Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
Authors: Han Laura K. M. , Dinga Richard , Hahn Tim , Ching Christopher R. K. , Eyler Lisa T. , Aftanas Lyubomir , Aghajani Moji , Aleman André , Baune Bernhard T. , Berger Klaus , Brak Ivan , Filho Geraldo Busatto , Carballedo Angela , Connolly Colm G. , Couvy-Duchesne Baptiste , Cullen Kathryn R. , Dannlowski Udo , Davey Christopher G. , Dima Danai , Duran Fabio L. S. , Enneking Verena , Filimonova Elena , Frenzel Stefan , Frodl Thomas , Fu Cynthia H. Y. , Godlewska Beata R. , Gotlib Ian H. , Grabe Hans J. , Groenewold Nynke A. , Grotegerd Dominik , Gruber Oliver , Hall Geoffrey B. , Harrison Ben J. , Hatton Sean N. , Hermesdorf Marco , Hickie Ian B. , Ho Tiffany C. , Hosten Norbert , Jansen Andreas , Kähler Claas , Kircher Tilo , Klimes-Dougan Bonnie , Krämer Bernd , Krug Axel , Lagopoulos Jim , Leenings Ramona , MacMaster Frank P. , MacQueen Glenda , McIntosh Andrew , McLellan Quinn , McMahon Katie L. , Medland Sarah E. , Mueller Bryon A. , Mwangi Benson , Osipov Evgeny , Portella Maria J. , Pozzi Elena , Reneman Liesbeth , Repple Jonathan , Rosa Pedro G. P. , Sacchet Matthew D. , Sämann Philipp G. , Schnell Knut , Schrantee Anouk , Simulionyte Egle , Soares Jair C. , Sommer Jens , Stein Dan J. , Steinsträter Olaf , Strike Lachlan T. , Thomopoulos Sophia I. , van Tol Marie-José , Veer Ilya M. , Vermeiren Robert R. J. M. , Walter Henrik , van der Wee Nic J. A. , van der Werff Steven J. A. , Whalley Heather , Winter Nils R. , Wittfeld Katharina , Wright Margaret J. , Wu Mon-Ju , Völzke Henry , Yang Tony T. , Zannias Vasileios , de Zubicaray Greig I. , Zunta-Soares Giovana B. , Abé Christoph , Alda Martin , Andreassen Ole A. , Bøen Erlend , Bonnin Caterina M. , Canales-Rodriguez Erick J. , Cannon Dara , Caseras Xavier , Chaim-Avancini Tiffany M. , Elvsåshagen Torbjørn , Favre Pauline , Foley Sonya F. , Fullerton Janice M. , Goikolea Jose M. , Haarman Bartholomeus C. M. , Hajek Tomas , Henry Chantal , Houenou Josselin , Howells Fleur M. , Ingvar Martin , Kuplicki Rayus , Lafer Beny , Landén Mikael , Machado-Vieira Rodrigo , Malt Ulrik F. , McDonald Colm , Mitchell Philip B. , Nabulsi Leila , Otaduy Maria Concepcion Garcia , Overs Bronwyn J. , Polosan Mircea , Pomarol-Clotet Edith , Radua Joaquim , Rive Maria M. , Roberts Gloria , Ruhe Henricus G. , Salvador Raymond , Sarró Salvador , Satterthwaite Theodore D. , Savitz Jonathan , Schene Aart H. , Schofield Peter R. , Serpa Mauricio H. , Sim Kang , Soeiro-de-Souza Marcio Gerhardt , Sutherland Ashley N. , Temmingh Henk S. , Timmons Garrett M. , Uhlmann Anne , Vieta Eduard , Wolf Daniel H. , Zanetti Marcus V. , Jahanshad Neda , Thompson Paul M. , Veltman Dick J. , Penninx Brenda W. J. H. , Marquand Andre F. , Cole James H. , Schmaal Lianne 
Published: May 2020

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.