ArticleTranslational psychiatry2026
Decomposing neuroanatomical heterogeneity in depression: insights from an ENIGMA major depressive disorder working group study in 5146 individuals.
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Article in Translational psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Decoding Transdiagnostic Subtypes in Emotional Disorders.CNS neuroscience & therapeutics · 2026Article
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Authors and funding
91 authors.
Lukas SempachDepartment of Clinical Research (DKF), University of Basel, Basel, Switzerland. lukas.sempach@unibas.ch.ORCID http://orcid.org/0009-0000-7785-0052
Sarah UlrichCenter for Affective, Stress and Sleep Disorders, University Psychiatric Clinics (UPK) Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1516-8362
Stéphanie E E C BauduinDepartment of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0003-1253-7377
Jochen BauerDepartment of Radiology, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-9345-2126
Francesco BenedettiDivision of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy.ORCID http://orcid.org/0000-0003-4949-856X
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Bianca BesteherDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.ORCID http://orcid.org/0000-0001-7989-9298
Robin BülowInstitute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-1884-5784
Colm G ConnollyDepartment of Biomedical Science, Florida State University, Tallahassee, FL, USA.
Emmanuelle CorrubleService Hospitalo-Universitaire de Psychiatrie de Bicêtre, Mood Center Paris Saclay, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Saclay, Hôpital de Bicêtre, Le Kremlin Bicêtre, Paris, France.
Baptiste Couvy-DuchesneInstitute for Molecular Bioscience, the University of Queensland, St Lucia, QLD, Australia.
Kathryn R CullenDepartment of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-9631-3770
Udo DannlowskiInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0002-0623-3759
Christopher G DaveyDepartment of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0003-1431-3852
Danai DimaDepartment of Psychology, School of Health and Psychological Sciences, City St George's, University of London, London, UK.
Annemiek DolsDepartment of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Jennifer W EvansExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0009-0002-7176-5759
Cynthia FuCentre for Affective Disorders, Department of Psychological Medicine, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0003-4313-3500
Paola Fuentes-ClaramonteFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.ORCID http://orcid.org/0000-0002-1428-7976
Ali Saffet GonulDepartment of Psychiatry, Ege University, Izmir, Turkey.ORCID http://orcid.org/0000-0003-3522-1359
Ian H GotlibDepartment of Psychology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3622-3199
Roberto Goya-MaldonadoLaboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.ORCID http://orcid.org/0000-0002-7368-1332
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Nynke A GroenewoldDepartment of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID http://orcid.org/0000-0002-0865-8427
Dominik GrotegerdInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Oliver GruberSection for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
Tim HahnInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-6541-3795
J Paul HamiltonDepartment of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
Laura K M HanAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-9647-3723
Ben J HarrisonDepartment of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.
Sean N HattonBrain and Mind Center, University of Sydney, Sydney, NSW, Australia.
Marco HermesdorfInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Ian B HickieBrain and Mind Center, University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-8832-9895
Tiffany C HoDepartment of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
Julia M HubbertInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Neda JahanshadMark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Marina del Rey, CA, USA.
Hamidreza JamalabadiDepartment of Psychiatry, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0003-2485-2374
Alec J JamiesonDepartment of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-5598-0240
Christoph JurischkaInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0009-0006-9008-5758
Antonia JülligSection for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
Toshiharu KamishikiryoDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID http://orcid.org/0000-0002-4933-0161
Tilo KircherDepartment of Psychiatry, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0002-2514-2625
Sheri-Michelle KoopowitzDepartment of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Bernd KrämerSection for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
Anna KrausInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0003-2627-4563
Judith KriegerInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Axel KrugDepartment of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-0564-2497
Jim LagopoulosBrain and Mind Center, University of Sydney, Sydney, NSW, Australia.
Meng LiDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.ORCID http://orcid.org/0000-0002-8320-5241
Andrew McIntoshCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0198-4588
Susanne MeinertInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0003-2177-7161
Elisa M T MelloniDivision of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy.
Benson MwangiSchool of Behavioral Health Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1717-4395
Igor NenadicDepartment of Psychiatry, University of Marburg, Marburg, Germany.
Amar OjhaCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-1038-0225
Go OkadaDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID http://orcid.org/0000-0002-5451-8513
Mardien L OudegaAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Brenda W J H PenninxAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Sara PolettiDivision of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy.ORCID http://orcid.org/0000-0001-9594-0246
Edith Pomarol-ClotetFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
Maria J PortellaCIBERSAM, ISCIII, Madrid, Spain.ORCID http://orcid.org/0000-0002-2007-9516
Liesbeth RenemanDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Elena Rodriguez-CanoFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
Matthew SacchetMeditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Raymond SalvadorFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
Anouk SchranteeDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-4035-4845
Hotaka ShinzatoDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID http://orcid.org/0000-0002-0354-1801
Kang SimWest Region, Institute of Mental Health, Singapore, Singapore.
Theresa M SlumpInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Jair C SoaresSchool of Behavioral Health Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5466-5628
Dan J SteinSAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID http://orcid.org/0000-0001-7218-7810
Frederike SteinDepartment of Psychiatry, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0002-5052-6022
Lea TeutenbergDepartment of Psychiatry, University of Marburg, Marburg, Germany.
Florian Thomas-OdenthalDepartment of Psychiatry, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0003-4912-8307
Sophia I ThomopoulosImaging Genetics Center, Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID http://orcid.org/0000-0002-0046-4070
Nic J A van der WeeDepartment of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.
Steven J A van der WerffDepartment of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Martin WalterDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.ORCID http://orcid.org/0000-0001-7857-4483
Heather C WhalleyCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4505-8869
Sarah WhittleCentre for Youth Mental Health, The University of Melbourne, Parkville, Australia.ORCID http://orcid.org/0000-0003-3145-1528
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-4383-5043
Mon-Ju WuSchool of Behavioral Health Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0540-8027
Tony T YangDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA.
Carlos ZarateExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Giovana B Zunta-SoaresSchool of Behavioral Health Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Paul M ThompsonImaging Genetics Center, Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID http://orcid.org/0000-0002-4720-8867
Dick J VeltmanAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Elena PozziCentre for Youth Mental Health, The University of Melbourne, Parkville, Australia.
Lianne SchmaalCentre for Youth Mental Health, The University of Melbourne, Parkville, Australia.ORCID http://orcid.org/0000-0001-9822-048X
André SchmidtDepartment of Clinical Research (DKF), University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-6055-8397
Funding
Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1MTarget validation of novel therapeutic agents in mood disordersZIAMH002927 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2010 to 2025
$37.1MZOOMED FUNCT IMAGING IN HUMAN BRAIN AT 7T W/ SIMULT HIGH SPATIAL &TEMPORAL RESP41RR008079 · NCRR · UNIVERSITY OF MINNESOTA TWIN CITIES · PI UGURBIL, KAMIL · 1993 to 2011
$16.3MPsychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across AdolescenceR37MH101495 · NIMH · STANFORD UNIVERSITY · PI IAN H GOTLIB · 2018 to 2026
$6.6MENIGMA Bipolar Initiative: A Global Study of Imaging Genomics & Clinical OutcomesR01MH129742 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christopher Ching, PAUL M THOMPSON · 2022 to 2026
$3.0MSearching for Endophenotypes of Bipolar DisorderR01MH085667 · NIMH · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI SOARES, JAIR C · 2012 to 2016
$3.0MA Cross-Sectional and Longitudinal Functional MRI Study of Adolescent DepressionR01MH085734 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YANG, TONY TUNG-I · 2010 to 2014
$2.7MGlobal studies into the Genetic Architecture of the Brain's White Matter Network through Harmonized and Coordinated Analyses in the ENIGMA-ConsortiumR01MH134004 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Neda Jahanshad · 2023 to 2026
$2.6MGlobal Deep Learning Initiative to Understand Outcomes in Major DepressionR01MH131806 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Roberto Goya-Maldonado, PAUL M THOMPSON · 2023 to 2026
$2.6MNeurobiologically-Based Subtyping of Multi-Cohort Samples with MDD and PTSD SymptomsR01MH129832 · NIMH · DUKE UNIVERSITY · PI MOREY, RAJENDRA A, SCHMAAL, LIANNE · 2022 to 2025
$2.3MNeural mechanisms of meditation training in healthy and depressed adolescents: An MRI connectome studyR33AT009864 · NCCIH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YANG, TONY TUNG-I · 2022 to 2024
$1.9MDisentangling the anatomical, functional and clinical heterogeneity of major depression, using machine learning methodsR01MH134236 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS, FU, CYNTHIA · 2023 to 2024
$1.5MAmerican Foundation for Suicide Prevention (AFSP) SRG-1-141-18Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) OPP 1017641Department of Health | National Health and Medical Research Council (NHMRC) 1064643 1024570Department of Health | National Health and Medical Research Council (NHMRC) 2017962Deutsche Forschungsgemeinschaft (German Research Foundation) 521379614Deutsche Forschungsgemeinschaft (German Research Foundation) DA1151/5-1, DA1151/5-2, DA1151/9-1, DA1151/10-1, DA1151/11-1Deutsche Forschungsgemeinschaft (German Research Foundation) KI588/14-1, and KI588/14-2, and KI588/20-1, KI588/22-1Deutsche Forschungsgemeinschaft (German Research Foundation) NE2254/1-2, NE2254/2-1, NE2254/3-1, NE2254/4-1International Psychoanalytical Association (IPA) IPA158102845Intramural NIH HHS ZIA MH002927Japan Agency for Medical Research and Development (AMED) JP18dm0307002 and JP24wm0625204National Healthcare Group (NHG) SIG/15012NCATS NIH HHS UL1 TR001872NCCIH NIH HHS R21 AT009173NCCIH NIH HHS R33 AT009864NCCIH NIH HHS R61 AT009864NCRR NIH HHS P41 RR008079NIMH NIH HHS K01 MH117442NIMH NIH HHS K23 MH090421NIMH NIH HHS R01 MH085667NIMH NIH HHS R01 MH085734NIMH NIH HHS R01 MH117601NIMH NIH HHS R01 MH125850NIMH NIH HHS R01 MH129742NIMH NIH HHS R01 MH129832NIMH NIH HHS R01 MH131806NIMH NIH HHS R01 MH134004NIMH NIH HHS R01 MH134236NIMH NIH HHS R37 MH101495Rosetrees Trust CF20212104U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01MH117601, R01MH134004U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01MH131806 and R01MH129742U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01MH131806, R01MH129742U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) UL1TR001872U.S. Department of Health & Human Services | NIH | National Center for Complementary and Integrative Health (NCCIH) R21AT009173, R61AT009864, and R33AT009864U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 1R01MH085667-01A1U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K01MH117442U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K23MH090421U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH085734U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH125850U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH134236U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R37MH101495U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) RO1MH129832 and RO1MH129742583U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) ZIAMH002927
Abstract
The clinical and biological heterogeneity of major depressive disorder (MDD) may reflect the aggregation of different conditions with distinct pathologies under a single diagnostic label. Neuroanatomical heterogeneity in MDD was examined using a harmonized, age- and sex-matched sample from the ENIGMA MDD consortium (N = 5146; age range: 9-82 years; 64% female). Analyses of global neurostrucutral variability revealed greater cortical thickness heterogeneity in MDD compared with healthy controls (Cohen's d = -0.26). Regionally, increased variability in cortical thickness was most prominent in the cingulate (+6.1 to +6.6% more variation in MDD) and insular (+5.8%) cortices, as well as in the frontal (+5.7 to +6.8%) and temporal (+6.1 to +6.8%) lobes. Heterogeneity in cortical thickness was more pronounced among patients using antidepressant medication (Cohen's d = -0.39). Patient-specific analyses further showed that individuals with markedly increased cortical thickness variability (<5
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Cerebral CortexMajor Depressive DisorderAdolescentAdultAgedAged, 80 and overAntidepressive AgentsBrain Cortical ThicknessChildFemaleGyrus CinguliHumansMagnetic Resonance ImagingMaleMiddle AgedYoung AdultAntidepressive Agents
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