Abstract
Childhood adversity can have life-long consequences for the response to stressful events later in life. Abuse or severe neglect are well-known risk factors for post-traumatic stress disorder (PTSD), at least in part via changes in neural systems mediating the endocrine response to stress. Determining the biological signatures of risk for stress-related mental disorders such as PTSD is important for identifying homogenous subgroups and improving treatment options. This review will focus on epigenetic regulation in early life by adversity and parental care – prime mediators of offspring neurodevelopment – in order to address several questions: (1) what have studies of humans and analogous animal models taught us about molecular mechanisms underlying changes in stress-sensitive physiological systems in response to early life trauma? (2) What are the considerations for studies relating early adversity and PTSD risk, going forward? I will summarize studies in animals and humans that address the epigenetic response to early adversity in the brain and in peripheral tissues. In so doing, I will describe work on the glucocorticoid receptor and other well-characterized genes within the stress response pathway and then turn to genomic studies to illustrate the use of increasingly powerful high-throughput approaches to the study of epigenomic mechanisms.
Highlights
Childhood adversity can have life-long consequences for the response to stressful events later in life [1]
We conclude by providing examples of the ways in which research in this area may provide insights for post-traumatic stress disorder (PTSD) researchers on the epigenetic impacts of early adversity and highlight challenges for the field going forward
We found higher levels of DNA methylation of the Glucocorticoid Receptor (GR) promoter region among suicide victims with a history of abuse or severe neglect in childhood, but not among suicide victims who were not abused in childhood or among a control group who had died of causes unrelated to suicide [22]
Summary
Childhood adversity can have life-long consequences for the response to stressful events later in life [1]. ANIMAL MODELS OF EPIGENETIC MECHANISMS IN EARLY LIFE SHAPING THE RESPONSE TO STRESS IN ADULTHOOD Animal models of maternal care and perinatal stress have helped to provide a mechanistic understanding of the impacts of early life adversity, allowing for control of genetic variation and a temporal dynamics of environmental exposures.
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