PTSD and epigenetic aging: a longitudinal meta-analysis
Psychological Medicine, vol. 55, pp. e142
Abstract
Abstract Background Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points. Methods We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367). Results Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals. Conclusions Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
Authors 37
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Affiliation as printed
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
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Affiliation as printed
Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA
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Boston University · VA Boston Healthcare System
Affiliation as printed
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA
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Boston University · VA Boston Healthcare System
Affiliation as printed
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA
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Affiliation as printed
Department of Emergency Medicine, Alpert Brown Medical School, Providence, RI, USA
Department of Pediatrics, Alpert Brown Medical School, Providence, RI, USA
Department of Psychiatry and Human Behavior, Alpert Brown Medical School, Providence, RI, USA
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Affiliation as printed
Genomics Program, University of South Florida College of Public Health, Tampa, FL, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
Carolina Stress Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Affiliation as printed
Department of Epidemiology, Robert N Butler Columbia Aging Center, Columbia University, New York, NY, USA
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University of California San Diego
Affiliation as printed
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht, Netherlands
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Affiliation as printed
Translational Sciences, Biogen Inc., Cambridge, MA, USA
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Harvard University · VA Boston Healthcare System
Affiliation as printed
Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA
Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, USA
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Yale University · VA Connecticut Healthcare System
Affiliation as printed
Department of Genetics and Neuroscience, Yale University School of Medicine, New Haven, CT, USA
Psychiatry Service, VA Connecticut Healthcare Center, West Haven, CT, USA
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Utrecht University · University Medical Center Utrecht · Ministry of Defence
Affiliation as printed
Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, Netherlands
Netherlands Ministry of Defence, Brain Research and Innovation Centre, Utrecht, Netherlands
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Broad Institute · Harvard University · Massachusetts General Hospital · Stanley Center for Psychiatric Research
Affiliation as printed
Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Amsterdam UMC Location University of Amsterdam · Amsterdam Neuroscience · Amsterdam Public Health · Amsterdam University Medical Centers
Affiliation as printed
Amsterdam Neuroscience Research Institute, Mood, Anxiety, Psychosis, Stress & Sleep Program, Amsterdam University Medical Center, Amsterdam, Netherlands
Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, Netherlands
Mental Health Program, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands
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University of California San Diego · VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
Affiliation as printed
Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Harvard University · VA Boston Healthcare System
Affiliation as printed
Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA
Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, USA
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Harvard University · Columbia University
Affiliation as printed
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Harvard University · Emory University · McLean Hospital
Affiliation as printed
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA
Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA
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University of California San Diego · VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
Affiliation as printed
Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
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Broad Institute · Maastricht University Medical Centre · Maastricht University · Stanley Center for Psychiatric Research
Affiliation as printed
Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA
School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht Universitair Medisch Centrum, Maastricht, Netherlands
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Broad Institute · Massachusetts General Hospital · Stanley Center for Psychiatric Research
Affiliation as printed
Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA
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University of California San Diego · VA San Diego Healthcare System
Affiliation as printed
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
School of Public Health, University of California San Diego, La Jolla, CA, USA
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Uniformed Services University of the Health Sciences
Affiliation as printed
Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of Health Sciences, Bethesda, MD, USA
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Leiden University Medical Center · NYU Langone Health · New York University
Affiliation as printed
Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands
Department of Psychiatry, New York University School of Medicine, New York, NY, USA
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience Research Institute, Mood, Anxiety, Psychosis, Stress & Sleep Program, Amsterdam University Medical Center, Amsterdam, Netherlands
Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
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Affiliation as printed
Survey Research Center, University of Michigan, Ann Arbor, MI, USA
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Affiliation as printed
Genomics Program, University of South Florida College of Public Health, Tampa, FL, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Boston University · VA Boston Healthcare System · University of California San Diego · VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
Affiliation as printed
Department of Biomedical Genetics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA
Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
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Emory University · University of California San Diego · VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
Affiliation as printed
Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA
Department of Human Genetics, Emory University, Atlanta, GA, USA
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA
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Emory University · University of South Florida
Affiliation as printed
Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA
Department of Human Genetics, Emory University, Atlanta, GA, USA
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA
Genomics Program, University of South Florida College of Public Health, Tampa, FL, USA
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Boston University · University of South Florida · VA Boston Healthcare System
Affiliation as printed
Genomics Program, University of South Florida College of Public Health, Tampa, FL, USA
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA
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Erika J. Wolf corresponding
Boston University · VA Boston Healthcare System
Affiliation as printed
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA
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