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Boundaries of Schizoaffective Disorder Revisiting Kraepelin

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Boundaries of Schizoaffective Disorder Revisiting Kraepelin Research Original Investigation Boundaries of Schizoaffective Disorder Revisiting Kraepelin Roman Kotov, PhD; Shirley H. Leong, PhD; Ramin Mojtabai, MD, PhD, MPH; Ann C. Eckardt Erlanger, PsyD; Laura J. Fochtmann, MD; Eduardo Constantino, MD; Gabrielle A. Carlson, MD; Evelyn J. Bromet, PhD Editorial page 1263 IMPORTANCE Established nosology identifies schizoaffective disorder as a distinct category Author Audio Interview at with boundaries separating it from mood disorders with psychosis and from schizophrenia. jamapsychiatry.com Alternative models argue for a single boundary distinguishing mood disorders with psychosis Supplemental content at from schizophrenia (kraepelinian dichotomy) or a continuous spectrum from affective to jamapsychiatry.com 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 Author Affiliations: Department of that could simplify diagnosis, improve its reliability, and align it with the natural taxonomy. Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, New York (Kotov, Fochtmann, Constantino, Carlson, Bromet); Department of Psychiatry, University of Pennsylvania, Philadelphia (Leong); Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Mojtabai); Department of Cardiology and Comprehensive Care, New York University, New York (Erlanger). Corresponding Author: Roman Kotov, PhD, Department of Psychiatry and Behavioral Science, Putnam Hall-South Campus, Stony JAMA Psychiatry. 2013;70(12):1276-1286. doi:10.1001/jamapsychiatry.2013.2350 Brook University, Stony Brook, NY Published online October 2, 2013. 11794 ([email protected]). 1276 jamapsychiatry.com Copyright 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Boundaries of Schizoaffective Disorder Original Investigation Research he delineation of schizophrenia (dementia praecox) and was that a natural boundary would manifest as a significant psychotic mood disorders (manic-depressive insanity) drop in the outcome at some point along the spectrum, whereas T as 2 distinct entities was one of Emil Kraepelin’s semi- a continuum would result in a linear decline. Kendell and nal contributions to nosology.1 More than 100 years later, this Brockington found no evidence of a boundary, but their study kraepelinian dichotomy remains highly influential.2 How- was underpowered and analyses were limited to visual inspec- ever, some patients exhibit features of both schizophrenia and tion of graphs.22 The latter shortcoming might explain why this psychotic mood disorders, which led Kasanin3 to propose a new technique has not been widely adopted. More recent devel- category labeled schizoaffective disorder. Conceptualization of opments in statistical methods23 make it possible to test such this condition evolved across editions of the DSM from a sub- data for nonlinearity rigorously. type of schizophrenia to a distinct disorder. DSM-IV4 defines The aim of the present study was to test for the existence it as (A) co-occurrence of schizophrenia symptoms and mood of natural boundaries in psychotic disorders using modern sta- episodes, (B) psychosis present for at least 2 weeks in the ab- tistical methods. We analyzed detailed symptom course data sence of mood symptoms, and (C) mood episodes present for from an epidemiologic cohort of inpatients with psychosis a substantial portion of illness duration. Thus, DSM-IV elabo- monitored prospectively for 10 years after their first hospital- rates on the kraepelinian dichotomy by adding an intermedi- ization. In particular, we examined links between nonaffec- ate condition, with criterion B defining its boundary with psy- tive psychosis ratio during the first 4 years of the study and chotic mood disorder and criterion C with schizophrenia. The outcomes at year 10. The continuum model predicts a linear key to classifying these disorders is the ratio of nonaffective association, the kraepelinian model predicts a single bound- psychosis to mood disturbance: in psychotic mood disorder, ary between psychotic mood disorder and the schizophrenia nonaffective psychosis is absent; in schizoaffective disorder, spectrum, and the DSM-IV model predicts 2 boundaries, one both nonaffective psychosis and mood episodes are promi- between psychotic mood disorder and schizoaffective disor- nent; and in schizophrenia, nonaffective psychosis predomi- der and another between schizoaffective disorder and schizo- nates. However, some have argued that these boundaries are phrenia (Supplement [eFigure 1]). In the latter 2 models, dif- artificial and that psychotic disorders fall along a continuous ferences are expected between groups (eg, low nonaffective spectrum that ranges from psychotic mood disorder to psychosis and high nonaffective psychosis), but no associa- schizophrenia.5,6 tion is predicted between nonaffective psychosis and out- These conflicting accounts inspired a substantial body of come within groups. We constructed statistical models to test literature that evaluated the validity of schizoaffective disor- these hypotheses. We also used this method to explore natu- der using several basic approaches. Investigations of phenom- ral boundaries within depression and mania. enology found support for the continuum model,7 the krae- pelinian 2-disorders model,8,9 and the DSM-IV 3-disorders 10 model. Studies of neurobiological and cognitive function- Methods ing, as well as family and genetic research, reported evidence favoring the continuum7,11 and 3-disorders12-14 models. Lon- Participants gitudinal studies of illness course produced the most support Data for this study came from the Suffolk County Mental for the continuum15,16 and 2-disorders8,17-20 models. Thus, to Health Project, an epidemiologic study of first-admission date, the literature is too conflicting to offer firm recommen- psychosis.24-26 Patients were recruited from the 12 psychiat- dations for nosology. Some of these inconsistencies likely re- ric inpatient units of Suffolk County, New York, between Oc- sult from changes in schizoaffective diagnosis, which was de- tober 1989 and December 1995. Inclusion criteria were first ad- fined more broadly by earlier diagnostic manuals. mission, either current or within 6 months; clinical evidence Among diagnostic validators, illness course is of particu- of psychosis; age 15 to 60 years; IQ higher than 70; profi- lar interest. Indeed, it was most central to Kraepelin’s work be- ciency with English; and no apparent general medical etiol- cause he sought to develop diagnoses that would be prognos- ogy. The study was approved annually by the institutional re- tic of future symptoms and functioning (ie, global outcome).2 view boards of Stony Brook University and the participating Unfortunately, existing longitudinal studies were not de- hospitals. Treating physicians determined participants’ ca- signed to answer questions about the natural organization of pacity to provide consent. Written consent was obtained from psychotic disorders. They typically compared outcomes among adults and from parents of patients younger than 18 years. diagnostic groups: schizophrenia, schizoaffective disorder, and We initially interviewed 675 participants (72% of refer- psychotic mood disorder, but such analyses cannot distin- rals); 628 of them met the eligibility criteria. By the 4-year point, guish gradual differences (ie, a continuum) from qualitative 10 participants had died, 29 were untraceable, 41 refused fur- changes (ie, natural boundaries). Indeed, in many studies15,16 ther participation, and 22 provided insufficient information outcome of schizoaffective disorder fell between that of schizo- about symptom course;
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