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. 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.
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.
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.