to have
`schizophrenia than the relatives of mood disorder probands.
`But these relatives had a generally lower risk rate for schizo-
`phrenia than for mood disorder. DSM-III—R emphasizes the
`familial pattern of increased risk for schizophrenia in the rela-
`tives of schizoaffective patients. In general, the risk rate for
`schizophrenia in the relatives of schizoaffective patients was
`lower than the corresponding risk rate for schizophrenic rela-
`tives in schizophrenic patients.
`Some studies have looked specifically at schizomanics, but
`none has found significant numbers of cases of schizophrenia
`among the relatives of schizomanic probands. Similar risk
`rates for mood disorder were found in the relatives of the
`schizomanics and in the relatives of patients with bipolar
`manic disorder. Several studies examined schizodepressives
`and reported either mixed results (i.e., either a risk rate in-
`termediate between the risk rate seen in mood disorder and
`that seen in schizophrenia) or a risk rate similar to that seen in
`mood disorder.
`
`These family history studies cannot be considered conclu-
`sive, but the general findings show the rate of mood disorder
`in the relatives of schizoaffective probands to be lower than
`the rate of mood disorder in the relatives of mood disorder
`
`probands, but still substantially higher than that of the general
`population