Long-term effects of early life stress exposure: Role of epigenetic mechanisms

Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress during the first years of life has been shown to have profound effects on the growth and development of an adult individual. There are evidences demonstrating that stressful experiences during gestation or in early life can lead to enhanced susceptibility to mental disorders. Early-life stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and the associated neurochemical reactions following glucocorticoid release are accompanied by a rapid physiological response. An excessive response may affect the developing brain resulting in neurobehavioral and neurochemical changes later in life. This article reviews the data from experimental studies aimed to investigate hormonal, functional, molecular and epigenetic mechanisms involved in the stress response during early-life programming. We think these studies might prove useful for the identification of novel pharmacological targets for more effective treatments of mental disorders.

Pre and postnatal exposure to adverse events like stress exerts short- and long-term consequences, leading to long-lasting effects on neuronal structure and behavior and playing a critical role in the etiology and evolution of several diseases, including metabolic syndromes and psychiatric disorders. Disruption of the HPA axis’s regulatory function is a key feature observed during the response to perinatal stress. The variability in the response to stress depends on both genetic and epigenetic background and the mechanisms underlying these processes remain to be fully characterized.Figure optionsDownload high-quality image (158 K)Download as PowerPoint slide