Affective disorders increase markedly during adolescence, and girls experience roughly twice the risk observed in boys. The neurodevelopmental mechanisms underlying this sex difference remain unclear. This review advances a heuristic model proposing that pubertal hormones modulate the maturation of mesocorticolimbic circuitry—including the amygdala, nucleus accumbens, ventral tegmental area, and ventromedial prefrontal cortex—in sex-specific ways that increase vulnerability to anxiety and depression. In girls, such vulnerability may arise from the effects of gonadal hormones on this circuitry, heightening neural sensitivity to threat and dampening reward responsiveness, thereby biasing socio-affective learning toward avoidance during a period of heightened neuroplasticity. Integrating evidence from human neuroimaging and animal studies, this review highlights convergent hormonal pathways that shape this circuitry and confer risk for affective disorders. The review underscores the importance of developmental neuroscience frameworks for identifying sex-specific risk markers and informing mechanism-based early interventions.
Cecile D. Ladouceur (Thu,) studied this question.