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

Journal: Molecular psychiatry

Volume: 26

Issue: 9

Year of Publication: 2022

Affiliated Institutions:  Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit & GGZinGeest, Amsterdam, The Netherlands. l.han@amsterdamumc.nl. Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit & GGZinGeest, Amsterdam, The Netherlands. Department of Psychiatry, University of Münster, Münster, Germany. Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Desert-Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare, San Diego, CA, USA. FSSBI "Scientific Research Institute of Physiology & Basic Medicine", Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia. Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany. Laboratory of Psychiatric Neuroimaging (LIM-), Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Department for Psychiatry, Trinity College Dublin, Dublin, Ireland. Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia. Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, Minnesota, USA. Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia. Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. Department of Psychiatry, University of Oxford, Oxford, UK. Department of Psychology, Stanford University, Stanford, CA, USA. Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Section for Experimental Psychopathology and Neuroimaging, Department of Psychiatry, University of Heidelberg, Heidelberg, Germany. Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, VIC, Australia. Youth Mental Health Team, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. Department of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. Department of Psychiatry, Philipps-University Marburg, Marburg, Germany. Department of Psychology, University of Minnesota, Minneapolis, MN, USA. Departments of Psychiatry and Pediatrics, University of Calgary, Calgary, AB, Canada. Department of Psychiatry, University of Calgary, Calgary, AB, Canada. Division of Psychiatry, University of Edinburgh, Edinburgh, UK. School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. QIMR Berghofer Medical Research Instititute, Brisbane, QLD, Australia. Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA. Laboratory of Experimental & Translational Neuroscience, Novosibirsk State University, Novosibirsk, Russia. Institut d'Investigació Biomèdica Sant Pau, Barcelona, Catalonia, Spain. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, AMC, Amsterdam, The Netherlands. Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, MA, USA. Max Planck Institute of Psychiatry, Munich, Germany. Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. Cognitive Neuroscience Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy CCM, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Department of Child Psychiatry, University Medical Center, Leiden, The Netherlands. Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. Department of Psychiatry, Division of Child and Adolescent Psychiatry, UCSF School of Medicine, UCSF, San Francisco, CA, USA. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. Department of Clinical Neuroscience, Osher Center, Karolinska Institutet, Stockholm, Sweden. Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Clinic for Mental Health and Dependency, C-L psychiatry and Psychosomatic Unit, Oslo University Hospital, Oslo, Norway. Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. FIDMAG Germanes Hospitalàries Research Foundation, CIBERSAM, Barcelona, Catalonia, Spain. Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, H TK, Galway, Ireland. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK. Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. UNIACT, Psychiatry Team, Neurospin, Atomic Energy Commission, Gif-Sur-Yvette, France. Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK. Neuroscience Research Australia, Randwick, Sydney, NSW, Australia. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Université de Paris, Service Hospitalo-Universitaire, GHU Paris Psychiatrie & Neuroscience, F-, Paris, France. Laureate Institute for Brain Research, Tulsa, OK, USA. Department of Psychiatry, School of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil. Department of Clinical Neuroscience, University of Oslo, Oslo, Norway. School of Psychiatry, University of New South Wales, Kingsford, Sydney, NSW, Australia. Instituto de Radiologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Department of Psychiatry and Neurology, CHU Grenoble Alpes, Université Grenoble Alpes, F-, Grenoble, France. Department of Psychiatry, Amsterdam University Medical Centers, AMC, Amsterdam, The Netherlands. Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands. Department of Psychiatry, University of Pennsylvannia Perelman School of Medicine, Philadelphia, PA, USA. West Region and Research Division, Institute of Mental Health, Singapore, Singapore. Department of Psychiatry, University of California San Diego, Los Angeles, CA, USA. Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College, London, UK.

Abstract summary 

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.

Authors & Co-authors:  Han Laura K M LKM Dinga Richard R Hahn Tim T Ching Christopher R K CRK Eyler Lisa T LT Aftanas Lyubomir L Aghajani Moji M Aleman André A Baune Bernhard T BT Berger Klaus K Brak Ivan I Filho Geraldo Busatto GB Carballedo Angela A Connolly Colm G CG Couvy-Duchesne Baptiste B Cullen Kathryn R KR Dannlowski Udo U Davey Christopher G CG Dima Danai D Duran Fabio L S FLS Enneking Verena V Filimonova Elena E Frenzel Stefan S Frodl Thomas T Fu Cynthia H Y CHY Godlewska Beata R BR Gotlib Ian H IH Grabe Hans J HJ Groenewold Nynke A NA Grotegerd Dominik D Gruber Oliver O Hall Geoffrey B GB Harrison Ben J BJ Hatton Sean N SN Hermesdorf Marco M Hickie Ian B IB Ho Tiffany C TC Hosten Norbert N Jansen Andreas A Kähler Claas C Kircher Tilo T Klimes-Dougan Bonnie B Krämer Bernd B Krug Axel A Lagopoulos Jim J Leenings Ramona R MacMaster Frank P FP MacQueen Glenda G McIntosh Andrew A McLellan Quinn Q McMahon Katie L KL Medland Sarah E SE Mueller Bryon A BA Mwangi Benson B Osipov Evgeny E Portella Maria J MJ Pozzi Elena E Reneman Liesbeth L Repple Jonathan J Rosa Pedro G P PGP Sacchet Matthew D MD Sämann Philipp G PG Schnell Knut K Schrantee Anouk A Simulionyte Egle E Soares Jair C JC Sommer Jens J Stein Dan J DJ Steinsträter Olaf O Strike Lachlan T LT Thomopoulos Sophia I SI van Tol Marie-José MJ Veer Ilya M IM Vermeiren Robert R J M RRJM Walter Henrik H van der Wee Nic J A NJA van der Werff Steven J A SJA Whalley Heather H Winter Nils R NR Wittfeld Katharina K Wright Margaret J MJ Wu Mon-Ju MJ Völzke Henry H Yang Tony T TT Zannias Vasileios V de Zubicaray Greig I GI Zunta-Soares Giovana B GB Abé Christoph C Alda Martin M Andreassen Ole A OA Bøen Erlend E Bonnin Caterina M CM Canales-Rodriguez Erick J EJ Cannon Dara D Caseras Xavier X Chaim-Avancini Tiffany M TM Elvsåshagen Torbjørn T Favre Pauline P Foley Sonya F SF Fullerton Janice M JM Goikolea Jose M JM Haarman Bartholomeus C M BCM Hajek Tomas T Henry Chantal C Houenou Josselin J Howells Fleur M FM Ingvar Martin M Kuplicki Rayus R Lafer Beny B Landén Mikael M Machado-Vieira Rodrigo R Malt Ulrik F UF McDonald Colm C Mitchell Philip B PB Nabulsi Leila L Otaduy Maria Concepcion Garcia MCG Overs Bronwyn J BJ Polosan Mircea M Pomarol-Clotet Edith E Radua Joaquim J Rive Maria M MM Roberts Gloria G Ruhe Henricus G HG Salvador Raymond R Sarró Salvador S Satterthwaite Theodore D TD Savitz Jonathan J Schene Aart H AH Schofield Peter R PR Serpa Mauricio H MH Sim Kang K Soeiro-de-Souza Marcio Gerhardt MG Sutherland Ashley N AN Temmingh Henk S HS Timmons Garrett M GM Uhlmann Anne A Vieta Eduard E Wolf Daniel H DH Zanetti Marcus V MV Jahanshad Neda N Thompson Paul M PM Veltman Dick J DJ Penninx Brenda W J H BWJH Marquand Andre F AF Cole James H JH Schmaal Lianne L

Study Outcome 

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Statistics
Citations :  John A, Patel U, Rusted J, Richards M, Gaysina D. Affective problems and decline in cognitive state in older adults: a systematic review and meta-analysis. Psychol Med. 2018;49:353–65.
Authors :  146
Identifiers
Doi : 10.1038/s41380-020-0754-0
SSN : 1476-5578
Study Population
Male,Female,Females
Mesh Terms
Adolescent
Other Terms
Study Design
Longitudinal Study,Cross Sectional Study
Study Approach
Country of Study
Mali
Publication Country
England