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

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

Posted 26 Feb 2019
bioRxiv DOI: 10.1101/560623

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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