Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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33748971
TITLE
Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.
ABSTRACT
OBJECTIVE NlmCategory: OBJECTIVE
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.
METHODS NlmCategory: METHODS
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. 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.
RESULTS NlmCategory: RESULTS
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. 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. 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 (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .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 d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.
CONCLUSION NlmCategory: CONCLUSIONS
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. 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. 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 (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .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 d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. 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.
© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.
DATE PUBLISHED
2021 Mar 22
HISTORY
PUBSTATUS PUBSTATUSDATE
accepted 2021/12/19
entrez 2021/03/22 08:39
pubmed 2021/03/23 06:00
medline 2021/03/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Postema MC Postema Merel C MC Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
Hoogman M Hoogman Martine M Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
Ambrosino S Ambrosino Sara S NICHE lab, Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
Asherson P Asherson Philip P Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Banaschewski T Banaschewski Tobias T Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Bandeira CE Bandeira Cibele E CE Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Baranov A Baranov Alexandr A 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.
Bau CHD Bau Claiton H D CHD Developmental Psychiatry Program, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Baumeister S Baumeister Sarah S Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Baur-Streubel R Baur-Streubel Ramona R Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Würzburg, Germany.
Bellgrove MA Bellgrove Mark A MA Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, Vic., Australia.
Biederman J Biederman Joseph J Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Bralten J Bralten Janita J Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
Brandeis D Brandeis Daniel D The Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
Brem S Brem Silvia S Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
Buitelaar JK Buitelaar Jan K JK Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands.
Busatto GF Busatto Geraldo F GF 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.
Castellanos FX Castellanos Francisco X FX Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Cercignani M Cercignani Mara M Department of Neuroscience, Brighton and Sussex Medical School, Falmer, Brighton, UK.
Chaim-Avancini TM Chaim-Avancini Tiffany M TM 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.
Chantiluke KC Chantiluke Kaylita C KC Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Christakou A Christakou Anastasia A School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading, UK.
Coghill D Coghill David D Murdoch Children's Research Institute, Melbourne, Vic., Australia.
Conzelmann A Conzelmann Annette A Department of Psychology (Clinical Psychology II), PFH - Private University of Applied Sciences, Göttingen, Germany.
Cubillo AI Cubillo Ana I AI Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Cupertino RB Cupertino Renata B RB Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
de Zeeuw P de Zeeuw Patrick P NICHE Lab, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Doyle AE Doyle Alysa E AE Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Durston S Durston Sarah S NICHE Lab, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Earl EA Earl Eric A EA Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Epstein JN Epstein Jeffery N JN Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Ethofer T Ethofer Thomas T Clinic for Psychiatry/Psychotherapy Tübingen/Department for Biomedical Magnetic Resonance, Tübingen, Germany.
Fair DA Fair Damien A DA Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Fallgatter AJ Fallgatter Andreas J AJ LEAD Graduate School, University of Tuebingen, Tübingen, Germany.
Faraone SV Faraone Stephen V SV Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
Frodl T Frodl Thomas T Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Gabel MC Gabel Matt C MC Department of Neuroscience, Brighton and Sussex Medical School, Falmer, Brighton, UK.
Gogberashvili T Gogberashvili Tinatin T Laboratory of Neurology and Cognitive Health, National Medical Research Center for Children's Health, Moscow, Russia.
Grevet EH Grevet Eugenio H EH Developmental Psychiatry Program, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Haavik J Haavik Jan J Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
Harrison NA Harrison Neil A NA Sussex Partnership NHS Foundation Trust, Swandean, East Sussex, UK.
Hartman CA Hartman Catharina A CA Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Heslenfeld DJ Heslenfeld Dirk J DJ Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Hoekstra PJ Hoekstra Pieter J PJ Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hohmann S Hohmann Sarah S Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Høvik MF Høvik Marie F MF Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Jernigan TL Jernigan Terry L TL Center for Human Development, UC San Diego, La Jolla, CA, USA.
Kardatzki B Kardatzki Bernd B Department of Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen, Germany.
Karkashadze G Karkashadze Georgii G 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.
Kelly C Kelly Clare C Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Kohls G Kohls Gregor G Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital RWTH, Aachen, Germany.
Konrad K Konrad Kerstin K JARA Institute Molecular Neuroscience and Neuroimaging (INM-11), Institute for Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.
Kuntsi J Kuntsi Jonna J Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Lazaro L Lazaro Luisa L Department of Medicine, University of Barcelona, Barcelona, Spain.
Lera-Miguel S Lera-Miguel Sara S Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciencies, Hospital Clinic, Barcelona, Spain.
Lesch KP Lesch Klaus-Peter KP Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands.
Louza MR Louza Mario R MR Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Lundervold AJ Lundervold Astri J AJ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
Malpas CB Malpas Charles B CB Clinical Outcomes Research Unit (CORe), Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Vic., Australia.
Mattos P Mattos Paulo P Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
McCarthy H McCarthy Hazel H Centre of Advanced Medical Imaging, St James's Hospital, Dublin, Ireland.
Namazova-Baranova L Namazova-Baranova Leyla L Russian National Research Medical University Ministry of Health of the Russian Federation, Moscow, Russia.
Nicolau R Nicolau Rosa R Department of Child and Adolescent Psychiatry and Psychology, Institut of Neurosciencies, Hospital Clinic, Barcelona, Spain.
Nigg JT Nigg Joel T JT Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.
Novotny SE Novotny Stephanie E SE Olin Neuropsychiatry Research Center, Hartford Hospital, Hartford, CT, USA.
Oberwelland Weiss E Oberwelland Weiss Eileen E Cognitive Neuroscience (INM-3), Institute for Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.
O'Gorman Tuura RL O'Gorman Tuura Ruth L RL Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland.
Oosterlaan J Oosterlaan Jaap J Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Emma Children's Hospital Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Oranje B Oranje Bob B NICHE Lab, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Paloyelis Y Paloyelis Yannis Y Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Pauli P Pauli Paul P Department of Psychology (Biological Psychology, Clinical Psychology and Psychotherapy) and Center of Mental Health, University of Würzburg, Würzburg, Germany.
Picon FA Picon Felipe A FA Adulthood ADHD Outpatient Program (ProDAH), Clinical Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Plessen KJ Plessen Kerstin J KJ Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne, Lausanne, Switzerland.
Ramos-Quiroga JA Ramos-Quiroga J Antoni JA Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
Reif A Reif Andreas A Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Reneman L Reneman Liesbeth L Academic Medical Center, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Rosa PGP Rosa Pedro G P PGP 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.
Rubia K Rubia Katya K Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Schrantee A Schrantee Anouk A Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Schweren LJS Schweren Lizanne J S LJS Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Seitz J Seitz Jochen J Child and Adolescent Psychiatry, University Hospital RWTH Aachen, Aachen, Germany.
Shaw P Shaw Philip P National Human Genome Research Institute and National Institute of Mental health, Bethesda, MD, USA.
Silk TJ Silk Tim J TJ Murdoch Children's Research Institute, Developmental Imaging, Melbourne, Vic., Australia.
Skokauskas N Skokauskas Norbert N Institute of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
Soliva Vila JC Soliva Vila Juan C JC Department of Psychiatry and Forensic Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.
Stevens MC Stevens Michael C MC Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Sudre G Sudre Gustavo G National Human Genome Research Institute, Bethesda, MD, USA.
Tamm L Tamm Leanne L College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Tovar-Moll F Tovar-Moll Fernanda F Morphological Sciences Program, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
van Erp TGM van Erp Theo G M TGM Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
Vance A Vance Alasdair A Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.
Vilarroya O Vilarroya Oscar O Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Vives-Gilabert Y Vives-Gilabert Yolanda Y Instituto ITACA, Universitat Politècnica de València, València, Spain.
von Polier GG von Polier Georg G GG Brain and Behavior (INM-7), Institute for Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.
Walitza S Walitza Susanne S Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
Yoncheva YN Yoncheva Yuliya N YN Department of Child and Adolescent Psychiatry, NYU Child Study Center, Hassenfeld Children's Hospital at NYU Langone, New York, NY, USA.
Zanetti MV Zanetti Marcus V MV Hospital Sírio-Libanês, São Paulo, Brazil.
Ziegler GC Ziegler Georg C GC Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
Glahn DC Glahn David C DC Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Jahanshad N Jahanshad Neda N Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, CA, USA.
Medland SE Medland Sarah E SE Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
ENIGMA ADHD Working Group
Thompson PM Thompson Paul M PM Imaging Genetics Center, Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Fisher SE Fisher Simon E SE Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
Franke B Franke Barbara B Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands.
Francks C Francks Clyde C Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Journal of child psychology and psychiatry, and allied disciplines
ISOABBREVIATION: J Child Psychol Psychiatry
YEAR: 2021
MONTH: Mar
DAY: 22
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1469-7610
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Child Psychol Psychiatry
COUNTRY: England
ISSNLINKING: 0021-9630
NLMUNIQUEID: 0375361
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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Max Planck Society
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GENERAL NOTE
KEYWORDS
KEYWORD
Attention-deficit
brain asymmetry
brain laterality
hyperactivity disorder
large-scale data
structural MRI
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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