Is the earlier age at onset of schizophrenia in males a confounded finding? Results from a cross-cultural investigation

Background The finding of an earlier age at onset of schizophrenia in males compared with females, replicated across a number of studies, appears to be so robust as to support hypotheses about gender differences in the aetiology of the disorder. However, the possibility that this observed gender effect might reflect other confounding variables has not been adequately explored. Method We analysed data on 778 men and 653 women, in three developing countries and in seven developed countries, who had been assessed in the WHO 10-country study of schizophrenia. We applied a generalised linear modelling strategy to estimate the unconfounded contributions of gender, family history, premorbid personality and marital status to age at onset. Results The model that explained the highest percentage of the total variance indicated strong main effects (P<0.001) for marital status and premorbid personality, a weak effect for family history, and an attenuated effect for gen der. Two independent verification procedures suggested an independent onset-delaying effect for marital status (married), more marked in males. Conclusions The gender difference in the age at onset of schizophrenia is not a robust biological characteristic of the disorder. Failure to control for marital status and premorbid personality in male/female comparisons of age at onset may explain a large part of the differences reported previously.