We provide an overview of recent progress in elucidating the epigenetic mechanisms through which the impacts of psychosocial stressors become biologically embedded, thereby influencing physiology and modulating disease susceptibility. We focus on the stress-induced epigenetic and other regulatory changes to biological pathways that are associated with altered hypothalamo-pituitary-adrenal (HPA) axis activity and proinflammatory signaling. Topics with increasing salience, with respect to the causal pathways linking neuroendocrine stress to elevated risk of chronic disease, are how psychosocial stressors, such as low socioeconomic status, act as inducers of chronic inflammation, and how the glucocorticoid resistance that results from such chronic stress impairs the antiinflammatory functions of glucocorticoids. Altered levels of HPA axis activity, inflammation, and their sensitivity to exogenous glucocorticoids are some of the characteristics of major depressive disorder and posttraumatic stress disorder, and we review current knowledge of the roles of epigenetic changes induced by psychosocial stress in the underlying pathobiology of these disorders. Glucocorticoid resistance is also a characteristic feature of endocrine diseases such as Cushing's disease and Chrousos syndrome, and we consider the pathobiological mechanisms that are at work in these disorders. Finally, we discuss the role of chronic stress in promoting epigenetic age acceleration.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)