Sex and brain abnormalities in schizophrenia: fact or fiction?

Abstract

Evidence is growing from studies in our laboratory and others'-' that there are significant differences between males and females in cognition, brain structure, and neural function in schizophrenia. However, an understanding of the sexual dimorphism of the human brain is still in its infancy. Evidence for these differences has previously been derived from animal studies,B'g postmortem pathology,'0* and cognitive studies of brain function. Recently, researcher~'~'' have become interested in identifying sex differences in the normal brain using in vivo structural and functional imaging techniques. They have demonstrated sex differences in the volume of specific brain regions, in brain blood flow and glucose metabolism in the resting state and during cognitive challenge, and in lateralization of specific verbal functions. Further, some evidence suggests that sex differences in cognition in normals vary according to the sensory modality of the cognitive stimuli (e.g., visual versus auditory).''* Thus, identifying normal sex differences in brain function and structure is critical in understanding how these interact with the pathological processes involved in schizophrenia to produce sex differences in the expression of the disorder. SEX AND THE NORMAL BRAIN Several animal studies have shown that estrogens and androgens have specific effects on fetal brain development. Sexually dimorphic areas of the brain include the preoptic area of the hypothalamus,'8 the massa intermedia, the anterior commissure, the stria terminalis,l' the corpus callosum,20 and the hippocampus.' lho recent structural magnetic resonance imaging (MRI) studies in normal humans have found that compared to men, women have a greater ratio of gray matter volume to total volume in the