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.
Readers interested in the genetics of psychosis, the independent contribution of cannabis to psychotic symptoms, and transdiagnostic approaches to mental illness.
Cannabis adds risk beyond genetic predisposition
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Large multicentric study with sophisticated genetic and dimensional analysis, but cross-sectional design.
When this study was published
Published in 2021; EU-GEI is one of the largest international studies of first-episode psychosis.
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.
Questions still open
- 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?
Common questions
Does cannabis cause psychosis or is it just genetics?
Does genetic risk matter for cannabis effects?
Read the original research
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
Citation
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
Explore the wider topic
- How THC Affects Your Amygdala: The Brain's Threat Detector and Cannabis
- The Anandamide Connection: Your Body's Natural Bliss Molecule
- How Long for Cannabinoid Receptors to Return to Normal
- Cannabis and the Developing Brain: What Every Teenager (and Parent) Should Know
- Why Can't I Enjoy Anything Without Weed? The Science Behind It
- Dopamine Recovery After Quitting Weed: What the Science Says
- The Endocannabinoid System Explained Simply: What It Does and Why It Matters
- Your Endocannabinoid System Explained: Why Withdrawal Happens
- Your Nervous System After Quitting Weed: Fight or Flight
- Using Weed Under 18: What It Does to Your Developing Brain
- What THC Does to Your Brain: Why Withdrawal Happens
- THC and Your Prefrontal Cortex: What Cannabis Does to Your Decision-Making Brain
- Weed, Cortisol, and Stress: What Cannabis Does to Your Stress Hormones
- Weed and Memory: What the Science Says About THC and Your Hippocampus
- Weed and Motivation: Is Amotivational Syndrome Real?
- Weed and Your Nervous System: What THC Actually Does to Your Brain and Body
- How Weed Rewires Your Reward System (And How to Reset It)