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

Lior Carmi, Joseph Zohar, Alzbeta Juven-Wetzler, Frank Desarnaud, Louri Makotkine, Linda M. Bierer, Hagit Cohen, Rachel Yehuda

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations


    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 NR3C1 (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 (n = 42) and again at the end of the study (13 months later, n = 27) to determine NR3C1-1F 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 (n = 4) showed significantly lower NR3C1-1F promoter sum percent methylation compared to the non-PTSD group (n = 38). Further, NR3C1-1F methylation at ED intake was inversely correlated with PTSD severity 13 months later, indicating that lower NR3C1-1F 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.

    Original languageEnglish
    Pages (from-to)578-586
    Number of pages9
    JournalWorld Journal of Biological Psychiatry
    Issue number7
    StatePublished - 1 Jan 2023


    • DNA cytosine methylation
    • cortisol
    • emergency department
    • glucocorticoid receptor
    • posttraumatic stress disorder (PTSD)

    ASJC Scopus subject areas

    • Psychiatry and Mental health
    • Biological Psychiatry


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