Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study - 29/04/21
Doi : 10.1016/j.jaac.2020.08.443
Iliyan Ivanov, MD a, ⁎ 
, Muhammad A. Parvaz, PhD a, Eva Velthorst, PhD a, Riaz B. Shaik, PhD a, Sven Sandin, PhD a, b, Gabriela Gan, PhD c, Philip Spechler, PhD e, Matthew D. Albaugh, PhD f, Bader Chaarani, PhD f, Scott Mackey, PhD f, Tobias Banaschewski, MD, PhD c, Arun L.W. Bokde, PhD g, Uli Bromberg, PhD h, Christian Büchel, MD h, Erin Burke Quinlan, PhD i, Sylvane Desrivières, PhD i, Herta Flor, PhD c, d, Antoine Grigis, PhD j, Penny Gowland, PhD k, Andreas Heinz, MD, PhD l, Bernd Ittermann, PhD m, Jean-Luc Martinot, MD, PhD n, Marie-Laure Paillère Martinot, MD, PhD n, Eric Artiges, MD, PhD n, Herve Lemaitre, PhD n, Frauke Nees, PhD c, Dimitri Papadopoulos Orfanos, PhD j, Tomáš Paus, MD, PhD o, Luise Poustka, MD p, Sarah Hohmann, MD c, Sabina Millenet, Dipl-Psych c, Juliane H. Fröhner, Dipl-Psych q, Michael N. Smolka, MD q, Henrik Walter, MD, PhD l, Robert Whelan, PhD g, Gunter Schumann, MD i, Hugh Garavan, PhD f
, Muhammad A. Parvaz, PhD a, Eva Velthorst, PhD a, Riaz B. Shaik, PhD a, Sven Sandin, PhD a, b, Gabriela Gan, PhD c, Philip Spechler, PhD e, Matthew D. Albaugh, PhD f, Bader Chaarani, PhD f, Scott Mackey, PhD f, Tobias Banaschewski, MD, PhD c, Arun L.W. Bokde, PhD g, Uli Bromberg, PhD h, Christian Büchel, MD h, Erin Burke Quinlan, PhD i, Sylvane Desrivières, PhD i, Herta Flor, PhD c, d, Antoine Grigis, PhD j, Penny Gowland, PhD k, Andreas Heinz, MD, PhD l, Bernd Ittermann, PhD m, Jean-Luc Martinot, MD, PhD n, Marie-Laure Paillère Martinot, MD, PhD n, Eric Artiges, MD, PhD n, Herve Lemaitre, PhD n, Frauke Nees, PhD c, Dimitri Papadopoulos Orfanos, PhD j, Tomáš Paus, MD, PhD o, Luise Poustka, MD p, Sarah Hohmann, MD c, Sabina Millenet, Dipl-Psych c, Juliane H. Fröhner, Dipl-Psych q, Michael N. Smolka, MD q, Henrik Walter, MD, PhD l, Robert Whelan, PhD g, Gunter Schumann, MD i, Hugh Garavan, PhD fIMAGEN Consortium
Michael Rapp, Dr., Eric Artiges, Dr., Sophia Schneider, Tomas Paus, Prof. Dr., Alexis Barbot, Gareth Barker, Prof. Dr., Arun Bokde, Dr., Nora Vetter, Dr., Christian Büchel, Prof. Dr., Anna Cattrell, Dr., Patrick Constant, Penny Gowland, Prof., Hans Crombag, Dr., Jeffrey Dalley, Dr., Benjamin Decideur, Tade Spranger, Dr., Tamzin Ripley, Dr., Nadja Heym, Dr., Herta Flor, Prof., Wolfgang Sommer, Dr., Birgit Fuchs, Jürgen Gallinat, Dr., Hugh Garavan, Dr., Rainer Spanagel, Prof. Dr., Mehri Kaviani, Bert Heinrichs, Dr., Andreas Heinz, Prof. Dr., Naresh Subramaniam, Tianye Jia, Dr., Albrecht Ihlenfeld, James Ireland, Bernd Ittermann, Dr., Patricia Conrod, Dr., Tobias Banaschewski, Prof. Dr., Jennifer Jones, Arno Klaassen, Dr., Christophe Lalanne, Dirk Lanzerath, Dr., Claire Lawrence, Dr., Hervé Lemaitre, Dr., Sylvane Desrivieres, Dr., Catherine Mallik, Karl Mann, Prof. Dr., Adam Mar, Dr., Lourdes Martinez-Medina, Jean-Luc Martinot, Prof. Dr., Eva Mennigen, Fabiana Mesquita de Carvahlo, Dr., Yannick Schwartz, Ruediger Bruehl, Dr., Kathrin Müller, Frauke Nees, Charlotte Nymberg, Mark Lathrop, Dr., Trevor Robbins, Prof. Dr., Zdenka Pausova, Dr., Jani Pentilla, Dr., Francesca Biondo, Dr., Jean-Baptiste Poline, Dr., Luise Poustka, sDr., Sabina Millenet, Michael Smolka, Prof. Dr., Juliane Fröhner, Maren Struve, Dr., Steve Williams, Prof. Dr., Thomas Hübner, Dr., Uli Bromberg, Semiha Aydin, John Rogers, Alexander Romanowski, Christine Schmäl, Dr., Dirk Schmidt, Stephan Ripke, Mercedes Arroyo, Dr., Florian Schubert, Dr., Yolanda Pena-Oliver, Dr., Mira Fauth-Bühler, Xavier Mignon, Robert Whelan, Dr., Claudia Speiser, Dr., Tahmine Fadai, Dai Stephens, Prof. Dr., Andreas Ströhle, Dr., Marie-Laure Paillere, Dr., Nicole Strache, David Theobald, Sarah Jurk, Helene Vulser, Dr., Ruben Miranda, Juliana Yacubilin, Dr., Vincent Frouin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina WeiB, Henrik Walter, Dr., Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Barbara Ruggeri, Dr., Bing Xu, Christine Macare, Congying Chu, Dr., Eanna Hanratty, Erin Burke Quinlan, Dr., Gabriel Robert, Dr., Gunter Schumann, Prof. Dr., Tao Yu, Dr., Veronika Ziesch, Alicia Stedman
a Icahn School of Medicine at Mount Sinai, New York
b Karolinska Institutet, Stockholm, Sweden
c Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
d University of Mannheim, Mannheim, Germany
e Laureate Institute for Brain Research, Tulsa, Oklahoma
f of Vermont, Burlington
g School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland
h University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
i King’s College London, United Kingdom
j NeuroSpin, CEA, Université Paris-Saclay, France
k University of Nottingham, University Park, Nottingham, United Kingdom
l 12Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
m Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
n Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000, University Paris Sud, University Paris Descartes - Sorbonne Paris Cité; and Maison de Solenn, Paris, France
o University of Toronto, Ontario, M6A 2E1, Canada
p University Medical Centre Göttingen, Göttingen, Germany; and the Medical University of Vienna, Vienna, Austria
q Technische Universität Dresden, Dresden, Germany
∗Correspondence to Iliyan Ivanov, MD, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY 10029Department of PsychiatryIcahn School of Medicine at Mount SinaiOne Gustave L. Levy PlaceBox 1230New YorkNY10029
Abstract |
Objective |
It is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences.
Method |
Among 304 drug-naive adolescents at baseline (age 14 years) from the IMAGEN dataset, 83 stayed drug-naive, 133 used alcohol on 1 to 9 occasions, 42 on 10 to 19 occasions, 27 on 20 to 39 occasions, and 19 on >40 occasions at follow-up (age 16 years). Baseline measures included brain activation during the Monetary Incentive Delay task. Data at both baseline and follow-up included measures of trait impulsivity and delay discounting.
Results |
From baseline to follow-up, impulsivity decreased in the 0 and 1- to 9-occasions groups (p < .004), did not change in the 10- to 19-occasions and 20- to 29-occasions groups (p > .294), and uncharacteristically increased in the >40-occasions group (p = .046). Furthermore, blunted medial orbitofrontal cortex activation during reward outcome at baseline significantly predicted higher alcohol use frequency at follow-up, above and beyond behavioral and clinical variables (p = .008).
Conclusion |
These results suggest that the transition from no use to frequent drinking in early to mid-adolescence may disrupt normative developmental changes in behavioral control. In addition, blunted activity of the medial orbitofrontal cortex during reward outcome may underscore a predisposition toward the development of more severe alcohol use in adolescents. This distinction is clinically important, as it informs early intervention efforts in preventing the onset of substance use disorder in adolescents.
Le texte complet de cet article est disponible en PDF.Key words : adolescence, alcohol use, IMAGEN, impulsivity, reward processing
Plan
| Drs. Ivanov and Parvaz contributed equally to this research. |
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| 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 Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313), Human Brain Project (HBP SGA 2, 785907, and HBP SGA 3, 945539), the Medical Research Council Grant 'c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the National Institute of Health (NIH) (R01DA049238, A decentralized macro and micro gene-by-environment interaction analysis of substance use behavior and its brain biomarkers), 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; Forschungsnetz AERIAL 01EE1406A, 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940, TRR 265, NE 1383/14-1), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), and the National Institutes of Health (NIH) funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01). Further support was provided by grants from: the ANR (ANR-12-SAMA-0004, AAPG2019 - GeBra), the Eranet Neuron (AF12-NEUR0008-01 - WM2NA; and ANR-18-NEUR00002-01 - ADORe), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), 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 Fondation de l’Avenir (grant AP-RM-17-013 ), the Fédération pour la Recherche sur le Cerveau; 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. Additional funding from the NIH includes KL2TR001435 and K01DA043615 to M.A.P. and R01MH085772 to T.P. E.V. is supported by the Seaver Research Foundation and NARSAD Young Investigator Award from the Brain and Behavior Foundation. |
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| ImagenPathways “Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways” is a collaborative project supported by the European Research Area Network on Illicit Drugs (ERANID). This paper is based on independent research commissioned and funded in England by the National Institute for Health Research (NIHR) Policy Research Programme (project ref. PR-ST-0416-10001). The views expressed in this article are those of the authors and not necessarily those of the national funding agencies or ERANID. |
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| Dr. Sandin served as the statistical expert for this research. |
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| Author Contributions |
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| Conceptualization: Whelan, Schumann, Garavan |
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| Data curation: Ivanov, Parvaz, Sandin, Gan, Spechler, Albaugh, Chaarani, Mackey, Banaschewski |
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| Formal analysis: Ivanov, Parvaz |
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| Investigation: Banaschewski, Bokde, Bromberg, Büchel, Burke Quinlan, Desrivières, Flor, Gowland, Heinz, Artiges, Lemaitre, Papadopoulos Orfanos, Paus, Millenet, Smolka, Walter |
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| Methodology: Banaschewski, Bokde, Bromberg, Büchel, Burke Quinlan, Desrivières, Flor, Grigis, Gowland, Heinz, Ittermann, Paillère Martinot, Artiges, Lemaitre, Nees, Paus, Poustka, Hohmann, Millenet, Fröhner, Smolka, Walter, Whelan |
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| Project administration: Büchel, Grigis, Gowland, Heinz, Ittermann, Paillère Martinot, Lemaitre, Nees, Paus, Poustka, Hohmann, Millenet, Fröhner, Smolka, Walter |
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| Resources: Ittermann, Paillère Martinot, Nees, Papadopoulos Orfanos, Poustka, Hohmann, Fröhner, Smolka, Walter, Whelan, Schumann, Garavan |
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| Supervision: Martinot, Artiges |
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| Validation: Büchel, Burke Quinlan, Desrivières, Martinot |
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| Visualization: Martinot |
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| Writing – original draft: Ivanov, Parvaz, Velthorst, Shaik, Sandin, Gan, Garavan |
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| Writing – review and editing: Ivanov, Parvaz, Velthorst, Shaik, Sandin, Albaugh, Garavan |
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| ORCID |
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| Iliyan Ivanov, MD: 0000-0003-4340-6695 |
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| Muhammad A. Parvaz, PhD: 0000-0002-2671-2327 |
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| Riaz B. Shaik, PhD: 0000-0002-3502-7903 |
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| Sven Sandin, PhD: 0000-0001-6994-4884 |
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| Gabriela Gan, PhD: 0000-0001-6589-6168 |
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| Philip Spechler, PhD: 0000-0003-3833-7672 |
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| Matthew D. Albaugh, PhD: 0000-0002-5971-6658 |
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| Bader Chaarani, PhD: 0000-0002-3932-6273 |
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| Tobias Banaschewski, MD, PhD: 0000-0003-4595-1144 |
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| Arun L.W. Bokde, PhD: 0000-0003-0114-4914 |
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| Uli Bromberg, PhD: 0000-0003-4974-971X |
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| Christian Büchel, MD: 0000-0003-1965-906X |
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| Erin Burke Quinlan, PhD: 0000-0003-2927-1632 |
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| Sylvane Desrivières, PhD: 0000-0002-9120-7060 |
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| Penny Gowland, PhD: 0000-0002-4900-4817 |
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| Andreas Heinz, MD, PhD: 0000-0001-5405-9065 |
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| Jean-Luc Martinot, MD, PhD: 0000-0002-0136-0388 |
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| Marie-Laure Paillère Martinot, MD, PhD: 0000-0002-0452-2450 |
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| Eric Artiges, MD, PhD: 0000-0003-4461-7646 |
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| Herve Lemaitre, PhD: 0000-0002-5952-076X |
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| Frauke Nees, PhD: 0000-0002-7796-8234 |
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| Dimitri Papadopoulos Orfanos, PhD: 0000-0002-1242-8990 |
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| Luise Poustka, MD: 0000-0002-7738-4394 |
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| Sarah Hohmann, MD: 0000-0002-5175-6698 |
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| Juliane H. Fröhner, Dipl-Psych: 0000-0002-8493-6396 |
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| Michael N. Smolka, MD: 0000-0001-5398-5569 |
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| Henrik Walter, MD, PhD: 0000-0002-9403-6121 |
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| Robert Whelan, PhD: 0000-0002-2790-7281 |
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| Gunter Schumann, MD: 0000-0002-7740-6469 |
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| The IMAGEN Consortium consists of: Dr. Michael Rapp, Charite; Dr. Eric Artiges, INSERM; Sophia Schneider, University of Hamburg; Christine Bach, Central Institute of Mental Health; Prof. Dr. Tomas Paus, University of Toronto; Alexis Barbot, Commissariat à l'Energie Atomique; Prof. Dr. Gareth Barker, King's College London; Dr. Arun Bokde, Trinity College Dublin; Dr. Nora Vetter, Technische Universität Dresden; Prof. Dr. Christian Büchel, University of Hamburg; Dr. Anna Cattrell, King's College London; Patrick Constant, PERTIMM; Prof. Penny Gowland, University of Nottingham; Dr. Hans Crombag, University of Sussex; Katharina Czech, Charite; Dr. Jeffrey Dalley, Cambridge University; Benjamin Decideur, Commissariat à l'Energie Atomique; Dr. Tade Spranger, Deutsches Referenzzentrum für Ethik / Institut of Science and Ethics; Dr. Tamzin Ripley, University of Sussex; Dr. Nadja Heym, University of Nottingham; Prof. Herta Flor, Central Institute of Mental Health; Dr. Wolfgang Sommer, Central Institute of Mental Health; Birgit Fuchs, GABO: milliarium mbH and Co. KG; Dr. Jürgen Gallinat, Charite; Dr. Hugh Garavan, Trinity College Dublin; Prof. Dr. Rainer Spanagel, Central Institute of Mental Health; Mehri Kaviani, University of Nottingham; Dr. Bert Heinrichs, Deutsches Referenzzentrum für Ethik; Prof. Dr. Andreas Heinz, Charite; Naresh Subramaniam, Cambridge University; Dr. Tianye Jia, King’s College London; Albrecht Ihlenfeld, PTB; James Ireland, Delosis; Dr. Bernd Ittermann, PTB; Dr. Patricia Conrod, King's College London; Prof. Dr. Tobias Banaschewski, Central Institute of Mental Health; Jennifer Jones, Trinity College Dublin; Dr. Arno Klaassen, Scito; Christophe Lalanne, Commissariat à l'Energie Atomique; Dr. Dirk Lanzerath, Deutsches Referenzzentrum für Ethik; Dr. Claire Lawrence, University of Nottingham; Dr. Hervé Lemaitre, INSERM; Dr. Sylvane Desrivieres, King's College London; Catherine Mallik, King's College London; Prof. Dr. Karl Mann, Central Institute of Mental Health; Dr. Adam Mar, Cambridge University; Lourdes Martinez-Medina, King's College London; Prof. Dr. Jean-Luc Martinot, INSERM; Eva Mennigen, Technische Universität Dresden; Dr. Fabiana Mesquita de Carvahlo, King's College London; Yannick Schwartz, Commissariat à l'Energie Atomique; Dr. Ruediger Bruehl, PTB; Kathrin Müller, Technische Universität Dresden; Frauke Nees, Central Institute of Mental Health; Charlotte Nymberg, King's College London; Dr. Mark Lathrop, CNG; Prof. Dr. Trevor Robbins, Cambridge University; Dr. Zdenka Pausova, University of Toronto; Dr. Jani Pentilla, INSERMIERTEE; Dr. Francesca Biondo, King's College London; Dr. Jean-Baptiste Poline, Commissariat à l'Energie Atomique; sDr. Luise Poustka, University Medical Centre Göttingen/Medical University of Vienna; Sabina Millenet, Central Institute of Mental Health; Prof. Dr. Michael Smolka, Technische Universität Dresden; Juliane Fröhner, Technische Universität Dresden; Dr. Maren Struve, Central Institute of Mental Health; Prof. Dr. Steve Williams, King's College London; Dr. Thomas Hübner, Technische Universität Dresden; Uli Bromberg, University of Hamburg; Semiha Aydin, PTB; John Rogers, Delosis; Alexander Romanowski, Charite; Dr. Christine Schmäl, Central Institute of Mental Health; Dirk Schmidt, Technische Universität Dresden; Stephan Ripke, Technische Universität Dresden; Dr. Mercedes Arroyo, Cambridge University; Dr. Florian Schubert, PTB; Dr. Yolanda Pena-Oliver, University of Sussex; Mira Fauth-Bühler, FOM Hochschule für Oekonomie and Management/Central Institute of Mental Health; Xavier Mignon, PERTIMM; Dr. Robert Whelan, Trinity College Dublin; Dr. Claudia Speiser, GABO:milliarium mbH and Co. KG; Tahmine Fadai, University of Hamburg; Prof. Dr. Dai Stephens, University of Sussex; Dr. Andreas Ströhle, Charite; Dr. Marie-Laure Paillere, INSERM; Nicole Strache, Charite; David Theobald, Cambridge University; Sarah Jurk, Technische Universität Dresden; Dr. Helene Vulser, INSERM; Ruben Miranda, INSERM; Dr. Juliana Yacubilin, University of Hamburg; Vincent Frouin, Commissariat à l'Energie Atomique; Alexander Genauck, Charite; Caroline Parchetka, Charite; Isabel Gemmeke, Charite; Johann Kruschwitz, Charite; Katharina WeiB, Charite; Dr. Henrik Walter, Charité Universitätsmedizin Berlin; Jianfeng Feng, Fudan University/Warwick University; Dimitri Papadopoulos, INSERM; Irina Filippi, INSERM; Alex Ing, King's College London; Dr. Barbara Ruggeri, King's College London; Bing Xu, King's College London; Christine Macare, King's College London; Dr. Congying Chu, King’s College London; Eanna Hanratty, King's College London; Dr. Erin Burke Quinlan, King's College London; Dr. Gabriel Robert, King's College London; Prof. Dr. Gunter Schumann, King's College London; Dr. Tao Yu, King's College London; Veronika Ziesch, Technische Universität Dresden; Alicia Stedman, University of Nottingham. imagen-europe.com/ |
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| Disclosure: Dr. Banaschewski has served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, and Shire (a Takeda company). He has received conference support or speaker’s fee by Eli Lilly and Co., Medice, Novartis, and Shire. He has been involved in clinical trials conducted by Shire and Viforpharma. He has received royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. Drs. Ivanov, Parvaz, Velthorst, Shaik, Sandin, Gan, Spechler, Albaugh, Chaarani, Mackey, Bokde, Bromberg, Büchel, Burke Quinlan, Desrivières, Flor, Grigis, Gowland, Heinz, Ittermann, Martinot, Paillère Martinot, Artiges, Lemaitre, Nees, Papadopoulos Orfanos, Paus, Poustka, Hohmann, Millenet, Fröhner, Smolka, Walter, Whelan, Schumann, and Garavan have reported no biomedical financial interests or potential conflicts of interest. |
© 2020
American Academy of Child and Adolescent Psychiatry. Publié par Elsevier Masson SAS. Tous droits réservés.
Vol 60 - N° 5
P. 623-636 - mai 2021 Retour au numéro
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