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.
Original language | English |
---|---|
Pages (from-to) | 5124-5139 |
Number of pages | 16 |
Journal | Molecular psychiatry |
Volume | 26 |
Issue number | 9 |
Early online date | 18 May 2020 |
DOIs | |
Publication status | Published - Sept 2021 |
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In: Molecular psychiatry, Vol. 26, No. 9, 09.2021, p. 5124-5139.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Brain aging in major depressive disorder
T2 - results from the ENIGMA major depressive disorder working group
AU - Han, Laura K.M.
AU - Dinga, Richard
AU - Hahn, Tim
AU - Ching, Christopher R.K.
AU - Eyler, Lisa T.
AU - Aftanas, Lyubomir
AU - Aghajani, Moji
AU - Aleman, André
AU - Baune, Bernhard T.
AU - Berger, Klaus
AU - Brak, Ivan
AU - Filho, Geraldo Busatto
AU - Carballedo, Angela
AU - Connolly, Colm G.
AU - Couvy-Duchesne, Baptiste
AU - Cullen, Kathryn R.
AU - Dannlowski, Udo
AU - Davey, Christopher G.
AU - Dima, Danai
AU - Duran, Fabio L.S.
AU - Enneking, Verena
AU - Filimonova, Elena
AU - Frenzel, Stefan
AU - Frodl, Thomas
AU - Fu, Cynthia H.Y.
AU - Godlewska, Beata R.
AU - Gotlib, Ian H.
AU - Grabe, Hans J.
AU - Groenewold, Nynke A.
AU - Grotegerd, Dominik
AU - Gruber, Oliver
AU - Hall, Geoffrey B.
AU - Harrison, Ben J.
AU - Hatton, Sean N.
AU - Hermesdorf, Marco
AU - Hickie, Ian B.
AU - Ho, Tiffany C.
AU - Hosten, Norbert
AU - Jansen, Andreas
AU - Kähler, Claas
AU - Kircher, Tilo
AU - Klimes-Dougan, Bonnie
AU - Krämer, Bernd
AU - Krug, Axel
AU - Lagopoulos, Jim
AU - Leenings, Ramona
AU - MacMaster, Frank P.
AU - MacQueen, Glenda
AU - McIntosh, Andrew
AU - McLellan, Quinn
AU - McMahon, Katie L.
AU - Medland, Sarah E.
AU - Mueller, Bryon A.
AU - Mwangi, Benson
AU - Osipov, Evgeny
AU - Portella, Maria J.
AU - Pozzi, Elena
AU - Reneman, Liesbeth
AU - Repple, Jonathan
AU - Rosa, Pedro G.P.
AU - Sacchet, Matthew D.
AU - Sämann, Philipp G.
AU - Schnell, Knut
AU - Schrantee, Anouk
AU - Simulionyte, Egle
AU - Soares, Jair C.
AU - Sommer, Jens
AU - Stein, Dan J.
AU - Steinsträter, Olaf
AU - Strike, Lachlan T.
AU - Thomopoulos, Sophia I.
AU - van Tol, Marie José
AU - Veer, Ilya M.
AU - Vermeiren, Robert R.J.M.
AU - Walter, Henrik
AU - van der Wee, Nic J.A.
AU - van der Werff, Steven J.A.
AU - Whalley, Heather
AU - Winter, Nils R.
AU - Wittfeld, Katharina
AU - Wright, Margaret J.
AU - Wu, Mon Ju
AU - Völzke, Henry
AU - Yang, Tony T.
AU - Zannias, Vasileios
AU - de Zubicaray, Greig I.
AU - Zunta-Soares, Giovana B.
AU - Abé, Christoph
AU - Alda, Martin
AU - Andreassen, Ole A.
AU - Bøen, Erlend
AU - Bonnin, Caterina M.
AU - Canales-Rodriguez, Erick J.
AU - Cannon, Dara
AU - Caseras, Xavier
AU - Chaim-Avancini, Tiffany M.
AU - Elvsåshagen, Torbjørn
AU - Favre, Pauline
AU - Foley, Sonya F.
AU - Fullerton, Janice M.
AU - Goikolea, Jose M.
AU - Haarman, Bartholomeus C.M.
AU - Hajek, Tomas
AU - Henry, Chantal
AU - Houenou, Josselin
AU - Howells, Fleur M.
AU - Ingvar, Martin
AU - Kuplicki, Rayus
AU - Lafer, Beny
AU - Landén, Mikael
AU - Machado-Vieira, Rodrigo
AU - Malt, Ulrik F.
AU - McDonald, Colm
AU - Mitchell, Philip B.
AU - Nabulsi, Leila
AU - Otaduy, Maria Concepcion Garcia
AU - Overs, Bronwyn J.
AU - Polosan, Mircea
AU - Pomarol-Clotet, Edith
AU - Radua, Joaquim
AU - Rive, Maria M.
AU - Roberts, Gloria
AU - Ruhe, Henricus G.
AU - Salvador, Raymond
AU - Sarró, Salvador
AU - Satterthwaite, Theodore D.
AU - Savitz, Jonathan
AU - Schene, Aart H.
AU - Schofield, Peter R.
AU - Serpa, Mauricio H.
AU - Sim, Kang
AU - Soeiro-de-Souza, Marcio Gerhardt
AU - Sutherland, Ashley N.
AU - Temmingh, Henk S.
AU - Timmons, Garrett M.
AU - Uhlmann, Anne
AU - Vieta, Eduard
AU - Wolf, Daniel H.
AU - Zanetti, Marcus V.
AU - Jahanshad, Neda
AU - Thompson, Paul M.
AU - Veltman, Dick J.
AU - Penninx, Brenda W.J.H.
AU - Marquand, Andre F.
AU - Cole, James H.
AU - Schmaal, Lianne
N1 - With supplementary information
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085208849&partnerID=8YFLogxK
UR - https://pure.uva.nl/ws/files/67941372/41380_2020_754_MOESM1_ESM.docx
UR - https://pure.uva.nl/ws/files/67941374/41380_2020_754_MOESM2_ESM.docx
U2 - https://doi.org/10.1038/s41380-020-0754-0
DO - https://doi.org/10.1038/s41380-020-0754-0
M3 - Article
C2 - 32424236
SN - 1359-4184
VL - 26
SP - 5124
EP - 5139
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 9
ER -