Going beyond risk factor: Childhood maltreatment and associated modifiable targets to improve life-long outcomes in mood disorders.

Childhood maltreatment increases risk for mood disorders and is associated with earlier onset-and more pernicious disease course following onset-of mood disorders. While the majority of studies to date have been cross-sectional, longitudinal studies are emerging and support the devastating role(s) childhood maltreatment has on development of, and illness course in, mood disorders. This manuscript extends prior reviews to emphasize more recent work, highlighting longitudinal data, and discusses treatment studies that provide clues to mechanisms that mediate disease risk, course, relapse, and treatment response. Evidence suggesting systemic inflammation, alterations in hypothalamic-pituitary-adrenal (HPA) axis function and corticotropin-releasing factor (CRF) neural systems, genetic and other familial factors as mechanisms that mediate risk and onset of, and illness course in, mood disorders following childhood maltreatment is discussed. Risky behaviors following maltreatment, e.g., substance use and unhealthy lifestyles, may further exacerbate alterations in the HPA axis, CRF neural systems, and systematic inflammation to contribute to a more pernicious disease course. More research on sex differences and the impact of maltreatment in vulnerable populations is needed. Future research needs to be aimed at leveraging knowledge on modifiable targets, going beyond childhood maltreatment as a risk factor, to inform prevention and treatment strategies and foster trauma-informed care.