Erika J Wolf1, Hannah Maniates2, Nicole Nugent3, Adam X Maihofer4, Don Armstrong5, Andrew Ratanatharathorn6, Allison E Ashley-Koch7, Melanie Garrett8, Nathan A Kimbrel9, Adriana Lori10, Allison E Aiello11, Dewleen G Baker12, Jean C Beckham9, Marco P Boks13, Sandro Galea14, Elbert Geuze15, Michael A Hauser7, Ronald C Kessler16, Karestan C Koenen17, Mark W Miller18, Kerry J Ressler19, Victoria Risbrough12, Bart P F Rutten20, Murray B Stein21, Robert J Ursano22, Eric Vermetten23, Christiaan H Vinkers13, Monica Uddin24, Alicia K Smith25, Caroline M Nievergelt12, Mark W Logue26. 1. National Center for PTSD at VA Boston Healthcare System, United States; Department of Psychiatry, Boston University School of Medicine, United States. Electronic address: erika.wolf@va.gov. 2. National Center for PTSD at VA Boston Healthcare System, United States. 3. Bradley Hasbro Children's Research Center, Rhode Island Hospital, United States; Departments of Psychiatry and Human Behavior and Pediatrics, Brown Medical School, United States. 4. University of California San Diego, Department of Psychiatry, United States. 5. University of Illinois Urbana-Champaign, Carl R. Woese Institute for Genomic Biology, United States. 6. Columbia University, Department of Epidemiology, United States. 7. Duke Molecular Physiology Institute, Duke University School of Medicine, United States. 8. Department of Psychiatry & Behavioral Sciences, Duke University Medical Center, United States. 9. Department of Psychiatry & Behavioral Sciences, Duke University Medical Center, United States; VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center, United States; Durham VA Medical Center, United States. 10. Department of Psychiatry and Behavioral Sciences, Emory University, United States. 11. Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, United States. 12. University of California San Diego, Department of Psychiatry, United States; Veterans Affairs San Diego Healthcare System, United States; Veterans Affairs Center of Excellence for Stress and Mental Health, United States. 13. University Medical Center Utrecht, Brain Center Rudolf Magnus, Department of Psychiatry, Utrecht, The Netherlands. 14. Boston University School of Public Health, United States. 15. University Medical Center Utrecht, Brain Center Rudolf Magnus, Department of Psychiatry, Utrecht, The Netherlands; Ministry of Defence, Military Mental Healthcare, Utrecht, The Netherlands. 16. Harvard Medical School, Department of Health Care Policy, United States. 17. Harvard T.H. Chan School of Public Health, Department of Epidemiology, United States; Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, and Department of Psychiatry, United States. 18. National Center for PTSD at VA Boston Healthcare System, United States; Department of Psychiatry, Boston University School of Medicine, United States. 19. Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, United States. 20. School for Mental Health and Neuroscience and the European Graduate School of Neuroscience (EURON), Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands. 21. University of California San Diego, Department of Psychiatry, United States; Veterans Affairs San Diego Healthcare System, United States; University of California San Diego, Department of Family Medicine and Public Health, United States. 22. Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, United States. 23. University Medical Center Utrecht, Brain Center Rudolf Magnus, Department of Psychiatry, Utrecht, The Netherlands; Ministry of Defence, Military Mental Healthcare, Utrecht, The Netherlands; Arq Psychotrauma Expert Group, The Netherlands. 24. University of Illinois Urbana-Champaign, Carl R. Woese Institute for Genomic Biology, United States; University of Illinois Urbana-Champaign, Department of Psychology, United States. 25. Department of Psychiatry and Behavioral Sciences, Emory University, United States; Department of Gynecology and Obstetrics, Emory University, United States. 26. National Center for PTSD at VA Boston Healthcare System, United States; Department of Psychiatry, Boston University School of Medicine, United States; Biomedical Genetics, Boston University School of Medicine, United States.
Abstract
BACKGROUND: Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. METHODS: We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. RESULTS: Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex, CD4T cell proportions, and natural killer cell proportions were also significantly associated with accelerated DNA methylation age (all ps < 0.02). PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA methylation age. There was no evidence of moderation of the trauma or PTSD variables by demographic factors. CONCLUSIONS: Results suggest that traumatic stress is associated with advanced epigenetic age and raise the possibility that cells integral to immune system maintenance and responsivity play a role in this. This study highlights the need for additional research into the biological mechanisms linking traumatic stress to accelerated DNA methylation age and the importance of furthering our understanding of the neurobiological and health consequences of PTSD. Published by Elsevier Ltd.
BACKGROUND: Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. METHODS: We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. RESULTS: Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex, CD4T cell proportions, and natural killer cell proportions were also significantly associated with accelerated DNA methylation age (all ps < 0.02). PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA methylation age. There was no evidence of moderation of the trauma or PTSD variables by demographic factors. CONCLUSIONS: Results suggest that traumatic stress is associated with advanced epigenetic age and raise the possibility that cells integral to immune system maintenance and responsivity play a role in this. This study highlights the need for additional research into the biological mechanisms linking traumatic stress to accelerated DNA methylation age and the importance of furthering our understanding of the neurobiological and health consequences of PTSD. Published by Elsevier Ltd.
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