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

A.N. Clausen; K.A. Fercho; M. Monsour; S.G. Disner; L.E. Salminen; C.C. Haswell; E.C. Rubright; A.A. Watts; M.N. Buckley; A. Maron-Katz; A. Sierk; A. Manthey; B. Suarez-Jimenez; B.O. Olatunji; C.L. Averill; D. Hofmann; D.J. Veltman; E.A. Olson; G. Li; G.L. Forster; H. Walter; J. Fitzgerald; J. Théberge; J.S. Simons; J.A. Bomyea; J.L. Frijling; J.H. Krystal; J.T. Baker; K.L. Phan; K. Ressler; L.K.M. Han; L. Nawijn; L.A.M. Lebois; L. Schmaal; M. Densmore; M.E. Shenton; Mirjam van Zuiden; M. Stein; N. Fani; R.M. Simons; R.W.J. Neufeld; R. Lanius; S. van Rooij; S.B.J. Koch; S. Bonomo; T. Jovanovic; T. deRoon-Cassini; T.D. Ely; V.A. Magnotta; X. He; C.G. Abdallah; A. Etkin; C. Schmahl; C. Larson; I.M. Rosso; J.U. Blackford; J.S. Stevens; J.K. Daniels; J. Herzog; M.L. Kaufman; M. Olff; R.J. Davidson; S.R. Sponheim; S.C. Mueller; T. Straube; X. Zhu; Y. Neria; L.A. Baugh; J.H. Cole; P.M. Thompson; R.A. Morey

doi:10.1002/brb3.2413

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

A.N. Clausen^*
, K.A. Fercho
, M. Monsour
, S.G. Disner
, L.E. Salminen
, C.C. Haswell
, E.C. Rubright
, A.A. Watts
, M.N. Buckley
, A. Maron-Katz
, A. Sierk
, A. Manthey
, B. Suarez-Jimenez
, B.O. Olatunji
, C.L. Averill
, D. Hofmann
, D.J. Veltman
, E.A. Olson
, G. Li
, G.L. Forster

H. Walter, J. Fitzgerald, J. Théberge, J.S. Simons, J.A. Bomyea, J.L. Frijling, J.H. Krystal, J.T. Baker, K.L. Phan, K. Ressler, L.K.M. Han, L. Nawijn, L.A.M. Lebois, L. Schmaal, M. Densmore, M.E. Shenton, Mirjam van Zuiden, M. Stein, N. Fani, R.M. Simons, R.W.J. Neufeld, R. Lanius, S. van Rooij, S.B.J. Koch, S. Bonomo, T. Jovanovic, T. deRoon-Cassini, T.D. Ely, V.A. Magnotta, X. He, C.G. Abdallah, A. Etkin, C. Schmahl, C. Larson, I.M. Rosso, J.U. Blackford, J.S. Stevens, J.K. Daniels, J. Herzog, M.L. Kaufman, M. Olff, R.J. Davidson, S.R. Sponheim, S.C. Mueller, T. Straube, X. Zhu, Y. Neria, L.A. Baugh, J.H. Cole, P.M. Thompson, R.A. Morey

^*Corresponding author for this work

Clinical Research Center
South Dakota State University
Duke University Brain Imaging and Analysis Center
University of Southern California
Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305;
University Medical Centre Charite
Columbia University Medical Center
Vanderbilt University
National Center for PTSD
University of Münster
Amsterdam University Medical Center
Harvard Medical School
University of Chinese Academy of Sciences
University of Otago
Marquette University
Western University
UC San Diego Department of Psychiatry
University of Amsterdam, VU University Amsterdam
Harvard University
Ohio State University
University of Melbourne
Department of Psychiatry
UC San Diego Department of Family Medicine and Public Health
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
New York State Psychiatric Institute
Wayne State University
Medical College of Wisconsin
University of Iowa
Medical Faculty Mannheim/Heidelberg University
University of Wisconsin-Milwaukee
University Medical Center Groningen
McLean Hospital/Harvard Medical School
ARQ National Psychotrauma Centrum
University of Wisconsin-Madison
University of Minnesota Medical School
Ghent University
University College London
University of Amsterdam

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Article number	e2413
Journal	Brain and Behavior
Volume	12
Issue number	1
DOIs	https://doi.org/10.1002/brb3.2413
Publication status	Published - Jan 2022
Externally published	Yes

Bibliographical note

Keywords

Adolescent
Adult
Aged
Aging
Brain/diagnostic imaging
Female
Humans
Machine Learning
Magnetic Resonance Imaging/methods
Male
Middle Aged
Stress Disorders, Post-Traumatic/diagnostic imaging
Young Adult

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Clausen, A. N., Fercho, K. A., Monsour, M., Disner, S. G., Salminen, L. E., Haswell, C. C., Rubright, E. C., Watts, A. A., Buckley, M. N., Maron-Katz, A., Sierk, A., Manthey, A., Suarez-Jimenez, B., Olatunji, B. O., Averill, C. L., Hofmann, D., Veltman, D. J., Olson, E. A., Li, G., ... Morey, R. A. (2022). Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups. Brain and Behavior, 12(1), Article e2413. https://doi.org/10.1002/brb3.2413

@article{ab03657efe7f451fb13f5cc94e8918e5,

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

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.",

keywords = "Adolescent, Adult, Aged, Aging, Brain/diagnostic imaging, Female, Humans, Machine Learning, Magnetic Resonance Imaging/methods, Male, Middle Aged, Stress Disorders, Post-Traumatic/diagnostic imaging, Young Adult",

author = "A.N. Clausen and K.A. Fercho and M. Monsour and S.G. Disner and L.E. Salminen and C.C. Haswell and E.C. Rubright and A.A. Watts and M.N. Buckley and A. Maron-Katz and A. Sierk and A. Manthey and B. Suarez-Jimenez and B.O. Olatunji and C.L. Averill and D. Hofmann and D.J. Veltman and E.A. Olson and G. Li and G.L. Forster and H. Walter and J. Fitzgerald and J. Th{\'e}berge and J.S. Simons and J.A. Bomyea and J.L. Frijling and J.H. Krystal and J.T. Baker and K.L. Phan and K. Ressler and L.K.M. Han and L. Nawijn and L.A.M. Lebois and L. Schmaal and M. Densmore and M.E. Shenton and \{van Zuiden\}, Mirjam and M. Stein and N. Fani and R.M. Simons and R.W.J. Neufeld and R. Lanius and \{van Rooij\}, S. and S.B.J. Koch and S. Bonomo and T. Jovanovic and T. deRoon-Cassini and T.D. Ely and V.A. Magnotta and X. He and C.G. Abdallah and A. Etkin and C. Schmahl and C. Larson and I.M. Rosso and J.U. Blackford and J.S. Stevens and J.K. Daniels and J. Herzog and M.L. Kaufman and M. Olff and R.J. Davidson and S.R. Sponheim and S.C. Mueller and T. Straube and X. Zhu and Y. Neria and L.A. Baugh and J.H. Cole and P.M. Thompson and R.A. Morey",

note = "{\textcopyright} 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.",

year = "2022",

month = jan,

doi = "10.1002/brb3.2413",

language = "English",

volume = "12",

journal = "Brain and Behavior",

issn = "2157-9032",

publisher = "John Wiley and Sons Ltd",

number = "1",

}

Clausen, AN, Fercho, KA, Monsour, M, Disner, SG, Salminen, LE, Haswell, CC, Rubright, EC, Watts, AA, Buckley, MN, Maron-Katz, A, Sierk, A, Manthey, A, Suarez-Jimenez, B, Olatunji, BO, Averill, CL, Hofmann, D, Veltman, DJ, Olson, EA, Li, G, Forster, GL, Walter, H, Fitzgerald, J, Théberge, J, Simons, JS, Bomyea, JA, Frijling, JL, Krystal, JH, Baker, JT, Phan, KL, Ressler, K, Han, LKM, Nawijn, L, Lebois, LAM, Schmaal, L, Densmore, M, Shenton, ME, van Zuiden, M, Stein, M, Fani, N, Simons, RM, Neufeld, RWJ, Lanius, R, van Rooij, S, Koch, SBJ, Bonomo, S, Jovanovic, T, deRoon-Cassini, T, Ely, TD, Magnotta, VA, He, X, Abdallah, CG, Etkin, A, Schmahl, C, Larson, C, Rosso, IM, Blackford, JU, Stevens, JS, Daniels, JK, Herzog, J, Kaufman, ML, Olff, M, Davidson, RJ, Sponheim, SR, Mueller, SC, Straube, T, Zhu, X, Neria, Y, Baugh, LA, Cole, JH, Thompson, PM & Morey, RA 2022, 'Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups', Brain and Behavior, vol. 12, no. 1, e2413. https://doi.org/10.1002/brb3.2413

TY - JOUR

T1 - Assessment of brain age in posttraumatic stress disorder

T2 - Findings from the ENIGMA PTSD and brain age working groups

AU - Clausen, A.N.

AU - Fercho, K.A.

AU - Monsour, M.

AU - Disner, S.G.

AU - Salminen, L.E.

AU - Haswell, C.C.

AU - Rubright, E.C.

AU - Watts, A.A.

AU - Buckley, M.N.

AU - Maron-Katz, A.

AU - Sierk, A.

AU - Manthey, A.

AU - Suarez-Jimenez, B.

AU - Olatunji, B.O.

AU - Averill, C.L.

AU - Hofmann, D.

AU - Veltman, D.J.

AU - Olson, E.A.

AU - Li, G.

AU - Forster, G.L.

AU - Walter, H.

AU - Fitzgerald, J.

AU - Théberge, J.

AU - Simons, J.S.

AU - Bomyea, J.A.

AU - Frijling, J.L.

AU - Krystal, J.H.

AU - Baker, J.T.

AU - Phan, K.L.

AU - Ressler, K.

AU - Han, L.K.M.

AU - Nawijn, L.

AU - Lebois, L.A.M.

AU - Schmaal, L.

AU - Densmore, M.

AU - Shenton, M.E.

AU - van Zuiden, Mirjam

AU - Stein, M.

AU - Fani, N.

AU - Simons, R.M.

AU - Neufeld, R.W.J.

AU - Lanius, R.

AU - van Rooij, S.

AU - Koch, S.B.J.

AU - Bonomo, S.

AU - Jovanovic, T.

AU - deRoon-Cassini, T.

AU - Ely, T.D.

AU - Magnotta, V.A.

AU - He, X.

AU - Abdallah, C.G.

AU - Etkin, A.

AU - Schmahl, C.

AU - Larson, C.

AU - Rosso, I.M.

AU - Blackford, J.U.

AU - Stevens, J.S.

AU - Daniels, J.K.

AU - Herzog, J.

AU - Kaufman, M.L.

AU - Olff, M.

AU - Davidson, R.J.

AU - Sponheim, S.R.

AU - Mueller, S.C.

AU - Straube, T.

AU - Zhu, X.

AU - Neria, Y.

AU - Baugh, L.A.

AU - Cole, J.H.

AU - Thompson, P.M.

AU - Morey, R.A.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aging

KW - Brain/diagnostic imaging

KW - Female

KW - Humans

KW - Machine Learning

KW - Magnetic Resonance Imaging/methods

KW - Male

KW - Middle Aged

KW - Stress Disorders, Post-Traumatic/diagnostic imaging

KW - Young Adult

U2 - 10.1002/brb3.2413

DO - 10.1002/brb3.2413

M3 - Article

C2 - 34907666

SN - 2157-9032

VL - 12

JO - Brain and Behavior

JF - Brain and Behavior

IS - 1

M1 - e2413

ER -

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

Abstract

Bibliographical note

Keywords

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