TY - JOUR

T1 - Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

AU - The ENIGMA-MDD DTI Working Group

AU - Han, Laura K.M.

AU - Dinga, Richard

AU - Hahn, Tim

AU - Ching, Christopher R.K.

AU - Eyler, Lisa T.

AU - Aftanas, Lyubomir

AU - Aghajani, Moji

AU - Aleman, André

AU - Baune, Bernhard T.

AU - Berger, Klaus

AU - Brak, Ivan

AU - Filho, Geraldo Busatto

AU - Carballedo, Angela

AU - Connolly, Colm G.

AU - Couvy-Duchesne, Baptiste

AU - Cullen, Kathryn R.

AU - Dannlowski, Udo

AU - Davey, Christopher G.

AU - Dima, Danai

AU - Duran, Fabio L.S.

AU - Enneking, Verena

AU - Filimonova, Elena

AU - Frenzel, Stefan

AU - Frodl, Thomas

AU - Fu, Cynthia H.Y.

AU - Godlewska, Beata R.

AU - Gotlib, Ian H.

AU - Grabe, Hans J.

AU - Groenewold, Nynke A.

AU - Grotegerd, Dominik

AU - Gruber, Oliver

AU - Hall, Geoffrey B.

AU - Harrison, Ben J.

AU - Hatton, Sean N.

AU - Hermesdorf, Marco

AU - Hickie, Ian B.

AU - Ho, Tiffany C.

AU - Hosten, Norbert

AU - Jansen, Andreas

AU - Kähler, Claas

AU - Kircher, Tilo

AU - Klimes-Dougan, Bonnie

AU - Krämer, Bernd

AU - Krug, Axel

AU - Lagopoulos, Jim

AU - Leenings, Ramona

AU - MacMaster, Frank P.

AU - MacQueen, Glenda

AU - McIntosh, Andrew

AU - McLellan, Quinn

PY - 2021/9

Y1 - 2021/9

N2 - Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

AB - Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aging

KW - Brain/diagnostic imaging

KW - Depressive Disorder, Major

KW - Female

KW - Humans

KW - Longitudinal Studies

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85085208849&partnerID=8YFLogxK

U2 - 10.1038/s41380-020-0754-0

DO - 10.1038/s41380-020-0754-0

M3 - Article

C2 - 32424236

AN - SCOPUS:85085208849

VL - 26

SP - 5124

EP - 5139

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 9

ER -