Sex Differences in the Risk of Schizophrenia: Evidence From Meta-analysis.
Aleman A, Kahn RS and Selten JP;
Commented by , 25 Jun 2003
Aim of the study
Already in 1919 Emil Kraepelin postulated that men appear in general to suffer somewhat more frequently from schizophrenia than women. However, the evidence for a sex difference in the risk of schizophrenia is inconclusive.
It has been argued that frequently reported findings of a male excess are confounded by various sources of bias. The aim of this study was to perform a systematic review and meta-analysis to provide quantitative estimates of the male-female ratio for the incidence of schizophrenia.
Method
The authors searched for English-language studies on "incidence and schizophrenia" that were published during the period between January 1980 and September 2001 using the electronic databases MEDLINE and PsychLIT. Trials were eligible for inclusion if they were population-based incidence studies, if standard clinical diagnostic criteria were included and if they reported sex-specific incidence rates. Sex-specific incidence numbers were extracted directly from each study.
In order to minimize three important sources of bias - criterion bias, hospital bias, and age bias - categorical analyses were conducted on a subset of studies that met specific criteria. Two reviewers independently extracted data and categorised the studies.
Disagreement between reviewers was resolved by discussion. The log risk ratio was used as an effect size measure and the meta-analysis was based on a random-effects model.
Results
Almost all analyses found an increased risk ratio for men for developing schizophrenia. The relative risk compared to women was
- 1.42 (95% confidence interval [CI], 1.30-1.56) in the overall analysis (49 effect sizes)
- 1.31 (95% CI, 1.13-1.51) when studies that minimized sources of bias were analyzed separately (23 effect sizes)
- 1.39 (95% CI, 1.15-1.68) when only studies with high quality were included (11 effect sizes)
The sex difference was significantly smaller in studies before 1980 than in studies after 1980. When only studies from developing countries were analysed, no significant sex differences were reported. Finally, when the meta-analysis was limited to studies with an age cut-off of 64 years or older (16 effect sizes), the mean risk ratio was 1.32 (95% CI, 1.13-1.55).
Discussion
This meta-analysis suggests that there is a gender difference in the risk of developing schizophrenia. The authors discuss several potential sources of bias.
There might be a criterion bias. If only narrow criteria are applied and if schizophrenic men tend to be more severely ill than women, this would lead to an overestimation of the risk for men. The same holds true for the “hospital bias”. Again, if male patients are more severely ill, they might be overrepresented in trials which only examine inpatients.
A particular point of concern is the use of an age cut-off in trials, because women in older age groups are at higher risk for developing the disorder than men. The authors state that these sources of bias were at least partly ruled out by their subanalyses of trials using different diagnostic standards, populations and age cut-offs.
However, the possibility remains that women are less likely to seek treatment or that their symptoms go unrecognised by clinicians more frequently. Thus, the existence of a true sex difference remains controversial.