Publications

Journal Article Ahead of print

PubMed: 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, MDD, and Anxiety Working Groups.

Biol Psychiatry

Authors: Sophie Townend, Marlene Staginnus, Yidian Gao, Nina Alexander, Volker Arolt, Tobias Banaschewski, Mark A Bellgrove, Vivek Benegal, Robert J Blair, Laura Blanco-Hinojo, Ole Jonas Boeken, Joscha Böhnlein, Sven Bölte, Linda M Bonnekoh, Daniel Brandeis, Rodrigo A Bressan, Fabian Breuer, Willem B Bruin, Jan K Buitelaar, Katie L Burkhouse, Monica E Calkins, Marta Cano, Narcis Cardoner, Hui Chen, Xianliang Chen, David R Coghill, Olivier F Colins, Colm G Connolly, Michael C Craig, Kathryn R Cullen, Udo Dannlowski, Christopher G Davey, Andrea Dietrich, Daifeng Dong, Christine M Freitag, Thomas Frodl, Liesbet Goossens, Dominik Grotegerd, Raquel E Gur, Ruben C Gur, Jan Haavik, Cindy C Hagan, Tim Hahn, Alfons O Hamm, Ben J Harrison, Catharina A Hartman, Martin J Herrmann, Tiffany C Ho, Pieter J Hoekstra, Bharath Holla … and 102 other authors

Affiliations

  • Department of Psychology, University of Bath, Bath, United Kingdom.
  • Department of Psychology, University of Bath, Bath, United Kingdom.
  • Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom.
  • Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany.
  • Institute for Translational Psychiatry, University of Münster, Münster, Germany.
  • Department of Child and Adolescent Psychiatry and Psychotherapy, Medical Faculty Mannheim, Heidelberg University Central Institute of Mental Health, Mannheim, Germany.
  • School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
  • Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.
  • Child and Adolescent Psychiatric Center, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
  • MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain; ISGlobal Barcelona Institute for Global Health, Barcelona, Spain.
  • Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet & 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, Australia.
  • Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Münster, Münster, Germany.
  • Department of Child and Adolescent Psychiatry and Psychotherapy, Medical Faculty Mannheim, Heidelberg University Central Institute of Mental Health, Mannheim, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zürich, University of Zürich, Zürich, Switzerland.
  • Department of Psychiatry, Interdisciplinary Lab for Clinical Neurosciences (LiNC), Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.
  • Section Forensic Family & Youth Care, Institute of Education & Child Studies, Leiden University, Leiden, The Netherlands.
  • Department of Medical Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
  • The Research Institute, Nationwide Children's Hospital, Columbus, OH, United States.
  • Neurodevelopment and Psychosis Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
  • Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain; Network Centre for Biomedical Research on Mental Health (CIBERSAM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
  • 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, Hunan, China.
  • Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.
  • Department of Special Needs Education, Faculty of Psychology and Educational Sciences, Ghent University, Gent, Belgium.
  • Department of Biomedical Sciences, Florida State University, Tallahassee, FL, United States.
  • Department of Forensic and Neurodevelopmental Sciences, The Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Department of Psychiatry and Behavioural Sciences, University of Minnesota Medical School, Minneapolis, MN, United States.
  • Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.
  • Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Accare Child Study Center, Groningen, The Netherlands.
  • Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; China National Clinical Research Center for Mental Disorders (Xiangya), Changsha, Hunan, China.
  • Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe University, Frankfurt am Main, Germany.
  • Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH, Aachen, Germany.
  • Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands.
  • Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Lifespan Brain Institute, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
  • Brain Behavior Laboratory, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
  • Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
  • Independent researcher.
  • Department of Biological and Clinical Psychology/Psychotherapy, University of Greifswald, Greifswald, Germany; Department of Psychology, University of Greifswald, Greifswald, Germany.
  • Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Department of Psychiatry, University Medical Center Groningen, University of Groningen, The Netherlands.
  • Center for Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
  • Department of Psychology, University of California, Los Angeles, CA, United States.
  • Department of Integrative Medicine, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.

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 Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing disorders (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) in youth.

METHODS

3D T1-weighted MRI data from youth (aged 4-21 years) with anxiety disorders (n=1,044), depression (n=504), ADHD (n=1,317), and CD (n=1,172), along with healthy controls (n=4,743) were analyzed. We assessed group differences in regional cortical thickness, surface area, and subcortical volume using linear models, adjusted for site, age, and sex, and total intracranial volume in the surface area and subcortical volume models.

RESULTS

We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower surface area 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 surface area and intracranial volume (ds=-0.11 to -0.25). Externalizing-specific reductions in surface area were observed in fronto-parietal 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 findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders.

MeSH

Depression, Brain, Psychophysiology, Psychopharmacology, Anxiety Disorders, Research, Psychiatry, Attention Deficit Disorder With Hyperactivity

Cited by