Genetic heterogeneity may in part explain sex differences in the familial risk for schizophrenia.

The purpose of this study was to attempt, in part, to explain significant sex differences in the familial risk (FMR) for schizophrenia found in previous studies. We hypothesized that, like probands, relatives of male vs. female probands may express different forms or subsyndromal symptoms of schizophrenia, i.e., differential expression of flat affect. Studied were 332 schizophrenic probands defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (DSM-III), criteria and 725 first-degree relatives from well-known retrospective cohort family studies. Results showed that relatives of male probands were at significantly higher risk for expressing flat affect than relatives of female probands, which did not hold for relatives of normal controls. Logistic regression was used to show that when flat affect was incorporated into the definition of affected among relatives, sex differences in FMR disappeared.