Figure 1.

Schematic representing potential brain regions and genes involved in stress-related disease that are implicated in putative sex differences. These brain areas are highly interconnected with one another with numerous efferent and afferent projections involved in emotion, stress reactivity, and reward. Importantly, studies implicate sex differences in structure and/or function as modeled by prenatal or postnatal or adult stress experience. Uterine environment, including stress and gonadal hormones, can influence life susceptibility toward disease. Gonadal hormones (e.g., testosterone, estradiol, and progesterone) and neurotrophic factors (BDNF) elicit effects throughout the lifespan, particularly during perinatal and adolescent development. Sex-specific HPA axis stress responsivity can also promote differing vulnerabilities resulting from higher glucocorticoid levels in females and may be related to central CRF regulation. Hormone-independent, genetically programmed sex differences (XX, XY), and disparate life experiences can also play a role in gender-biased vulnerabilities. Together, these factors may predispose females to a higher incidence of stress-related disorders such as affective disorders and drug abuse.