. 2019 Jul 1;176(7):531-542.

doi: 10.1176/appi.ajp.2019.18091033. Epub 2019 Apr 24.

Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

Martine Hoogman¹, Ryan Muetzel¹, Joao P Guimaraes¹, Elena Shumskaya¹, Maarten Mennes¹, Marcel P Zwiers¹, Neda Jahanshad¹, Gustavo Sudre¹, Thomas Wolfers¹, Eric A Earl¹, Juan Carlos Soliva Vila¹, Yolanda Vives-Gilabert¹, Sabin Khadka¹, Stephanie E Novotny¹, Catharina A Hartman¹, Dirk J Heslenfeld¹, Lizanne J S Schweren¹, Sara Ambrosino¹, Bob Oranje¹, Patrick de Zeeuw¹, Tiffany M Chaim-Avancini¹, Pedro G P Rosa¹, Marcus V Zanetti¹, Charles B Malpas¹, Gregor Kohls¹, Georg G von Polier¹, Jochen Seitz¹, Joseph Biederman¹, Alysa E Doyle¹, Anders M Dale¹, Theo G M van Erp¹, Jeffery N Epstein¹, Terry L Jernigan¹, Ramona Baur-Streubel¹, Georg C Ziegler¹, Kathrin C Zierhut¹, Anouk Schrantee¹, Marie F Høvik¹, Astri J Lundervold¹, Clare Kelly¹, Hazel McCarthy¹, Norbert Skokauskas¹, Ruth L O'Gorman Tuura¹, Anna Calvo¹, Sara Lera-Miguel¹, Rosa Nicolau¹, Kaylita C Chantiluke¹, Anastasia Christakou¹, Alasdair Vance¹, Mara Cercignani¹, Matt C Gabel¹, Philip Asherson¹, Sarah Baumeister¹, Daniel Brandeis¹, Sarah Hohmann¹, Ivanei E Bramati¹, Fernanda Tovar-Moll¹, Andreas J Fallgatter¹, Bernd Kardatzki¹, Lena Schwarz¹, Anatoly Anikin¹, Alexandr Baranov¹, Tinatin Gogberashvili¹, Dmitry Kapilushniy¹, Anastasia Solovieva¹, Hanan El Marroun¹, Tonya White¹, Georgii Karkashadze¹, Leyla Namazova-Baranova¹, Thomas Ethofer¹, Paulo Mattos¹, Tobias Banaschewski¹, David Coghill¹, Kerstin J Plessen¹, Jonna Kuntsi¹, Mitul A Mehta¹, Yannis Paloyelis¹, Neil A Harrison¹, Mark A Bellgrove¹, Tim J Silk¹, Ana I Cubillo¹, Katya Rubia¹, Luisa Lazaro¹, Silvia Brem¹, Susanne Walitza¹, Thomas Frodl¹, Mariam Zentis¹, Francisco X Castellanos¹, Yuliya N Yoncheva¹, Jan Haavik¹, Liesbeth Reneman¹, Annette Conzelmann¹, Klaus-Peter Lesch¹, Paul Pauli¹, Andreas Reif¹, Leanne Tamm¹, Kerstin Konrad¹, Eileen Oberwelland Weiss¹, Geraldo F Busatto¹, Mario R Louza¹, Sarah Durston¹, Pieter J Hoekstra¹, Jaap Oosterlaan¹, Michael C Stevens¹, J Antoni Ramos-Quiroga¹, Oscar Vilarroya¹, Damien A Fair¹, Joel T Nigg¹, Paul M Thompson¹, Jan K Buitelaar¹, Stephen V Faraone¹, Philip Shaw¹, Henning Tiemeier¹, Janita Bralten¹, Barbara Franke¹

Affiliations

Affiliation

¹ The Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands (Hoogman, Guimaraes, Shumskaya, Wolfers, Bralten, Franke); the Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, the Netherlands (Hoogman, Shumskaya, Mennes, Wolfers, Buitelaar, Bralten, Franke); the Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (Muetzel, El Marroun, White, Tiemeier); the Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (Muetzel); the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands (Guimaraes, Zwiers, Buitelaar); the Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, Calif. (Jahanshad, Thompson); National Human Genome Research Institute, Bethesda, Md. (Sudre, Shaw); the Department of Behavioral Neuroscience, Oregon Health and Science University, Portland (Earl, Fair, Nigg); the Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona, Cerdanyola del Vallès, Spain (Soliva Vila, Ramos-Quiroga, Vilarroya); Instituto ITACA, Polytechnic University of Valencia, Valencia, Spain (Vives-Gilabert); the Olin Neuropsychiatry Research Center, Hartford Hospital, Hartford, Conn. (Khadka, Novotny, Stevens); University of Groningen, University Medical Center Groningen (UMCG), Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Groningen, the Netherlands (Hartman, Schweren); Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam (Heslenfeld); the Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, the Netherlands (Hoekstra); NICHE Lab, Department of Psychiatry, UMC Utrecht Brain Center, Utrecht, the Netherlands (Ambrosino, Oranje, de Zeeuw, Durston); Laboratory of Psychiatric Neuroimaging (LIM-21), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Chaim-Avancini, Rosa, Zanetti, Busatto); the Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil (Chaim-Avancini, Rosa, Zanetti, Busatto); the Developmental Imaging Group, Murdoch Children's Research Institute, Melbourne, Australia (Malpas); the Clinical Outcomes Research Unit (CORe), Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia (Malpas); the Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia (Malpas); the Child Neuropsychology Section, University Hospital RWTH Aachen, Aachen, Germany (Kohls, Konrad; Child and Adolescent Psychiatry, University Hospital RWTH Aachen, Aachen, Germany (Polier, Seitz); Institute of Neuroscience and Medicine-Brain and Behavior (INM-7), Research Center Jülich, Jülich, Germany (Polier); the Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Department of Psychiatry, Massachusetts General Hospital, Boston (Biederman); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Biederman, Doyle); the Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (Doyle); the Departments of Neurosciences, Radiology, and Psychiatry and the Center for Multimodal Imaging and Genetics, University of California San Diego (Dale); the Clinical and Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine (van Erp); the Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati (Epstein, Tamm); the Center for Human Development, University of California San Diego, San Diego (Jernigan); the Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany (Ziegler, Lesch); the Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam (Schrantee, Reneman); the Department of Clinical Medicine, University of Bergen, Bergen, Norway (Høvik); the Division of Psychiatry, Haukeland University Hospital, Bergen, Norway (Høvik, Haavik); the Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway (Lundervold); the K.G. Jebsen Center for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway (Lundervold, Haavik); the School of Psychology and the Department of Psychiatry, School of Medicine, and the Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland (Kelly); the Department of Child and Adolescent Psychiatry, NYU Langone Medical Center, New York (Kelly, Castellanos, Yoncheva); the Department of Psychiatry, Trinity College Dublin, Ireland (McCarthy, Skokauskas, Frodl); the Centre for Advanced Medical Imaging, St. James's Hospital, Dublin, Ireland (McCarthy); the Center for Child and Adolescent Mental Health, NTNU, Norway, Norwegian University of Science and Technology, Norway (Skokauskas); the Center for MR Research, University Children's Hospital, and the Zurich Center for Integrative Human Physiology, Zurich (O'Gorman Tuura); Magnetic Resonance Image Core Facility, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain (Calvo, Lazaro); the Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic, Barcelona, Spain (Lera-Miguel, Nicolau, Lazaro); the Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Chantiluke, Christakou, Cubillo, Rubia); the School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading, U.K. (Christakou); the Department of Paediatrics, University of Melbourne, Australia (Vance, Coghill, Silk); the Department of Neuroscience, Brighton and Sussex Medical School, Falmer, Brighton, U.K. (Cercignani, Gabel, Harrison); the Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Asherson, Kuntsi); the Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Baumeister, Brandeis, Hohmann, Banaschewski); the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich (Brandeis, Brem, Walitza); the Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich (Brandeis, Brem, Walitza); the D'Or Institute for Research and Education, Rio de Janeiro (Bramati, Tovar-Moll, Mattos); the Morphological Sciences Program, Federal University of Rio de Janeiro, Rio de Janeiro (Tovar-Moll); the Department of Psychiatry and Psychotherapy, University Hospital of Tübingen, Tübingen, Germany (Fallgatter, Schwarz, Ethofer); LEAD Graduate School, University of Tübingen, Germany (Fallgatter); the Department of Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany (Kardatzki, Ethofer); the National Medical Research Center for Children's Health, Department of Magnetic Resonance Imaging and Densitometry, Moscow (Anikin); the National Medical Research Center for Children's Health, Moscow (Baranov, Solovieva); Russian National Research Medical University, Ministry of Health and Social Development of the Russian Federation, Central Clinical Hospital MSHE, Moscow (Namazova-Baranova); the National Medical Research Center for Children's Health, Laboratory of Neurology and Cognitive Health, Moscow (Gogberashvili, Karkashadze); the National Medical Research Center for Children's Health, Department of Information Technologies, Moscow (Kapilushniy); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, the Netherlands (El Marroun); the Department of Psychology, Education, and Child Studies, Erasmus University Rotterdam, Rotterdam, the Netherlands (El Marroun); the Department of Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (White); Federal University of Rio de Janeiro, Rio de Janeiro (Mattos); the Department of Psychiatry, University of Melbourne, Melbourne, Australia (Coghill); the Murdoch Children's Research Institute, Melbourne, Australia (Coghill, Silk); the Division of Neuroscience, University of Dundee, Dundee, U.K. (Coghill); the Child and Adolescent Mental Health Center, Capital Region Copenhagen (Plessen); the Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne, Switzerland (Plessen); the Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Mehta, Paloyelis); Sussex Partnership NHS Foundation Trust, Swandean, East Sussex, U.K. (Harrison); the Monash Institute for Cognitive and Clinical Neurosciences (MICCN) and the School of Psychological Sciences, Monash University, Melbourne, Australia (Bellgrove); Deakin University, School of Psychology, Geelong, Australia (Silk); the Department of Medicine, University of Barcelona, Barcelona, Spain (Lazaro); the Department of Psychiatry and Psychotherapy, Otto von Guericke University Magdeburg, Germany (Frodl); the German Center for Neurodegenerative Diseases (DZNE), Germany (Frodl); Bezirksklinikum Regensburg, Germany (Zentis); the Nathan Kline Institute for Psychiatric Research, Orangeburg, N.Y. (Castellanos); the Brain Imaging Center, Amsterdam University Medical Centers, Amsterdam (Reneman); the Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Tübingen, Germany (Conzelmann); the Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, Germany (Conzelmann, Pauli, Baur-Streubel, Zierhut); the Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow (Lesch); the Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands (Lesch); the Department of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany (Reif); JARA Institute Molecular Neuroscience and Neuroimaging (INM-11), Institute for Neuroscience and Medicine, Research Center Jülich, Germany (Konrad); Translational Neuroscience, Child and Adolescent Psychiatry, University Hospital RWTH Aachen, Aachen, Germany (Oberwelland Weiss); Cognitive Neuroscience (INM-3), Institute for Neuroscience and Medicine, Research Center Jülich, Germany (Oberwelland Weiss); the Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Busatto, Louza); the Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam (Oosterlaan); Emma Children's Hospital Amsterdam Medical Center, Amsterdam (Oosterlaan); the Department of Pediatrics, VU Medical Center, Amsterdam (Oosterlaan); the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. (Stevens); the Department of Psychiatry, Vall d'Hebron University Hospital, Barcelona, Spain (Ramos-Quiroga); Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Spain (Lazaro, Ramos-Quiroga); Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain (Vilarroya); the Department of Psychiatry, Oregon Health and Science University, Portland (Fair, Nigg); Karakter Child and Adolescent Psychiatry University Center, Nijmegen, the Netherlands (Buitelaar); Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York (Faraone); NIHM, Bethesda, Md. (Shaw); the Department of Social and Behavioral Science, Harvard T.H. Chan School of Public Health, Boston (Tiemeier).

PMID: 31014101
PMCID: PMC6879185
DOI: 10.1176/appi.ajp.2019.18091033

Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

Martine Hoogman et al. Am J Psychiatry. 2019.

. 2019 Jul 1;176(7):531-542.

doi: 10.1176/appi.ajp.2019.18091033. Epub 2019 Apr 24.

Authors

Affiliation

¹ The Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands (Hoogman, Guimaraes, Shumskaya, Wolfers, Bralten, Franke); the Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, the Netherlands (Hoogman, Shumskaya, Mennes, Wolfers, Buitelaar, Bralten, Franke); the Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (Muetzel, El Marroun, White, Tiemeier); the Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (Muetzel); the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands (Guimaraes, Zwiers, Buitelaar); the Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, Calif. (Jahanshad, Thompson); National Human Genome Research Institute, Bethesda, Md. (Sudre, Shaw); the Department of Behavioral Neuroscience, Oregon Health and Science University, Portland (Earl, Fair, Nigg); the Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona, Cerdanyola del Vallès, Spain (Soliva Vila, Ramos-Quiroga, Vilarroya); Instituto ITACA, Polytechnic University of Valencia, Valencia, Spain (Vives-Gilabert); the Olin Neuropsychiatry Research Center, Hartford Hospital, Hartford, Conn. (Khadka, Novotny, Stevens); University of Groningen, University Medical Center Groningen (UMCG), Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Groningen, the Netherlands (Hartman, Schweren); Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam (Heslenfeld); the Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, the Netherlands (Hoekstra); NICHE Lab, Department of Psychiatry, UMC Utrecht Brain Center, Utrecht, the Netherlands (Ambrosino, Oranje, de Zeeuw, Durston); Laboratory of Psychiatric Neuroimaging (LIM-21), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Chaim-Avancini, Rosa, Zanetti, Busatto); the Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil (Chaim-Avancini, Rosa, Zanetti, Busatto); the Developmental Imaging Group, Murdoch Children's Research Institute, Melbourne, Australia (Malpas); the Clinical Outcomes Research Unit (CORe), Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia (Malpas); the Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia (Malpas); the Child Neuropsychology Section, University Hospital RWTH Aachen, Aachen, Germany (Kohls, Konrad; Child and Adolescent Psychiatry, University Hospital RWTH Aachen, Aachen, Germany (Polier, Seitz); Institute of Neuroscience and Medicine-Brain and Behavior (INM-7), Research Center Jülich, Jülich, Germany (Polier); the Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Department of Psychiatry, Massachusetts General Hospital, Boston (Biederman); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Biederman, Doyle); the Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (Doyle); the Departments of Neurosciences, Radiology, and Psychiatry and the Center for Multimodal Imaging and Genetics, University of California San Diego (Dale); the Clinical and Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine (van Erp); the Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati (Epstein, Tamm); the Center for Human Development, University of California San Diego, San Diego (Jernigan); the Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany (Ziegler, Lesch); the Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam (Schrantee, Reneman); the Department of Clinical Medicine, University of Bergen, Bergen, Norway (Høvik); the Division of Psychiatry, Haukeland University Hospital, Bergen, Norway (Høvik, Haavik); the Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway (Lundervold); the K.G. Jebsen Center for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway (Lundervold, Haavik); the School of Psychology and the Department of Psychiatry, School of Medicine, and the Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland (Kelly); the Department of Child and Adolescent Psychiatry, NYU Langone Medical Center, New York (Kelly, Castellanos, Yoncheva); the Department of Psychiatry, Trinity College Dublin, Ireland (McCarthy, Skokauskas, Frodl); the Centre for Advanced Medical Imaging, St. James's Hospital, Dublin, Ireland (McCarthy); the Center for Child and Adolescent Mental Health, NTNU, Norway, Norwegian University of Science and Technology, Norway (Skokauskas); the Center for MR Research, University Children's Hospital, and the Zurich Center for Integrative Human Physiology, Zurich (O'Gorman Tuura); Magnetic Resonance Image Core Facility, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain (Calvo, Lazaro); the Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic, Barcelona, Spain (Lera-Miguel, Nicolau, Lazaro); the Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Chantiluke, Christakou, Cubillo, Rubia); the School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading, U.K. (Christakou); the Department of Paediatrics, University of Melbourne, Australia (Vance, Coghill, Silk); the Department of Neuroscience, Brighton and Sussex Medical School, Falmer, Brighton, U.K. (Cercignani, Gabel, Harrison); the Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Asherson, Kuntsi); the Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Baumeister, Brandeis, Hohmann, Banaschewski); the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich (Brandeis, Brem, Walitza); the Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich (Brandeis, Brem, Walitza); the D'Or Institute for Research and Education, Rio de Janeiro (Bramati, Tovar-Moll, Mattos); the Morphological Sciences Program, Federal University of Rio de Janeiro, Rio de Janeiro (Tovar-Moll); the Department of Psychiatry and Psychotherapy, University Hospital of Tübingen, Tübingen, Germany (Fallgatter, Schwarz, Ethofer); LEAD Graduate School, University of Tübingen, Germany (Fallgatter); the Department of Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany (Kardatzki, Ethofer); the National Medical Research Center for Children's Health, Department of Magnetic Resonance Imaging and Densitometry, Moscow (Anikin); the National Medical Research Center for Children's Health, Moscow (Baranov, Solovieva); Russian National Research Medical University, Ministry of Health and Social Development of the Russian Federation, Central Clinical Hospital MSHE, Moscow (Namazova-Baranova); the National Medical Research Center for Children's Health, Laboratory of Neurology and Cognitive Health, Moscow (Gogberashvili, Karkashadze); the National Medical Research Center for Children's Health, Department of Information Technologies, Moscow (Kapilushniy); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, the Netherlands (El Marroun); the Department of Psychology, Education, and Child Studies, Erasmus University Rotterdam, Rotterdam, the Netherlands (El Marroun); the Department of Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (White); Federal University of Rio de Janeiro, Rio de Janeiro (Mattos); the Department of Psychiatry, University of Melbourne, Melbourne, Australia (Coghill); the Murdoch Children's Research Institute, Melbourne, Australia (Coghill, Silk); the Division of Neuroscience, University of Dundee, Dundee, U.K. (Coghill); the Child and Adolescent Mental Health Center, Capital Region Copenhagen (Plessen); the Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne, Switzerland (Plessen); the Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Mehta, Paloyelis); Sussex Partnership NHS Foundation Trust, Swandean, East Sussex, U.K. (Harrison); the Monash Institute for Cognitive and Clinical Neurosciences (MICCN) and the School of Psychological Sciences, Monash University, Melbourne, Australia (Bellgrove); Deakin University, School of Psychology, Geelong, Australia (Silk); the Department of Medicine, University of Barcelona, Barcelona, Spain (Lazaro); the Department of Psychiatry and Psychotherapy, Otto von Guericke University Magdeburg, Germany (Frodl); the German Center for Neurodegenerative Diseases (DZNE), Germany (Frodl); Bezirksklinikum Regensburg, Germany (Zentis); the Nathan Kline Institute for Psychiatric Research, Orangeburg, N.Y. (Castellanos); the Brain Imaging Center, Amsterdam University Medical Centers, Amsterdam (Reneman); the Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Tübingen, Germany (Conzelmann); the Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, Germany (Conzelmann, Pauli, Baur-Streubel, Zierhut); the Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow (Lesch); the Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands (Lesch); the Department of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany (Reif); JARA Institute Molecular Neuroscience and Neuroimaging (INM-11), Institute for Neuroscience and Medicine, Research Center Jülich, Germany (Konrad); Translational Neuroscience, Child and Adolescent Psychiatry, University Hospital RWTH Aachen, Aachen, Germany (Oberwelland Weiss); Cognitive Neuroscience (INM-3), Institute for Neuroscience and Medicine, Research Center Jülich, Germany (Oberwelland Weiss); the Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Busatto, Louza); the Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam (Oosterlaan); Emma Children's Hospital Amsterdam Medical Center, Amsterdam (Oosterlaan); the Department of Pediatrics, VU Medical Center, Amsterdam (Oosterlaan); the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. (Stevens); the Department of Psychiatry, Vall d'Hebron University Hospital, Barcelona, Spain (Ramos-Quiroga); Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Spain (Lazaro, Ramos-Quiroga); Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain (Vilarroya); the Department of Psychiatry, Oregon Health and Science University, Portland (Fair, Nigg); Karakter Child and Adolescent Psychiatry University Center, Nijmegen, the Netherlands (Buitelaar); Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York (Faraone); NIHM, Bethesda, Md. (Shaw); the Department of Social and Behavioral Science, Harvard T.H. Chan School of Public Health, Boston (Tiemeier).

PMID: 31014101
PMCID: PMC6879185
DOI: 10.1176/appi.ajp.2019.18091033

Abstract

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.

Methods: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).

Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.

Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

Keywords: Attention Deficit Hyperactivity Disorder; Cortical Surface Area; Cortical Thickness; Imaging; Meta-Analysis; Neuroanatomy.

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Conflict of interest statement

Potential conflict of Interest and financial support

These authors all declare no conflicts of Interest:

Hoogman, Muetzel, Guimaraes, Shumskaya, Mennes, Zwiers, Jahanshad, Sudre, Mostert, Wolfers, Earl, Soliva Vila, Vives-Gilabert, Khadka, Novotny, Hartman, Heslenfeld, Schweren, Ambrosino, Oranje, de Zeeuw, Chaim-Avancini, Rosa, Zanetti, Malpas, Kohls, von Polier, Seitz, Doyle, Epstein, Jernigan, Baur-Streubel, Ziegler, Zierhut, Schrantee, Høvik, Lundervold, Kelly, McCarthy, Skokauskas, O'Gorman Tuura, Calvo, Lera-Miguel, Nicolau, Chantiluke, Christakou, Vance, Cercignani, Gabel, Asherson, Baumeister, Hohmann, Bramati, Tovar-Moll, Fallgatter, Kardatzki, Schwarz, Anikin, Baranov, Gogberashvili, Kapilushniy, Solovieva, El Marroun, White, Namazova-Baranova, Ethofer, Plessen, Mehta, Paloyelis, Harrison, Bellgrove, Silk, Cubillo, Lazaro, Brem, Frodl, Zentis, Castellanos, Yoncheva, Reneman, Conzelmann, Pauli, Reif, Tamm, Oberwelland Weiss, Busatto, Louza, Durston, Oosterlaan, Stevens, Vilarroya, Fair, Nigg, Thompson, Shaw, Tiemeier, Bralten.

Potential conflicts of interest for the following authors are reported:

David Coghill served in an advisory or consultancy role for Lilly, Medice, Novartis, Oxford outcomes, Shire and Viforpharma. He received conference support or speaker’s fee by Janssen McNeil, Lilly, Medice, Novartis, Shire and Sunovian. He is/has been involved in clinical trials conducted by Lilly & Shire. The present work is unrelated to the above grants and relationships.

Jonna Kuntsi has given talks at educational events sponsored by Medice; all funds are received by King’s College London and used for studies of ADHD.

Theo Van Erp consulted for Roche Pharmaceuticals and has a contract with Otsuka Pharmaceutical, Ltd.

Anders Dale is a Founder of CorTechs Labs, Inc. He serves on the Scientific Advisory Boards of CorTechs Labs and Human Longevity, Inc., and receives research funding through a Research Agreement with General Electric Healhcare.

Paulo Mattos was on the speakers’ bureau and/or acted as consultant for Janssen-Cilag, Novartis, and Shire in the previous five years; he also received travel awards to participate in scientific meetings from those companies. The ADHD outpatient program (Grupo de Estudos do Déficit de Atenção/Institute of Psychiatry) chaired by Dr. Mattos has also received research support from Novartis and Shire.The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.

Tobias Banaschewski served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis and Shire. He received conference support or speaker’s fee by Lilly, Medice, Novartis and Shire. He is/has been involved in clinical trials conducted by Shire & Viforpharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships.

Katya Rubia received speaker's fees form Shire, Medice and a grant from Lilly for another project.

Jan Haavik has received speaker fees from Lilly, Novartis and Janssen Cilag.

Stephen V. Faraone, in the past year, received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili Interactive Labs, VAYA, Ironshore, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD.

Joseph Biederman is currently receiving research support from the following sources: The Department of Defense, Food & Drug Administration, Ironshore, Lundbeck, Magceutics Inc., Merck, PamLab, Pfizer, Shire Pharmaceuticals Inc., SPRITES, Sunovion, Vaya Pharma/Enzymotec, and NIH. In 2015, Dr. Joseph Biederman received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. He has a US Patent Application pending (Provisional Number #61/233,686) through MGH corporate licensing, on a method to prevent stimulant abuse. In 2014, Dr. Joseph Biederman received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. He received research support from AACAP, Alcobra, Forest Research Institute, and Shire Pharmaceuticals Inc. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Ingenix, Prophase, Shire, Bracket Global, Sunovion, and Theravance; these royalties were paid to the Department of Psychiatry at MGH.

Kerstin Konrad received speaking fees from Medice, Lilly and Shire.

Josep-Antoni Ramos-Quiroga Josep-Antoni Ramos-Quiroga was on the speakers’ bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis, Shire, Lundbeck, Almirall, Braingaze, Sincrolab, Medice and Rubió in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Medice, Rubió, Shire, and Eli- Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli-Lilly, Lundbeck, Janssen- Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious, and Rubió.

Klaus-Peter Lesch served as a speaker for Eli Lilly and received research support from Medice, and travel support from Shire, all outside the submitted work.

Pieter Hoekstra received a research grant from Shire and was part of the advisory board of Shire.

Jan Buitelaar has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Janssen Cilag BV, Eli Lilly, Medice, Shire, Roche, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties.

Barbara Franke has received educational speaking fees from Shire and Medice.

Susanne Walitza has received lecture honoraria from Eli-Lilly, Opopharma in the last five years and her outside professional activities and interests are declared under the link of the University of Zurich www.uzh.ch/prof/ssl-dir/interessenbindungen/client/web.

Daniel Brandeis serves as an unpaid scientific consultant for an EU-funded neurofeedback trial.

Georgii Karkashadze received payment for the authorship of the article and speaker fees from Sanofi and from Pikfarma.

Figures

**FIGURE 1.. Subcortical and cortical brain differences across the lifespan.**
A. Cohen’s d effect sizes with error bars showing the 95% confidence intervals for case-control differences in ENIGMA-ADHD cortical and subcortical structural features stratified by 3 age groups: children of 14 years of age and younger, adolescents from age 15 to 21 years, and adults older than 21 years. Structural features of all regions listed on the x-axis showed significant case-control differences in children; in analyses of cortical and subcortical features, no significant effects were seen in adolescents or adults. This is reflected in the effects sizes shown, all of which reached case-control statistical significance for children but not for adolescent and adult groups, except for the hippocampus, which shows a significant case-control difference in the adolescent group as well. B. Displayed are the heatmaps of validated case-control differences in the childhood subset for both surface area (left) and thickness (right) in each hemisphere.

**FIGURE 2.**
Bar graphs showing results of familiality analyses, comparing healthy controls, unaffaected siblings and cases, in the ADHD-affected cortical regions in the NeuroIMAGE datasets (n=506). Displayed are the cortical surface areas showing effects of familiality in the NeuroIMAGE datasets. For these regions, unaffected siblings differed from healthy controls (M_eff-corrected results). Cortical values are adjusted for age, gender, ICV and site.

See this image and copyright information in PMC

Comment in

The Enigma of Neuroimaging in ADHD.
Giedd JN. Giedd JN. Am J Psychiatry. 2019 Jul 1;176(7):503-504. doi: 10.1176/appi.ajp.2019.19050540. Am J Psychiatry. 2019. PMID: 31256625 No abstract available.

References

1. Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, Rohde LA, Sonuga-Barke EJ, Tannock R, Franke B. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers. 2015;1:15020. - PubMed
1. Thomas R, Sanders S, Doust J, Beller E, Glasziou P. Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Pediatrics. 2015;135:e994–1001. - PubMed
1. Le HH, Hodgkins P, Postma MJ, Kahle J, Sikirica V, Setyawan J, Erder MH, Doshi JA. Economic impact of childhood/adolescent ADHD in a European setting: the Netherlands as a reference case. Eur Child Adolesc Psychiatry. 2014;23:587–598. - PMC - PubMed
1. Valera EM, Faraone SV, Murray KE, Seidman LJ. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biological Psychiatry. 2007;61:1361–1369. - PubMed
1. Ellison-Wright I, Ellison-Wright Z, Bullmore E. Structural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis. BMC Psychiatry. 2008;8:51. - PMC - PubMed

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Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

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Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

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