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J Am Acad Child Adolesc Psychiatry. 2019 Jul 18. pii: S0890-8567(19)30469-1. doi: 10.1016/j.jaac.2019.05.034. [Epub ahead of print]

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

Author information

1
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China; Medical Research Council - 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
Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Centre for Computational Systems Biology, Fudan University, Shanghai, China.
3
Shanghai Center for Women and Children's Health, China.
4
Medical Research Council - 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
Centre for Computational Systems Biology, 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; Medical Research Council - 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.
22
Medical Research Council - 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 ill-described.

METHOD:

706 adolescents from the general population that were recruited by the IMAGEN consortium had structural MRI scans both at 14 and 19 years-old. We used deformation-based morphometry to map voxel-wise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a-priori region of interest (ROI) approach focusing on the hippocampus/parahippocampus to perform voxel-wise linear regressions. Life time 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). We first tested whether hippocampus/para-hippocampus development was associated with PLEs. Then, we formulated and tested an a-priori simple mediation model where uncus development mediates the association between lifetime cannabis consumption and PLEs.

RESULTS:

We found that PLEs was associated with reduced expansion within a specific region of the right hippocampus/para-hippocampus formation, the uncus (p=0.002 at the cluster level, p=0.018 at the peak-level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b=0.069 95CI [0.04-0.1], p=2 x 10-16), as well as a small yet significant, indirect effect of right uncus development (0.004, 95IC [0.0004-0.01], p=0.026).

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

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

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