title: Epigenomic Mechanisms of Early Adversity and HPA Dysfunction: Considerations for PTSD Research.
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.
authors.affiliation: Centre for Environmental Epigenetics and Development , Toronto, ON , Canada ; Department of Biological Sciences, University of Toronto , Scarborough, ON , Canada ; Cell and Systems Biology, University of Toronto , Toronto, ON , Canada.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: McGowan
keywords: DNA methylation; brain development; childhood abuse; early adversity; epigenetics; glucocorticoid receptor; hypothalamic-pituitary-adrenal axis; stress response