Sex Differences Shape Brain Development and Function, in Health and Disease: Policy Implications

Abstract

Sex differences profoundly impact health and disease. Despite this, the inclusion of females in clinical and fundamental research lags far behind advances in other aspects of medicine, especially in the brain sciences. Regardless of whether neuroscientists are intrinsically interested in sex differences per se, observing a sex disparity in the incidence or presentation of a given neurological disorder provides a significant clue into the neurobiology of that disorder. Autism spectrum disorder (ASD) is one of the most sex-biased disorders, with a 4:1 male-to-female ratio, an important aspect of its etiology and biology that has largely been ignored in the preclinical literature. This article briefly overviews what is known about the sexual differentiation of the developing healthy brain, with a focus on the preclinical literature. This places observed sex differences in neurological disorders such as ASD into the context of known sex differences in neurobiology—along with insight from known sex-specific mechanisms in other systems that impact the brain (e.g., immune system, microbiome). Finally, the article provides recommendations for progress forward.