Journal
MOLECULAR PSYCHIATRY
Volume 26, Issue 9, Pages 5124-5139Publisher
SPRINGERNATURE
DOI: 10.1038/s41380-020-0754-0
Keywords
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Funding
- NIH [R01 MH117601, R01 AG059874, U54 EB020403, RF1 AG041915, RF1AG051710, P41EB015922, R01MH116147, R56AG058854]
- German Federal Ministry of Education and Research (BMBF) [FKZ-01ER0816, FKZ-01ER1506]
- Alberta Children's Hospital Foundation
- Deutsche Forschungsgemeinschaft (DFG) [GR1950/5-1, GR1950/10-1, SA 1358/2-1, HA7070/2-2, HA7070/3, HA7070/4, FOR2107 DA1151/5-1, SFB-TRR58]
- Lundbeck
- German Research Foundation [WA 1539/4-1, SCHN 1205/3-1, SCHR443/11-1]
- Gratama Foundation, the Netherlands [2012/35]
- Science Foundation Ireland
- Stokes Professorship Grant
- IMAGEMEND from the European Community [602450]
- Wellcome Trust [104036/Z/14/Z]
- German Research Foundation (DFG) [HA7070/2-2, HA7070/3, HA7070/4, FOR2107 KR 3822/7-2, FOR2107 KI 588/14-2, FOR2107 JA 1890/7-2]
- National Health and Medical Research Council of Australia (NHMRC) [1064643, 1024570]
- National Institute of Mental Health [R21MH113871, K23MH090421]
- National Alliance for Research on Schizophrenia and Depression
- University of Minnesota Graduate School
- Minnesota Medical Foundation
- Biotechnology Research Center [P41 RR008079]
- University of Minnesota
- Deborah E. Powell Center for Women's Health Seed Grant, University of Minnesota
- Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Munster [Dan3/012/17]
- Russian Science Foundation (RSF) [16-15-00128]
- German Federal State of Mecklenburg-West Pomerania
- Siemens Healthineers, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- National Health and Medical Research Council [566529, 264611, 511921, 402864]
- Australian National Health and Medical Research Council [496682, 1009064]
- US National Institute of Child Health and Human Development [RO1HD050735]
- FAPESP, Brazil
- CNPq, Brazil
- UKRI Innovation Fellowship
- NHMRC CJ Martin Fellowship [APP1161356]
- MRC grant
- NIHR BRC grant
- Medical Research Council
- Endeavour Leadership Award by the Australian Government Department of Education, Skills and Employment (DESE)
- National Institute of Health [K01MH117442]
- Dutch Organization of Scientific Research under a Vernieuwingsimpuls 'VIDI' Fellowship [016.156.415]
- Australian National Health and Medical Research Council Senior Research Fellowship [APP1103623]
- Ministerio de Ciencia e Innovacion of Spanish Government (ISCIII) through a Miguel Servet II [CP16/00020]
- Max Planck Institute of Psychiatry, Munich
- NHMRC Career Development Fellowship [1140764]
- Pat Rutherford Chair in Psychiatry, UTHealth
- National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1TR001872]
- American Foundation for Suicide Prevention (AFSP)
- UCSF Research Evaluation and Allocation Committee (REAC)
- J. Jacobson Fund
- Brain and Behavior Research Foundation
- 2010 NARSAD Young Investigator Award [17319]
- University Research Council of the University of Cape Town
- National Research Foundation of South Africa
- Generalitat de Catalunya [2014 SGR 1573]
- Instituto de Salud Carlos III [CPII16/00018, PI14/01151, PI14/01148]
- Health Research Board, Ireland
- Irish Research Council
- Grenoble University Hospital
- Canadian Institutes of Health Research [103703, 106469, 142255]
- South-Eastern Norway Regional Health Authority [2014097]
- FRM (Fondation pour la recherche Biomedicale) Bio-informatique pour la biologie 2014 grant
- Singapore Bioimaging Consortium Research Grant [SBIC RP C-009/2006]
- NHG [SIG/15012]
- Australian NHMRC [1037196, 1063960, 1066177]
- Janette Mary O'Neil Research Fellowship
- US National Science Foundation (Science Gateways Community Institutes
- XSEDE)
- Swedish Research Council [201802653, 2018-02653]
- Swedish foundation for Strategic Research [KF10-0039]
- Swedish Brain foundation
- Swedish Federal Government under the LUA/ALF [ALF 20170019, ALFGBG-716801]
- Research Council of Norway [223273, 248778, 273291]
- Departament de Salut CERCA Programme/Generalitat de Catalunya [SLT002/16/00331]
- CIBERSAM
- Comissionat per a Universitats i Recerca del DIUE de la Generalitat de Catalunya [2017 SGR 1365]
- PERIS 2016-2020 (Departament de Salut) [SLT006/17/00357]
- Nova Scotia Health Research Foundation
- Dalhousie Clinical Research Scholarship
- Brain & Behavior Research Foundation
- Spanish Ministerio de Ciencia, Innovacion y Universidades
- National Institute of General Medical Sciences [P20GM121312]
- CAPES, Brazil
- SAMRC
- National Institutes of Health [T35 AG026757/AG/NIA]
- University of California San Diego, Stein Institute for Research on Aging
- Spanish Ministry of Science, Innovation and Universities integrated into the Plan Nacional de I+D+I [PI15/00283]
- ISCIII-Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER)
- FAPESP, Brazil [2013/03905-4]
- NIA [T32AG058507]
- NIH/NIMH [5T32MH073526]
- NIH grant Big Data to Knowledge (BD2K) Program [U54EB020403]
- EU-JPND Funding for BRIDGET [FKZ:01ED1615]
- NCCIH [R61AT009864, R21AT009173]
- NIMH [R01MH085734]
- ZonMW OOG 2007, the Netherlands [100002034]
- Desert-Pacific Mental Illness Research Education and Clinical Center
- NIH (ENIGMA grants)
- CERCA Programme/Generalitat de Catalunya
- Swedish state under the ALF-agreement [ALF 20170019, ALFGBG-716801]
- [EU-FP7-HEALTH-222963]
- [EU-FP7-PEOPLE- 286334]
- [R01MH083968]
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Major depressive disorder is associated with increased risk of brain atrophy, aging-related diseases, and mortality. This study found that MDD patients showed a higher brain-predicted age difference compared to controls, but this difference did not seem to be driven by specific clinical characteristics. Subtle patterns of age-related structural brain abnormalities in MDD were observed, highlighting the need for further longitudinal studies to assess the clinical value of these findings.
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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