Shared and Distinct Alterations in Brain Structure of Youth With Internalizing or Externalizing Disorders: Findings From the ENIGMA Antisocial Behavior, ADHD, Major Depressive Disorder, and Anxiety Working Groups

Sophie Townend¹, Marlene Staginnus², Yidian Gao³, Nina Alexander⁴, Volker Arolt⁵, Tobias Banaschewski⁶, Katja Beesdo-Baum⁷, Mark A Bellgrove⁸, Vivek Benegal⁹, Robert J Blair¹⁰, Laura Blanco-Hinojo¹¹, Ole Jonas Boeken¹², Joscha Böhnlein⁵, Sven Bölte¹³, Linda M Bonnekoh¹⁴, Daniel Brandeis¹⁵, Rodrigo A Bressan¹⁶, Fabian Breuer⁵, Willem B Bruin¹⁷, Jan K Buitelaar¹⁸, Katie L Burkhouse¹⁹, Monica E Calkins²⁰, Marta Cano²¹, Narcis Cardoner²¹, Hui Chen²², Xianliang Chen²², David R Coghill²³, Olivier F Colins²⁴, Colm G Connolly²⁵, Michael C Craig²⁶, Kathryn R Cullen²⁷, Udo Dannlowski²⁸, Christopher G Davey²⁹, Andrea Dietrich³⁰, Daifeng Dong³¹, Christine M Freitag³², Thomas Frodl³³, Liesbet Goossens³⁴, Dominik Grotegerd⁵, Raquel E Gur³⁵, Ruben C Gur³⁶, Jan Haavik³⁷, Cindy C Hagan³⁸, Tim Hahn⁵, Alfons O Hamm³⁹, Ben J Harrison²⁹, Catharina A Hartman⁴⁰, Martin J Herrmann⁴¹, Tiffany C Ho⁴², Pieter J Hoekstra³⁰, Bharath Holla⁴³, Karim Ibrahim⁴⁴, Andrea Jackowski⁴⁵, Hamidreza Jamalabadi⁴⁶, Yali Jiang⁴⁷, Tilo Kircher⁴⁶, Kerstin Konrad⁴⁸, Anna Kraus⁵, Jonna Kuntsi⁴⁹, Till Langhammer⁵⁰, Luisa Lazaro⁵¹, Elisabeth J Leehr⁵, Ulrike Lueken⁵², Ren Ma⁵³, Frank P MacMaster⁵⁴, Gisele G Manfro⁵⁵, Anne Martinelli⁵⁶, Hannah Meinert⁵, Susanne Meinert⁵⁷, Jarosław M Michałowski⁵⁸, Qingsen Ming⁵⁹, Robert Moeck⁶⁰, Markus Muehlhan⁶¹, Lilianne R Mujica-Parodi⁶², Benson Mwangi⁶³, Janina Neufeld⁶⁴, Joel T Nigg⁶⁵, Ruth L O'Gorman Tuura⁶⁶, Hyuntaek Oh⁶⁷, Jaap Oosterlaan⁶⁸, Yannis Paloyelis⁶⁹, Pedro M Pan¹⁶, Luca Passamonti⁷⁰, Wenceslao Peñate⁷¹, K Luan Phan⁷², Kerstin J Plessen⁷³, Jesus Pujol⁷⁴, Karl Lundin Remnélius⁷⁵, Francisco Rivero⁷⁶, Katya Rubia⁷⁷, Ramiro Salas⁷⁸, Giovanni A Salum⁷⁹, Theodore D Satterthwaite⁸⁰, Anne Schienle⁸¹, Elisabeth Schrammen⁵, Koen R J Schruers⁸², Gunter Schumann⁸³, Arjun Sethi²⁶, Tim Silk⁸⁴, Norbert Skokauskas⁸⁵, Jordan W Smoller⁸⁶, Jair C Soares⁶³, Lin Sørensen⁸⁷, Christina Stadler⁸⁸, Michael C Stevens⁸⁹, Benjamin Straube⁴⁶, Thomas Straube⁶⁰, Andreas Ströhle⁹⁰, Gustavo Sudre⁷⁷, Denis G Sukhodolsky⁴⁴, Kate Sully⁹¹, Xiaoqiang Sun⁵³, Chad M Sylvester⁹², Nicola Toschi⁹³, Steven J A van der Werff⁹⁴, Alasdair Vance⁹⁵, Robert Vermeiren⁹⁶, Albert Wabnegger⁸¹, Xiaoping Wang²², Julia Wendt⁹⁷, Sarah Whittle⁹⁸, Julian Wiemer⁹⁹, Anderson M Winkler¹⁰⁰, Hans U Wittchen¹⁰¹, Mon-Ju Wu⁶³, Qiong Wu¹⁰², Tony T Yang¹⁰³, Yunbo Yang¹⁰⁴, Shuqiao Yao⁵³, Jibiao Zhang⁵³, Jiansong Zhou²², Andre Zugman¹⁰⁵, Giovana B Zunta-Soares⁶³, Peter M Zwanzger¹⁰⁶, Sophia I Thomopoulos¹⁰⁷, Neda Jahanshad¹⁰⁷, Paul M Thompson¹⁰⁷, Kevin Hilbert¹⁰⁸, Arielle Baskin-Sommers¹⁰⁹, Charlotte A M Cecil¹¹⁰, Moji Aghajani¹⁷, Daniel S Pine¹⁰⁵, Nic J A van der Wee⁹⁴, Dan J Stein¹¹¹, Nynke A Groenewold¹¹², Janna Marie Bas-Hoogendam¹¹³, Laura K M Han¹¹⁴, Elena Pozzi⁹⁸, Lianne Schmaal⁹⁸, Barbara Franke¹¹⁵, Martine Hoogman¹¹⁶, Esther Walton², Stephane A De Brito¹¹⁷, Graeme Fairchild²; ENIGMA Antisocial Behavior, Anxiety, ADHD, and MDD Working Groups

Affiliations

¹ Department of Psychology, University of Bath, Bath, United Kingdom. Electronic address: st2325@bath.ac.uk.
² Department of Psychology, University of Bath, Bath, United Kingdom.
³ Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom.
⁴ Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany.
⁵ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁶ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany.
⁷ Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Dresden University of Technology, Dresden, Germany.
⁸ School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
⁹ Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India.
¹⁰ Child and Adolescent Mental Health Center, Copenhagen University Hospital - Mental Health Services, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
¹¹ MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain; Barcelona Institute for Global Health, Barcelona, Spain.
¹² Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹³ Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet and Region Stockholm, Stockholm, Sweden; Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, Western Australia, Australia.
¹⁴ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Münster, Münster, Germany.
¹⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zürich, University of Zürich, Zürich, Switzerland.
¹⁶ Department of Psychiatry, Laboratory of Integrative Neurosciences, Universidade Federal de São Paulo, São Paulo, Brazil.
¹⁷ Section Forensic Family and Youth Care, Institute of Education and Child Studies, Leiden University, Leiden, the Netherlands.
¹⁸ Department of Medical Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁹ Department of Psychology, Penn State University, University Park, Pennsylvania.
²⁰ Neurodevelopment and Psychosis Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
²¹ Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau, Barcelona, Spain; Centre for Biomedical Research in the Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain.
²² Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
²³ Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.
²⁴ Department of Special Needs Education, Faculty of Psychology and Educational Sciences, Ghent University, Gent, Belgium.
²⁵ Department of Biomedical Sciences, Florida State University, Tallahassee, Florida.
²⁶ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
²⁷ Department of Psychiatry and Behavioural Sciences, University of Minnesota Medical School, Minneapolis, Minnesota.
²⁸ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Bielefeld, Germany.
²⁹ Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
³⁰ Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Accare Child Study Center, Groningen, the Netherlands.
³¹ Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China; National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
³² Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe University, Frankfurt am Main, Germany.
³³ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Rhineland-Westphalian Technical University, Aachen, Germany.
³⁴ Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.
³⁵ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Lifespan Brain Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
³⁶ Brain Behavior Laboratory, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
³⁷ Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
³⁸ California Institute of Technology, Pasadena, California.
³⁹ Department of Biological and Clinical Psychology/Psychotherapy, University of Greifswald, Greifswald, Germany; Department of Psychology, University of Greifswald, Greifswald, Germany.
⁴⁰ Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴¹ Center for Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
⁴² Department of Psychology, University of California Los Angeles, Los Angeles, California.
⁴³ Department of Integrative Medicine, National Institute of Mental Health and Neurosciences, Bengaluru, India.
⁴⁴ Child Study Center, Yale University School of Medicine, New Haven, Connecticut.
⁴⁵ Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil; Department of Health and Wellness Design, School of Public Health, Indiana University, Bloomington, Indiana.
⁴⁶ Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
⁴⁷ School of Psychology, South China Normal University, Guangzhou, China.
⁴⁸ Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Rhineland-Westphalian Technical University, Aachen, Germany; JARA-BRAIN Institute II, Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH, and RWTH Aachen, Jülich, Germany.
⁴⁹ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁵⁰ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵¹ Department of Child and Adolescent Psychiatry and Psychology, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Centre for Biomedical Research in the Mental Health Network, Barcelona, Spain; Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
⁵² Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Mental Health, partner site Berlin/Potsdam, Germany.
⁵³ Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China.
⁵⁴ IWK Health, Halifax, Nova Scotia, Canada; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
⁵⁵ Department of Psychiatry, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Psychiatry Services, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁵⁶ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe University, Frankfurt am Main, Germany; Psychology School, Fresenius University of Applied Sciences, Frankfurt am Main, Germany.
⁵⁷ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁵⁸ Poznań Laboratory of Affective Neuroscience, University SWPS, Poznań, Poland.
⁵⁹ Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China; Department of Psychiatry, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁶⁰ Institute of Medical Psychology and Systems Neuroscience, University Hospital Münster, Münster, Germany.
⁶¹ Department of Psychology, Faculty of Human Sciences, Medical School Hamburg, Hamburg, Germany.
⁶² Biomedical Engineering, Laufer Center for Physical and Quantitative Biology, State University of New York at Stony Brook, Stony Brook, New York; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
⁶³ Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, UTHealth Houston, Houston, Texas.
⁶⁴ Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet and Region Stockholm, Stockholm, Sweden; Swedish Collegium for Advanced Study, Uppsala, Sweden.
⁶⁵ Department of Psychiatry, Oregon Health and Science University, Portland, Oregon.
⁶⁶ University Children's Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland.
⁶⁷ Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas; Menninger Clinic, Houston, Texas.
⁶⁸ Clinical Neuropsychology Section, Vrije Universiteit, Amsterdam, the Netherlands; Emma Children's Hospital, Amsterdam University Medical Center location University of Amsterdam, Department of Pediatrics, Emma Children's Hospital Amsterdam University Medical Center Follow-Me program & Emma Neuroscience Group, Amsterdam, the Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
⁶⁹ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁰ Clinical Neuroscience Department, University of Cambridge, Cambridge, United Kingdom.
⁷¹ Department of Clinical Psychology, Psychobiology and Methodology, University of La Laguna, La Laguna, Tenerife, Spain; University Institute of Neuroscience, La Laguna, Tenerife, Spain.
⁷² Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, Ohio.
⁷³ Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne and University of Lausanne, Lausanne, Switzerland.
⁷⁴ MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.
⁷⁵ Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet and Region Stockholm, Stockholm, Sweden.
⁷⁶ Facultad de Ciencias de la Salud, Universidad Europea de Canarias, La Orotava, Tenerife, Spain.
⁷⁷ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁸ Menninger Clinic, Houston, Texas; Department of Neuroscience, Baylor College of Medicine, Houston, Texas; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
⁷⁹ Department of Psychiatry, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Psychiatry Services, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Child Mind Institute, New York, New York.
⁸⁰ Penn Lifespan Informatics and Neuroimaging Center, Philadelphia, Pennsylvania; Penn-CHOP Lifespan Brain Institute, Philadelphia, Pennsylvania.
⁸¹ Clinical Psychology, University of Graz, Graz, Austria.
⁸² Research Institute for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Mondriaan Mental Health Center, Maastricht, the Netherlands.
⁸³ Centre for Population Neuroscience and Stratified Medicine, The Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China; Centre for Population Neuroscience and Precision Medicine, Department of Psychiatry and Neuroscience, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁸⁴ School of Psychology and the Centre for Social and Early Emotional Development, Deakin University, Geelong, Victoria, Australia.
⁸⁵ Regional Centre for Child and Youth Mental Health and Child Welfare, Norwegian University of Science and Technology, Trondheim, Norway.
⁸⁶ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.
⁸⁷ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
⁸⁸ Child and Adolescent Psychiatric Research Department, Universitäre Psychiatrische Kliniken Basel, Basel, Switzerland.
⁸⁹ Olin Neuropsychiatry Research Center, Hartford, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
⁹⁰ Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁹¹ School of Psychology, University of Southampton, Southampton, United Kingdom.
⁹² Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri; Department of Radiology, Washington University in St. Louis, St. Louis, Missouri; Taylor Family Institute for Innovative Psychiatric Research, Washington University in St. Louis, St. Louis, Missouri.
⁹³ Department of Biomedicine and Prevention, University of Rome "Tor Vergata," Rome, Italy; Martinos Center for Biomedical Imaging, Boston, Massachusetts.
⁹⁴ Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.
⁹⁵ Academic Child Psychiatry Unit, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁹⁶ Leiden University Medical Center Curium, Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.
⁹⁷ Biological Psychology and Affective Science, University of Potsdam, Potsdam, Germany; Oberberg Clinic Potsdam, Potsdam, Germany.
⁹⁸ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria, Australia.
⁹⁹ Institute of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
¹⁰⁰ Division of Human Genetics, The University of Texas Rio Grande Valley, Browsville, Texas.
¹⁰¹ Department Psychiatry and Psychotherapy, Ludwig Maximilians University, München, Germany.
¹⁰² Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Clinic for Neurology, University of Leipzig Medical Center, Leipzig, Germany.
¹⁰³ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California.
¹⁰⁴ Institut for Psychology, University of Hildesheim, Hildesheim, Germany.
¹⁰⁵ National Institute of Mental Health Intramural Research Program, Bethesda, Maryland.
¹⁰⁶ Department Psychiatry and Psychotherapy, Ludwig Maximilians University, München, Germany; kbo-Inn-Salzach-Hospital Clinical Center for Psychiatry, Psychotherapy and Psychosomatics, Wasserburg am Inn, Germany.
¹⁰⁷ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California.
¹⁰⁸ Department of Psychology, Health and Medical University Erfurt, Erfurt, Germany.
¹⁰⁹ Department of Psychology, Yale University, New Haven, Connecticut.
¹¹⁰ Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
¹¹¹ South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Psychiatry, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.
¹¹² Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹¹³ Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands; Institute of Psychology, Leiden University, Leiden, the Netherlands.
¹¹⁴ Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria, Australia; Department of Psychiatry, Amsterdam University Medical Center location Vrije Universiteit, Amsterdam Neuroscience, Amsterdam, the Netherlands.
¹¹⁵ Department of Medical Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
¹¹⁶ Department of Medical Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
¹¹⁷ Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Centre for Developmental Science, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Birmingham Centre for Neurogenetics, School of Psychology, University of Birmingham, Birmingham, United Kingdom.

PMID: 40812743
DOI: 10.1016/j.biopsych.2025.08.003

Shared and Distinct Alterations in Brain Structure of Youth With Internalizing or Externalizing Disorders: Findings From the ENIGMA Antisocial Behavior, ADHD, Major Depressive Disorder, and Anxiety Working Groups

Sophie Townend et al. Biol Psychiatry. 2025.

. 2025 Aug 12:S0006-3223(25)01405-2.

doi: 10.1016/j.biopsych.2025.08.003. Online ahead of print.

Authors

Affiliations

¹ Department of Psychology, University of Bath, Bath, United Kingdom. Electronic address: st2325@bath.ac.uk.
² Department of Psychology, University of Bath, Bath, United Kingdom.
³ Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom.
⁴ Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany.
⁵ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁶ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany.
⁷ Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Dresden University of Technology, Dresden, Germany.
⁸ School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
⁹ Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India.
¹⁰ Child and Adolescent Mental Health Center, Copenhagen University Hospital - Mental Health Services, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
¹¹ MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain; Barcelona Institute for Global Health, Barcelona, Spain.
¹² Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹³ Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet and Region Stockholm, Stockholm, Sweden; Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, Western Australia, Australia.
¹⁴ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Münster, Münster, Germany.
¹⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zürich, University of Zürich, Zürich, Switzerland.
¹⁶ Department of Psychiatry, Laboratory of Integrative Neurosciences, Universidade Federal de São Paulo, São Paulo, Brazil.
¹⁷ Section Forensic Family and Youth Care, Institute of Education and Child Studies, Leiden University, Leiden, the Netherlands.
¹⁸ Department of Medical Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁹ Department of Psychology, Penn State University, University Park, Pennsylvania.
²⁰ Neurodevelopment and Psychosis Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
²¹ Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau, Barcelona, Spain; Centre for Biomedical Research in the Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain.
²² Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
²³ Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.
²⁴ Department of Special Needs Education, Faculty of Psychology and Educational Sciences, Ghent University, Gent, Belgium.
²⁵ Department of Biomedical Sciences, Florida State University, Tallahassee, Florida.
²⁶ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
²⁷ Department of Psychiatry and Behavioural Sciences, University of Minnesota Medical School, Minneapolis, Minnesota.
²⁸ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Bielefeld, Germany.
²⁹ Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
³⁰ Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Accare Child Study Center, Groningen, the Netherlands.
³¹ Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China; National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
³² Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe University, Frankfurt am Main, Germany.
³³ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Rhineland-Westphalian Technical University, Aachen, Germany.
³⁴ Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.
³⁵ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Lifespan Brain Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
³⁶ Brain Behavior Laboratory, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
³⁷ Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
³⁸ California Institute of Technology, Pasadena, California.
³⁹ Department of Biological and Clinical Psychology/Psychotherapy, University of Greifswald, Greifswald, Germany; Department of Psychology, University of Greifswald, Greifswald, Germany.
⁴⁰ Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴¹ Center for Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
⁴² Department of Psychology, University of California Los Angeles, Los Angeles, California.
⁴³ Department of Integrative Medicine, National Institute of Mental Health and Neurosciences, Bengaluru, India.
⁴⁴ Child Study Center, Yale University School of Medicine, New Haven, Connecticut.
⁴⁵ Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil; Department of Health and Wellness Design, School of Public Health, Indiana University, Bloomington, Indiana.
⁴⁶ Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
⁴⁷ School of Psychology, South China Normal University, Guangzhou, China.
⁴⁸ Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Rhineland-Westphalian Technical University, Aachen, Germany; JARA-BRAIN Institute II, Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH, and RWTH Aachen, Jülich, Germany.
⁴⁹ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁵⁰ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵¹ Department of Child and Adolescent Psychiatry and Psychology, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Centre for Biomedical Research in the Mental Health Network, Barcelona, Spain; Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
⁵² Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Mental Health, partner site Berlin/Potsdam, Germany.
⁵³ Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China.
⁵⁴ IWK Health, Halifax, Nova Scotia, Canada; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
⁵⁵ Department of Psychiatry, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Psychiatry Services, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁵⁶ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe University, Frankfurt am Main, Germany; Psychology School, Fresenius University of Applied Sciences, Frankfurt am Main, Germany.
⁵⁷ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁵⁸ Poznań Laboratory of Affective Neuroscience, University SWPS, Poznań, Poland.
⁵⁹ Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China; Department of Psychiatry, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁶⁰ Institute of Medical Psychology and Systems Neuroscience, University Hospital Münster, Münster, Germany.
⁶¹ Department of Psychology, Faculty of Human Sciences, Medical School Hamburg, Hamburg, Germany.
⁶² Biomedical Engineering, Laufer Center for Physical and Quantitative Biology, State University of New York at Stony Brook, Stony Brook, New York; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
⁶³ Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, UTHealth Houston, Houston, Texas.
⁶⁴ Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet and Region Stockholm, Stockholm, Sweden; Swedish Collegium for Advanced Study, Uppsala, Sweden.
⁶⁵ Department of Psychiatry, Oregon Health and Science University, Portland, Oregon.
⁶⁶ University Children's Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland.
⁶⁷ Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas; Menninger Clinic, Houston, Texas.
⁶⁸ Clinical Neuropsychology Section, Vrije Universiteit, Amsterdam, the Netherlands; Emma Children's Hospital, Amsterdam University Medical Center location University of Amsterdam, Department of Pediatrics, Emma Children's Hospital Amsterdam University Medical Center Follow-Me program & Emma Neuroscience Group, Amsterdam, the Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
⁶⁹ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁰ Clinical Neuroscience Department, University of Cambridge, Cambridge, United Kingdom.
⁷¹ Department of Clinical Psychology, Psychobiology and Methodology, University of La Laguna, La Laguna, Tenerife, Spain; University Institute of Neuroscience, La Laguna, Tenerife, Spain.
⁷² Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, Ohio.
⁷³ Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne and University of Lausanne, Lausanne, Switzerland.
⁷⁴ MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.
⁷⁵ Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet and Region Stockholm, Stockholm, Sweden.
⁷⁶ Facultad de Ciencias de la Salud, Universidad Europea de Canarias, La Orotava, Tenerife, Spain.
⁷⁷ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁸ Menninger Clinic, Houston, Texas; Department of Neuroscience, Baylor College of Medicine, Houston, Texas; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
⁷⁹ Department of Psychiatry, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Psychiatry Services, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Child Mind Institute, New York, New York.
⁸⁰ Penn Lifespan Informatics and Neuroimaging Center, Philadelphia, Pennsylvania; Penn-CHOP Lifespan Brain Institute, Philadelphia, Pennsylvania.
⁸¹ Clinical Psychology, University of Graz, Graz, Austria.
⁸² Research Institute for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Mondriaan Mental Health Center, Maastricht, the Netherlands.
⁸³ Centre for Population Neuroscience and Stratified Medicine, The Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China; Centre for Population Neuroscience and Precision Medicine, Department of Psychiatry and Neuroscience, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁸⁴ School of Psychology and the Centre for Social and Early Emotional Development, Deakin University, Geelong, Victoria, Australia.
⁸⁵ Regional Centre for Child and Youth Mental Health and Child Welfare, Norwegian University of Science and Technology, Trondheim, Norway.
⁸⁶ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.
⁸⁷ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
⁸⁸ Child and Adolescent Psychiatric Research Department, Universitäre Psychiatrische Kliniken Basel, Basel, Switzerland.
⁸⁹ Olin Neuropsychiatry Research Center, Hartford, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
⁹⁰ Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁹¹ School of Psychology, University of Southampton, Southampton, United Kingdom.
⁹² Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri; Department of Radiology, Washington University in St. Louis, St. Louis, Missouri; Taylor Family Institute for Innovative Psychiatric Research, Washington University in St. Louis, St. Louis, Missouri.
⁹³ Department of Biomedicine and Prevention, University of Rome "Tor Vergata," Rome, Italy; Martinos Center for Biomedical Imaging, Boston, Massachusetts.
⁹⁴ Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.
⁹⁵ Academic Child Psychiatry Unit, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁹⁶ Leiden University Medical Center Curium, Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.
⁹⁷ Biological Psychology and Affective Science, University of Potsdam, Potsdam, Germany; Oberberg Clinic Potsdam, Potsdam, Germany.
⁹⁸ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria, Australia.
⁹⁹ Institute of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
¹⁰⁰ Division of Human Genetics, The University of Texas Rio Grande Valley, Browsville, Texas.
¹⁰¹ Department Psychiatry and Psychotherapy, Ludwig Maximilians University, München, Germany.
¹⁰² Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Clinic for Neurology, University of Leipzig Medical Center, Leipzig, Germany.
¹⁰³ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California.
¹⁰⁴ Institut for Psychology, University of Hildesheim, Hildesheim, Germany.
¹⁰⁵ National Institute of Mental Health Intramural Research Program, Bethesda, Maryland.
¹⁰⁶ Department Psychiatry and Psychotherapy, Ludwig Maximilians University, München, Germany; kbo-Inn-Salzach-Hospital Clinical Center for Psychiatry, Psychotherapy and Psychosomatics, Wasserburg am Inn, Germany.
¹⁰⁷ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California.
¹⁰⁸ Department of Psychology, Health and Medical University Erfurt, Erfurt, Germany.
¹⁰⁹ Department of Psychology, Yale University, New Haven, Connecticut.
¹¹⁰ Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
¹¹¹ South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Psychiatry, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.
¹¹² Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹¹³ Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands; Institute of Psychology, Leiden University, Leiden, the Netherlands.
¹¹⁴ Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria, Australia; Department of Psychiatry, Amsterdam University Medical Center location Vrije Universiteit, Amsterdam Neuroscience, Amsterdam, the Netherlands.
¹¹⁵ Department of Medical Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
¹¹⁶ Department of Medical Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
¹¹⁷ Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Centre for Developmental Science, School of Psychology, University of Birmingham, Birmingham, United Kingdom; Birmingham Centre for Neurogenetics, School of Psychology, University of Birmingham, Birmingham, United Kingdom.

PMID: 40812743
DOI: 10.1016/j.biopsych.2025.08.003

Abstract

Background: Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure. Using data from the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) disorders in youth.

Methods: 3D T1-weighted magnetic resonance imaging data from youths (age range 4-21 years) with anxiety disorders (n = 1044), depression (n = 504), ADHD (n = 1317), and CD (n = 1172) along with healthy control participants (n = 4743) were analyzed. We assessed group differences in regional cortical thickness, surface area (SA), and subcortical volume using linear models, adjusted for site, age, and sex, as well as total intracranial volume in the SA and subcortical volume models.

Results: We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower SA in the insula, entorhinal cortex, and middle temporal gyrus and lower amygdala volume (Cohen's ds = -0.07 to -0.24) as well as total SA and intracranial volume (ds = -0.11 to -0.25). Externalizing-specific reductions in SA were observed in frontoparietal regions (ds = -0.08 to -0.13), but no internalizing-specific associations were identified. Disorder-specific alterations were identified for ADHD, CD, and anxiety disorders but not depression.

Conclusions: Both common and disorder-specific alterations were identified, with regions involved in salience attribution and emotion processing implicated across internalizing and externalizing disorders. These novel findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders.

Keywords: Child and adolescent psychiatry; ENIGMA; Meta-analysis; Structural MRI; Transdiagnostic; Youth.

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Shared and Distinct Alterations in Brain Structure of Youth With Internalizing or Externalizing Disorders: Findings From the ENIGMA Antisocial Behavior, ADHD, Major Depressive Disorder, and Anxiety Working Groups

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Shared and Distinct Alterations in Brain Structure of Youth With Internalizing or Externalizing Disorders: Findings From the ENIGMA Antisocial Behavior, ADHD, Major Depressive Disorder, and Anxiety Working Groups

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Abstract

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