Childhood Maltreatment and Deviations From Normative Brain Structure: A Mega-Analysis of 3711 Individuals From the ENIGMA Major Depressive Disorder and ENIGMA Posttraumatic Stress Disorder Working Groups
Biological Psychiatry, vol. 100, pp. 648–661
Abstract
BACKGROUND: Childhood maltreatment (CM), encompassing abuse and neglect, is highly prevalent and associated with elevated risk for major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and other related conditions. However, the extent to which neuroanatomical alterations in MDD and PTSD are attributable to CM is uncertain. METHODS: Here, we analyzed CM and whole-brain magnetic resonance imaging (MRI) data from 3711 participants in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) MDD and PTSD Working Groups (25 sites; mean age = 33.3 ± 13.0 years; 59.9% female). Normative modeling estimated deviation z scores for 14 subcortical volume, 68 cortical thickness (CT), and 68 surface area (SA) measures. To identify transdiagnostic effects, associations between CM and brain deviation scores were evaluated across all participants (patients and healthy control participants) stratified by sex and 3 age bins (pediatric, young adult, older adult). RESULTS: In young adults (ages 18-35), abuse was associated with larger volumes in the thalamus and pallidum, thinner isthmus cingulate and middle frontal regions, and thicker medial orbitofrontal cortex; there were no significant effects in pediatric (≤18 years) participants. The strongest effects were observed in young female adults (|β| = 0.07-0.22, q < .05): Greater abuse and neglect were correlated with smaller hippocampus and putamen volumes, thinner entorhinal cortex, and smaller SA in fusiform/inferior parietal regions and with larger SA in the orbitofrontal and occipital cortices. In males, abuse had widespread effects on CT and SA (|β| = 0.1-0.18, q < .05); effects for neglect were minimal. CONCLUSIONS: Our findings of age- and sex-specific instantiations of CM on brain morphometry highlight the importance of developmental context in understanding how adverse experiences shape neurobiological vulnerability to MDD and PTSD.
Authors 100
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University of California, Los Angeles
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Department of Psychology, University of California Los Angeles, Los Angeles, California; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California
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Montreal Neurological Institute and Hospital · McGill University
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Montréal Neurological Institute, McGill University, Montréal, Québec, Canada
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The University of Melbourne · Orygen
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Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia
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Affiliation as printed
Brain Imaging and Analysis Center, Duke University, Durham, North Carolina
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University of California, Los Angeles
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Department of Psychiatry and Behavioral Sciences, University of California Los Angeles, Los Angeles, California
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Baylor College of Medicine · Yale University
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Department of Psychiatry, Baylor College of Medicine, Houston, Texas; Department of Psychiatry, Yale University, New Haven, Connecticut
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Philipps University of Marburg
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Department of Psychiatry, University of Marburg, Marburg, Germany
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Harvard University · McLean Hospital
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McLean Hospital, Belmont, Massachusetts; Harvard Medical School, Boston, Massachusetts
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University of Münster · University Hospital Münster
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Clinic for Radiology, University of Münster, Münster, Germany
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Vanderbilt University · University of Nebraska Medical Center · Vanderbilt University Medical Center
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Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
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The University of Texas at Austin
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University of Texas at Austin, Austin, Texas
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Affiliation as printed
Department of Biomedical Sciences, Florida State University, Tallahassee, Florida
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Johns Hopkins University · Johns Hopkins Medicine
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Division of Cognitive Neuroscience, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Affiliation as printed
Department of Clinical Psychology, University of Groningen, Groningen, the Netherlands; Trauma Centrum Beilen, Geestelijke Gezondheidszorg Drenthe, Beilen, the Netherlands
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Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Western University · Lawson Health Research Institute · Lawson Research Institute
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Department of Psychiatry, Western University, London, Ontario, Canada; Imaging Division, Lawson Research Institute, London, Ontario, Canada
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Affiliation as printed
Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin; Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, Wisconsin
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King's College London · City St George's, University of London
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Department of Psychology, City St. George's, University of London, London, United Kingdom; Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
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South African Medical Research Council · Stellenbosch University
Affiliation as printed
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
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Stanford University, Stanford, California
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Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Department of Psychology, Marquette University, Milwaukee, Wisconsin
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Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen, Aachen, Germany
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University of East London · King's College London
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Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Psychology, University of East London, London, United Kingdom
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Department of Psychiatry, Ege Üniversitesi School of Medicine, Izmir, Turkey
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Washington University in St. Louis
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Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
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Department of Psychology, Stanford University, Stanford, California
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Universitätsmedizin Göttingen · University of Göttingen
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Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
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Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Affiliation as printed
Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway
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Amsterdam Neuroscience · Amsterdam Public Health · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
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Department of Psychiatry, Amsterdam University Medical Center location, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Mood, Anxiety, Psychosis, Sleep and Stress program, Amsterdam Neuroscience, Amsterdam, the Netherlands; Mental Health program, Amsterdam Public Health, Amsterdam, the Netherlands
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Affiliation as printed
Departments of Psychiatry and of Psychology, Yale University, New Haven, Connecticut
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Duke University · VA Connecticut Healthcare System · National Center for Post Traumatic Stress Disorder
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Brain Imaging and Analysis Center, Duke University, Durham, North Carolina; Clinical Neuroscience Division, National Center for PTSD, Veterans Affairs (VA) Connecticut Healthcare System, West Haven, Connecticut
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University of Wisconsin–Madison
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Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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Heidelberg University · Central Institute of Mental Health
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Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
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Affiliation as printed
Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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University of Southern California
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Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California
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Affiliation as printed
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan
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Harvard University · McLean Hospital
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McLean Hospital, Belmont, Massachusetts; Harvard Medical School, Boston, Massachusetts
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Philipps University of Marburg
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Department of Psychiatry, University of Marburg, Marburg, Germany
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Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Affiliation as printed
Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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University of Bonn · University Hospital Bonn
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Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany
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Yale University · VA Connecticut Healthcare System · National Center for Post Traumatic Stress Disorder
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Clinical Neuroscience Division, National Center for PTSD, Veterans Affairs (VA) Connecticut Healthcare System, West Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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Department of Neuroscience, Western University, London, Ontario, Canada
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University of Wisconsin–Milwaukee
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Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin
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Tel Aviv University · Columbia University Irving Medical Center · Columbia University
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School of Psychological Science, Tel Aviv University, Tel Aviv, Israel; Irving Medical Center, Columbia University, New York, New York
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Harvard University · McLean Hospital
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McLean Hospital, Belmont, Massachusetts; Harvard Medical School, Boston, Massachusetts
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Departments of Comparative Medicine, Neuroscience, and Psychology, Yale University, New Haven, Connecticut
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Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany
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HMU Health and Medical University · Charité - Universitätsmedizin Berlin
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Health and Medical University Potsdam, Potsdam, Germany; Charité Universitätsmedizin Berlin Campus Charité Mitte: Charité Universitätsmedizin Berlin, Berlin, Germany
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Stanford Medicine · Stanford University
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Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California
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Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom
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Harvard University · University of Oregon
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Department of Psychology, Harvard University, Cambridge, Massachusetts; Ballmer Institute for Children's Behavioral Health, University of Oregon, Eugene, Oregon
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Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany
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The University of Texas Health Science Center at Houston
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Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas; School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston, Texas
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Affiliation as printed
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, Minnesota
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Philipps University of Marburg
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Department of Psychiatry, University of Marburg, Marburg, Germany
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Columbia University Irving Medical Center · Columbia University
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Irving Medical Center, Columbia University, New York, New York
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Western University · University of British Columbia · University of British Columbia, Okanagan Campus
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Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, Ontario, Canada; Department of Psychology, University of British Columbia, Kelowna, British Columbia, Canada
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University of Pittsburgh · Center for the Neural Basis of Cognition
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Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania
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Department of Psychology, Vanderbilt University, Nashville, Tennessee
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Crisis Text Line, New York, New York
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University of Münster · Deutsches Zentrum für Psychische Gesundheit
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Institute for Translational Psychiatry, University of Münster, Münster, Germany; German Center for Mental Health, Berlin, Germany
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University of Wisconsin–Madison
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Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin
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Harvard University · McLean Hospital
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Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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Northwestern University, Evanston, Illinois
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Harvard University · McLean Hospital
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Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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Harvard University · Massachusetts General Hospital
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Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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University of Washington, Seattle, Washington
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Heidelberg University · Central Institute of Mental Health · Medizinische Fakultät Mannheim
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Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; German Center for Mental Health, Partner Site Mannheim-Heidelberg-Ulm, Mannheim, Germany
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South African Medical Research Council · Stellenbosch University
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Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
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Brigham and Women's Hospital · Harvard University · Mass General Brigham
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Department of Psychiatry, Mass General Brigham, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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Heidelberg University · Central Institute of Mental Health · Medizinische Fakultät Mannheim
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Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; German Center for Mental Health, Partner Site Mannheim-Heidelberg-Ulm, Mannheim, Germany
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Charité - Universitätsmedizin Berlin
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Charité Universitätsmedizin Berlin Campus Charité Mitte: Charité Universitätsmedizin Berlin, Berlin, Germany
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The University of Texas Health Science Center at Houston
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Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas; School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston, Texas
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South African Medical Research Council · University of Cape Town
Affiliation as printed
South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Philipps University of Marburg
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Department of Psychiatry, University of Marburg, Marburg, Germany
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University of California San Diego
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Department of Psychiatry, University of California San Diego, La Jolla, California
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University of Rochester Medicine · University of Rochester
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Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York
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Western University · Lawson Health Research Institute · Lawson Research Institute
Affiliation as printed
Department of Psychiatry, Western University, London, Ontario, Canada; Imaging Division, Lawson Research Institute, London, Ontario, Canada
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University of Southern California
Affiliation as printed
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California
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Affiliation as printed
Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Epidemiology and Social Sciences, Institute of Health and Humanity, Medical College of Wisconsin, Milwaukee, Wisconsin
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Philipps University of Marburg
Affiliation as printed
Department of Psychiatry, University of Marburg, Marburg, Germany
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South African Medical Research Council · Stellenbosch University
Affiliation as printed
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
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Affiliation as printed
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Division of Mind and Brain Research, Department for Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany
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Affiliation as printed
Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany; German Center for Mental Health, Partner Site Halle-Jena-Magdeburg, Jena, Germany
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Affiliation as printed
Department of Neuroscience and Psychiatry, University of Toledo, Toledo, Ohio
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Affiliation as printed
Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom
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Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
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The University of Texas Health Science Center at Houston
Affiliation as printed
Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas; School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston, Texas
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Affiliation as printed
Department of Neuroscience and Psychiatry, University of Toledo, Toledo, Ohio
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University of California, San Francisco · University of California San Francisco Medical Center
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Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco School of Medicine, San Francisco, California
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The University of Texas at Arlington
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Department of Bioengineering, University of Texas at Arlington, Arlington, Texas
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Affiliation as printed
School of Psychological Science, University of Haifa, Haifa, Israel
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