Ashley N. Clausen, Duke University
Kelene A. Fercho, University of South Dakota
Molly Monsour, Duke University
Seth Disner, University of Minnesota Medical School
Lauren Salminen, University of Southern California
Courtney C. Haswell, Duke University
Emily Clarke Rubright, Duke University
Amanda A. Watts, Duke University
M. Nicole Buckley, Duke University
Adi Maron-Katz, Stanford University of Medicine
Anika Sierk, University Medical Centre Charite
Antje Manthey, University Medical Centre Charite
Benjamin Suarez-Jimenez, Columbia University Medical Center
Bunmi O. Olatunji, Vanderbilt University
Christopher L. Averill, Yale University School of Medicine
David Hofmann, University of Muenster
Dick J. Veltman, Amsterdam University Medical Centers
Elizabeth A. Olson, Harvard Medical School
Gen Li, University of Chinese Academy of Sciences
Gina L. Forster, University of Otago
Henrik Walter, University Medical Centre Charite
Jacklynn M. Fitzgerald, Marquette UniversityFollow
Jean Théberge, University of Western Ontario
Jeffrey S. Simons, University of South Dakota
Jessica A. Bomyea, University of Southern California - San Diego
Jessie L. Frijling, Amsterdam University Medical Centers
John H. Krystal, National Center for PTSD
Justin T. Baker, Harvard University
K. Luan Phan, Ohio State University
Kerry Ressler, Harvard Medical School
Laura K. M. Han, Amsterdam University Medical Centers
Laura Nawijn, Amsterdam University Medical Centers
Lauren A. M. Lebois, Harvard Medical School
Lianne Schmaal, University of Melbourne
Maria Densmore, Western University
Martha E. Shenton, Harvard Medical School
Mirjam Van Zuiden, Amsterdam University Medical Centers
Murray Stein, University of Southern California - San Diego
Negar Fani, Emory University School of Medicine
Raluca M. Simons, University of South Dakota
Richard W. J. Neufeld, Western University
Ruth Lanius, Western University
Sanne Van Rooij, Emory University School of Medicine
Sadkia B. J. Koch, Amsterdam University Medical Centers
Serena Bonomo, New York State Psychiatric Institute
Tanja Jovanovic, Wayne State University
Terri A deRoon-Cassini, Medical College of WisconsinFollow
Timothy D. Ely, Emory University School of Medicine
Vincent A. Magnotta, University of Iowa
Xiaofu He, Columbia University Medical Center
Chadi G. Abdallah, National Center for PTSD
Amit Etkin, Stanford University of Medicine
Christian Schmahl, Heidelberg University
Christine L. Larson, University of Wisconsin - Milwaukee
Isabelle M. Rosso, Harvard Medical School
Jennifer Urbano Blackford, Vanderbilt University Medical Center
Jennifer S. Stevens, Emory University School of Medicine
Judith K. Daniels, University of Groningen
Julia Herzog, Heidelberg University
Milissa L. Kaufman, McLean Hospital
Miranda Olff, ARQ National Psychotrauma Centrum
Richard J. Davidson, University of Wisconsin - Madison
Scott R. Sponheim, University of Minnesota - MinneapolisFollow
Sven C. Mueller, Ghent University
Thomas Straube, University of Muenster
Xi Zhu, Columbia University Medical Center
Yuval Neria, Columbia University Medical Center
Lee A. Baugh, University of South Dakota
James H. Cole, University College London
Paul M. Thompson, University of Southern California
Rajendra A. Morey, Duke University

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Wiley Open Access

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Brain and Behavior

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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.


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.


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.


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.


Published version. Brain and Behavior, Vol. 12, No. 1 (January 2022): e2413. DOI. © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC. Used with permission.

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