Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis.


Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects' sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22-7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39-16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use.

DOI: 10.1093/schbul/sbv032
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@article{Colizzi2015InteractionBF, title={Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis.}, author={Marco Colizzi and Conrad O. Iyegbe and John Francis Powell and Gianluca Ursini and Annamaria Porcelli and Aurora Bonvino and Paolo Taurisano and Raffaella Romano and Rita Masellis and Giuseppe Blasi and Craig Morgan and Katherine J . Aitchison and Valeria Mondelli and Sonija Luzi and Anna Kolliakou and Anthony S. David and Robin M. Murray and Alessandro Bertolino and Marta di Forti}, journal={Schizophrenia bulletin}, year={2015}, volume={41 5}, pages={1171-82} }