Epigenetics of Posttraumatic Stress Disorder: Current Evidence, Challenges, and Future Directions

Abstract

Posttraumatic stress disorder (PTSD) is a stress-related psychiatric disorder that is thought to emerge from complex interactions among traumatic events and multiple genetic factors. Epigenetic regulation lies at the heart of these interactions and mediates the lasting effects of the environment on gene regulation. An increasing body of evidence in human subjects with PTSD supports a role for epigenetic regulation of distinct genes and pathways in the pathogenesis of PTSD. The role of epigenetic regulation is further supported by studies examining fear conditioning in rodent models. Although this line of research offers an exciting outlook for future epigenetic research in PTSD, important limitations include the tissue specificity of epigenetic modifications, the phenomenologic definition of the disorder, and the challenge of translating molecular evidence across species. These limitations call for studies that combine data from postmortem human brain tissue and animal models, assess longitudinal epigenetic changes in living subjects, and examine dimensional phenotypes in addition to diagnoses. Moreover, examining the environmental, genetic, and epigenetic factors that promote resilience to trauma may lead to important advances in the field.

Keywords: DNA Methylation; Epigenetics; Fear Conditioning; Hypothalamic-Pituitary-Adrenal Axis; Posttraumatic Growth; Posttraumatic Stress Disorder.