Genetics of sex differences in neuroanatomy and function

Sex differences are observed at many distinct biologic levels, such as in the anatomy and functioning of the brain, behavior, and susceptibility to neuropsychiatric disorders. Previously, these differences were believed to entirely result from the secretion of gonadal hormones; however, recent research has demonstrated that differences are also the consequence of direct or nonhormonal effects of genes located on the sex chromosomes. This chapter reviews the four core genotype model that separates the effects of hormones and sex chromosomes and highlights a few genes that are believed to be partly responsible for sex dimorphism of the brain, in particular, the Sry gene. Genetics of the brain's neurochemistry is discussed and the susceptibility to certain neurologic and psychiatric disorders is reviewed. Lastly, we discuss the sex-specific genetic contribution in disorders of sexual development. The precise molecular mechanisms underlying these differences are currently not entirely known. An increased knowledge and understanding of the role of candidate genes will undeniably be of great aid in elucidating the molecular basis of sex-biased disorders and potentially allow for more sex-specific therapies.