The role of gender differences in the reduction of etiologic heterogeneity in schizophrenia

Recent research has shown a resurgence of interest in the study of gender differences in schizophrenia. Accumulated evidence suggests that, compared with women, men have a higher incidence of schizophrenia, earlier age of onset, poorer course and medication response, poorer premorbid social and intellectual functioning, fewer affective symptoms, lower family morbid risk of schizophrenia and affective disorders, more evidence of obstetric complications in their mothers, and greater structural brain abnormalities. The roles of estrogen, neurodevelopment, and family history of affective disorder are evaluated as co-contributors to the observed gender differences in schizophrenia. Particular emphasis is given to evaluating the hypothesis that men are more prone to a hypothesized poor-prognosis, neurodevelopmental subtype of schizophrenia, for which early environmental brain insults play an important etiologic role, whereas women may be more prone to a hypothesized good-prognosis, affective subtype that is genetically related to the affective disorders. This hypothesis is evaluated in terms of (a) its ability to account for gender differences in schizophrenia, (b) its ability to link differences in clinical presentation to proposed differences in etiology; and (c) its potential to generate testable predictions for future schizophrenia research.