Successful treatment of post-traumatic stress disorder reverses DNA methylation marks
Open accessAbstract
Epigenetic mechanisms play a role in the detrimental effects of traumatic stress and the development of post-traumatic stress disorder (PTSD). However, it is unknown whether successful treatment of PTSD restores these epigenetic marks. This study investigated longitudinal changes of blood-based genome-wide DNA methylation levels in relation to trauma-focused psychotherapy for PTSD in soldiers that obtained remission (N = 21), non-remitted PTSD patients (N = 23), and trauma-exposed military controls (N = 23). In an independent prospective cohort, we then examined whether these DMRs were also relevant for the development of deployment-related PTSD (N = 85). Successful treatment of PTSD was accompanied by significant changes in DNA methylation at 12 differentially methylated regions (DMRs) in the genes: APOB, MUC4, EDN2, ZFP57, GPX6, CFAP45, AFF3, TP73, UBCLP1, RPL13P, and two intergenic regions (p values < 0.0001 were confirmed using permutation and sensitivity analyses). Of the 12 DMRs related to PTSD symptom reduction, consistent prospective evidence was found for ZFP57 methylation changes related to changing PTSD symptoms (B = -0.84, t = -2.49, p = 0.014). Increasing ZFP57 methylation related to PTSD symptom reduction was present over and above the relation with symptoms, suggesting that psychological treatments exert biological effects independent of symptom reduction. Together, these data provide longitudinal evidence that ZFP57 methylation is involved in both the development and successful treatment of deployment-related PTSD. This study is a first step to disentangle the interaction between psychological and biological systems to identify genomic regions relevant for the etiology and treatment of stress-related disorders such as PTSD.
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ZFP57 methylation is increased in responders at follow-up.
“↑ ZFP57 methylation in responders (n=11) at FU”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Vinkers et al., 2019
The Results section ('Relevance of the treatment-related DMRs for PTSD development'; page unavailable) reports increased ZFP57 methylation following symptomatic remission. But 'PTSD treatment efficacy' reports remission in 21 patients, not 11, so the cited paper does not support the stated responder count. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn PTSD patients, response to trauma-focused CBT partially supplemented by EMDR has been observed to be accompanied by dynamic alterations in 12 differentially methylated genomic regions (DMRs) six to eight months after treatment, with most consistent evidence for increasing methylation of the ZFP57 genomic region along with successful treatment.
“In PTSD patients, response to trauma-focused CBT partially supplemented by Eye Movement Desensitization and Reprocessing (EMDR) has been observed to be accompanied by dynamic alterations in 12 differentially methylated genomic regions (DMRs) six to eight months after treatment, with most consistent evidence for increasing methylation of the zinc-finger protein 57 (ZFP57) genomic region along with”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Vinkers et al., 2019
Changes in 12 DMRs were found.
“Changes in 12 DMRs”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Vinkers et al., 2019
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The role of epigenetics in psychological resilience
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- Authors
- Vinkers, C. H., Geuze, E., van Rooij, S. J. H., Kennis, M., Schür, R. R., Nispeling, D. M., Smith, A. K., Nievergelt, C. M., Uddin, M., Rutten, B. P. F., Vermetten, E., & Boks, M. P.
- Affiliations
- GGZ inGeest (NL)
- Utrecht University (NL)
- Emory University (US)
- Maastricht University Medical Centre (NL)
- University of South Florida (US)
- Leiden University Medical Center (NL)
- Corresponding author
- Vinkers, Christiaan H.
- Boks, Marco P.
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2019-10-23
- Volume
- 26
- Issue
- 4
- Pages
- 1264-1271
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2982079712
- Cited by
- 111
- References
- 3
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 23 · 2023: 15 · 2022: 20 · 2021: 17 · 2020: 8
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- post-traumatic stress disorder, DNA methylation, epigenetics, trauma-focused psychotherapy, ZFP57, differentially methylated regions, PTSD remission, military personnel, blood DNA methylation, stress-related disorders
- MeSH terms
- Humans, Military Personnel, Prospective Studies, Stress Disorders, Post-Traumatic, Genome, DNA Methylation
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