Epigenetic Programming by Early-Life Stress

Abstract

Studies show that adverse conditions during early life can increase risks of developing mood disorders later in life. It is currently hypothesized that levels of environmental adversity in this early developmental period are able to shape the experience-dependent maturation of stress-regulating pathways leading to long-lasting alterations in stress responsivity during adulthood; a phenomenon often referred to as "early-life programming." Research is addressing the molecular mechanisms underlying this programming by which gene-environment interactions can predispose individuals toward psychopathology. Here we review key findings from animal and clinical studies examining the effects of prenatal and postnatal environment in shaping development of the neuroendocrine regulation of stress and the role of epigenetic mechanisms in translating early-life conditions into long-lasting gene expression changes underpinning stress-related behaviors. We also review latest ideas regarding interactions between environments at different developmental stages and evidence for transgenerational effects. Understanding how prenatal and postnatal experiences can give rise to lasting epigenetic marks conferring increased vulnerability to mental disorders is a major focus of molecular psychiatry and should pave new guidelines for therapeutic interventions.

Keywords: early-life programming; environmental adversity; epigenetic mechanisms; molecular mechanisms; stress-regulating pathways; therapeutic interventions.