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Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

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

Posted 26 Feb 2019
bioRxiv DOI: 10.1101/560623 (published DOI: 10.1038/s41380-020-0754-0)

Background: 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 MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset. Methods: We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 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). Findings: On average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen's d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004). Interpretation: This highly powered collaborative effort showed subtle patterns of abnormal structural brain aging 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 predictive value of these brain-PAD estimates.

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