Abstract

The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.

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Acknowledgements

The IMAGEN study receives research funding from the European Community's Sixth Framework Programme (LSHM-CT-2007-037286). Further support was provided by the FP7 projects ADAMS (genomic variations underlying common neuropsychiatric diseases and disease-related cognitive traits in different human populations; 242257) and the Innovative Medicine Initiative Project EU-AIMS (115300-2), as well as the UK National Institute for Health Research Biomedical Research Centre Mental Health and the Medical Research Council Programme Grant 'Developmental pathways into adolescent substance abuse' (93558).

Author information

Affiliations

  1. Departments of Psychiatry and Psychology, University of Vermont, Burlington, Vermont, USA.

    • Robert Whelan
    •  & Hugh Garavan
  2. Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.

    • Robert Whelan
    • , Mark Byrne
    • , Edmund C Lalor
    •  & Hugh Garavan
  3. Institute of Psychiatry, King's College London, London, UK.

    • Patricia J Conrod
    • , Anbarasu Lourdusamy
    • , Gareth J Barker
    • , Eva Loth
    •  & Gunter Schumann
  4. Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, Canada.

    • Patricia J Conrod
  5. Neurospin, Commissariat à l'Energie Atomique, Gif-sur-Yvette, France.

    • Jean-Baptiste Poline
    •  & Benjamin Thyreau
  6. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.

    • Tobias Banaschewski
  7. Queensland Brain Institute and School of Psychology, The University of Queensland, St. Lucia, Australia.

    • Mark A Bellgrove
    •  & Tarrant D R Cummins
  8. Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.

    • Christian Büchel
  9. Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany.

    • Mira Fauth-Bühler
    • , Karl Mann
    •  & Sabine Vollstaedt-Klein
  10. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

    • Herta Flor
    • , Frauke Nees
    •  & Maren Struve
  11. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany.

    • Jürgen Gallinat
    •  & Andreas Heinz
  12. Physikalisch-Technische Bundesanstalt, Berlin, Germany.

    • Bernd Ittermann
  13. Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 'Imaging & Psychiatry,' University Paris Sud, Orsay, France.

    • Jean-Luc Martinot
  14. Assistance Publique Hopitaux de Paris Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.

    • Jean-Luc Martinot
  15. Centre National de Génotypage, Evry, France.

    • Mark Lathrop
  16. MRC Social, Genetic and Developmental Psychiatry Centre, London, UK.

    • Eva Loth
    •  & Gunter Schumann
  17. Rotman Research Institute, University of Toronto, Toronto, Canada.

    • Tomas Paus
  18. School of Psychology, University of Nottingham, Nottingham, UK.

    • Tomas Paus
  19. Montreal Neurological Institute, McGill University, Montreal, Canada.

    • Tomas Paus
  20. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.

    • Marcella Rietschel
  21. Department of Psychiatry and Psychotherapy, Technische Universität, Dresden, Germany.

    • Michael N Smolka
  22. Neuroimaging Center, Department of Psychology, Technische Universität, Dresden, Germany.

    • Michael N Smolka
  23. Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

    • Rainer Spanagel
  24. Department of Psychology, University of Sussex, Sussex, UK.

    • David N Stephens
  25. Behavioral and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK.

    • Trevor W Robbins

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  1. the IMAGEN Consortium

    Institute of Psychiatry, King's College London, London, UK.

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Contributions

H.G., T.W.R. and G.S. conceived the study. P.J.C., H.G., T.W.R. and R.W. designed the study. M.F.-B., H.G. and T.W.R. carried out the functional neuroimaging. G.J.B., C.B., P.J.C., H.F., J.G., H.G., A.H., B.I., E.L., K.M., J.-L.M, F.N., M.N.S., T.P., M.R., R.S., D.S., T.W.R., M.S. and A.S. acquired the data. J.-B.P., B.T. and R.W. carried out neuroimaging data processing and analysis. M.B., M.F.-B., E.C.L., M.S. and S.V.-K. analyzed behavioral data. M.A.B., T.D.R.C., M.L., A.L. and G.S. carried out genotyping and genetic analysis. R.W. and H.G. prepared the manuscript. M.A.B., P.J.C., T.B., T.P., T.W.R. and G.S. edited the manuscript.

Competing interests

G.J.B. received honoraria for teaching from General Electric during the course of this study. T.W.R. consults for Cambridge Cognition, E Lilly, GlaxoSmithKline, Merck and Lundbeck and has received recent research grants from Lilly, GSK and Lundbeck. T.B. served in an advisory or consultancy role for Bristol Myers-Sqibb, Develco Pharma, Lilly, Medice, Novartis, Shire and Viforpharma and received conference attendance support and conference support or received speaker's fee from Lilly, Janssen McNeil, Medice, Novartis and Shire. He is/has been involved in clinical trials conducted by Lilly and Shire. The present work is unrelated to the T.B.'s grants and relationships.

Corresponding authors

Correspondence to Robert Whelan or Hugh Garavan.

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DOI

https://doi.org/10.1038/nn.3092

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