Promoter methylation of the glucocorticoid receptor following trauma may be associated with subsequent development of PTSD.

OBJECTIVES

The ability to identify persons at elevated risk for post-traumatic stress disorder (PTSD) soon after exposure to trauma, could aid clinical decision-making and treatment. In this study, we explored whether cytosine methylation of the 1 F promoter of the (glucocorticoid receptor [GR]) gene obtained immediately following a trauma could predict PTSD.

METHODS

Our sample comprised 52 trauma survivors (28 women, 24 men), presenting to the Emergency Department (ED) within six hours of a traumatic event and followed for 13 months. Blood samples were taken at intake ( = 42) and again at the end of the study (13 months later,  = 27) to determine promoter methylation as well as plasma levels of cortisol, adrenocorticotropic-hormone (ACTH), and neuropeptide-Y (NPY).

RESULTS

At the 13-month follow-up, participants who met the PTSD criteria ( = 4) showed significantly lower promoter sum percent methylation compared to the non-PTSD group ( = 38). Further, methylation at ED intake was inversely correlated with PTSD severity 13 months later, indicating that lower promoter methylation in the immediate aftermath of trauma was associated with the development of PTSD.

CONCLUSION

To the extent that reduced promoter methylation is associated with greater GR expression and responsivity, this finding is consistent with the hypothalamic-pituitary-adrenal dysregulation previously described for PTSD.