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Front Psychiatry. 2019 Nov 8;10:808. doi: 10.3389/fpsyt.2019.00808. eCollection 2019.

Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma.

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Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
Department of Oncology, University of Alberta, Edmonton, AB, Canada.
Biological Psychiatric Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.


Adverse childhood experiences (ACEs) may be referred to by other terms (e.g., early life adversity or stress and childhood trauma) and have a lifelong impact on mental and physical health. For example, childhood trauma has been associated with posttraumatic stress disorder (PTSD), anxiety, depression, bipolar disorder, diabetes, and cardiovascular disease. The heritability of ACE-related phenotypes such as PTSD, depression, and resilience is low to moderate, and, moreover, is very variable for a given phenotype, which implies that gene by environment interactions (such as through epigenetic modifications) may be involved in the onset of these phenotypes. Currently, there is increasing interest in the investigation of epigenetic contributions to ACE-induced differential health outcomes. Although there are a number of studies in this field, there are still research gaps. In this review, the basic concepts of epigenetic modifications (such as methylation) and the function of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response are outlined. Examples of specific genes undergoing methylation in association with ACE-induced differential health outcomes are provided. Limitations in this field, e.g., uncertain clinical diagnosis, conceptual inconsistencies, and technical drawbacks, are reviewed, with suggestions for advances using new technologies and novel research directions. We thereby provide a platform on which the field of ACE-induced phenotypes in mental health may build.


childhood trauma; epigenetic association studies; mental health; stress disorders; the hypothalamic-pituitary-adrenal axis (HPA)

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