Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets

  • Merel C. Postema
    Language and Genetics Department Max Planck Institute for Psycholinguistics Nijmegen The Netherlands
  • Martine Hoogman
    Department of Human Genetics Radboud University Medical Center Nijmegen Netherlands
  • Sara Ambrosino
    NICHE lab Department of Psychiatry University Medical Center Utrecht Brain Center Utrecht University Utrecht The Netherlands
  • Philip Asherson
    Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
  • Tobias Banaschewski
    Department of Child and Adolescent Psychiatry and Psychotherapy Central Institute of Mental Health Medical Faculty Mannheim/Heidelberg University Mannheim Germany
  • Cibele E. Bandeira
    Adulthood ADHD Outpatient Program (ProDAH) Clinical Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
  • Alexandr Baranov
    Research Institute of Pediatrics and Child Health of Central Clinical Hospital of the Russian Academy of Sciences of the Ministry of Science and Higher Education of the Russian Federation Moscow Russia
  • Claiton H.D. Bau
    Adulthood ADHD Outpatient Program (ProDAH) Clinical Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
  • Sarah Baumeister
    Department of Child and Adolescent Psychiatry and Psychotherapy Central Institute of Mental Health Medical Faculty Mannheim/Heidelberg University Mannheim Germany
  • Ramona Baur‐Streubel
    Department of Biological Psychology Clinical Psychology and Psychotherapy University of Würzburg Würzburg Germany
  • Mark A. Bellgrove
    Turner Institute for Brain and Mental Health and School of Psychological Sciences Monash University Melbourne Vic. Australia
  • Joseph Biederman
    Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD Boston MA USA
  • Janita Bralten
    Department of Human Genetics Radboud University Medical Center Nijmegen Netherlands
  • Daniel Brandeis
    Department of Child and Adolescent Psychiatry and Psychotherapy Psychiatric Hospital University of Zurich Zurich Switzerland
  • Silvia Brem
    The Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland
  • Jan K. Buitelaar
    Department of Cognitive Neuroscience Donders Institute for Brain, Cognition and Behaviour Radboudumc Nijmegen The Netherlands
  • Geraldo F. Busatto
    Laboratory of Psychiatric Neuroimaging (LIM‐21 Department and Institute of Psychiatry Hospital das Clinicas HCFMUSP Faculty of Medicine University of São Paulo Sao Paulo Sao Paulo Brazil
  • Francisco X. Castellanos
    Department of Child and Adolescent Psychiatry NYU Grossman School of Medicine New York NY USA
  • Mara Cercignani
    Department of Neuroscience Brighton and Sussex Medical School Falmer, Brighton UK
  • Tiffany M. Chaim‐Avancini
    Laboratory of Psychiatric Neuroimaging (LIM‐21 Department and Institute of Psychiatry Hospital das Clinicas HCFMUSP Faculty of Medicine University of São Paulo Sao Paulo Sao Paulo Brazil
  • Kaylita C. Chantiluke
    Department of Child and Adolescent Psychiatry Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
  • Anastasia Christakou
    Department of Child and Adolescent Psychiatry Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
  • David Coghill
    Departments of Paediatrics and Psychiatry University of Melbourne Melbourne Vic. Australia
  • Annette Conzelmann
    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University Hospital of Tübingen Tübingen Germany
  • Ana I. Cubillo
    Department of Child and Adolescent Psychiatry Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
  • Renata B. Cupertino
    Adulthood ADHD Outpatient Program (ProDAH) Clinical Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
  • Patrick de Zeeuw
    NICHE Lab Department of Psychiatry Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands
  • Alysa E. Doyle
    Department of Psychiatry Massachusetts General Hospital Harvard Medical School Boston MA USA
  • Sarah Durston
    NICHE Lab Department of Psychiatry Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands
  • Eric A. Earl
    Department of Behavioral Neuroscience Oregon Health & Science University Portland OR USA
  • Jeffery N. Epstein
    Division of Behavioral Medicine and Clinical Psychology Cincinnati Children’s Hospital Medical Center Cincinnati OH USA
  • Thomas Ethofer
    Clinic for Psychiatry/Psychotherapy Tübingen/Department for Biomedical Magnetic Resonance Tübingen Germany
  • Damien A. Fair
    Department of Behavioral Neuroscience Oregon Health & Science University Portland OR USA
  • Andreas J. Fallgatter
    Department of Psychiatry and Psychotherapy University Hospital of Tuebingen Tuebingen Germany
  • Stephen V. Faraone
    Departments of Psychiatry and of Neuroscience and Physiology SUNY Upstate Medical University Syracuse NY USA
  • Thomas Frodl
    Department of Psychiatry and Psychotherapy Otto von Guericke University Magdeburg Germany
  • Matt C. Gabel
    Department of Neuroscience Brighton and Sussex Medical School Falmer, Brighton UK
  • Tinatin Gogberashvili
    Laboratory of Neurology and Cognitive Health National Medical Research Center for Children's Health Moscow Russia
  • Eugenio H. Grevet
    Adulthood ADHD Outpatient Program (ProDAH) Clinical Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
  • Jan Haavik
    Department of Biomedicine K.G. Jebsen Centre for Neuropsychiatric Disorders University of Bergen Bergen Norway
  • Neil A. Harrison
    Department of Neuroscience Brighton and Sussex Medical School Falmer, Brighton UK
  • Catharina A. Hartman
    Department of Psychiatry Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE) University Medical Center Groningen University of Groningen Groningen The Netherlands
  • Dirk J. Heslenfeld
    Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam Amsterdam The Netherlands
  • Pieter J. Hoekstra
    Department of Child and Adolescent Psychiatry University Medical Center Groningen University of Groningen Groningen The Netherlands
  • Sarah Hohmann
    Department of Child and Adolescent Psychiatry and Psychotherapy Central Institute of Mental Health Medical Faculty Mannheim/Heidelberg University Mannheim Germany
  • Marie F. Høvik
    Division of Psychiatry Haukeland University Hospital Bergen Norway
  • Terry L. Jernigan
    Center for Human Development UC San Diego La Jolla CA USA
  • Bernd Kardatzki
    Department of Biomedical Magnetic Resonance University of Tuebingen Tuebingen Germany
  • Georgii Karkashadze
    Research Institute of Pediatrics and Child Health of Central Clinical Hospital of the Russian Academy of Sciences of the Ministry of Science and Higher Education of the Russian Federation Moscow Russia
  • Clare Kelly
    School of Psychology and Department of Psychiatry at the School of Medicine Trinity College Dublin Ireland
  • Gregor Kohls
    Child Neuropsychology Section Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy University Hospital RWTH Aachen Germany
  • Kerstin Konrad
    Child Neuropsychology Section Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy University Hospital RWTH Aachen Germany
  • Jonna Kuntsi
    Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
  • Luisa Lazaro
    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Biomedical Network Research Center on Mental Health (CIBERSAM) Barcelona Spain
  • Sara Lera‐Miguel
    Department of Child and Adolescent Psychiatry and Psychology Institute of Neurosciencies Hospital Clinic Barcelona Spain
  • Klaus‐Peter Lesch
    Division of Molecular Psychiatry Center of Mental Health University of Würzburg Würzburg Germany
  • Mario R. Louza
    Institute of Psychiatry Faculty of Medicine University of São Paulo São Paulo Brazil
  • Astri J. Lundervold
    Department of Biomedicine K.G. Jebsen Centre for Neuropsychiatric Disorders University of Bergen Bergen Norway
  • Charles B Malpas
    Developmental Imaging Group Murdoch Children's Research Institute Melbourne Vic. Australia
  • Paulo Mattos
    D'Or Institute for Research and Education Rio de Janeiro Brazil
  • Hazel McCarthy
    Department of Psychiatry Trinity College Dublin Dublin Ireland
  • Leyla Namazova‐Baranova
    Research Institute of Pediatrics and Child Health of Central Clinical Hospital of the Russian Academy of Sciences of the Ministry of Science and Higher Education of the Russian Federation Moscow Russia
  • Rosa Nicolau
    Department of Child and Adolescent Psychiatry and Psychology Institut of Neurosciencies Hospital Clinic Barcelona Spain
  • Joel T. Nigg
    Department of Behavioral Neuroscience Oregon Health & Science University Portland OR USA
  • Stephanie E. Novotny
    Olin Neuropsychiatry Research Center Hartford Hospital Hartford CT USA
  • Eileen Oberwelland Weiss
    Translational Neuroscience, Child and Adolescent Psychiatry University Hospital RWTH Aachen Aachen Germany
  • Ruth L. O'Gorman Tuura
    Center for MR Research University Children's Hospital Zurich Switzerland
  • Jaap Oosterlaan
    Clinical Neuropsychology Section Vrije Universiteit Amsterdam Amsterdam The Netherlands
  • Bob Oranje
    NICHE Lab Department of Psychiatry Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands
  • Yannis Paloyelis
    Department of Neuroimaging Institute of Psychiatry, Psychology and Neuroscience King’s College London London UK
  • Paul Pauli
    Department of Psychology (Biological Psychology Clinical Psychology and Psychotherapy) and Center of Mental Health University of Würzburg Würzburg Germany
  • Felipe A. Picon
    Adulthood ADHD Outpatient Program (ProDAH) Clinical Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
  • Kerstin J. Plessen
    Child and Adolescent Mental Health Centre Capital Region Copenhagen Copenhagen Denmark
  • J. Antoni Ramos‐Quiroga
    Department of Psychiatry Hospital Universitari Vall d’Hebron Barcelona Catalonia Spain
  • Andreas Reif
    Department of Psychiatry, Psychosomatic Medicine and Psychotherapy University Hospital Frankfurt Frankfurt Germany
  • Liesbeth Reneman
    Academic Medical Center Amsterdam University Medical Center Amsterdam The Netherlands
  • Pedro G.P. Rosa
    Laboratory of Psychiatric Neuroimaging (LIM‐21 Department and Institute of Psychiatry Hospital das Clinicas HCFMUSP Faculty of Medicine University of São Paulo Sao Paulo Sao Paulo Brazil
  • Katya Rubia
    Department of Child and Adolescent Psychiatry Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
  • Anouk Schrantee
    Department of Radiology and Nuclear Medicine Amsterdam University Medical Centers Amsterdam The Netherlands
  • Lizanne J.S. Schweren
    Department of Psychiatry Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE) University Medical Center Groningen University of Groningen Groningen The Netherlands
  • Jochen Seitz
    Child and Adolescent Psychiatry University Hospital RWTH Aachen Aachen Germany
  • Philip Shaw
    National Human Genome Research Institute and National Institute of Mental health Bethesda MD USA
  • Tim J. Silk
    School of Psychology Deakin University Geelong Vic. Australia
  • Norbert Skokauskas
    Centre for Child and Adolescent Mental Health NTNU Trondheim Norway
  • Juan C. Soliva Vila
    Department of Psychiatry and Forensic Medicine Universitat Autonoma de Barcelona Barcelona Spain
  • Michael C. Stevens
    Olin Neuropsychiatry Research Center Hartford Hospital Hartford CT USA
  • Gustavo Sudre
    National Human Genome Research Institute Bethesda MD USA
  • Leanne Tamm
    Department of Pediatrics Cincinnati Children's Hospital Medical Center Cincinnati OH USA
  • Fernanda Tovar‐Moll
    D'Or Institute for Research and Education Rio de Janeiro Brazil
  • Theo G.M. van Erp
    Clinical Translational Neuroscience Laboratory Department of Psychiatry and Human Behavior University of California Irvine Irvine CA USA
  • Alasdair Vance
    Department of Paediatrics University of Melbourne Parkville Vic. Australia
  • Oscar Vilarroya
    Department of Psychiatry and Forensic Medicine Universitat Autonoma de Barcelona Barcelona Spain
  • Yolanda Vives‐Gilabert
    Instituto ITACA Universitat Politècnica de València València Spain
  • Georg G. von Polier
    Child and Adolescent Psychiatry University Hospital RWTH Aachen Aachen Germany
  • Susanne Walitza
    Department of Child and Adolescent Psychiatry and Psychotherapy Psychiatric Hospital University of Zurich Zurich Switzerland
  • Yuliya N. Yoncheva
    Department of Child and Adolescent Psychiatry NYU Child Study Center Hassenfeld Children’s Hospital at NYU Langone New York NY USA
  • Marcus V. Zanetti
    Department of Psychiatry Faculty of Medicine University of São Paulo São Paulo Brazil
  • Georg C. Ziegler
    Division of Molecular Psychiatry Center of Mental Health University of Würzburg Würzburg Germany
  • David C. Glahn
    Olin Neuropsychiatry Research Center Hartford Hospital Hartford CT USA
  • Neda Jahanshad
    Imaging Genetics Center Stevens Neuroimaging and Informatics Institute Keck School of Medicine of USC Los Angeles CA USA
  • Sarah E. Medland
    Psychiatric Genetics QIMR Berghofer Medical Research Institute Brisbane Qld Australia
  • Paul M. Thompson
    Imaging Genetics Center Stevens Institute for Neuroimaging & Informatics Keck School of Medicine University of Southern California Los Angeles CA USA
  • Simon E. Fisher
    Language and Genetics Department Max Planck Institute for Psycholinguistics Nijmegen The Netherlands
  • Barbara Franke
    Department of Human Genetics Radboud University Medical Center Nijmegen Netherlands
  • Clyde Francks
    Language and Genetics Department Max Planck Institute for Psycholinguistics Nijmegen The Netherlands

抄録

<jats:sec><jats:title>Objective</jats:title><jats:p>Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (<jats:italic>t</jats:italic> = 2.1, <jats:italic>p</jats:italic> = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (<jats:italic>t</jats:italic> = 2.7, <jats:italic>p</jats:italic> = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s <jats:italic>d</jats:italic> from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.</jats:p></jats:sec>

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