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 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

*Corresponding author for this work

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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
Article numbere2413
Number of pages14
JournalBrain and Behavior
Volume12
Issue number1
Early online date14-Dec-2021
DOIs
Publication statusPublished - Jan-2022

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