Traumatic stress and accelerated DNA methylation age: A meta-analysis

PSYCHONEUROENDOCRINOLOGY

卷:92

Article

Wolf, Erika J.^1,2  Maniates, Hannah¹  Nugent, Nicole^3,4  Maihofer, Adam X.⁵  Armstrong, Don⁶  Ratanatharathorn, Andrew⁷  Ashley-Koch, Allison E.⁸  Garrett, Melanie⁹  Kimbrel, Nathan A.^9,10,11  Lori, Adriana¹²  Aiello, Allison E.¹³  Baker, Dewleen G.^5,14,15  Beckham, Jean C.^9,10,11  Boks, Marco P.¹⁶  Galea, Sandro¹⁷  Geuze, Elbert^16,18  Hauser, Michael A.⁸  Kessler, Ronald C.¹⁹  Koenen, Karestan C.^20,21,22  Miller, Mark W.^1,2  Ressler, Kerry J.²³  Risbrough, Victoria^5,14,15  Rutten, Bart P. P.^24,25  Stein, Murray B.^5,14,26  Ursano, Robert J.²⁷  Vermetten, Eric^16,18,28  Vinkers, Christiaan H.¹⁶  Uddin, Monica^6,29  Smith, Alicia K.^12,30  Nievergelt, Caroline M.^5,14,15  Logue, Mark W.^1,2,3,31 

[1] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA

[2] Boston Univ, Sch Med, Dept Psychiat, Boston, MA USA

[3] Rhode Isl Hosp, Bradley Hasbro Childrens Res Ctr, Providence, RI USA

[4] Brown Med Sch, Dept Psychiat & Human Behav & Pediat, Providence, RI USA

[5] Univ Calif San Diego, Dept Psychiat, San Diego, CA USA

[6] Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL USA

[7] Columbia Univ, Dept Epidemiol, New York, NY USA

[8] Duke Univ, Sch Med, Duke Mol Physiol Inst, Durham, NC USA

[9] Duke Univ, Metr Ctr, Dept Psychiat & Behav Sci, Durham, NC USA

[10] VA Mid Atlantic, Mental Illness Res Educ & Clin Ctr, New York, NY USA

[11] Durham VA Med Ctr, Durham, NC USA

[12] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA USA

[13] Univ N Carolina, Chapel Hill Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA

[14] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA

[15] Vet Affairs Ctr Excellence Stress & Mental Hlth, San Diego, CA USA

[16] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, Utrecht, Netherlands

[17] Boston Univ, Sch Publ Hlth, Boston, MA USA

[18] Minist Def, Mil Mental Healthcare, Utrecht, Netherlands

[19] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA

[20] Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[21] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA

[22] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA

[23] Harvard Med Sch, Dept Psychiat, Belmont, MA USA

[24] Maastricht Univ, Med Ctr, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands

[25] Maastricht Univ, Med Ctr, European Grad Sch Neurosci EURON, Dept Psychiat & Neuropsychol, Maastricht, Netherlands

[26] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA USA

[27] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Dept Psychiat, Bethesda, MD USA

[28] Arq Psychotrauma Expert Grp, Diemen, Netherlands

[29] Univ Illinois, Dept Psychol, Urbana, IL USA

[30] Emory Univ, Dept Gynecol & Obstet, Atlanta, GA USA

[31] Boston Univ, Sch Med, Biomed Genet, Boston, MA USA

关键词: DNA methylation;    Traumatic stress;    PTSD;    Accelerated aging;    Meta-analysis;    Epigenetic clock;   

DOI  :  10.1016/j.psyneuen.2017.12.007

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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