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Evidence From Meta-analysis

André Aleman, PhD; René S. Kahn, MD, PhD; Jean-Paul Selten, MD, PhD

Arch Gen Psychiatry. 2003;60:565-571.

Background  Sex differences in the risk of a particular disorder can yield important clues regarding its pathogenesis. The evidence for a sex difference in the risk of schizophrenia is inconclusive. The purpose of this study was to integrate results from the published literature and to provide a quantitative index of the male-female ratio for the incidence of schizophrenia.

Methods  The MEDLINE and PsychLIT databases were searched for English-language publications on "incidence and schizophrenia" that appeared during the period between January 1980 and September 2001. Population-based incidence studies using standard clinical diagnostic criteria were included if they reported sex-specific incidence rates. Sex-specific incidence figures were extracted directly from each study. Categorical analyses were conducted on a subset of studies that met specific methodological criteria (to minimize criterion bias, hospital bias, and age bias). Study categorization and data extraction were performed independently by 2 of us (A. A. and J.-P.S.).

Results  Log risk ratio meta-analysis was conducted using a random-effects model. The incidence risk ratios for men to develop schizophrenia relative to women were 1.42 (95% confidence interval [CI], 1.30-1.56) when all studies were included in the analysis (49 effect sizes), 1.31 (95% CI, 1.13-1.51) when studies that minimized selection biases were analyzed separately (23 effect sizes), and 1.39 (95% CI, 1.15-1.68) when only high-quality studies were included (11 effect sizes). The sex difference was significantly smaller in studies with sample years before 1980 than those with sample years after 1980. No significant sex differences were reported in studies from developing countries. A final analysis, limited to studies with an age cutoff of 64 years or older (16 effect sizes), yielded a mean risk ratio of 1.32 (95% CI, 1.13-1.55).

Conclusion  This meta-analysis provides evidence for a sex difference in the risk of developing schizophrenia, as reported in the published literature from the last 2 decades.

From the Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.

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