Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups

Ashley N. Clausen, Kelene A. Fercho, Molly Monsour, Seth G Disner, Lauren Salminen, Courtney C. Haswell, Emily Clarke Rubright, Amanda A. Watts, M. Nicole Buckley, Adi Maron-Katz, Anika Sierk, Antje Manthey, Benjamin Suarez-Jimenez, Bunmi O. Olatunji, Christopher L. Averill, David Hofmann, Dick J. Veltman, Elizabeth A. Olson, Gen Li, Gina L. ForsterHenrik Walter, Jacklynn Fitzgerald, Jean Théberge, Jeffrey S. Simons, Jessica A. Bomyea, Jessie L. Frijling, John H. Krystal, Justin T. Baker, K. Luan Phan, Kerry Ressler, Laura K.M. Han, Laura Nawijn, Lauren A.M. Lebois, Lianne Schmaal, Maria Densmore, Martha E. Shenton, Mirjam van Zuiden, Murray Stein, Negar Fani, Raluca M. Simons, Richard W.J. Neufeld, Ruth Lanius, Sanne van Rooij, Saskia B.J. Koch, Serena Bonomo, Tanja Jovanovic, Terri deRoon-Cassini, Timothy D. Ely, Vincent A. Magnotta, Xiaofu He, Chadi G. Abdallah, Amit Etkin, Christian Schmahl, Christine Larson, Isabelle M. Rosso, Jennifer Urbano Blackford, Jennifer S. Stevens, Judith K. Daniels, Julia Herzog, Milissa L. Kaufman, Miranda Olff, Richard J. Davidson, Scott R. Sponheim, Sven C. Mueller, Thomas Straube, Xi Zhu, Yuval Neria, Lee A. Baugh, James H. Cole, Paul M. Thompson, Rajendra A. Morey

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. Method: Adult subjects (N = 2229; 56.2% male) aged 18–69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA-PGC PTSD sites underwent T1-weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel-wise (brainageR) and region-of-interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age − chronological age) controlling for chronological age, sex, and scan site. Results: BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three-way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. Discussion: Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age-related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan.

Original languageEnglish (US)
Article numbere2413
JournalBrain and Behavior
Volume12
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
Department of Veterans Affairs via support for the National Center for PTSD; DoD W81XWH‐10‐1‐0925; Center for Brain and Behavior Research Pilot Grant; South Dakota Governor's Research Center Grant; Vanderbilt Psychiatric Genotype/Phenotype Project, and the Vanderbilt Institute for Clinical and Translational Research (through grant 1‐UL‐1‐TR000445 from the National Center for Research Resources/NIH); CX001600 VA CDA; MRC/UKRI Innovation Fellowship; German Research Foundation grant to Judith K. Daniels (numbers DA 1222/4‐1 and WA 1539/8‐2); NIMH R01‐MH043454; NIMH T32‐MH018931; VA RR&D IK2RX002922‐01A1; MH101380; National Institute of Mental Health training grant (T32MH13043); German Federal Ministry of Education and Research (BMBF RELEASE 01KR1303A); German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07); MH098212; MH071537; M01RR00039; UL1TR000454; HD071982; HD085850; R21MH112956; R01MH096987; Anonymous Women's Health Fund; Kasparian Fund; Trauma Scholars Fund; Barlow Family Fund; K01 MH118467; ZonMw, the Netherlands organization for Health Research and Development (40‐00812‐98‐10041) and a grant from the Academic Medical Center Research Council (110614) both awarded to Miranda Olff; NIAAA via support for (P50) Center for the Translational Neuroscience of Alcohol; NCATS via support of (CTSA) Yale Center for Clinical Investigation; CIHR; CIMVHR; NIH R01 MH106574; F32MH109274; VISN6 MIRECC; BOF 2–4 year project to Sven C. Mueller (01J05415); R01MH105355; National Institute of Mental Health F31 MH113271; NIMH K23MH112873; Veterans Affairs Merit Review Program (10/01/08–09/30/13); NHMRC Career Development Fellowship (1140764); DoD W81XWH08‐2‐0159 to Murray Stein; CDMRP, W81XWH‐08‐2‐0038; VA RR&D, I01RX000622; Narsad Young Investigator; German Research Society; K01 MH118428; Brain and Behavior Research Foundation Grant 07040. ENIGMA was also supported in part by NIH U54 EB020403 from the Big Data to Knowledge (BD2K) program, R56AG058854, R01MH116147, R01MH111671, and P41 EB015922. Writing of this paper was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the Durham VA Health Care System, and the Department of Veterans Affairs Mid‐Atlantic MIRECC. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the United States government, or any other funding sources listed here.

Funding Information:
Department of Veterans Affairs via support for the National Center for PTSD; DoD W81XWH-10-1-0925; Center for Brain and Behavior Research Pilot Grant; South Dakota Governor's Research Center Grant; Vanderbilt Psychiatric Genotype/Phenotype Project, and the Vanderbilt Institute for Clinical and Translational Research (through grant 1-UL-1-TR000445 from the National Center for Research Resources/NIH); CX001600 VA CDA; MRC/UKRI Innovation Fellowship; German Research Foundation grant to Judith K. Daniels (numbers DA 1222/4-1 and WA 1539/8-2); NIMH R01-MH043454; NIMH T32-MH018931; VA RR&D IK2RX002922-01A1; MH101380; National Institute of Mental Health training grant (T32MH13043); German Federal Ministry of Education and Research (BMBF RELEASE 01KR1303A); German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07); MH098212; MH071537; M01RR00039; UL1TR000454; HD071982; HD085850; R21MH112956; R01MH096987; Anonymous Women's Health Fund; Kasparian Fund; Trauma Scholars Fund; Barlow Family Fund; K01 MH118467; ZonMw, the Netherlands organization for Health Research and Development (40-00812-98-10041) and a grant from the Academic Medical Center Research Council (110614) both awarded to Miranda Olff; NIAAA via support for (P50) Center for the Translational Neuroscience of Alcohol; NCATS via support of (CTSA) Yale Center for Clinical Investigation; CIHR; CIMVHR; NIH R01 MH106574; F32MH109274; VISN6 MIRECC; BOF 2–4 year project to Sven C. Mueller (01J05415); R01MH105355; National Institute of Mental Health F31 MH113271; NIMH K23MH112873; Veterans Affairs Merit Review Program (10/01/08–09/30/13); NHMRC Career Development Fellowship (1140764); DoD W81XWH08-2-0159 to Murray Stein; CDMRP, W81XWH-08-2-0038; VA RR&D, I01RX000622; Narsad Young Investigator; German Research Society; K01 MH118428; Brain and Behavior Research Foundation Grant 07040. ENIGMA was also supported in part by NIH U54 EB020403 from the Big Data to Knowledge (BD2K) program, R56AG058854, R01MH116147, R01MH111671, and P41 EB015922. Writing of this paper was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the Durham VA Health Care System, and the Department of Veterans Affairs Mid-Atlantic MIRECC. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the United States government, or any other funding sources listed here.

Publisher Copyright:
© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC

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