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Abstract

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

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Change history

  • 13 August 2014

    The affiliations list was updated to include a missing address.

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Acknowledgements

This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the FP7 projects IMAGEMEND (602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), a Medical Research Council Programme Grant “Developmental pathways into adolescent substance abuse” (93558), the Swedish funding agency FORMAS, the Medical Research Council and the Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministerium für Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc 01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG): Reinhart-Koselleck Award SP 383/5-1 and grants SM 80/7-1, SFB 940/1, FOR 1617), the French MILDT (Mission Interministérielle de Lutte contre la Drogue et la Toxicomanie), the CENIR (Centre de NeuroImagerie de Recherche, Pr. S. Lehéricy) within the ICM institute, the National Institute of Mental Health (MH082116), a National Institutes of Health Center of Biomedical Research Excellence award P20GM103644 from the National Institute of General Medical Sciences and the Tobacco Centers of Regulatory Science award P50DA036114. The authors acknowledge the Vermont Advanced Computing Core which is supported by NASA (NNX 06AC88G), at the University of Vermont for providing high performance computing resources that have contributed to the research results reported within this paper.

Author information

Affiliations

  1. Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA

    • Robert Whelan
    • , Nick Ortiz
    •  & Hugh Garavan
  2. Department of Psychology, University College Dublin, Dublin 4, Ireland

    • Robert Whelan
  3. Department of Radiology, University of Vermont, Burlington, Vermont 05401, USA

    • Richard Watts
  4. Vermont Center for Children, Youth, and Families, University of Vermont, Burlington, Vermont 05401, USA

    • Catherine A. Orr
  5. Department of Pediatrics, University of Vermont, Burlington, Vermont 05401, USA

    • Robert R. Althoff
  6. Department of Psychology, University of Vermont, Burlington, Vermont 05401, USA

    • Robert R. Althoff
    •  & Hugh Garavan
  7. Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 “Imaging & Psychiatry”, University Paris Sud, 91400 Orsay, France

    • Eric Artiges
    •  & Jean-Luc Martinot
  8. Department of Psychiatry, Orsay Hospital, 4 place du General Leclerc, 91400 Orsay, France

    • Eric Artiges
  9. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany

    • Tobias Banaschewski
    • , Herta Flor
    • , Mira Fauth-Bühler
    • , Karl Mann
    • , Frauke Nees
    •  & Marcella Rietschel
  10. Institute of Psychiatry, King’s College London, London SE5 8AF, UK

    • Gareth J. Barker
    • , Fabiana M. Carvalho
    • , Patricia J. Conrod
    •  & Gunter Schumann
  11. Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland

    • Arun L. W. Bokde
    •  & Hugh Garavan
  12. Department of Systems Neuroscience, Universitätsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany

    • Christian Büchel
    •  & Juergen Gallinat
  13. Department of Psychology, Stanford University, Stanford, California 94305, USA

    • Christian Büchel
  14. Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal H3T 1C5, Canada

    • Patricia J. Conrod
  15. Department of Addictive Behaviour and Addiction Medicine, Heidelberg University, 68159 Mannheim, Germany

    • Mira Fauth-Bühler
  16. 14 CEA, DSV, I2BM, Neurospin bat 145, 91191 Gif-Sur-Yvette, France

    • Vincent Frouin
  17. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité–Universitätsmedizin Berlin 10117, Germany

    • Juergen Gallinat
    • , Andreas Heinz
    • , Marie-Laure Paillère-Martinot
    •  & Andreas Ströhle
  18. Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, 01062 Dresden, Germany

    • Gabriela Gan
    •  & Michael N. Smolka
  19. School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK

    • Penny Gowland
  20. Physikalisch-Technische Bundesanstalt (PTB), 10587 Berlin, Germany

    • Bernd Ittermann
  21. School of Psychology, University of Nottingham, Nottingham NG7 2RD, UK

    • Claire Lawrence
  22. AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75006 Paris, France

    • Jean-Luc Martinot
    •  & Marie-Laure Paillère-Martinot
  23. Neuroscience Graduate Program, University of Vermont, Burlington, Vermont 05401, USA

    • Nick Ortiz
  24. Rotman Research Institute, University of Toronto, Toronto, Ontario M5R 0A3, Canada

    • Tomas Paus
  25. Montreal Neurological Institute, McGill University, H3A 2B4, Canada

    • Tomas Paus
  26. The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada

    • Zdenka Pausova
  27. Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge CB2 1TN, UK

    • Trevor W. Robbins
  28. MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, London WC2R 2LS, UK

    • Gunter Schumann
  29. Campus Charité Mitte, Charité–Universitätsmedizin, Berlin 10117, Germany.

    • Lisa Albrecht
    • , Katharina Czech
    • , Nikolay Ivanov
    • , Katharina Lüdemann
    • , Michael Rapp
    • , Alexander Romanowski
    •  & Nicole Strache
  30. University of Cambridge, Cambridge CB2 1TN, UK.

    • Mercedes Arroyo
    •  & Jeffrey Dalley
  31. Physikalisch-Technische Bundesanstalt (PTB), 10587 Berlin, Germany.

    • Semiha Aydin
    • , Ruediger Bruehl
    • , Albrecht Ihlenfeld
    • , Florian Schubert
    •  & Bernadeta Walaszek
  32. Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.

    • Christine Bach
    • , Luise Poustka
    • , Christine Schmäl
    • , Wolfgang Sommer
    • , Rainer Spanagel
    • , Sabina Steiner
    •  & Maren Struve
  33. Commissariat à l'Energie Atomique, 14 CEA, DSV, I2BM, Neurospin bat 145, 91191 Gif-Sur-Yvette, France.

    • Alexis Barbot
    •  & Jean-Baptiste Poline
  34. Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 “Imaging & Psychiatry”, University Paris Sud, 91400 Orsay, France.

    • Zuleima Bricaud
    • , Fanny Gollier Briand
    • , Hervé Lemaitre
    • , Ruben Miranda
    • , Jani Pentilla
    •  & Helene Vulser
  35. Universitätsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany.

    • Uli Bromberg
    • , Tahmine Fadai
    • , Sophia Schneider
    •  & Juliana Yacubian
  36. Institute of Psychiatry, King’s College London, London SE5 8AF, UK.

    • Anna Cattrell
    • , Sylvane Desrivieres
    • , Tianye Jia
    • , Agnes Kepa
    • , Lourdes Martinez-Medina
    • , Charlotte Nymberg
    • , Barbara Ruggeri
    • , David Stacey
    • , Lauren Topper
    • , Helen Werts
    • , Steve Williams
    •  & C. Peng Wong
  37. GABO:milliarium mbH & Co. KG 80333 Munich, Germany.

    • Birgit Fuchs
  38. University of Nottingham, Nottingham NG7 2RD, UK.

    • Kay Head
    •  & Nadja Heym
  39. Deutsches Referenzzentrum für Ethik, D 53113 Bonn, Germany.

    • Bert Heinrichs
    •  & Dirk Lanzerath
  40. Technische Universität Dresden, 01062 Dresden, Germany.

    • Thomas Hübner
    • , Kathrin Müller
    • , Stephan Ripke
    • , Sarah Rodehacke
    • , Dirk Schmidt
    •  & Veronika Ziesch.
  41. Delosis, Twickenham, Middlesex TW1 4AE, UK.

    • James Ireland
    •  & John Rogers
  42. Trinity College Dublin, Dublin 2, Ireland.

    • Jennifer Jones
  43. Centre National de Génotypage, 91057 Evry Cedex, France.

    • Mark Lathrop
  44. PERTIMM, 92600 Asnières-Sur-Seine, France.

    • Xavier Mignon
  45. Tembit Software GmbH, 13507 Berlin, Germany.

    • Markus Schroeder
  46. University of Sussex, Brighton BN1 9RH, UK.

    • Dai Stephens
  47. University of Toronto, Toronto, Ontario M5G 0A4, Canada.

    • Amir Tahmasebi

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Contributions

T.B., G.J.B., A.L.W.B., C.B., F.M.C., P.J.C., H.F., M.F.-B., J.G., H.G., P.G., A.H., B.I., K.M., J.-L.M., F.N., T.P., M.R., C.L., Z.P., M.-L.P.-M., M.N.S., A.S., M.R. and T.W.R. acquired the data. R. Whelan., H.G., C.A.O. and N.O. analysed the behavioural data. G.G. calculated the family history data. R. Whelan, R. Watts and E.A. carried out neuroimaging data processing and analysis. R.R.A., V.F. and G.S. carried out genotyping and genetic analysis. R. Whelan and H.G. prepared the manuscript. C.A.O, P.J.C., J.G., T.P., T.W.R. and G.S. edited the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Robert Whelan or Hugh Garavan.

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