Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus

Tao Yu; Tianye Jia; Liping Zhu; Sylvane Desrivières; Christine Macare; Yan Bi; Arun L W Bokde; Erin Burke Quinlan; Andreas Heinz; Bernd Ittermann; ChuanXin Liu; Lei Ji; Tobias Banaschewski; Decheng Ren; Li Du; Binyin Hou; Herta Flor; Vincent Frouin; Hugh Garavan; Penny Gowland; Jean-Luc Martinot; Marie-Laure Paillère Martinot; Frauke Nees; Dimitri Papadopoulos Orfanos; Qiang Luo; Congying Chu; Tomas Paus; Luise Poustka; Sarah Hohmann; Sabina Millenet; Michael N Smolka; Nora C Vetter; Eva Mennigen; Cai Lei; Henrik Walter; Juliane H Fröhner; Robert Whelan; Guang He; Lin He; Gunter Schumann; Gabriel Robert; IMAGEN Consortium

doi:10.1016/j.jaac.2019.05.034

Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus

J Am Acad Child Adolesc Psychiatry. 2020 May;59(5):642-649. doi: 10.1016/j.jaac.2019.05.034. Epub 2019 Jul 18.

Authors

Tao Yu¹, Tianye Jia², Liping Zhu³, Sylvane Desrivières⁴, Christine Macare⁴, Yan Bi⁵, Arun L W Bokde⁶, Erin Burke Quinlan⁴, Andreas Heinz⁷, Bernd Ittermann⁸, ChuanXin Liu⁹, Lei Ji⁵, Tobias Banaschewski¹⁰, Decheng Ren⁵, Li Du³, Binyin Hou⁵, Herta Flor¹¹, Vincent Frouin¹², Hugh Garavan¹³, Penny Gowland¹⁴, Jean-Luc Martinot¹⁵, Marie-Laure Paillère Martinot¹⁵, Frauke Nees¹⁰, Dimitri Papadopoulos Orfanos¹², Qiang Luo¹⁶, Congying Chu⁴, Tomas Paus¹⁷, Luise Poustka¹⁸, Sarah Hohmann¹⁰, Sabina Millenet¹⁰, Michael N Smolka¹⁹, Nora C Vetter¹⁹, Eva Mennigen¹⁹, Cai Lei⁵, Henrik Walter⁷, Juliane H Fröhner¹⁹, Robert Whelan²⁰, Guang He⁵, Lin He²¹, Gunter Schumann⁴, Gabriel Robert²²; IMAGEN Consortium

Collaborators

IMAGEN Consortium:
Michael Rapp, Eric Artiges, Sophia Schneider, Christine Bach, Tomas Paus, Alexis Barbot, Gareth Barker, Arun Bokde, Nora Vetter, Christian Büchel, Anna Cattrell, Patrick Constant, Penny Gowland, Hans Crombag, Katharina Czech, Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Tamzin Ripley, Nadja Heym, Herta Flor, Wolfgang Sommer, Birgit Fuchs, Jürgen Gallinat, Hugh Garavan, Rainer Spanagel, Mehri Kaviani, Bert Heinrichs, Andreas Heinz, Naresh Subramaniam, Tianye Jia, Albrecht Ihlenfeld, James Ireland Delosis, Bernd Ittermann, Patricia Conrod, Tobias Banaschewski, Jennifer Jones, Arno Klaassen, Christophe Lalanne, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Sylvane Desrivieres, Catherine Mallik, Karl Mann, Adam Mar, Lourdes Martinez-Medina, Jean-Luc Martinot, Eva Mennigen, Fabiana Mesquita de Carvahlo, Yannick Schwartz, Ruediger Bruehl, Kathrin Müller, Frauke Nees, Charlotte Nymberg, Mark Lathrop, Trevor Robbins, Zdenka Pausova, Jani Pentilla, Francesca Biondo, Jean-Baptiste Poline, Sarah Hohmann, Luise Poustka, Sabina Millenet, Michael Smolka, Juliane Fröhner, Maren Struve, Steve Williams, Thomas Hübner, Uli Bromberg, Semiha Aydin, John Rogers, Alexander Romanowski, Christine Schmäl, Dirk Schmidt, Stephan Ripke, Mercedes Arroyo, Florian Schubert, Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Robert Whelan, Claudia Speiser, Tahmine Fadai, Dai Stephens, Andreas Ströhle, Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Helene Vulser, Ruben Miranda, Juliana Yacubilin, Vincent Frouin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina WeiB, Henrik Walter, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Barbara Ruggeri, Bing Xu, Christine Macare, Congying Chu, Eanna Hanratty, Erin Burke Quinlan, Gabriel Robert, Gunter Schumann, Tao Yu, Veronika Ziesch, Alicia Stedman

Affiliations

¹ Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Shanghai Center for Women and Children's Health, China; Jining Medical University, Shandong, China.
² Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Institute of Science and Technology for Brain-Inspired Intelligence, MoE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
³ Shanghai Center for Women and Children's Health, China.
⁴ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
⁵ Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
⁶ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, College Green, Dublin, Ireland.
⁷ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Charité Mitte, Berlin, Germany.
⁸ Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Berlin, Germany.
⁹ Jining Medical University, Shandong, China.
¹⁰ Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
¹¹ Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; School of Social Sciences, University of Mannheim, Germany.
¹² NeuroSpin, Commissariat à l'Energie Atomique, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
¹³ University of Vermont, Burlington.
¹⁴ Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
¹⁵ Institut National de la Santé et de la Recherche Médicale (INSERM), University Paris Sud, Orsay, France.
¹⁶ Institute of Science and Technology for Brain-Inspired Intelligence, MoE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
¹⁷ Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and the University of Toronto, Ontario, Canada.
¹⁸ University Medical Centre Göttingen, Göttingen, Germany.
¹⁹ Technische Universität Dresden, Germany.
²⁰ School of Psychology and Global Brain Health Institute, Trinity College Dublin, Ireland.
²¹ Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Shanghai Center for Women and Children's Health, China; Baoan Maternal and Child Health Hospital, Jinan University, Shenzhen, China. IMAGEN consortium authors, affiliations, and acknowledgement are listed in the supplementary materials.
²² Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Behavior and Basal Ganglia Unit, Medical University of Rennes, France. Electronic address: gabriel.hadrien.robert@gmail.com.

PMID: 31326579
DOI: 10.1016/j.jaac.2019.05.034

Abstract

Objective: Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described.

Method: A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs.

Results: We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04-0.1, p =2 × 10^-16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004-0.01, p = .026).

Conclusion: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents.

Keywords: cannabis; deformation-based morphometry; paired designed MRI; psychotic-like experiences (PLEs); uncus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Cannabis*
Humans
Marijuana Abuse* / epidemiology
Parahippocampal Gyrus
Psychotic Disorders* / diagnostic imaging
Psychotic Disorders* / epidemiology
Psychotic Disorders* / etiology
Risk Factors
Surveys and Questionnaires

Abstract

Publication types

MeSH terms

Grants and funding