Sexual Differentiation of the Brain and ADHD: What is a Sex Difference in Prevalence Telling Us?

Sexual differentiation of the brain is a function of various processes that prepare the organism for successful reproduction in adulthood. Release of gonadal steroids during both the perinatal and the pubertal stages of development organizes many sex differences, producing changes in brain excitability and morphology that endure across the lifespan. To achieve these sexual dimorphisms, gonadal steroids capitalize on a number of distinct mechanisms across brain regions. Comparison of the developing male and female brain provides insight into the mechanisms through which synaptic connections are made, and circuits are organized that mediate sexually dimorphic behaviors. The prevalence of most psychiatric and neurological disorders differ in males versus females, including disorders of attention, activity and impulse control. While there is a strong male bias in incidence of attention deficit and hyperactivity disorders, the source of that bias remains controversial. By elucidating the biological underpinnings of male versus female brain development, we gain a greater understanding of how hormones and genes do and do not contribute to the differential vulnerability in one sex versus the other.