by King's College London

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New research from 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) summarize 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 1,592 participants from EU-GEI and 145,244 participants from UK Biobank.

Probability of psychosis case status within EU-GEI cohort as schizophrenia PRS increases, across seven levels of cannabis potency–frequency composite measure. Credit: Psychological Medicine (2024). DOI: 10.1017/S0033291724002058

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% 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.

Corresponding author Dr. Edoardo Spinazzola, Research Assistant at the Institute of Psychology, Psychiatry & Neuroscience (IoPPN), King's College London and Consultant Adult Psychiatrist, South London and Maudsley NHS Foundation Trust said, "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."

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.

Senior author, Professor Marta di Forti, Professor of Drug Use, Genetics and Psychosis at King's IoPPN said, "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."

More information: Isabelle Austin-Zimmerman et al, 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, Psychological Medicine (2024). DOI: 10.1017/S0033291724002058

Journal information: Psychological Medicine 

Provided by King's College London