ArticleMolecular psychiatry2020
White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group.
Abstract readMulticenter Study
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Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 13 of them syntheses that pooled it.
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209citing papers in PubMed, 13 pooled it
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Who cites it
209 citing papers in PubMed, 13 syntheses or guidelines pooled it.
- The association between white matter hyperintensities and suicide attempts in affective disorders: a systematic review and meta-analysis.Translational psychiatry · 2025Pooled it
- Structural brain correlates in major depressive disorder, anxiety disorders, and post-traumatic stress disorder: a diffusion tensor imaging meta-analysis.Psychological medicine · 2025Pooled it
- Behavioral and psychological symptoms of dementia associated with vascular impairment: a systematic review and meta-analysis.Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) · 2025Pooled it
- Cerebellar Microstructural Abnormalities in Obsessive-Compulsive Disorder (OCD): a Systematic Review of Diffusion Tensor Imaging Studies.Cerebellum (London, England) · 2024Pooled it
- Brain-based correlates of depression and traumatic brain injury: a systematic review of structural and functional magnetic resonance imaging studies.Frontiers in neuroimaging · 2024Pooled it
- Brain-based Sex Differences in Depression: A Systematic Review of Neuroimaging Studies.Brain imaging and behavior · 2023Pooled it
- Brain connectivity in major depressive disorder: a precision component of treatment modalities?Translational psychiatry · 2023Pooled it
- Measuring white matter microstructure in 1,457 cannabis users and 1,441 controls: A systematic review of diffusion-weighted MRI studies.Frontiers in neuroimaging · 2023Pooled it
- Brain microstructural alterations of depression in Parkinson's disease: A systematic review of diffusion tensor imaging studies.Human brain mapping · 2022Pooled it
- Microstructural white matter alterations associated with migraine headaches: a systematic review of diffusion tensor imaging studies.Brain imaging and behavior · 2022Pooled it
- Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury.Human brain mapping · 2022Pooled it
- Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings.Psychiatry and clinical neurosciences · 2022Pooled it
- Cerebral Small-Vessel Disease and Risk of Incidence of Depression: A Meta-Analysis of Longitudinal Cohort Studies.Journal of the American Heart Association · 2020Pooled it
- Neuroplastic white matter changes in patients with major depression following lysergic acid diethylamide treatment.Cell reports. Medicine · 2026Trial
- Effects of antidepressant medications on brain tissue microstructure in persistent depressive disorder across two randomized controlled trials.NeuroImage. Clinical · 2026Trial
- White matter tracts associated with iTBS-induced heart rate deceleration and treatment response in major depressive disorder.Translational psychiatry · 2025Trial
- Trial
- Association between peripheral inflammation and free-water imaging in Major Depressive Disorder before and after ketamine treatment - A pilot study.Journal of affective disorders · 2022Trial
- Cerebral diffusion kurtosis imaging to assess the pathophysiology of postpartum depression.Scientific reports · 2020Trial
- Sex-specific neurodevelopmental pathways to depressive symptoms.Molecular psychiatry · 2026Article
149 more citing papers are in PubMed but not listed here.
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Authors and funding
71 authors.
Laura S van Velzen *Department of Psychiatry, Amsterdam UMC, The Netherlands. laurasvanvelzen@gmail.com.
Sinead Kelly *Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Dmitry IsaevImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Andre AlemanCognitive Neuroscience Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Lyubomir I AftanasFSSBI "Scientific Research Institute of Physiology & Basic Medicine", Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia.
Jochen BauerUniversity of Münster, Institute of Clinical Radiology, Münster, Germany.
Bernhard T BauneDepartment of Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-6548-426X
Ivan V BrakFSSBI "Scientific Research Institute of Physiology & Basic Medicine", Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia.ORCID http://orcid.org/0000-0002-5146-0096
Angela CarballedoDepartment of Psychiatry and Trinity Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Colm G ConnollyDepartment of Psychiatry, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4051-3682
Baptiste Couvy-DuchesneInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Kathryn R CullenDepartment of Psychiatry and Behavioral Sciences, The University of Minnesota, Minneapolis, MN, USA.
Konstantin V DanilenkoFSSBI "Scientific Research Institute of Physiology & Basic Medicine", Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia.
Udo DannlowskiDepartment of Psychiatry, University of Münster, Münster, Germany.
Verena EnnekingDepartment of Psychiatry, University of Münster, Münster, Germany.
Elena FilimonovaFSSBI "Scientific Research Institute of Physiology & Basic Medicine", Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia.
Katharina FörsterDepartment of Psychiatry, University of Münster, Münster, Germany.
Thomas FrodlDepartment of Psychiatry and Trinity Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Ian H GotlibDepartment of Psychology, Stanford University, Stanford, CA, USA.
Nynke A GroenewoldDepartment of Psychiatry, University of Cape Town, Cape Town, South Africa.
Dominik GrotegerdDepartment of Psychiatry, University of Münster, Münster, Germany.
Mathew A HarrisDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-1135-4141
Sean N HattonYouth Mental Health Team, Brain and Mind Centre, University of Sydney, Camperdown, Australia.
Emma L HawkinsDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
Ian B HickieYouth Mental Health Team, Brain and Mind Centre, University of Sydney, Camperdown, Australia.
Tiffany C HoDepartment of Psychiatry, University of California, San Francisco, CA, USA.
Andreas JansenDepartment of Psychiatry, University of Marburg, Marburg, Germany.
Tilo KircherDepartment of Psychiatry, University of Marburg, Marburg, Germany.
Bonnie Klimes-DouganDepartment of Psychology, The University of Minnesota, Minneapolis, MN, USA.
Peter KochunovMaryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Axel KrugDepartment of Psychiatry, University of Marburg, Marburg, Germany.
Jim LagopoulosSunshine Coast Mind and Neuroscience-Thompson Institute, Birtinya, QLD, Australia.
Renick LeeResearch Division, Institute of Mental Health, Singapore, Singapore.
Tristram A LettDivision 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.ORCID http://orcid.org/0000-0002-0731-9626
Meng LiDepartment of Neurology, University of Magdeburg, Magdeburg, Germany.
Frank P MacMasterPsychiatry and Paediatrics, University of Calgary, Calgary, Canada.
Nicholas G MartinQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-4069-8020
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0198-4588
Quinn McLellanDepartment of Neuroscience, University of Calgary, Calgary, Canada.ORCID http://orcid.org/0000-0003-3806-2218
Susanne MeinertDepartment of Psychiatry, University of Münster, Münster, Germany.
Igor NenadićDepartment of Psychiatry, University of Marburg, Marburg, Germany.
Evgeny OsipovLab. of Experimental & Translational Neuroscience, Novosibirsk State University, Novosibirsk, Russia.
Brenda W J H PenninxDepartment of Psychiatry, Amsterdam UMC, The Netherlands.
Maria J PortellaDepartment of Psychiatry, Institute of Biomedical Research Sant Pau, Barcelona, Spain.
Jonathan ReppleDepartment of Psychiatry, University of Münster, Münster, Germany.
Annerine RoosSAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
Matthew D SacchetCenter for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
Philipp G SämannMax Planck Institute of Psychiatry, Munich, Germany.
Knut SchnellDepartment of Psychiatry, University of Heidelberg, Heidelberg, Germany.
Xueyi ShenDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
Kang SimWest Region and Research Division, Institute of Mental Health, Singapore, Singapore.
Dan J SteinSAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, South Africa.ORCID http://orcid.org/0000-0001-7218-7810
Marie-Jose van TolCognitive Neuroscience Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-9260-5490
Alexander S TomyshevMental Health Research Center, Moscow, Russia.
Leonardo TozziDepartment of Psychiatry and Psychotherapy, Otto von Guericke University, Madgeburg, Germany.
Ilya M VeerDivision 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.
Robert VermeirenCurium-LUMC Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Yolanda Vives-GilabertInstituto ITACA, Universitat Politècnica de València, València, Spain.
Henrik WalterDivision 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.ORCID http://orcid.org/0000-0002-9403-6121
Martin WalterDepartment of Psychiatry and Psychotherapy, University of Tübingen, Tubingen, Germany.
Nic J A van der WeeLeiden Institute for Brain and Cognition, Leiden, The Netherlands.
Steven J A van der WerffLeiden Institute for Brain and Cognition, Leiden, The Netherlands.
Melinda Westlund SchreinerDepartment of Psychology, The University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-2780-3327
Heather C WhalleyDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4505-8869
Margaret J WrightQueensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0001-7133-4970
Tony T YangDepartment of Psychiatry, University of California, San Francisco, CA, USA.
Alyssa ZhuImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Dick J VeltmanDepartment of Psychiatry, Amsterdam UMC, The Netherlands.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Neda Jahanshad *Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID http://orcid.org/0000-0003-4401-8950
Lianne Schmaal *Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.
Funding
ZOOMED FUNCT IMAGING IN HUMAN BRAIN AT 7T W/ SIMULT HIGH SPATIAL &TEMPORAL RESP41RR008079 · NCRR · UNIVERSITY OF MINNESOTA TWIN CITIES · PI DUBINSKY, JANET M · 1993 to 2011
$16.3MTR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VAN HORN, JOHN DARRELL · 2012 to 2022
$14.1MTraining U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1MPsychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across AdolescenceR37MH101495 · NIMH · STANFORD UNIVERSITY · PI IAN H GOTLIB · 2018 to 2026
$6.6MNeural and Behavioral Aspects of Information-Processing Biases in DepressionR01MH059259 · NIMH · STANFORD UNIVERSITY · PI GOTLIB, IAN H · 1999 to 2011
$5.9MSOLAR-Eclipse Computational Tools for Imaging GeneticsR01EB015611 · NIBIB · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KOCHUNOV, PETER V. · 2012 to 2024
$5.0MA Cross-Sectional and Longitudinal Functional MRI Study of Adolescent DepressionR01MH085734 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YANG, TONY TUNG-I · 2010 to 2014
$2.7MGenetic influences on the brain: A twin imaging studyR01HD050735 · NICHD · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI WRIGHT, MARGARET JANE · 2007 to 2011
$2.6MENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMAR01MH116147 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2018 to 2021
$2.5MA global alliance to unlock brain mechanisms influencing suicidal behaviors through the ENIGMA ConsortiumR01MH117601 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JAHANSHAD, NEDA, SCHMAAL, LIANNE · 2018 to 2021
$1.5MThe Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent DepressionK01MH117442 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HO, TIFFANY CHEING · 2018 to 2022
$881kFronto-limbic Connectivity in Adolescents with MDDK23MH090421 · NIMH · UNIVERSITY OF MINNESOTA · PI CULLEN, KATHRYN REGAN · 2010 to 2014
$811kNCRR NIH HHS P41 RR008079NIBIB NIH HHS P41 EB015922NIBIB NIH HHS R01 EB015611NIBIB NIH HHS U54 EB020403NICHD NIH HHS R01 HD050735NIH HHS S10 OD023696NIMH NIH HHS K01 MH117442NIMH NIH HHS K23 MH090421NIMH NIH HHS R01 MH059259NIMH NIH HHS R01 MH085734NIMH NIH HHS R01 MH116147NIMH NIH HHS R01 MH117601Wellcome TrustWellcome Trust 104036/Z/14/Z
Abstract
Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.
Indexed as
AdultAgedAged, 80 and overAnisotropyCohort StudiesCorpus CallosumDiffusion Tensor ImagingFemaleHumansMajor Depressive DisorderMaleMiddle AgedWhite MatterYoung Adult
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