Title

Boundaries of Schizoaffective Disorder: Revisiting Kraepelin

Document Type

Peer-Reviewed Article

Publication Date

12-2013

Journal Title or Book Title

JAMA Psychiatry

Volume

70

Issue

12

DOI

10.1001/jamapsychiatry.2013.2350

Abstract

Importance Established nosology identifies schizoaffective disorder as a distinct category with boundaries separating it from mood disorders with psychosis and from schizophrenia. Alternative models argue for a single boundary distinguishing mood disorders with psychosis from schizophrenia (kraepelinian dichotomy) or a continuous spectrum from affective to nonaffective psychosis.

Objective To identify natural boundaries within psychotic disorders by evaluating associations between symptom course and long-term outcome.

Design, Setting, and Participants The Suffolk County Mental Health Project cohort consists of first-admission patients with psychosis recruited from all inpatient units of Suffolk County, New York (72% response rate). In an inception cohort design, participants were monitored closely for 4 years after admission, and their symptom course was charted for 526 individuals; 10-year outcome was obtained for 413.

Main Outcomes and Measures Global Assessment of Functioning (GAF) and other consensus ratings of study psychiatrists.

Results We used nonlinear modeling (locally weighted scatterplot smoothing and spline regression) to examine links between 4-year symptom variables (ratio of nonaffective psychosis to mood disturbance, duration of mania/hypomania, depression, and psychosis) and 10-year outcomes. Nonaffective psychosis ratio exhibited a sharp discontinuity—10 days or more of psychosis outside mood episodes predicted an 11-point decrement in GAF—consistent with the kraepelinian dichotomy. Duration of mania/hypomania showed 2 discontinuities demarcating 3 groups: mania absent, episodic mania, and chronic mania (manic/hypomanic >1 year). The episodic group had a better outcome compared with the mania absent and chronic mania groups (12-point and 8-point difference on GAF). Duration of depression and psychosis had linear associations with worse outcome.

Conclusions and Relevance Our data support the kraepelinian dichotomy, although the study requires replication. A boundary between schizoaffective disorder and schizophrenia was not observed, which casts further doubt on schizoaffective diagnosis. Co-occurring schizophrenia and mood disorder may be better coded as separate diagnoses, an approach that could simplify diagnosis, improve its reliability, and align it with the natural taxonomy.

The delineation of schizophrenia (dementia praecox) and psychotic mood disorders (manic-depressive insanity) as 2 distinct entities was one of Emil Kraepelin’s seminal contributions to nosology.1 More than 100 years later, this kraepelinian dichotomy remains highly influential.2 However, some patients exhibit features of both schizophrenia and psychotic mood disorders, which led Kasanin3 to propose a new category labeled schizoaffective disorder. Conceptualization of this condition evolved across editions of the DSM from a subtype of schizophrenia to a distinct disorder. DSM-IV4 defines it as (A) co-occurrence of schizophrenia symptoms and mood episodes, (B) psychosis present for at least 2 weeks in the absence of mood symptoms, and (C) mood episodes present for a substantial portion of illness duration. Thus, DSM-IV elaborates on the kraepelinian dichotomy by adding an intermediate condition, with criterion B defining its boundary with psychotic mood disorder and criterion C with schizophrenia. The key to classifying these disorders is the ratio of nonaffective psychosis to mood disturbance: in psychotic mood disorder, nonaffective psychosis is absent; in schizoaffective disorder, both nonaffective psychosis and mood episodes are prominent; and in schizophrenia, nonaffective psychosis predominates. However, some have argued that these boundaries are artificial and that psychotic disorders fall along a continuous spectrum that ranges from psychotic mood disorder to schizophrenia.5,6

These conflicting accounts inspired a substantial body of literature that evaluated the validity of schizoaffective disorder using several basic approaches. Investigations of phenomenology found support for the continuum model,7 the kraepelinian 2-disorders model,8,9 and the DSM-IV 3-disorders model.10 Studies of neurobiological and cognitive functioning, as well as family and genetic research, reported evidence favoring the continuum7,11 and 3-disorders12-14 models. Longitudinal studies of illness course produced the most support for the continuum15,16 and 2-disorders8,17-20 models. Thus, to date, the literature is too conflicting to offer firm recommendations for nosology. Some of these inconsistencies likely result from changes in schizoaffective diagnosis, which was defined more broadly by earlier diagnostic manuals.

Among diagnostic validators, illness course is of particular interest. Indeed, it was most central to Kraepelin’s work because he sought to develop diagnoses that would be prognostic of future symptoms and functioning (ie, global outcome).2Unfortunately, existing longitudinal studies were not designed to answer questions about the natural organization of psychotic disorders. They typically compared outcomes among diagnostic groups: schizophrenia, schizoaffective disorder, and psychotic mood disorder, but such analyses cannot distinguish gradual differences (ie, a continuum) from qualitative changes (ie, natural boundaries). Indeed, in many studies15,16 outcome of schizoaffective disorder fell between that of schizophrenia and psychotic mood disorder, which is consistent with both the continuum and 3-disorders models.

Kendell and Brockington21 proposed a solution to this problem. They examined associations between the spectrum ranging from typical psychotic mood disorder to typical schizophrenia and continuous outcome measures. Their hypothesis was that a natural boundary would manifest as a significant drop in the outcome at some point along the spectrum, whereas a continuum would result in a linear decline. Kendell and Brockington found no evidence of a boundary, but their study was underpowered and analyses were limited to visual inspection of graphs.22 The latter shortcoming might explain why this technique has not been widely adopted. More recent developments in statistical methods23 make it possible to test such data for nonlinearity rigorously.

The aim of the present study was to test for the existence of natural boundaries in psychotic disorders using modern statistical methods. We analyzed detailed symptom course data from an epidemiologic cohort of inpatients with psychosis monitored prospectively for 10 years after their first hospitalization. In particular, we examined links between nonaffective psychosis ratio during the first 4 years of the study and outcomes at year 10. The continuum model predicts a linear association, the kraepelinian model predicts a single boundary between psychotic mood disorder and the schizophrenia spectrum, and the DSM-IV model predicts 2 boundaries, one between psychotic mood disorder and schizoaffective disorder and another between schizoaffective disorder and schizophrenia (Supplement [eFigure 1]). In the latter 2 models, differences are expected between groups (eg, low nonaffective psychosis and high nonaffective psychosis), but no association is predicted between nonaffective psychosis and outcome within groups. We constructed statistical models to test these hypotheses. We also used this method to explore natural boundaries within depression and mania.

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