Sex steroids and schizophrenia

The peak in incidence for schizophrenia is during late adolescence for both sexes, but within this time frame the peak is both earlier and steeper for males. Additionally, women have a second peak in incidence following menopause. Two meta-analyses have reported that men have an overall ∼40% greater chance of developing schizophrenia than do women (Aleman et al., 2003; McGrath et al., 2004). These and other findings have led to the suggestion that ovarian hormones may be protective against schizophrenia. Less explored is the potential role of testosterone in schizophrenia, although disruptions in steroid levels have also been reported in men with the illness. The relationship between increased gonadal hormone release per se and peri-adolescent vulnerability for psychiatric illness is difficult to tease apart from other potentially contributory factors in clinical studies, as adolescence is a turbulent period characterized by many social and biological changes. Despite the obvious opportunity provided by animal research, surprisingly little basic science effort has been devoted to this important issue. On the other hand, the animal work offers an understanding of the many ways in which gonadal steroids exert a powerful impact on the brain, both shaping its development and modifying its function during adulthood. Recently, investigators using preclinical models have described a greater male vulnerability to neurodevelopmental insults that are associated with schizophrenia; such studies may provide clinically relevant insights into the role of gonadal steroids in psychiatric illness.