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DNA methylation GrimAge acceleration in US military veterans with PTSD

Neuropsychopharmacology (2023)Cite this article

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Abstract

Epigenetic alterations in DNA methylation might mediate gene expression effects of trauma underlying PTSD symptoms, or effects of PTSD on related health problems. PTSD is associated with all-cause morbidity and premature mortality, suggesting accelerated biological aging. We measured genome-wide DNA methylation (Illumina MethylationEPIC BeadChip) in whole blood in a treatment study for combat-related PTSD - “PROGrESS”, a multisite RCT comparing sertraline plus enhanced medication management (SERT + EMM), prolonged exposure (PE) therapy plus placebo (PE + PLB), and the combination (SERT + PE). DNA methylation was measured in 140 US military veterans who served in Iraq and/or Afghanistan (112 current PTSD cases enrolled in a PTSD treatment study and 28 veterans without PTSD history controls), and also 59 non-trauma exposed controls at baseline posttreatment (24 weeks after baseline). Increased DNA methylation GrimAge acceleration (p = 8.8e−09) was observed in patients with PTSD compared to a pooled control group (trauma exposed and non-trauma exposed), suggesting a higher risk of premature mortality in those with PTSD. There was no difference in GrimAge acceleration between combat trauma and non-trauma exposed controls. No treatment-related changes in GrimAge acceleration were found in within-subject comparisons of PTSD patients pre- to post-treatment.

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Fig. 1: Distribution of GrimAge acceleration across groups.
Fig. 2: Pre- to post-treatment differences in immune cell proportions, PTSD symptoms, GrimAge, and plasma IL-6 concentration.
Fig. 3: Pre- to post-treatment differences in immune cell proportions, PTSD symptoms, GrimAge, and plasma IL-6 concentration by treatment group.

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Funding

Funding

The DOD had a role in design in that they wanted the study to include only OEF/OIF/OND service members with combat-related PTSD. DOD had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the paper; and decision to submit the paper for publication. This work was supported by the U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command (MRMC; Randomized Controlled Trial of Sertraline, Prolonged Exposure Therapy, and Their Combination in OEF/OIF Combat Veterans with PTSD; (Award #W81XWH-11-1-0073; PI: Rauch); the National Center for Advancing Translational Sciences of the National Institutes of Health (Award #UL1TR000433). This material is the result of work supported with resources and the use of facilities at Massachusetts General Hospital, the VA Ann Arbor Healthcare System, Ralph H. Johnson VA Medical Center, and VA San Diego Healthcare System. The views expressed in this paper presentation are solely those of the author(s) and do not reflect an endorsement by or the official policy of the Department of Veterans Affairs, Department of Defense, or the U.S. Government, or the official views of the National Institutes of Health.

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Author notes

  1. These authors contributed equally: Seyma Katrinli, Anthony P King, Israel Liberzon, Sheila AM Rauch.

Authors and Affiliations

  1. Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA

    Seyma Katrinli & Alicia K. Smith

  2. Department of Psychiatry & Behavioral Health, and Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA

    Anthony P. King

  3. Department of Psychiatry, Michigan Medicine, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI, 48109, USA

    Elizabeth R. Duval & Nirmala Rajaram

  4. Emory University, Department of Psychiatry & Behavioral Sciences, Atlanta, GA, USA

    Alicia K. Smith & Sheila A. M. Rauch

  5. Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA

    Nirmala Rajaram

  6. Department of Psychiatry & Behavioral Science, Texas A&M Health, Bryan, TX, USA

    Israel Liberzon

  7. Atlanta VA Healthcare System GA, Atlanta, GA, USA

    Sheila A. M. Rauch

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Contributions

Concept and design: APK, MS, IL, SAMR; Acquisition of data: APK, ERD, NR, and SAMR; Statistical analysis: SK; Interpretation of the data: SK, APK, ERD, AKS, SAMR; Drafting of the paper: SK, APK, ERD, SAMR; Critical revision of the paper for important intellectual content: SK, APK, ERD, AKS, MS, SAMR; Final approval of the version to be published: All authors.

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Correspondence to Anthony P. King.

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APK, SK, ERD, NR, AKS, IL, SAMR report no competing interests.

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Katrinli, S., King, A.P., Duval, E.R. et al. DNA methylation GrimAge acceleration in US military veterans with PTSD. Neuropsychopharmacol. (2023). https://doi.org/10.1038/s41386-023-01537-z

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