Attention-Deficit/Hyperactivity Disorder (ADHD) and conduct disorder (CD) exemplify top-down dysregulation conditions that show a large comorbidity and shared genetics. At the same time, they entail two different types of symptomology involving mainly non-emotional or emotional dysregulation. Few studies have tried to separate the specific biology underlying these two dimensions. It has also been suggested that both types of conditions consist of extreme cases in the general population where the symptoms are widely distributed. Here we test whether brain structure is specifically associated to ADHD or CD symptoms in a general population of adolescents (n = 1093) being part of the IMAGEN project. Both ADHD symptoms and CD symptoms were related to similar and overlapping MRI findings of a smaller structure in prefrontal and anterior cingulate cortex. However, our regions of interest (ROI) approach indicated that gray matter volume (GMV) and surface area (SA) in dorsolateral/dorsomedial prefrontal cortex and caudal anterior cingulate cortex were negatively associated to ADHD symptoms when controlling for CD symptoms while rostral anterior cingulate cortex GMV was negatively associated to CD symptoms when controlling for ADHD symptoms. The structural findings were mirrored in performance of neuropsychological tests dependent on prefrontal and anterior cingulate regions, showing that while performance on the Stop Signal test was specifically related to the ADHD trait, delayed discounting and working memory were related to both ADHD and CD traits. These results point towards a partially domain specific and dimensional capacity in different top-down regulatory systems associated with ADHD and CD symptoms.

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This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behavior in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), the FP7 projects IMAGEMEND(602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-1, SM 80/7-2, SFB 940/1). Further support was provided by grants from: ANR (project AF12-NEUR0008-01-WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), U.S.A. (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Also grants from Karolinska Institutet, (Karolinska Institutet Strategic Neuroscience Program, Clinical Scientist Training Programme (CSTP), Senior Researcher in Medical Science), Stockholm County Council (PPG project), Stockholm Swedish Society of Medicine, Söderström-Königska Foundation and Osher Center for Integrative Medicine supported this study.

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Author notes

  1. These authors contributed equally: Frida Bayard, Charlotte Nymberg.


  1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    • Frida Bayard
    • , Charlotte Nymberg Thunell
    • , Christoph Abé
    •  & Predrag Petrovic
  2. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    • Rita Almeida
  3. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    • Tobias Banaschewski
    • , Frauke Nees
    • , Maren Struve
    •  & Yvonne Grimmer
  4. Centre for Neuroimaging Sciences, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, UK

    • Gareth Barker
  5. Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland

    • Arun L. W. Bokde
  6. University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany

    • Uli Bromberg
    • , Christian Büchel
    •  & Tahmine Fadai
  7. Centre for Population Neuroscience and Stratified Medicine (PONS) and MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    • Erin Burke Quinlan
    • , Sylvane Desrivières
    •  & Gunter Schumann
  8. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    • Herta Flor
    •  & Frauke Nees
  9. Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany

    • Herta Flor
  10. NeuroSpin, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette, France

    • Vincent Frouin
    •  & Dimitri Papadopoulos Orfanos
  11. Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, 05405, USA

    • Hugh Garavan
  12. Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK

    • Penny Gowland
  13. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany

    • Andreas Heinz
    •  & Henrik Walter
  14. Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Berlin, Germany

    • Bernd Ittermann
  15. Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging and Psychiatry”, University Paris Sud–Paris Saclay, University Paris Descartes; Service Hospitalier Frédéric Joliot, Orsay; and Maison de Solenn, Paris, France

    • Jean-Luc Martinot
  16. Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging and Psychiatry”, University Paris Sud–Paris Saclay, University Paris Descartes; and AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France

    • Marie-Laure Paillère Martinot
  17. Rotman Research Institute, Baycrest and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada

    • Tomáš Paus
  18. Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    • Luise Poustka
  19. Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany

    • Luise Poustka
  20. Department of Psychiatry, Université de Montréal, CHU Ste Justine Hospital, Montréal, QC, Canada

    • Patricia Conrod
  21. National Institute of Mental Health, NIH, Bethesda, MD, 20892, USA

    • Argyris Stringaris
  22. Department of Social and Health Care, Psychosocial Services Adolescent Outpatient Clinic Kauppakatu 14, Lahti, Finland

    • Jani Penttilä
  23. Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany

    • Viola Kappel
  24. Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany

    • Betteke van Noort
  25. Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany

    • Michael N. Smolka
    •  & Nora C. Vetter
  26. School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland

    • Robert Whelan


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  1. the IMAGEN Consortium

    Conflict of interest

    Dr. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis, Shire. He received conference support or speaker’s fee by Lilly, Medice, Novartis, and Shire. He has been involved in clinical trials conducted by Shire and Viforpharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr. GB has received funding for a PhD student and honoraria for teaching on scanner programming courses from General Electric Healthcare; he acts as a consultant for IXICO. Dr. HW received a speaker honorarium from Servier (2014). The remaining authors declare no conflict of interest.

    Corresponding author

    Correspondence to Predrag Petrovic.

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