ArticleMolecular psychiatry2025
Regional brain morphology and current antidepressant use: findings from 32 international cohorts from the ENIGMA major depressive disorder working group.
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Article in Molecular psychiatry, 2025. 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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- Prenatal antidepressant exposure is associated withFrontiers in neuroscience · 2026Article
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104 authors.
Chaira SerrarensDepartment of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands.
Yara J ToendersOrygen, Parkville, VIC, Australia.ORCID 0000-0002-4117-1143
Elena PozziOrygen, Parkville, VIC, Australia.
André AlemanUniversity of Groningen, Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells & Systems, University Medical Center Groningen, Groningen, the Netherlands.
Nina AlexanderPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
Zeynep BaşgözeDepartment of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0002-0306-4849
Vladimir BelovLaboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen (UMG), Göttingen, Germany.
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany.
Katharina BroschPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0002-0526-8095
Robin BülowInstitute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0003-1884-5784
Geraldo Filho BusattoLaboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brasil.ORCID 0000-0003-4749-4602
Liliana P CapitãoPsychological Neuroscience Laboratory, Psychology Research Centre (CIPsi), School of Psychology, University of Minho, Braga, Portugal.ORCID 0000-0003-3117-5156
Colm G ConnollyDepartment of Biomedical Sciences, Florida State University, Tallahassee, FL, USA.
Baptiste Couvy-DuchesneUniversity of Queensland, Institute for Molecular Bioscience, St. Lucia, QLD, Australia.ORCID 0000-0002-0719-9302
Kathryn R CullenDepartment of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0001-9631-3770
Udo DannlowskiInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Christopher G DaveyDepartment of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0003-1431-3852
Greig I de ZubicaraySchool of Psychology and Counseling, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.ORCID 0000-0003-4506-0579
Danai DimaDepartment of Psychology, School of Health and Psychological Sciences, City, University of London, London, UK.
Katharina DohmInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Verena EnnekingInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Tracy Erwin-GrabnerLaboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen (UMG), Göttingen, Germany.
Ulrika EvermannPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0002-3250-7821
Cynthia H Y FuUniversity of East London, School of Psychology, London, UK.ORCID 0000-0003-4313-3500
Paola Fuentes-ClaramonteFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.ORCID 0000-0002-1428-7976
Beata R GodlewskaClinical Psychopharmacology Group, Department of Psychiatry, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-5973-3765
Ali Saffet GonulSoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.
Ian H GotlibDepartment of Psychology, Stanford University, Stanford, USA.ORCID 0000-0002-3622-3199
Roberto Goya-MaldonadoLaboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen (UMG), Göttingen, Germany.ORCID 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 0000-0002-0865-8427
Dominik GrotegerdInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0001-8718-0128
Oliver GruberSection for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
Tim HahnInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0001-6541-3795
Geoffrey HallDepartment of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada.
Ben J HarrisonDepartment of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.
Walter HeindelUniversity Clinic for Radiology, University of Münster, Münster, Germany.
Marco HermesdorfInstitute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany.
Tiffany C HoDepartment of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
Naho IchikawaDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Eri ItaiDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Neda JahanshadImaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Hamidreza JamalabadiPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0003-2485-2374
Alec J JamiesonDepartment of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0002-5598-0240
Andreas JansenPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
Tilo KircherPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0002-2514-2625
Bonnie Klimes-DouganDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0002-2107-0038
Bernd KrämerSection for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.ORCID 0000-0002-1145-9103
Axel KrugPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0002-0564-2497
Thomas M LancasterCardiff University Brain Research Imaging Center (CUBRIC), Cardiff University, Maindy Road, Cardiff, UK.
Elisabeth J LeehrInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0002-9264-5003
Meng LiDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.ORCID 0000-0002-8320-5241
David E J LindenDepartment of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands.
Frank MacMasterIWK Health, NS, Halifax, Canada.
Katie L McMahonSchool of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.ORCID 0000-0002-6357-615X
Sarah E MedlandQIMR Berghofer Medical Research Institute, Herston, Australia.ORCID 0000-0003-1382-380X
David M A MehlerInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0001-6587-2617
Susanne MeinertInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0003-2177-7161
Benson MwangiCenter of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA.
Igor NenadićPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
Go OkadaDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Yasumasa OkamotoDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Nils OpelInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0003-4749-3298
Julia-Katharina PfarrPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
Edith Pomarol-ClotetFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
Maria J PortellaCIBERSAM ISCIII, Madrid, Spain.ORCID 0000-0002-2007-9516
Ronny RedlichInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Liesbeth RenemanAmsterdam University Medical Centers, location AMC, department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands.
Jonathan ReppleInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Kai RingwaldPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
Elena Rodriguez-CanoFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.ORCID 0000-0002-5011-567X
Pedro G P RosaLaboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brasil.
Matthew D SacchetMeditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Philipp G SämannMax Planck Institute of Psychiatry, Munich, Germany.ORCID 0000-0001-8523-3628
Raymond SalvadorFIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
Anouk SchranteeAmsterdam University Medical Centers, location AMC, department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands.ORCID 0000-0002-4035-4845
Hotaka ShinzatoDepartment of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID 0000-0002-0354-1801
Kang SimWest Region, Institute of Mental Health, Singapore, Singapore.
Egle SimulionyteSection for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
Jair C SoaresCenter of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA.ORCID 0000-0002-5466-5628
Dan J SteinSAMRC Unit on Risk & Resilience, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID 0000-0001-7218-7810
Frederike SteinPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0002-5052-6022
Benjamin StraubePhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0002-9837-0944
Lachlan T StrikeQIMR Berghofer Medical Research Institute, Herston, Australia.
Florian Thomas-OdenthalPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
Sophia I ThomopoulosImaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-0046-4070
Paul M ThompsonImaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Marie-Jose van TolUniversity Medical Center Groningen, Cognitive Neuroscience Center, University of Groningen, Groningen, the Netherlands.ORCID 0000-0002-9260-5490
Paula UsemannPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
Aslihan UyarSoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.ORCID 0000-0002-0856-4260
Nic van der WeeDepartment of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Steven van der WerffDepartment of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Yolanda Vives-GilabertIntelligent Data Analysis Laboratory, Department of Electronic Engineering, University of Valencia (UV), Valencia, Spain.
Henry VölzkeGerman Center for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany.
Martin WalterDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.ORCID 0000-0001-7857-4483
Sarah WhittleDepartment of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0003-3145-1528
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0003-4383-5043
Adrian WroblewskiPhilipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.ORCID 0000-0002-0371-7686
Mon-Ju WuCenter of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA.ORCID 0000-0002-0540-8027
Tony T YangDepartment of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute of Neurosciences, UCSF School of Medicine, San Francisco, USA.
Giovana B Zunta-SoaresCenter of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA.
Dick J VeltmanAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands.
Lianne Schmaal *Orygen, Parkville, VIC, Australia. lianne.schmaal@unimelb.edu.au.ORCID 0000-0001-9822-048X
Laura S van Velzen *Orygen, Parkville, VIC, Australia.ORCID 0000-0002-6003-5227
Funding
Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1MZOOMED 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
$16.3MTR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2012 to 2022
$14.1MPsychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across AdolescenceR37MH101495 · NIMH · STANFORD UNIVERSITY · PI IAN H GOTLIB · 2018 to 2026
$6.6MInflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents with Depression: Toward Predictors of Treatment Response and Clinical CourseR01MH127176 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TIFFANY CHEING HO · 2022 to 2026
$3.1MENIGMA 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
$2.6MGenetic 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
$2.5MDepartment of Health | National Health and Medical Research Council (NHMRC) 1024570Department of Health | National Health and Medical Research Council (NHMRC) 1064643Department of Health | National Health and Medical Research Council (NHMRC) 1161356Department of Health | National Health and Medical Research Council (NHMRC) 2017962NCATS NIH HHS UL1 TR001872NCCIH NIH HHS R21 AT009173NCCIH NIH HHS R33 AT009864NCCIH NIH HHS R61 AT009864NCRR NIH HHS P41 RR008079NIBIB NIH HHS P41 EB015922NICHD NIH HHS R01 HD050735NIMH NIH HHS K01 MH117442NIMH NIH HHS K23 MH090421NIMH NIH HHS R01 MH085667NIMH NIH HHS R01 MH085734NIMH NIH HHS R01 MH116147NIMH NIH HHS R01 MH117601NIMH NIH HHS R01 MH125850NIMH NIH HHS R01 MH127176NIMH NIH HHS R01 MH129742NIMH NIH HHS R01 MH129832NIMH NIH HHS R01 MH131806NIMH NIH HHS R01 MH134004NIMH NIH HHS R01 MH134236NIMH NIH HHS R21 MH130817NIMH NIH HHS R37 MH101495NIMH NIH HHS U01 MH119740U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) K01MH117442, R01MH127176,R21MH130817U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) R01MH116147, R01MH117601, R01MH134004, P41EB015922U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 5U01MH119740-05U.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) MH117601U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH129742U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH129832U.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) R37MH101495
Abstract
The understanding of how antidepressant (AD) use is associated with brain structure in individuals with major depressive disorder (MDD) remains incomplete. We aimed to examine the association between AD medication use and brain morphology in relation to age and sex by pooling structural neuroimaging and clinical data from 32 cohorts within the ENIGMA-MDD working group. Interaction effects of group (2076 cases with current AD use (AD), 1495 cases not currently taking AD (nAD) and 5125 healthy controls (HC)) with age and sex, and main effects of group on regional brain structure (cortical surface area and thickness, and subcortical volume) were examined. Additionally, we examined the effect of AD type (SSRI, SNRI or mirtazapine) and duration of use on brain morphology. Younger individuals in the AD group showed lower bilateral middle temporal gyrus thickness compared to nAD and HC, but this was not seen in older individuals (crossover around 50 years). Lower hippocampal volume and thinner inferior temporal gyrus were shown in AD compared to nAD. These effects were independent of group differences in disease-course-related measures, but were driven by depressive symptom severity. Greater bilateral rostral anterior cingulate thickness was found in individuals older than approximately 40 years taking mirtazapine compared to individuals taking SSRIs or SNRIs. Evidence for subtle structural brain differences in temporal and limbic regions in individuals with MDD who currently use AD medication were found compared to those not currently taking AD medication. Future longitudinal studies are needed to determine the causality of these associations.
Indexed as
Antidepressive AgentsBrainMajor Depressive DisorderAdultAgedCohort StudiesFemaleHippocampusHumansMagnetic Resonance ImagingMaleMianserinMiddle AgedMirtazapineNeuroimagingSelective Serotonin Reuptake InhibitorsAntidepressive AgentsMianserinMirtazapineSelective Serotonin Reuptake Inhibitors
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