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Bayesian causal network modeling suggests adolescent cannabis use accelerates prefrontal cortical thinning

Research output: Contribution to journalArticlepeer-review

The IMAGEN Consortium, Max M. Owens, Matthew D. Albaugh, Nicholas Allgaier, Dekang Yuan, Gabriel Robert, Renata B. Cupertino, Philip A. Spechler, Anthony Juliano, Sage Hahn, Tobias Banaschewski, Arun L.W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean Luc Martinot, Marie Laure Paillère Martinot & 31 more Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Herve Lemaitre, Tomáš Paus, Luise Poustka, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Scott Mackey, Gunter Schumann, Hugh Garavan, Tobias Banaschewski, Gareth J. Barker, Arun L.W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean Luc Martinot, Marie Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Herve Lemaitre, Gunter Schumann

Original languageEnglish
Article number188
JournalTranslational psychiatry
Issue number1
Early online date6 May 2022
Accepted/In press22 Apr 2022
E-pub ahead of print6 May 2022
PublishedDec 2022

Bibliographical note

Funding Information: This work was funded by NIH/NIDA T32DA043593 and R01DA047119. MDA is supported by K08 MH121654 and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. 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), 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; Forschungsnetz IMAC-Mind 01GL1745B), 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), the National Institutes of Health (NIH) funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01), NSFC grant 82150710554 and environMENTAL grant. 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. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, 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 & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. LP served in an advisory or consultancy role for Roche and Viforpharm and received speaker’s fee by Shire. She received royalties from Hogrefe, Kohlhammer, and Schattauer. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: The IMAGEN consortium includes: Tobias Banaschewski, M.D., Ph.D.; Gareth J. Barker, Ph.D.; Arun L.W. Bokde, Ph.D.; Sylvane Desrivières, Ph.D.; Herta Flor, Ph.D.; Antoine Grigis, Ph.D.; Hugh Garavan, Ph.D.; Penny Gowland, Ph.D.; Andreas Heinz, M.D., Ph.D.; Rüdiger Brühl, Ph.D.; Jean-Luc Martinot, M.D., Ph.D.: Marie-Laure Paillère Martinot, M.D., Ph.D./Eric Artiges, M.D., Ph.D.; Frauke Nees, Ph.D; Dimitri Papadopoulos Orfanos, Ph.D., Herve Lemaitre, Ph.D; Tomáš Paus, M.D., Ph.D.; Luise Poustka, M.D., Sarah Hohmann, M.D., Sabina Millenet, PhD.; Juliane H. Fröhner, MSc; Michael N. Smolka, M.D; Henrik Walter, M.D., Ph.D.; Robert Whelan, Ph.D.; Gunter Schumann, M.D. 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. Publisher Copyright: © 2022, The Author(s).

King's Authors


While there is substantial evidence that cannabis use is associated with differences in human brain development, most of this evidence is correlational in nature. Bayesian causal network (BCN) modeling attempts to identify probable causal relationships in correlational data using conditional probabilities to estimate directional associations between a set of interrelated variables. In this study, we employed BCN modeling in 637 adolescents from the IMAGEN study who were cannabis naïve at age 14 to provide evidence that the accelerated prefrontal cortical thinning found previously in adolescent cannabis users by Albaugh et al. [1] is a result of cannabis use causally affecting neurodevelopment. BCNs incorporated data on cannabis use, prefrontal cortical thickness, and other factors related to both brain development and cannabis use, including demographics, psychopathology, childhood adversity, and other substance use. All BCN algorithms strongly suggested a directional relationship from adolescent cannabis use to accelerated cortical thinning. While BCN modeling alone does not prove a causal relationship, these results are consistent with a body of animal and human research suggesting that adolescent cannabis use adversely affects brain development.

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