title: Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.
abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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authors.initials: L
authors.lastname: Schmaal
authors.affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Hibar
authors.affiliation: Neuroimaging Core Unit, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: P G
authors.initials: PG
authors.lastname: Sämann
authors.affiliation: Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada.
authors.forename: G B
authors.initials: GB
authors.lastname: Hall
authors.affiliation: Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
authors.forename: B T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Cheung
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors.forename: T G M
authors.initials: TGM
authors.lastname: van Erp
authors.affiliation: Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Bos
authors.affiliation: Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Child and Adolescent Psychiatry, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: H
authors.identifier: 0000-0002-4395-1397
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
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authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wittfeld
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.|Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
authors.forename: H J
authors.initials: HJ
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authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
authors.forename: D
authors.identifier: 0000-0003-4324-9298
authors.initials: D
authors.lastname: Janowitz
authors.affiliation: Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bülow
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Selonke
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.|German Center for Cardiovascular Research (DZHK), partner site Griefswald, Greifswald, Germany.|German Center for Diabetes Research (DZD), partner site Griefswald, Greifswald, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Grotegerd
authors.affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany.|Department of Psychiatry, University of Marburg, Marburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Dannlowski
authors.affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Opel
authors.affiliation: Department of Clinical Radiology, University of Muenster, Muenster, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Heindel
authors.affiliation: Department of Clinical Radiology, University of Muenster, Muenster, Germany.
authors.forename: H
authors.identifier: 0000-0002-4349-1984
authors.initials: H
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authors.affiliation: Neuroimaging Core Unit, Max Planck Institute of Psychiatry, Munich, Germany.
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authors.affiliation: Neuroimaging Core Unit, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Czisch
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.|Center for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.|Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
authors.forename: B
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authors.affiliation: Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
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authors.initials: ME
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authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: L T
authors.initials: LT
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authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.|Center for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.
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authors.initials: MJ
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authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.|Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
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authors.initials: NT
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authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
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authors.initials: GI
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authors.affiliation: Center for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.
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authors.affiliation: Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
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authors.affiliation: Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
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authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA.
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authors.affiliation: Centre for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: R
authors.initials: R
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authors.affiliation: Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
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authors.affiliation: Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
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authors.affiliation: Clinical Research Unit, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
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authors.initials: SN
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authors.affiliation: Clinical Research Unit, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
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authors.affiliation: Clinical Research Unit, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
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authors.affiliation: Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany.|Department of Psychiatry and Institute of Neuroscience, Trinity College, Dublin, Ireland.
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authors.initials: T
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authors.affiliation: Department of Psychiatry and Institute of Neuroscience, Trinity College, Dublin, Ireland.
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authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
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authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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authors.affiliation: Neuroimaging Center, Section of Cognitive Neuropsychiatry, Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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authors.affiliation: Department of Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, The Netherlands.
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authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia.|Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.|Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.
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authors.affiliation: UT Center of Excellence on Mood Disoders, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
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authors.affiliation: UT Center of Excellence on Mood Disoders, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
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authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
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authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
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authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
authors.forename: D
authors.identifier: 0000-0001-5611-892X
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authors.affiliation: Center for Integrative Psychiatry, University of Lübeck, Lübeck, Germany.
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authors.affiliation: Department of Psychiatry, University of Marburg, Marburg, Germany.|Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum Rotenburg, Rotenburg, Germany.
authors.forename: C
authors.identifier: 0000-0001-7015-3860
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authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: E
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authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
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authors.affiliation: Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
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authors.affiliation: Neurosciences Program and Department of Psychology, Stanford University, Stanford, CA, USA.
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authors.initials: MD
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authors.affiliation: Neurosciences Program and Department of Psychology, Stanford University, Stanford, CA, USA.
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authors.affiliation: Department of Psychiatry, University of Calgary, Calgary, AB, Canada.
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authors.initials: GM
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authors.affiliation: University Department of Psychiatry, Warneford Hospital, Oxford, UK.
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authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
authors.forename: T
authors.initials: T
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authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.|Centre for Cogntive Ageing and Cogntive Epidemiology, University of Edinburgh, Edinburg, UK.
authors.forename: A M
authors.initials: AM
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authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.|Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
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authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
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authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.|Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
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authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.|Department of Psychiatry, NHS Borders, Melrose, UK.
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authors.affiliation: Leibniz Institute for Neurobiology, Magdeburg, Germany.
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authors.affiliation: Leibniz Institute for Neurobiology, Magdeburg, Germany.|Department of Psychiatry, University Tübingen, Tübingen, Germany.
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authors.affiliation: Department of Experimental and Clinical Neuroscience, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia.
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authors.initials: L
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authors.affiliation: Department of Experimental and Clinical Neuroscience, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia.
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authors.initials: I
authors.lastname: Brack
authors.affiliation: Mental Health Research Institute, Tomsk, Russia.|Faculty of Psychology, National Research Tomsk State University, Tomsk, Russia.|Department of General Medicine, Siberian State Medical University, Tomsk, Russia.
authors.forename: N A
authors.initials: NA
authors.lastname: Bokhan
authors.affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Veltman
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D066128:Gray Matter / Q000473:pathology; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D059906:Neuroimaging / Q000379:methods / Q000523:psychology; D017397:Prefrontal Cortex / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology