Summary: Heavy cannabis use and genetic risk for schizophrenia independently contribute to the likelihood of developing psychosis. Researchers used two large datasets to analyze the relationship between cannabis use, schizophrenia polygenic risk scores (PRS), and psychosis. They found no evidence that cannabis and genetic risks interact, suggesting these factors influence psychosis through separate pathways.
Daily use of high-potency cannabis showed the strongest link to psychosis risk, regardless of genetic predisposition. These findings highlight the need for targeted preventative strategies as cannabis use and potency rise globally. PRSs could potentially help identify individuals at heightened risk of psychosis among less frequent cannabis users.
Key Facts:
- Daily high-potency cannabis use significantly increases the risk of psychosis, independent of genetic predisposition.
- Schizophrenia polygenic risk scores were not associated with cannabis use frequency in those with psychosis.
- Cannabis and genetic risk appear to influence psychosis risk through separate, additive pathways.
Source: King’s College London
New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and South London and Maudsley NHS Foundation Trust has shown that genetic load for schizophrenia and frequent use of cannabis have independent links to the likelihood of developing clinical psychosis.
The results provide insight into possible future ways to identify those at higher risk of psychosis and help inform preventative strategies.
There is a well-established association between cannabis and psychosis but the underlying role of genetics in this relationship remains unclear.
Polygenic risk scores (PRSs) summarise the estimated small effects of many common genetic variants on the risk of developing a disease or disorder. Recent advances in the collection and analysis of genetic data have enabled PRSs to be calculated for a range of disorders.
Published in Psychological Medicine, the study aimed to explore the genetic mechanisms that underpin the relationship between heavy cannabis use and psychosis.
Researchers worked with two large datasets to establish PRSs for schizophrenia and for cannabis use disorder to investigate their relationship to psychosis and patterns of cannabis use.
The research was supported by the Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC).
The data were from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the UK Biobank which are large cohorts that both contain data on genetics, self-reported cannabis use and diagnoses of psychosis. There were 1592 participants from EU-GEI and 145,244 participants from UK Biobank.
In both samples, lifetime frequent cannabis use was associated with increased likelihood of psychosis and this was highest among those who were daily users of high potency cannabis. High potency cannabis was defined as having Delta-9 tetrahydrocannabinol (THC) content of 10 per cent or more.
This relationship remained the same when researchers accounted for the PRS for schizophrenia, suggesting that the environmental risk from cannabis use for psychosis is independent from the genetic risk.
“Our study is the first to estimate the risk of psychosis from both cannabis use and genetic predisposition to schizophrenia.
“Interestingly, we found no evidence of an interaction between the two, suggesting they influence the risk of psychosis through separate pathways and could potentially have an additive effect where those with increased genetic risk who use cannabis are highly likely to develop psychosis.
“Through further analysis of cannabis use of different frequencies and potencies, we have shown that highest risk for psychosis is in those with greater genetic predisposition to schizophrenia who use high potency cannabis daily,” said Dr Edoardo Spinazzola, Research Assistant at King’s IoPPN, Consultant Adult Psychiatrist, South London and Maudsley NHS Foundation Trust and corresponding author on the paper.
In the EU-GEI cohort researchers found that schizophrenia PRS was not associated with an individual’s propensity to try cannabis or the frequency of use. In the UK Biobank there was also no association between schizophrenia PRS and cannabis use in those with a psychosis diagnosis.
However, among those without psychosis in the UK Biobank, the PRS for schizophrenia was associated with lifetime and daily cannabis use, but the effect was substantially reduced when the PRS for cannabis use disorder was included in the model.
“These are important findings at a time of increasing use and potency of cannabis worldwide. Our study indicates that daily users of high potency cannabis are at increased risk of developing psychosis independently from their polygenic risk score for schizophrenia.
“Nevertheless, the polygenic risk score for schizophrenia might, in the near future, become useful to identify those at risk for psychosis among less frequent users to enable early preventative measures to be put in place.,” said Professor Marta di Forti, Professor of Drug Use, Genetics and Psychosis at King’s IoPPN and lead author on the paper.
About this genetics, psychosis, and cannabis research news
Author: Patrick O’Brien
Source: King’s College London
Contact: Patrick O’Brien – King’s College London
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies” by Edoardo Spinazzola et al. Psychological Medicine
Abstract
The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies
Background
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model.
In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
