In 706 adolescents scanned at ages 14 and 19, cannabis use was linked to psychotic-like experiences, and this relationship was partially mediated by reduced growth of the uncus, a specific region of the parahippocampal gyrus.
Adolescent psychiatrists, neuroimaging researchers, and public health professionals studying cannabis effects on developing brains.
Uncus development partially mediated cannabis-psychosis link (p=0.026)
What the researchers found
Psychotic-like experiences were associated with reduced expansion of the right uncus between ages 14 and 19 (p=0.002). A mediation analysis showed a significant total effect of cannabis use on psychotic-like experiences (b=0.069, p<0.001), with a small but significant indirect effect through uncus development (0.004, 95% CI 0.0004-0.01, p=0.026).
Why it matters
This study identifies a specific brain structural change that partly explains how cannabis use during adolescence may contribute to psychotic-like experiences, providing a biological mechanism for a well-documented epidemiological association.
The numbers in context
706 adolescents scanned at 14 and 19. Significant association between PLEs and reduced right uncus expansion (p=0.002 cluster, p=0.018 peak). Total cannabis-to-PLE effect: b=0.069, p<0.001. Indirect effect through uncus: 0.004, p=0.026.
How the study worked
Longitudinal neuroimaging study of 706 adolescents from the IMAGEN consortium with structural MRI at ages 14 and 19. Deformation-based morphometry mapped brain changes. Cannabis use assessed with ESPAD, psychotic-like experiences with CAPE questionnaire. A priori mediation model tested.
What this study cannot tell us
The mediation effect through the uncus was small, suggesting other pathways are also important. Observational study cannot establish causation. Cannabis use was self-reported. Only two imaging time points. Sample was from the general population with subclinical symptoms, not patients with psychotic disorders.
How to read the evidence
Longitudinal neuroimaging study with appropriate mediation analysis, but small indirect effect and observational design.
When this study was published
2020 study from the IMAGEN consortium. One of few studies identifying specific brain structural mediators of cannabis-related psychotic experiences.
The bigger picture
Finding a brain structural mediator between cannabis use and psychotic symptoms in the general population strengthens the biological plausibility of the cannabis-psychosis link and identifies a potential biomarker for vulnerability.
Questions still open
- Could uncus development be used to identify adolescents at risk for cannabis-related psychosis? What other brain regions contribute to the remaining cannabis-psychosis pathway? Would cannabis cessation allow normal uncus development to resume?
Common questions
What is the uncus?
Does this prove cannabis causes psychosis?
Read the original research
Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus.
Journal of the American Academy of Child and Adolescent Psychiatry, 59(5), 642-649
Citation
Yu, Tao; Jia, Tianye; Zhu, Liping; Desrivières, Sylvane; Macare, Christine; Bi, Yan; Bokde, Arun L W; Quinlan, Erin Burke; Heinz, Andreas; Ittermann, Bernd; Liu, ChuanXin; Ji, Lei; Banaschewski, Tobias; Ren, Decheng; Du, Li; Hou, Binyin; Flor, Herta; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Luo, Qiang; Chu, Congying; Paus, Tomas; Poustka, Luise; Hohmann, Sarah; Millenet, Sabina; Smolka, Michael N; Vetter, Nora C; Mennigen, Eva; Lei, Cai; Walter, Henrik; Fröhner, Juliane H; Whelan, Robert; He, Guang; He, Lin; Schumann, Gunter; Robert, Gabriel. (2020). Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus.. Journal of the American Academy of Child and Adolescent Psychiatry, 59(5), 642-649. https://doi.org/10.1016/j.jaac.2019.05.034
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