Outcome Studies of Schizoaffective Disorders

Transcription

1 VOL. 14, NO. 4, 1988 Outcome Studies of Schizoaffective Disorders 54 by Jacqueline A. Samson, John C. Simpson, and Ming T. Tsuang Abstract Outcome studies of schizoaffective disorder have taught us much about the long-term consequences of the syndrome, and they have provided some indication of the potential usefulness of maintaining "schizoaffective disorder" as a diagnostic category separate from schizophrenia and major affective disorder. In a review of outcome studies that compared schizoaffective patients to schizophrenic or affective patients, we found consistent results despite wide variations in diagnostic criteria, length of followup, and demographic characteristics. Global measures of outcome show that schizophrenic patients are more impaired than schizoaffective patients, who in turn are more impaired than affective patients. However, studies of specific outcome domains such as symptomatology, social functioning, and occupational functioning indicate that schizoaffective disorder is heterogeneous and that subtyping by polarity (e.g., schizoaffective-manic vs. schizoaffective-depressed) accounts for some of this variance. The consistency of these findings in the face of methodological variability suggests that it would be premature to classify schizoaffective patients with schizophrenia or affective disorder, but also that strict diagnostic criteria for schizoaffective disorder are at best preliminary and need to be thoroughly validated. work and providing suggestions for clinicians searching for systems of diagnosis that reliably predict response to treatment. These two goals are, by definition, interdependent, in that the usefulness of clinical diagnostic systems for prediction of outcome is limited by the quality of the research studies on which they are based. In a like manner, the accuracy of research findings is limited by the degree to which homogeneous groupings of patients are defined by clinical criteria. Hence, there is a need for constant interplay between the two disciplines, so that refinements in research methodologies resulting in new knowledge feed into revisions of diagnostic categories which are then applied in future research studies. Although this dynamic process is necessary for the refinement of our understanding of schizoaffective disorders, it increases the complexity of our task when attempting to execute an overview of findings from research carried out in different phases of scientific advancement. To address this complexity, we divided our review into two broad sections. The first section is focused on what is known about clinical outcome of schizoaffective disorders based on existing systems of classification. Our discussion in this section is centered on what is known generally about the longterm course of schizoaffective patients and what is known about the relative outcome of schizoaffective patients compared with schizophrenic or affective patient Downloaded from by guest on 22 November 218 The purpose of the present review is to examine the current state of our knowledge of the long-term outcome of schizoaffective patients, with the dual goals of providing guidelines to researchers for future Reprint requests should be sent to Dr. M T. Tsuang, Psychiatry Service, Brockton/West Roxbury VA Medical Center, 94 Belmont St., Brockton, MA 241

2 544 SCHIZOPHRENIA BULLETIN groupings. The second section of this review is more concerned with the current state of research methodology used to study schizoaffective illness We highlight key problems limiting interpretation of findings and suggest refinements to increase the quality of future studies. Lastly, we assess the implications of both clinical findings and research refinements for future clinical applications. Clinical Findings What is known about the long-term course and outcome of schizoaffective disorder is that this is indeed a heterogeneous diagnostic category. But, knowing this, we have yet to discover those aspects of the disorder that best discriminate patient groupings that are homogeneous with respect to prognosis, treatment response, and long-term course and outcome of the illness (Gross et al. 1986). The rates of recovery from schizoaffective episodes range from 8 percent reported in a short-term followup study (Clayton et al. 1968) to about 5 percent reported in studies using longer followup periods (Holmboe and Astrup 1957). Approximately 25 percent of schizoaffective patients go on to show a deteriorating course (Holmboe and Astrup 1957; Gross et al. 1986). Further, about 1 percent (Angst 1986) of patients show shifts in diagnoses over time, becoming either more affective or more psychotic in symptom manifestation. The average schizoaffective patient spends about 2 percent of his or her lifetime hospitalized or in an episode, and the median number of hospitalizations reported over a 25-year period is 6.7 (Angst 1986). Although many definitions of schizoaffective disorder allow for the sequential manifestation of psychotic and affective symptomatology, it appears that most patients show concurrent expressions of psychotic and affective symptoms (Marneros et al. 1986). In their 1984 review, Harrow and Grossman gave an indepth critique of the major studies of long-term outcome in schizoaffective patients. We added to their review several more recent studies (Maj 1985; Marneros et al. 1986; Williams and McGlashan 1987) and focused specifically on those studies that made use of a research design that compared outcome in schizoaffective patients against outcome in patients diagnosed as schizophrenic or affective (depressed, manic, or bipolar). Table 1 outlines the studies we considered and gives a brief overview of the design used in each. To examine the comparative findings more closely, we next separated results from each study to highlight findings pertinent to each of six broad categories of outcome. These included global outcome, marital status and functioning, deficits in social and occupational functioning, frequency of hospital admissions, and persistence of psychiatric symptomatology. Ten of the studies we reviewed examined outcome in schizophrenic and schizoaffective patients. These studies are summarized in table 2. Generally, schizophrenic patients showed more impairment than schizoaffective patients in global measures of outcome (five out of eight studies). There was a tendency for schizophrenic patients to show more impairment in occupational functioning as well as to exhibit more persistent psychiatric symptomatology. Outcome measures reflecting frequency of hospitalizarion and social functioning were mixed, with some studies showing equivalent impairment in schizophrenia and schizoaffective groups, and others finding more impairment in the schizophrenic patients. In only one study (Post 1971) was the schizoaffective group found to be more impaired than the schizophrenic group, and this study considered only elderly patients. In table, we review the findings from 11 studies comparing schizoaffective patients with affective patients. These comparisons were complex because some studies separated the affective patient group into manic and depressed patients, while others grouped together all affective patients. In yet other studies, affective patients were labeled bipolar, without a clear description of whether they had exhibited both mania and depression or mania with no depressive episodes. Similarly, the definition of schizoaffective disorder was in some studies broken down into schizoaffective-depressed and schizoaffective-manic. For the purposes of the present comparisons, we labeled patient groupings according to the definitions used in each study, while in our summary columns we tabulated overall frequencies for affective versus schizoaffective groupings. Studies that considered manic and depressive subtypes separately were counted as two studies for the purposes of our summary tabulations In general, schizoaffective patients showed more impairment on global measures of outcome (8 out of 1 reports). In three studies (Brockington et al ; Pope et al. 198; Maj 1985) schizoaffectivemanic patients were analyzed separately and were found to have global outcome equal to a compariso.i sample of manic patients Downloaded from by guest on 22 November 218

3 Downloaded from by guest on 22 November 218 o o CD OO OO Ol -p. en Table 1. Comparative studies of outcome in schizoaffective patients Investigators Country Case identification criteria Data collection methods Length of followup (in years) Comparison groups 1 Clark & Mallett (196) Post (1971) Tsuang et al. (1976) Great Britain Great Britain United States Own criteria Own criteria Feighner (modified) Chart & questionnaire Chart & clinical contact Chart S, D S, A, O S, M, D Tsuang & Dempsey (1979) United States Feighner (modified) -^4 S, M, D, C Angst (198) Brockington et al. (198a) Brockington et al. (198b) Switzerland Great Britain Great Britain Not specified CATEGO, RDC, and others CATEGO, RDC, and others Chart & telephone 27 (average) 1-4 ^-^ B S, A S, A Pope et al. (198) Grossman et al. (1984) United States United States RDC (modified) RDC S, M S, M, D Maj (1985) Mameros et al. (1986) Italy Germany RDC DSM-III (modified) 1-55 M, D S Williams & McGlashan (1987) United States DSM-III (modified) Chart & telephone 2-2 S, B, D 'Companson group codes are A = affective disorder, unspecified or mixed, B = bipolar disorder, C = nonpsychiatnc control, D = depressive disorder; S = schizophrenia; M - manic disorder, O = other, RDC = Research Diagnostic Critena

4 546 SCHIZOPHRENIA BULLETIN Table 2. Comparative findings of schizophrenic patients 1 Investigators Clark & Mallett (196) Post (1971) Tsuang et al (1976) Tsuang & Dempsey (1979) Brockington et al. (198a) Brockington et al (198b) Pope et al. (198) Grossman et al. (1985) Marneros et al. (1986) Williams & McGlashan (1987) Total frequency S - SA S - SA S < SA Global S < SA S > SD impairment Marital 2 by dimension of outcome: Schizoaffective Social Measure of impairment S > SD S - SA 2 Occupational S > SD S - SA 5 1 Hospital course S > SD VS. Symptoms S > SD 'Comparison group codes are S - schizophrenia. SA - schizoaffective disorder. SD - schizoafiective-depressed, SM - schizoaffective-manic Less severe impairment in the 1st ol 2 groups Equal impairment in both groups More severe impairment in the 1st of 2 groups (Pope et al. 198; Ma 1985) or a mixed affective group (Brockington et al. 198/i). Affective patients appeared to show marital status and functioning equal to schizoaffective patients in three sets of results (although Williams and McGlashan [1987) report a trend toward more impairment in heterosexual relations in their schizoaffective group). Results were mixed for social and occupational functioning as well as for the presence of persistent symptomatology, with either no difference between schi/oaffective and affective patients or else more impairment in the schizoaffective group. Lastly, three studies (Clark and Mallett 196; Angst et al. 198, Brockington et al. 198/') showed a higher frequency of hospitalizations for the affective patient groups than for schizoaffective patients. In two of these studies (Angst et al. 198; Brockington et al. 198/)), this reverse pattern of greater impairment for the affective disorder group may result from a high frequency of admissions for affective patients with manic episodes. Interestingly, outcome measures 4 2 reflecting presence of symptoms do not show differences between groups, although there is some indication that the persistence of psychotic symptomatology is greater in the schizoaffective patient groups and that the persistence of affective symptoms is greater in the affective patient groups (Maj 1985). From table as a whole, it appears that the global outcome for schizoaffective patients is characterized by somewhat greater impairment than in affective patients, whereas for functioning and symptom measures, schizoaffective and affective Downloaded from by guest on 22 November 218

5 VOL. 14, NO. 4, Table. Comparative findings patients 1 Investigators Clark & Mallett (196) Post (1971) Tsuang et al. (1976) Tsuang & Dempsey (1979) Angst (198) Brockmgton et al. (198a) Brockington et al. (198b) Popeet al. (198) Grossman et al (1985) Maj (1985) Williams & McGlashan (1987) Total frequency A < SA A = SA A > SA Global A < SA D < SA D < SA M < SA A = SM A < SD A < SA D < SD D < SA 8 5 of impairment by dimension of outcome: Schizoaffective vs. affective Marital D = SA M = SA D = SA 2 4 Social Measure of impairment A = SM A < SD A < SA D < SD D = SA 5 Occupational D < SA M = SA A = SM A< SD A = SA D < SD D = SA 7 Hospital course A > SA M < SA D< SA B > SA A > SM A< SD A = SA D = SD D < SA 4 4 Symptoms A > SA B < SA A < SD A = SA D = SD D < SA 'Comparison group codes are A = affective disorder, unspecified or mixed. B = bipolar disorder, D = depressive disorder. M = manic disorder. SA = schizoaffective disorder, unspecified, SD = schizoaftective-depressed, SM = schizoafiectrve-manic < Less severe impairment in the 1st of 2 groups = Equal impairment in both groups - More severe impairment in the 1st of 2 groups ^Trend for SA to show more impairment patients have similar outcomes, with both groups showing substantial heterogeneity. There is some indication that schizoaffective-manic patients look more like manic patients (or mixed affective groups) in outcome (12 out of 1 reports), whereas schizoaffective-depressed patients appear more impaired than depressive patients (8 out of 1 reports). Taken as a whole, outcome studies suggest that schizoaffective patients do less well than affective 5 1 patients and better than schizophrenic patients on global measures (Procci 1976; Tsuang and Dempsey 1979; Grossman et al. 1984). Moreover, for measures of symptom course, schizoaffective patients resemble affective patients. For measures of social and occupational functioning, schizoaffective patients look heterogeneous, with some showing deficits similar to schizophrenic patients and others showing deficits similar to affective patients. It appears that the distinction between manic and depressive forms of the illness is important to understanding this heterogeneity. One study (Grossman et al 1984) adds that patients with moodincongruent psychotic features generally show poorer outcome regardless of whether their diagnosis is schizoaffective or affective. This finding suggests that there is heterogeneity of outcome within the schizoaffective patient grouping and that the presence of moodincongruent psychotic features may Downloaded from by guest on 22 November 218

6 548 SCHIZOPHRENIA BULLETIN be a predictor of outcome that transcends current definitions of distinct psychiatric disorders. Methodological Issues Although the long-term outcome studies do show consistency of findings across studies, it is clear that more research is needed before our diagnostic systems can accurately predict treatment response and the long-term course and outcome for patients currently labeled schizoaffechve. This may be due in part to the early stage of our investigative efforts and in part to problems with research strategies. In this second section of our review, we consider five ma)or areas for improvement in future research studies. Sample Definition. The most basic of the methodological issues in outcome studies of schizoaffective patients is the problem of identification of homogeneous patient groups to be followed. Unlike the clinical descriptions in the early literature that included premorbid functioning, presence of an environmental precipitant, type of onset, course of the disorder, and family history, diagnostic systems used in research often rely more on type and severity of symptoms to assign a diagnosis of schizoaffective disorder. Therefore, studies that use symptom-based systems such as the DSM-11I to identify cases have moved toward a broader definition of schizoaffective disorder than was originally proposed. This shift in diagnostic emphasis makes the process of interpretation more difficult, as comparability of findings across studies is limited by differences in sampling methods over time. It is likely that our research strategies have prematurely forced patients into diagnostic classification groups based on cross-sectional symptoms. Multiaxial schemes, such as used by Endicott et al. (1986) and suggested by Ma and Perris (1985), are a step in the right direction. It may be that more radical strategies are needed, such as grouping patients according to course and outcome, and subsequently defining clinical characteristics based on discriminant function techniques. These empirically defined symptom clusters may then be validated by independent studies of outcome and family history. For example, Tsuang et al. (1986) have suggested preliminary criteria for subtyping schizoaffective disorders derived from baseline comparisons of their long-term followup patient samples. These include demographic characteristics, premorbid adjustment, and relative severity of psychotic and affective features. Delineation From Other Disorders. At the heart of the schizoaffective validation controversy is the question of the relationship between affective and schizophrenic disorders. The controversy rests upon a disagreement about the general nature of the relationship between schizophrenia and affective disorders. Some (Beck 1967; Crow 1986) see schizophrenia and affective disorders as opposite poles defining a continuum of severity, with schizoaffective disorders midway between the two poles (continuum hypothesis). Others (Kraepelin 191, Bleuler 1924) see schizophrenia and affective disorders as distinct and mutually exclusive illnesses (categorical hypothesis). Thus, categorical theorists view schizoaffective disorders as either a form of schizophrenia, a form of affective disorder, or an illness distinct from both schizophrenic and affective disorders. Continuum theorists view schizoaffective disorder as a heterogeneous spectrum of patients, some of whom are more schizophrenic, and others more affective. The typical design used to resolve these issues is to identify a group of schizoaffective patients, a group of schizophrenic patients, and a group of affective patients, and then to look for differences in outcome or family history between patient groups. Some researchers further divide schizoaffective and affective groups into manic and depressed types (Taylor and Abrams 1975; Pope et al. 198). Unfortunately, comparative studies are plagued by the problem of defining group membership discussed earlier. Further, it appears that schizophrenic and affective patients share certain symptoms, so that there are no symptoms that uniquely identify either type of illness (Pope and Lipinski 1978). Manic patients may present with positive symptoms of schizophrenia such as moodincongruent delusions or hallucinations, bizarre behavior, or formal thought disorder (Andreasen 1979; Harrow et al. 1982; Hoffman et al. 1986). Depressed patients may present with negative symptoms of schizophrenia such as poverty of speech, flat or blunted affect, or psychomotor retardation (Oltmanns et al. 1985). However, at the level of symptom persistence and course, differences emerge between schizophrenic and affective groups Harrow et al. (1986), as well as Marengo and Harrow (1985), find that while both schizophrenic and affective patients show severe symptoms episodically, schizophrenic patients generally show a more enduring pattern of lowerlevel symptoms between episodes. Therefore, symptom-based diagnos- Downloaded from by guest on 22 November 218

7 VOL. 14, NO. 4, tic schemas that do not include consideration of persistence or course of symptoms could misclassify patients. Moreover, the groups of schizophrenic and affectively disordered patients used as controls in studies of schizoaffective disorder are also thought to be heterogeneous, each composed of multiple subtypes that have yet to be clearly differentiated. Unless the lifetime diagnosis approach is used (see Schildkraut et al. 1978; Endicott et al. 1986), it is possible to misclassify patients. For example, patients with a past history of schizoaffective disorder and current major depression may be included in the unipolar control sample. In studies that attempt to discriminate schizoaffective disorders by making comparisons with affective or schizophrenic patients, the question thus becomes one of refining the diagnosis of one heterogeneous group of patients by differentiating it from two additional groups of heterogeneous patients. Future studies using the comparison group design must identify homogeneous groups of schizophrenic and affective patients to be used as controls. Timing. It has been suggested that many schizoaffective illnesses resolve, over time, into patterns that more clearly resemble affective or schizophrenic illnesses (see Angst 1986). The exact number of years from onset of first illness to this diagnostic resolution, however, remains unclear. It has also been observed (Morrison et al. 197; Harrow and Grossman 1984) that followup studies performed less than 2.5 years from the onset of the index episode show outcome similarities between schizoaffective and affective patients. However, studies performed at greater time intervals tend to show outcome similarities between schizoaffective and schizophrenic patients. Longitudinal followup studies with repeated observations of symptoms and functioning are needed to clarify homogeneity or heterogeneity of course and outcome in schizoaffective disorders and to clarify the degree to which outcome differences observed across studies result from variations in the timing of outcome measurement or from illness-based variations in symptom expression over time. Interestingly, McGlashan (1986) found duration of illness to be a key factor in identifying predictors of outcome in chronic schizophrenic patients. Early in the course of illness (the first decade), acquired skills are the best predictors of outcome. In the middle years of illness (the second decade), family environment and social supports best predict outcome, and in the later years (the third decade), family history of schizophrenia best predicts outcome. These findings also suggest that outcome data must be segregated by chronidty of illness in future studies of schizoaffective disorder. Prospective studies are needed that identify a homogeneous population of patients treated for a first episode of illness and then systematically assess symptoms and functioning at repeated intervals. Treatment. A fourth area of concern in longitudinal studies of schizoaffective patients is the effect of treatment interventions. Patient differences in adequacy of treatment trials and types of treatments received almost certainly affect measures of outcome. It is rare for these effects to be documented or statistically controlled in crossgroup comparison studies. It is imperative that future studies include documentation of treatments received. Moreover, information on differential response to treatment will contribute to future validation efforts. Systematic trials of antipsychotic medications, lithium, antidepressant drugs, or combinations thereof offer one avenue for the identification of homogeneous populations on the basis of drug response. Some work in this area has begun, with the suggestion that in schizoaffective-manic type patients, lithium treatment may be effective (Goodnick and Meltzer 1984), and that the combination of anhpsychotic and lithium therapy may be more effective than antipsychotic treatment alone for treatment-resistant psychotic patients (Small et al. 1975; Biederman et al. 1979; Carman et al. 1981; Nelson and Mazure 1986). For certain schizoaffective-depressed type patients, combinations of anhpsychotic and tricyclic antidepressant drugs have shown good results (Siris et al. 1978; Brockington et al. 198&7). This combination also has been shown effective in psychotically depressed patients (Spiker et al. 1985) and patients with depressions secondary to longstanding schizophrenia (Prusoff et al. 1979). Hence, these initial reports indicate that affective patients with psychotic features may benefit from treatment that includes antipsychotic medication and that psychotic patients with affective features may benefit from the addition of lithium or tricyclic antidepressants. Further prospective, random assignment trials are necessary before firm conclusions can be drawn. Choice of Measures. A final area for discussion in methodology con- Downloaded from by guest on 22 November 218

8 55 SCHIZOPHRENIA BULLETIN cerns the choice of outcome measures. As mentioned earlier, studies of outcome have focused primarily on variables such as number of hospitalizations, severity and persistence of symptoms, marital status, and social and occupational functioning. However, measures of outcome such as these may be weak or nonspecific discriminators of psychopathology. In a study of outcome across subtypes of schizophrenia, Strauss and Carpenter (1972) found little relationship between these measures of outcome and diagnostic subtype discriminations. Further, the authors demonstrated patterns of linkages between these measures which suggested that social environmental variables were important predictors of outcome status. For example, the number and duration of admissions to a hospital are greatly influenced by factors such as hospital policy, social and financial resources of the patient, alternative sources of treatment available, and the degree to which symptoms can be tolerated by family or community members. Occupational deficits may in turn be related to frequency and length of hospitalization and resulting interruptions in work performance. Similarly, disruptive symptoms are likely to result in frequent job terminations or low-level employment, thus also leading to poor occupational outcomes. Marital and social relations are equally likely to be affected by symptoms that interfere with the patient's ability to maintain a ]ob and to maintain mutually supportive relationships. Further, it is reasonable to hypothesize that the presence of symptoms associated with deviant and disruptive behaviors which cannot be tolerated in the community generally predicts scores on many of the outcome dimensions. The observation of Grossman et al. (1984) that moodincongruent psychotic features are a good predictor of outcome, regardless of diagnosis, is in keeping with this hypothesis. Hence, there is a need to expand our research models to include and control for additional measures that may influence outcome, such as life events, social supports, family resources, and disruptiveness of symptoms. To this same end, Strauss (1985) has suggested examining psychosocial variables as well as the more standard measures of outcome. In summary, the following guidelines are suggested to researchers of schizoaffective disorders: Future studies should return to a multidimensional strategy of describing clinical features of schizoaffective disorders (see Maj and Perns 1985). Research with laboratory measures should be continued to aid in the identification of homogeneous subtypes of patients. The multiaxial system described above should be applied in these efforts. Comparison studies should use homogeneous samples for control groups. Multiaxial diagnostic systems provide the flexibility to recategorize patients until greater homogeneity is achieved (e.g., Endicott et al. 1986). Outcome measures should be found which are less subject to problems of confounding from the presence of deviant or disruptive social behaviors. An alternative strategy would be to create predictive models that include social environmental variables. Followup studies should include repeated measurements of functioning and symptoms over extended periods of time. Naturalistic patient studies should include documentation of treatment history. Studies should include information gathered through direct interview methods. Data analysis should be multivariate and based on models that incorporate repeated measures of symptoms, laboratory tests, social functioning, and social environmental variables. Alternative methods of diagnostic categorization should be explored on the basis of findings from studies of outcome or family history. Implications for Diagnosis Although the diagnostic labels historically used to identify schizoaffective disorders vary, there are consistent descriptions in both the clinical and research literature that isolate a group of patients with the following characteristics (Procci 1976; Maj 1984rt, 1984/;; Tsuang and Simpson 1984): presence of symptoms resembling schizophrenia and affective disorder, acute onset with confusion or disorientation, good premorbid functioning, presence of a precipitant, and brief duration of episode followed by remission to full recovery or premorbid level of functioning. With the progress of psychiatric research methods, new standardized diagnostic systems have acknowledged the existence of schizoaffective disorders and incorporated definitions into diagnostic criteria. In the system of Feighner et al. (1972), patients who show affective symptoms as well as acute onset (< 6 months) of prominent delusions and hallucinations in the context of good premorbid psychosocial functioning are excluded from diagnostic categories of schizophrenia and primary affective Downloaded from by guest on 22 November 218

9 VOL. 14, NO. 4, disorder. These excluded patients are then classified in a heterogeneous residual category called "undiagnosed psychiatric disorder." In the Research Diagnostic Criteria (RDC) system of Spitzer et al. (1978), schizoaffective disorders are allocated into two categories, differentiated by the manic or depressive content of the affective symptoms. The diagnosis is made primarily on the basis of presenting symptoms and the degree to which symptoms of schizophrenia show temporal overlap with symptoms of affective disorder in an episode of illness. Additional ratings are made to document the course of the disorder (acute vs. chronic) and the relationship between schizophrenic and affective symptoms (mainly schizophrenic vs. mainly affective). Hence, in the RDC system, the critical dimension for identification of a current episode of schizoaffective disorder is the co-occurrence of schizophrenic and affective symptoms. Further refinements are then made by describing the course and temporal relationship of symptoms. Exclusions may be made later on the basis of lifetime diagnoses. Diagnostic systems used by clinicians have been less specific than those used in research, but they also have relied heavily on symptom manifestation. DSM-111 (American Psychiatric Association 198) defines schizoaffective disorders as episodes of illness in which delusions or hallucinations dominate when affective symptoms subside, or episodes of illness in which an affective syndrome and mood-incongruent psychotic features occur with inadequate information to differentiate between schizophrenia, schizophreniform disorder, or affective disorder. In DSM-1II, it is the overlap of schizophrenic and affective symptoms and the inability to categorize a patient as clearly schizophrenic, schizophreniform, or affective that is central to diagnosis. The revised DSM-IH (DSM-HI-R) (American Psychiatric Association 1987) defines schizoaffective disorder as an illness during which at some time there is an affective syndrome concurrent with psychotic symptoms. In a given episode of the illness, there must be at least 2 weeks of psychotic symptoms in the absence of prominent affective symptoms. Mood-incongruent psychotic features are not highlighted in this definition. Patients with psychotic features who cannot be clearly classified as affective with psychotic features, schizophrenic, or schizoaffective may be placed in a residual category of "psychotic disorders not otherwise specified." Hence, in DSM-1II-R, patients who show an overlap of psychotic symptoms and an affective syndrome, and a 2-week period in which psychotic symptoms (either moodcongruent or mood-incongruent) predominate, are called schizoaffective. DSM-H1-R further subtypes schizoaffective patients as depressed or bipolar. The 9th revision of the International Classification of Diseases (ICD-9) includes a category of schizoaffective disorder as a subtype of schizophrenia. The definition provided to guide clinical diagnosis (World Health Organization 1978) specifies that patients in this category should show a psychosis in which pronounced manic or depressive features are intermingled with schizophrenic features. Symptoms for these patients are said to tend toward remission and to recur. Unlike research applications, which attempt to identify etiology, clinical diagnostic schemas are created to assist in treatment choice. At present, the distinction of schizoaffective disorders appears to be useful, in that it separates from affective disorders those patients who might respond to a combination-therapy regime that includes antipsychotic medication, and separates from schizophrenic disorders those patients who might benefit from the addition of lithium or antidepressant medication to antipsychotic treatment. Beyond treatment-response issues, our review of the major studies of outcome revealed a surprising consistency of outcome in schizoaffective patients as compared with schizophrenic or affective patients. Despite differences in sample definitions, geographic location, or measurement techniques, schizoaffective patients consistently show long-term outcome that is less impaired than that of schizophrenic patients and more impaired than that of affective patients. Moreover, given the fact that these results were obtained by comparing schizoaffective patients to heterogeneous groups of schizophrenic and affective patients, it is likely that more distinctive findings would be obtained using narrower inclusion criteria for the schizophrenic and affective groups to be compared. The use of more restrictive definitions for schizophrenia and affective disorders has some appeal for clinical applications as well. In this approach, patients showing symptoms of both psychosis and affective disorders would be classified as schizoaffective. This category would include many cases currently defined as chronic schizophrenia with atypical affective disorder, atypical psychosis, and depressive or bipolar disorder with mood-incongruent psychotic features. The usefulness Downloaded from by guest on 22 November 218

10 552 SCHIZOPHRENIA BULLETIN of this broader definition of schizoaffective disorder is that it identifies those patients who are often the most difficult to treat and patients who might benefit most from a treatment strategy that includes some combinations of antipsychotic and antidepressant medication. Further subtyping might be made on the basis of the nature of affective symptoms (manic or depressive), as well as chronicity and associated features such as type of onset and premorbid functioning. Although the empirical evidence is not yet definitive in support of these subtypes of schizoaffective disorder, there is sufficient evidence that these features predict long-term outcome to warrant notation. Lastly, the use of broader inclusion criteria for schizoaffective disorder is more in keeping with the quality of clinical data available to the clinician when assigning a diagnosis. For example, DSM-III-R requires a 2-week period of psychotic symptom expression in the absence of affective symptomatology to make a diagnosis of schizoaffective disorder, but this criterion is difficult to assess clinically, particularly for the period of illness preceding admission for clinical care. In summary, outcome studies of schizoaffective patients suggest that the delineation of this syndrome from schizophrenia and major affective disorders is clinically useful. However, the exact diagnostic criteria that best predict treatment response for this heterogeneous group of patients remain unclear. In the absence of clear empirical data by which to define inclusion criteria for this diagnosis, we recommend that clinical definitions of schizoaffective disorder remain broad and, in fact, become more inclusive. We further recommend consideration of the nature of the affective symptoms (manic or depressed) for purposes of subtyping. Future longterm outcome studies should prove critical for the crucial steps of refining these concepts and testing their validity. References American Psychiatric Association. DSM-IIT Diagnostic and Statistical Manual of Mental Disorders. rd ed Washington, DC: The Association, 198. American Psychiatric Association. DSM-III-R- Diagnostic and Statistical Manual of Mental Disorders rd ed., revised. Washington, DC: The Association, Andreasen, N.C. Thought, language, and communication disorders: II. Diagnostic significance. Archives of General Psychiatry, 6:125-1, Angst, J.; Felder, W.; and Lohmeyer, B. Course of schizoaffective psychoses: Results of a followup study. Schizophrenia Bulletin, 6: , 198. Angst, J. The course of schizoaffective disorders. In. Marneros, A., and Tsuang, M.T., eds. Schizoaffective Psychoses. New York- Springer- Verlag, pp Beck, A.T. Depression: Causes and Treatment. Philadelphia: University of Pennsylvania Press, Biederman, J.; Lerner, Y.; and Belmaker, R.H. Combination of lithium carbonate and halopendol in schizoaffective disorder. Archives of General Psychiatry, 6:27-, Bleuler, E Textbook of Psychiatry. 4th German ed. Translated by A.A. Brill. New York: Macmillan, Brockington, I.F.; Kendell, R.E.; and Wainwnght, S. Depressed patients with schizophrenic or paranoid symptoms Psychological Medicine, 1: , Brockington, I.F.; Wainwright, S.; and Kendell, R.E. Manic patients with schizophrenic or paranoid symptoms. Psychological Medicine, 1:7-84, 198k Carman, J.S.; Bigelow, L.B.; and Wyatt, R.J. Lithium combined with neuroleptics in chronic schizophrenic and schizoaffective patients, journal of Clinical Psychiatry, 42: , Clark, J.A., and Mallett, B.L. A follow-up study of schizophrenia and depression in young adults. British loimial of Psychiatry, 19: , 196. Clayton, P ; Rodin, L.; and Winokur, G. Family history studies: III. Schizoaffective disorder, clinical and genetic factors including a one to two year follow-up. Comprehensive Psychiatry, 9:1-49, Crow, T.J. The continuum of psychosis and its implication for the structure of the gene. British Journal of Psychiatry, 149:419^29, Endicott, J.; Nee, J.; Coryell, W.; Keller, M.; Andreasen, N.; and Croughan, J. Schizoaffective, psychotic, and non-psychotic depression: Differential familial association. Comprehensive Psycluatry, 27:1-1, Feighner, J.P.; Robins, E.; Guze, S.B.; Woodruff, R.A.; Winokur, G.; and Munoz, R. Diagnostic criteria for use in psychiatric research Archives of General Psychiatry, 26:57-6, Goodnick, P.J., and Meltzer, H.Y. Treatment of schizoaffective disorder. Schizophrenia Bulletin, 1:-48, Gross, G.; Huber, G.; and Arm- Downloaded from by guest on 22 November 218

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12 554 SCHIZOPHRENIA BULLETIN treatment of delusional depression. American journal of Psychiatry, 142:4-46, Spitzer, R.L., Endicott, ].; and Robins, E. The Research Diagnostic Criteria: Rationale and reliability. Archives of General Psycluatn/, 5:77-782, Strauss, J.S. Negative symptoms: Future developments of the concept. Schizophrenia Bulletin, 11: , Strauss, j.s., and Carpenter, W.T., Jr. The prediction of outcome in schizophrenia. Archives of General Psychiatry, 27:79-746, Taylor, M.A., and Abrams, R. Manic-depressive illness and good prognosis schizophrenia. American lournal of Psychiatry, 12: , Tsuang, M.T., and Dempsey, G.M. Long-term outcome of major psychoses: II. Schizoaffective disorder compared with schizophrenia, affective disorders, and a surgical control group. Archives of General Psychiatry, 6:12-14, Tsuang, M.T.; Dempsey, G.M.; and Rauscher, F. A study of "atypical schizophrenia." Archives of General Psi/chiatn/, : , Tsuang, M.T., and Simpson, J.C. Schizoaffective disorder: Concept and reality. Schizophrenia Bulletin, 1:14-25, Tsuang, M.T.; Simpson, J.C; and Fleming, J.A. Diagnostic criteria for subtyping schizoaffective disorder. In- Marneros, A., and Tsuang, M.T., eds. Schizoaffective Psyclioscs New York: Springer-Verlag, pp Williams, P.V., and McGlashan, T.H. Schizoaffective psychosis: I. Comparative long-term outcome. Archives of General Psychiatry, 44:1-17, World Health Organization. Mental Disorders: G/osson/ and Guide to Their Classification in Accordance With the Ninth Revision of the International Classification of Diseases. Geneva: World Health Organization, Acknowledgment This work was supported by a Merit Review Grant from the Veterans Administration. The Authors Jacqueline A. Samson, Ph.D., is Instructor in Psychology, Department of Psychiatry, Harvard Medical School; Research Psychologist, Psychiatry Service, Brockton/ West Roxbury VA Medical Center; and Assistant Director, Depression Research Facility, McLean Hospital. John C. Simpson, Ph.D., is Instructor in Psychiatry, Harvard Medical School, and Health Statistician, Psychiatry Service, Brockton/West Roxbury VA Medical Center. Ming T. Tsuang, M.D., Ph.D., D.Sc, is Professor of Psychiatry, Harvard Program in Psychiatric Epidemiology, Harvard Schools of Medicine and Public Health, and Chief, Psychiatry Service, Brockton/West Roxbury VA Medical Center Downloaded from by guest on 22 November 218