This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. 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). 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. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). 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. 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. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. 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. Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. Timmons, Anne Uhlmann, Eduard Vieta, Daniel H. Serpa, Kang Sim, Marcio Gerhardt Soeiro-de-Souza, Ashley N. Ruhe, Raymond Salvador, Salvador Sarró, Theodore D. Overs, Mircea Polosan, Edith Pomarol-Clotet, Joaquim Radua, Maria M. Mitchell, Leila Nabulsi, Maria Concepcion Garcia Otaduy, Bronwyn J. Howells, Martin Ingvar, Rayus Kuplicki, Beny Lafer, Mikael Landén, Rodrigo Machado-Vieira, Ulrik F. Haarman, Tomas Hajek, Chantal Henry, Josselin Houenou, Fleur M. Chaim-Avancini, Torbjørn Elvsåshagen, Pauline Favre, Sonya F. Canales-Rodriguez, Dara Cannon, Xavier Caseras, Tiffany M. Zunta-Soares, Christoph Abé, Martin Alda, Ole A. Sämann, Knut Schnell, Anouk Schrantee, Egle Simulionyte, Jair C. Portella, Elena Pozzi, Liesbeth Reneman, Jonathan Repple, Pedro G.P. Mueller, Benson Mwangi, Evgeny Osipov, Maria J.
MacMaster, Glenda MacQueen, Andrew McIntosh, Quinn McLellan, Katie L. Ho, Norbert Hosten, Andreas Jansen, Claas Kähler, Tilo Kircher, Bonnie Klimes-Dougan, Bernd Krämer, Axel Krug, Jim Lagopoulos, Ramona Leenings, Frank P. Groenewold, Dominik Grotegerd, Oliver Gruber, Geoffrey B. Duran Show 126 others Show less Verena Enneking, Elena Filimonova, Stefan Frenzel, Thomas Frodl, Cynthia H.Y. Connolly, Baptiste Couvy-Duchesne, Kathryn R. Baune, Klaus Berger, Ivan Brak, Geraldo Busatto Filho, Angela Carballedo, Colm G.
Eyler, Lyubomir Aftanas, Moji Aghajani, André Aleman, Bernhard T. Han, Richard Dinga, Tim Hahn, Christopher R.K.
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