Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
Laura K. M. Han(Amsterdam Neuroscience), Richard Dinga(Radboud University Nijmegen), Tim Hahn(University of Münster), Christopher R. K. Ching(University of Southern California), Lisa T. Eyler(University of California San Diego), Lyubomir I. Aftanas(Novosibirsk State University), Moji Aghajani(Amsterdam Neuroscience), André Alemán(University Medical Center Groningen), Bernhard T. Baune(The University of Melbourne), Klaus Berger(University of Münster), И. В. Брак(Novosibirsk State University), Geraldo F. Busatto(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Angela Carballedo(Trinity College Dublin), Colm G. Connolly(Florida State University), Baptiste Couvy‐Duchesne(The University of Queensland), Kathryn R. Cullen(University of Minnesota Medical Center), Udo Dannlowski(University of Münster), Christopher G. Davey(The University of Melbourne), Danai Dima(City, University of London), Fábio Duran(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Verena Enneking(University of Münster), Elena Filimonova(Institute of Physiology and Basic Medicine), Stefan Frenzel(Universitätsmedizin Greifswald), Thomas Frodl(Trinity College Dublin), Cynthia H.Y. Fu(University of East London), Beata R. Godlewska(University of Oxford), Ian H. Gotlib(Stanford University), Hans J. Grabe(Universitätsmedizin Greifswald), Nynke A. Groenewold(University Medical Center Groningen), Dominik Grotegerd(University of Münster), Oliver Gruber(Heidelberg University), Geoffrey B. Hall(McMaster University), Ben J. Harrison(The University of Melbourne), Sean N. Hatton(The University of Sydney), Marco Hermesdorf(University of Münster), Ian B. Hickie(The University of Sydney), Tiffany C. Ho(Stanford University), Norbert Hosten(Universitätsmedizin Greifswald), Andreas Jansen(Philipps University of Marburg), Claas Kähler(University of Münster), Tilo Kircher(Philipps University of Marburg), Bonnie Klimes‐Dougan(University of Minnesota), Bernd Krämer(Heidelberg University), Axel Krug(University of Bonn), Jim Lagopoulos(The University of Sydney), Ramona Leenings(University of Münster), Frank P. MacMaster(University of Calgary), Glenda MacQueen(University of Calgary), Andrew M. McIntosh(University of Edinburgh), Quinn McLellan(University of Alberta), Katie L. McMahon(Queensland University of Technology), Sarah E. Medland(QIMR Berghofer Medical Research Institute), Bryon A. Mueller(University of Minnesota Medical Center), Benson Mwangi(The University of Texas Health Science Center at Houston), Evgeny Osipov(Novosibirsk State University), Marı́a J. Portella(Centro de Investigación Biomédica en Red de Salud Mental), Elena Pozzi(The University of Melbourne), Liesbeth Reneman(Amsterdam University Medical Centers), Jonathan Repple(University of Münster), Pedro G. P. Rosa(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Matthew D. Sacchet(Harvard University), Philipp G. Sämann(Max Planck Institute of Psychiatry), Knut Schnell(Universitätsmedizin Göttingen), Anouk Schrantee(Amsterdam University Medical Centers), Egle Simulionyte(McMaster University), Jair C. Soares(The University of Texas Health Science Center at Houston), Jens Sommer(University of Minnesota), Dan J. Stein(University of Cape Town), Olaf Steinsträter(Universitätsmedizin Greifswald), Lachlan T. Strike(The University of Queensland), Sophia I. Thomopoulos(University of Southern California), Marie‐José van Tol(University Medical Center Groningen), Ilya M. Veer(Humboldt-Universität zu Berlin), Robert Vermeiren(Leiden University), Henrik Walter(Humboldt-Universität zu Berlin), Nic J.A. van der Wee(Leiden University), Steven J.A. van der Werff(Leiden University), Heather C. Whalley(University of Edinburgh), Nils R. Winter(University of Münster), Katharina Wittfeld(Universitätsmedizin Greifswald), Margaret J. Wright(The University of Queensland), Mon‐Ju Wu(The University of Texas Health Science Center at Houston), Henry Völzke(Universitätsmedizin Greifswald), Tony T. Yang, Vasileios Zannias(University of Edinburgh), Greig I. de Zubicaray(Queensland University of Technology), Giovana Zunta‐Soares(The University of Texas Health Science Center at Houston), Christoph Abé(Karolinska Institutet), Martin Alda(Dalhousie University), Ole A. Andreassen(Oslo University Hospital), Erlend Bøen(Oslo University Hospital), Caterina del Mar Bonnín(Centro de Investigación Biomédica en Red de Salud Mental), Erick J. Canales‐Rodríguez(Hospital Mare de Déu de la Mercè), Dara M. Cannon(Ollscoil na Gaillimhe – University of Galway), Xavier Caseras(Cardiff University), Tiffany Chaim-Avancini(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Torbjørn Elvsåshagen(Oslo University Hospital), Pauline Favre(Inserm), Sonya Foley(Cardiff University), Janice M. Fullerton(UNSW Sydney), José Manuel Goikolea(Centro de Investigación Biomédica en Red de Salud Mental), Bartholomeus C. M. Haarman(University Medical Center Groningen), Tomáš Hájek(Dalhousie University), Chantal Henry(Université Paris Cité), Josselin Houenou(Inserm), Fleur M. Howells(University of Cape Town), Martin Ingvar(Karolinska Institutet), Rayus Kuplicki(Laureate Institute for Brain Research), Beny Lafer(Universidade de São Paulo), Mikael Landén(Karolinska Institutet), Rodrigo Machado‐Vieira(Universidade de São Paulo), Ulrik Fredrik Malt(Oslo University Hospital), Colm McDonald(Ollscoil na Gaillimhe – University of Galway), Philip B. Mitchell(Black Dog Institute), Leila Nabulsi(Ollscoil na Gaillimhe – University of Galway), Maria Concepción García Otaduy(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Bronwyn J. Overs(Neuroscience Research Australia), Mircea Polosan(Inserm), Edith Pomarol‐Clotet(Hospital Mare de Déu de la Mercè), Joaquim Raduà(Centro de Investigación Biomédica en Red de Salud Mental), Maria M. Rive(Amsterdam University Medical Centers), Gloria Roberts(Black Dog Institute), Henricus G. Ruhé(Radboud University Nijmegen), Raymond Salvador(Hospital Mare de Déu de la Mercè), Salvador Sarró(Hospital Mare de Déu de la Mercè), Theodore D. Satterthwaite(University of Pennsylvania), Jonathan Savitz(Tulsa Community College), Aart H. Schene(Radboud University Nijmegen), Peter R. Schofield(UNSW Sydney), Maurício H. Serpa(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Kang Sim(National University of Singapore), Márcio Gerhardt Soeiro‐de‐Souza(Universidade de São Paulo), Ashley Sutherland(University of California San Diego), Henk Temmingh(Heidelberg University), Garrett Timmons(University of California San Diego), Anne Uhlmann(University of Cape Town), Eduard Vieta(Centro de Investigación Biomédica en Red de Salud Mental), Daniel H. Wolf(University of Pennsylvania), Marcus V. Zanetti(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Neda Jahanshad(University of Southern California), Paul M. Thompson(University of Southern California), Dick J. Veltman(Amsterdam Neuroscience), Brenda W.J.H. Penninx(Amsterdam Neuroscience), André F. Marquand(Radboud University Nijmegen), James H. Cole(King's College London), Lianne Schmaal(The University of Melbourne)
Cited by 300Open Access
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.
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