Epigenetic Sex: Gene–Environment Contributions to Brain Sex Differences and their Impact on Mental Health Risk

The developing brain does not undergo maturation independently of environmental influences, but rather is the culmination of the interplay between genes and the environment. The acceptance of this concept implies that differences in male and female experiences during perinatal development can result in subtle, yet important, divergences in brain physiology and function. As males and females develop under different hormonal, genetic, and environmental influences, these influences create different epigenetic signatures within the brain. These intrinsic epigenetic differences may produce sex differences in neuroendocrine functioning, but may also underlie altered risk for some mental health disorders between the sexes. This review will focus on the neuroepigenetic mechanisms altered by biological sex and discuss these alterations with reference to mental health.