Brain Age in Conduct Disorder: A Mega-Analysis of the ENIGMA Antisocial Behavior Working Group

Conduct disorder (CD) is the leading global cause of mental health burden in children and adolescents and has recently been hypothesized to be a neurodevelopmental disorder. Although prior research has identified neuroanatomical differences associated with CD, it remains unclear whether these differences reflect atypical brain development. Here, we investigated the difference between an individual's brain age and chronological age as a proxy for variations in brain maturation. Using a pretrained model, we estimated brain age from structural neuroimaging data obtained from 1,119 youth with CD and 1,183 typically developing controls across 14 international cohorts participating in the ENIGMA-Antisocial Behavior Working Group. Youth with CD exhibited a statistically robust but small acceleration in brain age compared to typically developing youth (around 0.50 years), which was restricted to the adolescence-onset subtype of the disorder. Our large-scale, coordinated analysis provides the first evidence of accelerated neurodevelopment as a potential mechanism underlying CD.

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Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-01-21
DOI
https://doi.org/10.64898/2026.01.20.700567
Primary Topic
Psychopathy, Forensic Psychiatry, Sexual Offending
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article
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article

Brain Age in Conduct Disorder: A Mega-Analysis of the ENIGMA Antisocial Behavior Working Group

Olivier F. Colins, Cindy C. Hagan, Ana Isabel Lafuente Cubillo, Ruth Roberts et al.
bioRxiv (Cold Spring Harbor Laboratory)
Psychopathy, Forensic Psychiatry, Sexual Offending
article

Brain Age in Conduct Disorder: A Mega-Analysis of the ENIGMA Antisocial Behavior Working Group

Olivier F. Colins, Cindy C. Hagan, Ana Isabel Lafuente Cubillo, Ruth Roberts, Christopher Townsend, Luke W. Hyde, Anouk H. Dykstra, D. BRANDEIS, Elise M. Cardinale, Robert R. J. M. Vermeiren, C. Stadler, Essi Viding, Shulin Fang, Yidian Gao, Harriet Cornwell, Anka Bernhard, Christopher S. Monk, D. Craig Michael, Harriet Phillips, Colter Mitchell, Jules R. Dugré, J. L. Martinot, Heidi B. Westerman, Marlene Staginnus, Anne Martinelli, Charlotte P.S. Boateng, Abigail A. Marsh, Alexandra Kypta-Vivanco, Dana Diaz, Areti Smaragdi, Declan G. Murphy, G. Schumann, Arjun Sethi, Celso Arango, E. Sonuga‐Barke, P. Thompson, M. Kang, A. Dietrich, S. De Brito, B. Franke, Jan K. Buitelaar, Karim Ibrahim, Denis G. Sukhodolsky, Xiaoping Wang, Daniel S. Pine, Christine M. Freitag, Arun L.W. Bokde
article en

Abstract

Conduct disorder (CD) is the leading global cause of mental health burden in children and adolescents and has recently been hypothesized to be a neurodevelopmental disorder. Although prior research has identified neuroanatomical differences associated with CD, it remains unclear whether these differences reflect atypical brain development. Here, we investigated the difference between an individual's brain age and chronological age as a proxy for variations in brain maturation. Using a pretrained model, we estimated brain age from structural neuroimaging data obtained from 1,119 youth with CD and 1,183 typically developing controls across 14 international cohorts participating in the ENIGMA-Antisocial Behavior Working Group. Youth with CD exhibited a statistically robust but small acceleration in brain age compared to typically developing youth (around 0.50 years), which was restricted to the adolescence-onset subtype of the disorder. Our large-scale, coordinated analysis provides the first evidence of accelerated neurodevelopment as a potential mechanism underlying CD.

bioRxiv (Cold Spring Harbor Laboratory)
University College Dublin (IE), University of California, Riverside (US), University of East Anglia (GB), Goethe University Frankfurt (DE), University of Rome Tor Vergata (IT), University of Southern California (US), Leiden University (NL), California Institute of Technology (US), University of Copenhagen (DK), Birmingham City University (GB), University Medical Center Groningen (NL), The University of Texas MD Anderson Cancer Center (US), Central South University (CN), Radboud University Nijmegen (NL), Inserm (FR), University of America (US), University of Groningen (NL), Forschungszentrum Jülich (DE), Hunan Normal University (CN), King's College London (GB), Georgetown University (US), Virginia Commonwealth University (US), University of Basel (CH), Utrecht University (NL), Universität Ulm (DE), University of Zurich (CH), Université Paris Cité (FR), Trinity College Dublin (IE), University of Applied Sciences Leiden (NL), Heidelberg University (DE), University of Exeter (GB), University of Cambridge (GB), Université Paris-Saclay (FR), University of Michigan (US), Columbia University Irving Medical Center (US), Leiden University Medical Center (NL), Hospital Universitario La Paz (ES), Mental Health Services (DK), Instituto de Salud Carlos III (ES), Erasmus MC (NL), University Hospital Heidelberg (DE), University Medical Center (US), Radboud University Medical Center (NL), Hospital General Universitario Gregorio Marañón (ES), University College Birmingham (GB), Jianghan University (CN), Ghent University (BE), Yale University (US), ETH Zurich (CH), Soochow University (CN), Centro de Investigación Biomédica en Red de Salud Mental (ES), Sorbonne Paris Cité (FR), Neuropsychiatric Research Institute (US), Central Institute of Mental Health (DE), Dutch Expert Centre for Screening (NL), Hospital Clínic de Barcelona (ES), Maudsley Hospital (GB), German Center for Infection Research (DE), King's College School (GB), Accare (NL), Universitätsklinikum Aachen (DE), Max Planck Institute for Human Cognitive and Brain Sciences (DE), University Hospital Frankfurt (DE), Youth Development (US), Hochschule Fresenius (DE), Karakter (NL), Child Development Center (QA), Amsterdam University Medical Centers (NL), First Affiliated Hospital of Soochow University (CN), Second Xiangya Hospital of Central South University (CN), SRH Hochschule für Wirtschaft und Medien Calw (DE), National Institute of Mental Health (US), Einstein Center for Neurosciences Berlin (DE), National Institute of Mental Health (CZ), University of Southampton (GB), Hartford Financial Services (United States), University College London (GB), University of Bath (GB), Middlesex University London (GB), Universidad Autónoma de Madrid (ES), Universitat de Barcelona (ES), Washington State University (US), Freie Universität Berlin (DE), Technische Universität Dresden (DE), University of Birmingham (GB), Catholic University of America (US), Vrije Universiteit Amsterdam (NL), Michigan State University (US), RWTH Aachen University (DE)
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Psychopathy, Forensic Psychiatry, Sexual Offending
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