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

2020; Springer Nature; Volume: 26; Issue: 9 Linguagem: Inglês

10.1038/s41380-020-0754-0

1476-5578

Laura K. M. Han, Richard Dinga, Tim Hahn, Christopher R. K. Ching, Lisa T. Eyler, Lyubomir I. Aftanas, Moji Aghajani, André Alemán, Bernhard T. Baune, Klaus Berger, И. В. Брак, Geraldo F. Busatto, Angela Carballedo, Colm G. Connolly, Baptiste Couvy‐Duchesne, Kathryn R. Cullen, Udo Dannlowski, Christopher G. Davey, Danai Dima, Fábio 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 B. 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 E. Medland, Bryon A. Mueller, Benson Mwangi, Evgeny Osipov, Marı́a 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 Vermeiren, Henrik Walter, Nic J.A. van der Wee, Steven J.A. van der Werff, Heather C. Whalley, Nils R. Winter, Katharina Wittfeld, Margaret J. Wright, Mon‐Ju Wu, Henry Völzke, Tony T. Yang, Vasileios Zannias, Greig I. de Zubicaray, Giovana Zunta‐Soares, Christoph Abé, Martin Alda, Ole A. Andreassen, Erlend Bøen, Caterina del Mar Bonnín, Erick J. Canales‐Rodríguez, Dara M. Cannon, Xavier Caseras, Tiffany M. Chaim‐Avancini, Torbjørn Elvsåshagen, Pauline Favre, Sonya Foley, Janice M. Fullerton, José Manuel Goikolea, Bartholomeus C. M. Haarman, Tomáš Hájek, Chantal Henry, Josselin Houenou, Fleur M. Howells, Martin Ingvar, Rayus Kuplicki, Beny Lafer, Mikael Landén, Rodrigo Machado‐Vieira, Ulrik Fredrik Malt, Colm McDonald, Philip B. Mitchell, Leila Nabulsi, Maria Concepción García Otaduy, Bronwyn J. Overs, Mircea Polosan, Edith Pomarol‐Clotet, Joaquim Raduà, Maria M. Rive, Gloria Roberts, Henricus G. Ruhé, Raymond Salvador, Salvador Sarró, Theodore D. Satterthwaite, Jonathan Savitz, Aart H. Schene, Peter R. Schofield, Maurício H. Serpa, Kang Sim, Márcio Gerhardt Soeiro‐de‐Souza, Ashley Sutherland, Henk Temmingh, Garrett Timmons, Anne Uhlmann, Eduard Vieta, Daniel H. Wolf, Marcus V. Zanetti, Neda Jahanshad, Paul M. Thompson, Dick J. Veltman, Brenda W.J.H. Penninx, André F. Marquand, James H. Cole, Lianne Schmaal,

Tryptophan and brain disorders

Abstract 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.