Neuroendocrine Mechanisms of Depression
Studies have demonstrated that major depressive disorder (MDD) is intimately tied to neuroendocrine dysregulation. This arises, in part, from the fact that brain regions that regulate mood also regulate primary neuroendocrine axes and metabolic functions. We and others demonstrated that the origin of MDD-neuroendocrine deficits begins in fetal development, is sex-dependent, emerges just post-puberty, and can be catalyzed by pregnancy (postpartum) and menopause. Here, we critically review clinical and preclinical studies to argue that higher MDD risk in women may arise, in part, from hormone-dependent pathogenic processes initiated during fetal development that drive sex-dependent developmental alterations of HPA circuitry emerging post-puberty with lifelong consequences.