Sex differences in schizophrenia, a review of the literature

Objective: To comprehensively and critically review the literature on gender differences in schizophrenia. Method: An initial search of MEDLINE abstracts (1966-1999) was conducted using the terms sex or gender and schizophrenia, followed by systematic search of all relevant articles. Results: Males have consistently an earlier onset, poorer premorbid functioning and different premorbid behavioral predictors. Males show more negative symptoms and cognitive deficits, with greater structural brain and neurophysiological abnormalities. Females display more affective symptoms, auditory hallucinations and persecutory delusions with more rapid and greater responsivity to antipsychotics in the premenopausal period but increased side effects. Course of illness is more favorable in females in the short- and middle-term, with less smoking and substance abuse. Families of males are more critical, and expressed emotion has a greater negative impact on males. There are no clear sex differences in family history, obstetric complications, minor physical anomalies and neurological soft signs. Conclusion: This review supports the presence of significant differences between schizophrenic males and females arising from the interplay of sex hormones, neurodevelopmental and psychosocial sex differences.