Hypothalamus-Pituitary-Adrenal Axis Programming by Early-Life Stress: A Role Played by Inflammatory and Epigenetic Mechanisms

Abstract

Early-life stress exposure, regardless whether pre-, peri-, or post-natal, has been shown to increase the risk for psychiatric disorders in vulnerable subjects. One of the hypothesis that explains this association suggests that early-life stress can induce a programming of the main physiological system responsible for the stress response, namely, the hypothalamus-pituitary-adrenal (HPA) axis. Indeed, several lines of evidence suggest that exposure to early trauma or stressful events can induce permanent alterations in the HPA axis, some of which are also seen in patients with psychiatric disorders. This chapter will discuss clinical and preclinical evidence of HPA programming by early-life stress and the molecular mechanisms suggested to underlie it, i.e., inflammation and epigenetic mechanisms. Future perspectives and clinical implications of the HPA programming and its biological basis are also discussed.