Abstract and Keywords
Hormonal influences figure prominently in the development of major depressive disorder (MD). The chapter addresses the hypothalamic-pituitary-adrenal (HPA) axis and gonadal (i.e., estrogen and testosterone) hormones that are most relevant to MD. There is substantial evidence of HPA dysfunction in persons with MD, including adrenal hypersensitivity leading to elevated cortisol levels and deficient negative feedback control of the axis. These abnormalities may represent a marker of vulnerability for MD, as they are observed in high-risk populations prior to the development of the disorder. Gonadal hormones are related to specific presentations of MD. Estrogen sensitivity appears to underlie a “reproductive” form of MD in women, as seen during the menstrual cycle, postpartum period, and perimenopausal transition. Low testosterone, as occurs during normal aging, is associated with an increased risk for MD in men. These hormonal changes may be important in defining subtypes of MD that might be treated with targeted interventions.
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