Elsevier

Journal of Affective Disorders

Volume 191, February 2016, Pages 8-14
Journal of Affective Disorders

Review
Characteristics and heterogeneity of schizoaffective disorder compared with unipolar depression and schizophrenia – a systematic literature review and meta-analysis

https://doi.org/10.1016/j.jad.2015.10.045Get rights and content

Abstract

Background

Comparisons of illness characteristics between patients with schizoaffective disorder (SAD) patients and unipolar depression (UD) are rare, even though UD is one of the most important differential diagnoses of SAD. Also, the variability of illness characteristics (heterogeneity) has not been compared. We compared illness characteristics and their heterogeneity among SAD, UD, and – as another important differential diagnosis – schizophrenia (S).

Methods

In order to reduce sampling bias we systematically searched for studies simultaneously comparing samples of patients with SAD, UD, and S. Using random effects and Mantel–Haenszel models we estimated and compared demographic, illness course and psychopathology parameters, using pooled standard deviations as a measurement of heterogeneity.

Results

Out of 155 articles found by an earlier meta-analysis, 765 screened in Medline, 2738 screened in EMBASE, and 855 screened in PsycINFO we selected 24 studies, covering 3714 patients diagnosed according to RDC, DSM-III, DSM-IIIR, DSM-IV, or ICD-10. In almost all key characteristics, samples with schizoaffective disorders fell between unipolar depression and schizophrenia, with a tendency towards schizophrenia. On average, UD patients were significantly older at illness onset (33.0 years, SAD: 25.2, S: 23.4), more often women (59% vs. 57% vs. 39%) and more often married (53% vs. 39% vs. 27%). Their psychopathology was also less severe, as measured by BPRS, GAS, and HAMD. In demographic and clinical variables heterogeneity was roughly 5% larger in UD than in SAD, and samples of patients with schizophrenia had the lowest pooled heterogeneity. A similar picture emerged in a sensitivity analysis with coefficient of variation as the measurement of heterogeneity.

Limitations

Relative to bipolar disorder there are fewer studies including unipolar patients. No studies based on DSM-5 could be included.

Conclusions

Regarding unipolar affective disorder this study confirms what we have shown for bipolar disorders in earlier studies: schizoaffective disorder falls between schizophrenia and affective disorders, and there are relevant quantitative differences in key illness characteristics, which supports the validity of the schizoaffective disorder concept. Contrary to our expectations heterogeneity is not larger in SAD than in UD and not substantially higher than in S. Lower reliability of the diagnosis of SAD therefore cannot be ascribed to higher variability of illness characteristics in SAD.

Introduction

Schizoaffective disorder is one of the most controversial diagnoses in psychiatry. Its nosological status has been debated at length (for example, Crow 1995, Evans et al. 1999, Lake and Hurwitz 2007, Jager et al., 2011), as has its justification as disease entity in general (Maier, 2006, Malhi et al., 2008, Heckers, 2009). Nevertheless, the diagnosis is frequently applied in population based and clinical samples: For instance, a Finnish epidemiological study (Perala et al. 2007) estimated a prevalence of 0.32 percent – roughly 37% of the lifetime prevalence of schizophrenia in that study. Olfson et al. (2009) reported that among Medicaid patients doctors diagnosed schizoaffective disorder almost half as frequently as schizophrenia.

Since schizoaffective disorder shares characteristics of affective disorders and schizophrenia, the differentiation from both groups of disorders is a key issue in clinical practice and in research. In an earlier meta-analysis we compared samples of patients with schizoaffective disorder with samples of patients with bipolar disorder and schizophrenia and found that most demographic, clinical, and psychometric measures fell between these two poles of the Kraepelinian dichotomy. However, samples of patients diagnosed with schizoaffective disorder were slightly more similar to schizophrenia than to bipolar disorder (Pagel et al. 2013a).

The diagnostic reliability of schizoaffective disorder is low (Jager et al., 2011, Santelmann et al., 2015 ). One of several possible reasons for low diagnostic reliability is substantial variability of a disorder. Variability, or heterogeneity, means that key characteristics of a disorder can assume a wide variety of values. For example, age at onset may span a wide range or psychopathology may be highly variable. Applied to schizoaffective disorder this model means that its highly variable (heterogeneous) psychopathology (comprising symptoms of two different groups of diagnoses: schizophrenia and affective disorders) may erroneously be ascribed to other disorders. According to this model, the diagnostic reliability of schizoaffective disorder would be lower than that of other diagnoses. This has indeed been shown (Jager et al., 2011). Given the low diagnostic reliability, we hypothesized that schizoaffective disorder would be characterized by high heterogeneity, that is, the variability of key demographic, clinical, and psychopathological parameters would be particularly large in comparison to unipolar disorder and schizophrenia. In another, earlier meta-analysis (Pagel et al., 2013b), however, we found that this is not the case for the comparison of schizoaffective disorder with bipolar disorder and schizophrenia: heterogeneity as measured across a wide range of parameters was similar for all three diagnoses. In fact, heterogeneity was slightly smaller among samples of patients with schizoaffective disorder.

In addition to bipolar disorder and schizophrenia, unipolar affective disorder is the third main differential diagnosis of schizoaffective disorder. To our knowledge, however, unipolar disorder has not been compared with schizoaffective disorder in regard to key illness characteristics and illness heterogeneity in a systematic and quantitative way. To address this knowledge gap we carried out a systematic literature review and meta-analysis comparing (1) key illness characteristics and 2) heterogeneity of key illness characteristics among schizoaffective disorder, unipolar affective disorder and schizophrenia.

Section snippets

Methods

This is a systematic review and meta-analysis of key illness characteristics and heterogeneity of key illness characteristics of schizoaffective disorder, compared with unipolar disorder and schizophrenia. This study is part of a larger research project on illness characteristics and on heterogeneity of schizoaffective disorder (Pagel et al., 2013a, Pagel et al., 2013b, Pagel et al., 2014). Design and statistical details of the project have been described in depth elsewhere (Pagel et al., 2013a

Results

We included 24 studies (Amador et al., 1994, Banov et al., 1994, Coryell and Zimmerman, 1986, Fennig et al., 1996, Grossmann et al., 1991, Levinson, 1991, Lewine et al., 1995, Maier et al., 1993, Maj, 1986, Maj et al., 1991, Mokrani et al., 2000, Opjordsmoen, 1989, Pini et al., 2001, Radomsky et al., 1999, Ragin and Oltmanns, 1987, Reichenberg et al., 2009: Sauer et al., 1984; Schott et al., 2006; Sharma et al., 1994; Silverstein et al., 1990; Tsuang & Coryell, 1993; Walterfang et al., 2009;

Discussion

This study yielded two main results: Firstly, the majority of key characteristics of patients with schizoaffective disorder fell between those for patients with schizophrenia and unipolar depression, and they were slightly more similar to samples of schizophrenia. Relative to samples of patients with unipolar disorder, schizoaffective disorder patients were on average younger at onset, had a higher percentage of men and a lower percentage of married patients. Also, psychopathology scales

Limitations

This study is limited by the relatively small number of studies that simultaneously investigated samples of patients with unipolar, schizoaffective, and schizophrenic patients (N=24). In earlier comparisons of schizoaffective disorder and schizophrenia with bipolar disorder (Pagel et al., 2013a, Pagel et al., 2013b) we were able to include twice as many papers (key characteristics: 50 studies, heterogeneity: 47 studies). The low number of studies may explain why some figures for schizophrenia

Conclusions

Our results indicate that schizoaffective disorder indeed falls between schizophrenia and affective disorders, thereby adding to the validity of the diagnosis – at least as long as an intermediary position between schizophrenia and affective disorders is central to the definition of schizoaffective disorder. On the other hand, whether schizoaffective disorder is a useful clinical diagnosis depends on other factors as well, such as reliability and the presence of specific treatments. Finally,

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