Do genetic risk for schizophrenia and cannabis use independently affect psychosis symptoms?
A large EU-GEI study found that both genetic liability to schizophrenia and daily cannabis use independently contributed to positive psychotic symptoms, with cannabis adding risk beyond genetic predisposition across both patients and controls.
Quick Facts
What This Study Found
Schizophrenia polygenic risk score (SZ-PRS) was associated with both negative (B=0.18) and positive (B=0.19) symptom dimensions in 617 first-episode patients, regardless of diagnostic category. Daily current cannabis use was associated with positive symptom dimensions in both patients (B=0.31) and controls (B=0.26), over and above SZ-PRS. SZ-PRS was not associated with general or affective symptom dimensions in patients.
Key Numbers
617 FEP patients; 979 controls; SZ-PRS and negative symptoms B=0.18; SZ-PRS and positive symptoms B=0.19; daily cannabis and positive symptoms in FEP B=0.31; daily cannabis and positive symptoms in controls B=0.26
How They Did This
Large multicentric study from the EU-GEI consortium analyzing first-episode psychosis patients (n=617) and controls (n=979). Used item response bi-factor modeling to generate transdiagnostic symptom dimensions. Linear regression tested associations with schizophrenia polygenic risk scores and cannabis use patterns.
Why This Research Matters
This study disentangles genetic and environmental contributions to psychosis. Finding that cannabis use adds risk for positive symptoms beyond genetic predisposition supports a causal role for cannabis in psychosis, not just shared genetic vulnerability.
The Bigger Picture
The finding that psychotic experiences in healthy controls share genetic substrates with clinical psychosis supports a continuum model of psychosis. Cannabis appears to amplify positive symptoms along this continuum, whether someone is genetically predisposed or not.
What This Study Doesn't Tell Us
Cross-sectional design limits causal inference. Polygenic risk scores capture only a fraction of genetic liability. Cannabis use was self-reported. Different populations across EU-GEI sites may introduce heterogeneity.
Questions This Raises
- ?Does genetic risk modify the effect of cannabis on psychosis, or are the effects truly additive?
- ?Could polygenic risk scores predict which cannabis users are most vulnerable to psychosis?
- ?Do the transdiagnostic dimensions respond differently to treatment?
Trust & Context
- Key Stat:
- Cannabis adds risk beyond genetic predisposition
- Evidence Grade:
- Large multicentric study with sophisticated genetic and dimensional analysis, but cross-sectional design.
- Study Age:
- Published in 2021; EU-GEI is one of the largest international studies of first-episode psychosis.
- Original Title:
- The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.
- Published In:
- Translational psychiatry, 11(1), 423 (2021)
- Authors:
- Quattrone, Diego(18), Reininghaus, Ulrich(2), Richards, Alex L, Tripoli, Giada, Ferraro, Laura, Quattrone, Andrea, Marino, Paolo, Rodriguez, Victoria, Spinazzola, Edoardo, Gayer-Anderson, Charlotte, Jongsma, Hannah E, Jones, Peter B, La Cascia, Caterina, La Barbera, Daniele, Tarricone, Ilaria, Bonora, Elena, Tosato, Sarah, Lasalvia, Antonio, Szöke, Andrei, Arango, Celso, Bernardo, Miquel, Bobes, Julio, Del Ben, Cristina Marta, Menezes, Paulo Rossi, Llorca, Pierre-Michel, Santos, Jose Luis, Sanjuán, Julio, Arrojo, Manuel, Tortelli, Andrea, Velthorst, Eva, Berendsen, Steven, de Haan, Lieuwe, Rutten, Bart P F, Lynskey, Michael T, Freeman, Tom P, Kirkbride, James B, Sham, Pak C, O'Donovan, Michael C, Cardno, Alastair G, Vassos, Evangelos, van Os, Jim, Morgan, Craig, Murray, Robin M, Lewis, Cathryn M, Di Forti, Marta
- Database ID:
- RTHC-03444
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
Does cannabis cause psychosis or is it just genetics?
This study suggests both contribute independently. Daily cannabis use was associated with positive psychotic symptoms even after accounting for genetic risk, supporting the idea that cannabis has its own effect beyond genetic predisposition.
Does genetic risk matter for cannabis effects?
Higher genetic risk for schizophrenia was associated with more severe symptoms overall. Cannabis added additional risk for positive symptoms on top of genetic vulnerability, suggesting the risks may compound.
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Cite This Study
https://rethinkthc.com/research/RTHC-03444APA
Quattrone, Diego; Reininghaus, Ulrich; Richards, Alex L; Tripoli, Giada; Ferraro, Laura; Quattrone, Andrea; Marino, Paolo; Rodriguez, Victoria; Spinazzola, Edoardo; Gayer-Anderson, Charlotte; Jongsma, Hannah E; Jones, Peter B; La Cascia, Caterina; La Barbera, Daniele; Tarricone, Ilaria; Bonora, Elena; Tosato, Sarah; Lasalvia, Antonio; Szöke, Andrei; Arango, Celso; Bernardo, Miquel; Bobes, Julio; Del Ben, Cristina Marta; Menezes, Paulo Rossi; Llorca, Pierre-Michel; Santos, Jose Luis; Sanjuán, Julio; Arrojo, Manuel; Tortelli, Andrea; Velthorst, Eva; Berendsen, Steven; de Haan, Lieuwe; Rutten, Bart P F; Lynskey, Michael T; Freeman, Tom P; Kirkbride, James B; Sham, Pak C; O'Donovan, Michael C; Cardno, Alastair G; Vassos, Evangelos; van Os, Jim; Morgan, Craig; Murray, Robin M; Lewis, Cathryn M; Di Forti, Marta. (2021). The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.. Translational psychiatry, 11(1), 423. https://doi.org/10.1038/s41398-021-01526-0
MLA
Quattrone, Diego, et al. "The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.." Translational psychiatry, 2021. https://doi.org/10.1038/s41398-021-01526-0
RethinkTHC
RethinkTHC Research Database. "The continuity of effect of schizophrenia polygenic risk sco..." RTHC-03444. Retrieved from https://rethinkthc.com/research/quattrone-2021-the-continuity-of-effect
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.