IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Academic Child Psychiatry Unit Department of Pediatrics University of Melbourne Royal Children's Hospital Melbourne Australia

Amsterdam UMC University of Amsterdam Department of Psychiatry Amsterdam Neuroscience Amsterdam the Netherlands

Amsterdam UMC Vrije Universiteit Amsterdam Department of Psychiatry Department of Anatomy and Neuroscience Amsterdam Neuroscience Amsterdam the Netherlands

Anxiety Disorders Center The Institute of Living Hartford Connecticut

Behavioral Neuroscience Department Oregon Health and Science University Portland

Biomedical Network Research Centre on Mental Health Barcelona Catalonia Spain

Bloorview Research Institute Holland Bloorview Kids Rehabilitation Hospital Toronto Ontario Canada

Campbell Family Mental Health Institute Centre for Addiction and Mental Health University of Toronto Toronto Ontario Canada

Center for Child and Adolescent Mental Health Institute of Mental Health Norwegian University of Science and Technology Trondheim Norway

Center for Depression Anxiety and Stress Research McLean Hospital Harvard Medical School Belmont Massachusetts

Center for MR Research University Children's Hospital Zürich Switzerland

Center for Neurobehavioral Genetics University of California Los Angeles

Central Clinical Hospital of the Russian Academy Sciences Moscow Russia

Centre for Integrative Neuroscience and Neurodynamics School of Psychology and Clinical Language Sciences University of Reading Reading England

Centre for Neuroimaging and Cognitive Genomics Clinical Neuroimaging Laboratory NCBES Galway Neuroscience Centre College of Medicine Nursing and Health Sciences National University of Ireland Galway H91 TK33 Galway Ireland

Centre for Psychiatry Research Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Centre for Youth Mental Health The University of Melbourne Melbourne Australia

Centro de Investigación Biomédica en Red de Salud Mental ; University of Barcelona Spain

Child Neuropsychology Section Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy University Hospital RWTH Aachen Aachen Germany

Child Neuropsychology Section University Hospital RWTH Aachen German; JARA Brain Institute 2 Molecular Neuroscience and Neuroimaging Research Centre Juelich Juelich Germany

Child OCD and Anxiety Disorders Program Department of Psychiatry University of Michigan Medical School Ann Arbor

Clinical Translational Neuroscience Laboratory University of California Irvine Irvine CA; Center for the Neurobiology of Learning and Memory University of California Irvine

Columbia University Irving Medical Center New York New York

Department for Child and Adolescent Psychiatry University Hospital RWTH Aachen Aachen Germany

Department of Basic Medical Science Neuroscience and Sense Organs University of Bari 'Aldo Moro' Bari Italy

Department of Bioengineering Imperial College London London England

Department of Biological and Medical psychology University of Bergen Bergen Norway

Department of Biomedicine University of Bergen Bergen Norway

Department of Child and Adolescent Psychiatry and Psychology Hospital Clinic Barcelona Spain

Department of Child and Adolescent Psychiatry and Psychotherapy Central Institute of Mental Health Mannheim Medical Faculty Mannheim Heidelberg University Mannheim Germany

Department of Child and Adolescent Psychiatry Institute of Psychiatry and Mental Health Hospital General Universitario Gregorio Marañón IiSGM CIBERSAM Spain

Department of Child and Adolescent Psychiatry Institute of Psychiatry and Mental Health Hospital General Universitario Gregorio Marañón IiSGM Facultad de Psicologia Universidad Autónoma de Madrid

Department of Child and Adolescent Psychiatry Institute of Psychiatry and Mental Health Hospital General Universitario Gregorio Marañón IiSGM School of Medicine Universidad Complutense CIBERSAM

Department of Child and Adolescent Psychiatry Institute of Psychiatry Psychology and Neuroscience King's College London De Crespigny Park London UK; Zurich Center for Neuroeconomics University of Zurich Zurich Switzerland

Department of Child and Adolescent Psychiatry Institute of Psychiatry Psychology and Neuroscience King's College London London England

Department of Child and Adolescent Psychiatry New York University Child Study Center Hassenfeld Children's Hospital at NYU Langone New York

Department of Child and Adolescent Psychiatry Psychology Erasmus University Medical Centre Rotterdam the Netherlands

Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy University Hospital of Tübingen Tübingen Germany

Department of Child and Adolescent Psychiatry RWTH Aachen University Hospital Aachen Germany

Department of Clinical and Experimental Medicine University of Pisa

Department of Clinical Medicine University of Bergen Bergen Norway

Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Department of Cognitive Neuroscience Donders Institute for Brain Cognition and Behaviour Radboud UMC Nijmegen the Netherlands

Department of Developmental Neuroscience IRCCS Fondazione Stella Maris Pisa Italy

Department of Experimental Psychology Vrije Universiteit Amsterdam Netherlands

Department of Forensic and Neurodevelopmental Science King's College London London England

Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry Psychology and Neuroscience King's College London England

Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry Psychology and Neuroscience King's College London Sackler Institute for Translational Neurodevelopment London London England

Department of Genetics Instituto de Biociências Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil

Department of Human Genetics Radboud University Medical Center Donders Institute for Brain Cognition and Behaviour Nijmegen The Netherlands

Department of Internal Medicine 1st Affiliated Hospital of Kunming Medical University Kunming China

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Neuroimaging Institute of Psychiatry Psychology and Neuroscience King's College London De Crespigny Park London England

Department of Neuropsychiatry University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Toyama Japan

Department of Neuroradiology Klinikum Rechts der Isar Technische Universität München Munich Germany

Department of Neuroscience Brighton and Sussex Medical School Brighton England

Department of Neuroscience Brighton and Sussex Medical School University of Sussex Brighton England

Department of Pathology of Mental Diseases National Institute of Mental Health National Center of Neurology and Psychiatry Tokyo Japan

Department of Pediatrics University of California Irvine

Department of Pediatrics University of Toronto Ontario Canada

Department of Physiology and Pharmacology Wake Forest School of Medicine Winston Salem North Carolina

Department of Psychiatry 1st Affiliated Hospital of Kunming Medical University Kunming China

Department of Psychiatry Amsterdam UMC Amsterdam the Netherlands

Department of Psychiatry Amsterdam UMC location VUMC Amsterdam the Netherlands

Department of Psychiatry and Behavioral Sciences University of Minnesota Minneapolis Minnesota

Department of Psychiatry and Biological Sciences Albert Einstein College of Medicine the Bronx New York

Department of Psychiatry and Forensic Medicine Autonomous University of Barcelona Cerdanyola del Vallès Barcelona Spain

Department of Psychiatry and Human Behavior University of California Irvine

Department of Psychiatry and Mental Health University of Cape Town Cape Town South Africa

Department of Psychiatry and Neuropsychology Maastricht University Maastricht the Netherlands

Department of Psychiatry and Neuropsychology School of Mental Health and Neuroscience Maastricht University the Netherlands

Department of Psychiatry and Psychotherapy Philipps University Marburg Marburg Germany

Department of Psychiatry and Psychotherapy University Medicine Greifswald Greifswald Germany

Department of Psychiatry and Psychotherapy University of Bonn Germany

Department of Psychiatry and Weill Institute for Neurosciences University of California San Francisco

Department of Psychiatry Bellvitge University Hospital Bellvitge Biomedical Research Institute IDIBELL; Centro de Investigación Biomédica en Red de Salud Mental Barcelona Spain

Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada

Department of Psychiatry Faculdade de Medicina Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil

Department of Psychiatry Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan

Department of Psychiatry Hospital Universitari Vall d'Hebron Barcelona Catalonia Spain; Group of Psychiatry Mental Health and Addictions Vall d'Hebron Research Institute Barcelona Catalonia Spain; Department of Psychiatry and Forensic Medicine Universitat Autònoma de Barcelona Barcelona Catalonia Spain

Department of Psychiatry Johns Hopkins University School of Medicine Baltimore Maryland

Department of Psychiatry Leiden University Medical Center Leiden the Netherlands

Department of Psychiatry Marqués de Valdecilla University Hospital IDIVAL School of Medicine University of Cantabria; Centro de Investigación Biomédica en Red de Salud Mental Santander Spain

Department of Psychiatry Marqués de Valdecilla University Hospital IDIVAL School of Medicine University of Cantabria; Centro de Investigación Biomédica en Red de Salud Mental Sevilla Spain

Department of Psychiatry Maryland Psychiatric Research Center University of Maryland School of Medicine Baltimore Maryland

Department of Psychiatry New York University School of Medicine Nathan Kline Institute New York

Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia

Department of Psychiatry Philipps University Marburg Marburg Germany

Department of Psychiatry Psychosomatic Medicine and Psychotherapy University Hospital Frankfurt Germany

Department of Psychiatry Seoul National University College of Medicine Seoul Korea

Department of Psychiatry Trinity College Dublin Dublin Ireland

Department of Psychiatry University Medical Center Groningen University of Groningen Groningen the Netherlands

Department of Psychiatry University Medical Center Utrecht Utrecht University Utrecht the Netherlands

Department of Psychiatry University of Basel Basel Switzerland

Department of Psychiatry University of British Columbia Vancouver British Columbia Canada

Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania

Department of Psychiatry University of Tuebingen Tuebingen Germany

Department of Psychiatry Vagelos College of Physicians and Surgeons Columbia University New York New York

Department of Psychiatry Yale University New Haven Connecticut

Department of Psychology and Center of Mental Health University of Würzburg Würzburg Germany

Department of Psychology School of Arts and Social Sciences City University of London Northampton Square Clerkenwell London England

Department of Psychology Stanford University Stanford California

Department of Psychology University of Bath Bath England

Department of Psychology University of Oslo Oslo Norway

Department of Radiology and Nuclear Medicine Amsterdam University Medical Centers University of Amsterdam Amsterdam the Netherlands

Departments of Human Genetics and Psychiatry Radboud University Medical Center Donders Institute for Brain Cognition and Behaviour Nijmegen The Netherlands

Departments of Paediatrics and Psychiatry University of Melbourne Melbourne Australia

Departments of Psychiatry and of Neuroscience and Physiology SUNY Upstate Medical University Syracuse New York

Departments of Psychiatry and Pediatrics University of Calgary Calgary Alberta Canada

Departments of Psychology and Psychiatry University of Toronto Toronto Ontario Canada

Developmental Imaging Murdoch Children's Research Institute Melbourne Australia

Division of Child and Adolescent Psychiatry Department of Psychiatry Lausanne University Hospital Lausanne Switzerland; Child and Adolescent Mental Health Center Mental Health Services Capital Region of Denmark Denmark

Division of Molecular Psychiatry Center of Mental Health University of Würzburg Würzburg Germany

Division of Psychiatry University of Edinburgh Royal Edinburgh Hospital Edinburgh Scotland

Division of Psychological and Social Medicine and Developmental Neurosciences Faculty of Medicine TU Dresden Dresden Germany

Donders Centre for Cognitive Neuroimaging Radboud University Medical Centre Nijmegen the Netherlands

Emma Children's Hospital Amsterdam UMC University of Amsterdam Emma Neuroscience Group department of Pediatrics Amsterdam Reproduction and Development Amsterdam the Netherlands

FIDMAG Germanes Hospitalàries Research Foundation Barcelona Spain

FIDMAG Germanes Hospitalàries Research Foundation Centro de Investigación Biomédica en Red de Salud Mental Barcelona Catalonia Spain

Genentech Inc South San Francisco California

German Center for Neurodegenerative Diseases Rostock Greifswald Germany

Group of Research in Mental Health Institut d'Investigació Biomèdica Sant Pau IIBSant Pau; Centro de Investigación Biomédica en Red de Salud Mental Barcelona Spain

Hospital Clinic University of Barcelona Spain

Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine University of Southern California Los Angeles

Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Bipolar Disorders and Depressive Unit Hospital Clinic Institute of Neurosciences University of Barcelona Barcelona Spain

Institute for Community Medicine University Medicine Greifswald Greifswald Germany

Institute for Diagnostic Radiology and Neuroradiology University Medicine Greifswald Greifswald Germany

Institute of Medical Science University of Toronto Toronto Ontario Canada

Institute of Psychiatry University of Sao Paulo Sao Paulo Brazil

Instituto ITACA Universitat Politècnica de València Valencia Spain

INT UMR 7289 Aix Marseille Université CNRS Aix en Provence France

IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo Italy

Krembil Centre for Neuroinformatics Centre for Addiction and Mental Health Toronto Ontario Canada

Laboratory of Medical Physics and Magnetic Resonance IRCCS Fondazione Stella Maris Pisa Italy

Laboratory of Neuropsychiatry IRCCS Santa Lucia Foundation Rome Italy

Laboratory of Psychiatric Neuroimaging Departamento e Instituto de Psiquiatria Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Sao Paulo Brazil

Life and Health Sciences Research Institute School of Medicine University of Minho Braga Portugal

Louis A Faillace MD Department of Psychiatry and Behavioral Sciences The University of Texas Health Science Center at Houston

Magnetic Resonance Image Core Facility Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

McLean Hospital Harvard Medical School Belmont Massachusetts

McMaster University Mood Disorders Program SJH Hamilton Hamilton Ontario Canada

Melbourne Neuropsychiatry Centre Department of Psychiatry The University of Melbourne and Melbourne Health Melbourne Victoria Australia

Melbourne Neuropsychiatry Centre University of Melbourne Melbourne Australia

Mental Health Research Center Moscow Russia

Montreal Neurological Institute McGill University Montreal Quebec Canada

National Human Genome Research Institute and National Institute of Mental Health Bethesda Maryland

National Institute for Nuclear Physics Pisa Division Pisa Italy

National Institute of Mental Health Klecany Czech Republic

Neuroimaging Unit Technological Facilities Valdecilla Biomedical Research Institute IDIVAL; Centro de Investigación Biomédica en Red de Salud Mental Santander Spain

Neuroscience Institute University of Cape Town Cape Town South Africa

Neuroscience Research Australia Sydney Australia

Neuroscience Research Australia Sydney New South Wales Australia

Norwegian Centre for Mental Disorders Research Institute of Clinical Medicine University of Oslo Oslo Norway

OCD clinic Department of Psychiatry National Institute of Mental Health and Neurosciences Bangalore India

Orygen Melbourne Australia

Orygen The National Centre of Excellence in Youth Mental Health Parkville Australia

Pediatric OCD Consultation Clinic Anxiety Treatment and Research Center SJH Hamilton Ontario Canada

Priority Centre for Brain and Mental Health Research The University of Newcastle Callaghan New South Wales Australia

Psychiatry and Clinical Psychobiology Division of Neuroscience Scientific Institute Ospedale San Raffaele Milano Italy

Psychology Department and Neuroscience Institute Georgia State University Atlanta Georgia

Radboud University Medical Center Karakter University Center of Child And Adolescent Psychiatry Nijmegen the Netherlands

Research Center for Child Mental Development Chiba University Chiba Japan

Research Institute of Pediatrics and child health of the Central clinical hospital of the Ministry of Science and Education Moscow Russia

Rudolf Magnus Institute of Neuroscience University Medical Center Utrecht Department of Psychiatry Utrecht the Netherlands

SA MRC Unit on Risk and Resilience in Mental Disorders Department of Psychiatry Stellenbosch University Stellenbosch South Africa

SAMRC Unit on Risk and Resilience in Mental Disorders Department of Psychiatry and Neuroscience Institute University of Cape Town Cape Town South Africa

San Francisco VA Medical Center San Francisco California

School of Psychiatry University of New South Wales Randwick New South Wales Australia

School of Psychiatry University of New South Wales Sydney New South Wales Australia

School of Psychology Deakin University Geelong Melbourne Australia

Section for Experimental Psychopathology and Neuroimaging Department of General Psychiatry Heidelberg University Hospital Heidelberg Germany

Seoul National University Hospital Seoul Republic of Korea

Social Genetic and Developmental Psychiatry Centre; Institute of Psychiatry Psychology and Neuroscience; King's College London London England

The Centre for Addiction and Mental Health Campbell Family Mental Health Research Institute University of Toronto Toronto Ontario Canada

The Hospital for Sick Children Toronto Ontario Canada

The Mathison Centre for Mental Health Research and Education Hotchkiss Brain Institute Cumming School of Medicine University of Calgary Calgary Alberta Canada

The Research Institute of Pediatrics and Child Health of the Central Clinical Hospital of the Russian Academy of Sciences of the Ministry of Science and Higher Education of the Russian Federation Moscow Russia

Tommy Fuss Center for Neuropsychiatric Disease Research Department of Psychiatry Boston Children's Hospital Harvard Medical School Boston Massachusetts

Tri institutional Center for Translational Research in Neuroimaging and Data Science Georgia State University Georgia Institute of Technology Emory University Atlanta Georgia

Turner Institute for Brain and Mental Health School of Psychological Sciences Monash University Melbourne Australia

University Centre for Information Technology University of Oslo Oslo Norway

University Medical Center Goettingen Department of Psychiatry and Psychotherapy Systems Neuroscience and Imaging in Psychiatry Göettingen Germany

University of California San Francisco Department of Psychiatry Division of Child and Adolescent Psychiatry University of California San Francisco Weill Institute for Neurosciences

University of East London School of Psychology London England

University of Groningen University Medical Center Groningen Department of Biomedical Sciences of Cells and Systems Cognitive Neuroscience Center Groningen the Netherlands

University of Groningen University Medical Center Groningen Department of Child and Adolescent Psychiatry Groningen the Netherlands

University of Groningen University Medical Center Groningen Department of Psychiatry Interdisciplinary Center Psychopathology and Emotion regulation Groningen the Netherlands

University of Münster Department of Psychiatry Münster Germany

University of Oxford Oxford England

West Region Institute of Mental Health Singapore

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JAMA Psychiatry. 2021 Jan 1;78(1):112. doi: 10.1001/jamapsychiatry.2020.3094. PubMed

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Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study