Glucocorticoid Receptor: Genetics and Epigenetics in Veterans With PTSD

Posttraumatic stress disorder (PTSD) is conditional on exposure to trauma. Despite this, there is strong evidence from twin studies and widespread agreement that genetic factors also contribute to risk for PTSD. Large-scale genomic studies of PTSD are planned. DNA can be modified by epigenetic processes via environmental inputs, thereby influencing how genes are expressed, making this an equally important area of research for PTSD. Results from a succession of studies of PTSD suggested that the negative-feedback system of the HPA axis is overly sensitive, implicating the glucocorticoid receptor (GR) in the pathophysiology of PTSD. The GR gene and the related gene, FKBP5, have emerged as significant actors in epigenetic research of PTSD. DNA methylation of GR is associated with the PTSD diagnosis and also predicts treatment response to psychotherapy in veterans. FKBP5 methylation interacts with early adversity to confer risk for PTSD. Finally, FKBP5 methylation is associated with symptom change following psychotherapy in veterans with PTSD.