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

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 ORCID:, Chaim-Avancini, Tiffany M., Elvsåshagen, Torbjørn, Favre, Pauline, Foley, Sonya F. ORCID:, 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. and Schmaal, Lianne 2020. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group. Molecular Psychiatry 26 , pp. 5124-5139. 10.1038/s41380-020-0754-0

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Cardiff University Brain Research Imaging Centre (CUBRIC)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Springer Nature
ISSN: 1359-4184
Date of First Compliant Deposit: 12 June 2020
Date of Acceptance: 23 June 2020
Last Modified: 05 May 2023 08:29

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