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

Marco Colizzi; Conrad Iyegbe; John Powell; Gianluca Ursini; Annamaria Porcelli; Aurora Bonvino; Paolo Taurisano; Raffaella Romano; Rita Masellis; Giuseppe Blasi; Craig Morgan; Katherine Aitchison; Valeria Mondelli; Sonija Luzi; Anna Kolliakou; Anthony David; Robin M Murray; Alessandro Bertolino; Marta Di Forti

doi:10.1093/schbul/sbv032

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

Marco Colizzi, Conrad Iyegbe, John Powell, Gianluca Ursini, Annamaria Porcelli, Aurora Bonvino, Paolo Taurisano, Raffaella Romano, Rita Masellis, Giuseppe Blasi, Craig Morgan, Katherine Aitchison, Valeria Mondelli, Sonija Luzi, Anna Kolliakou, Anthony David, Robin M Murray, Alessandro Bertolino, Marta Di Forti

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Abstract

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.

Original language	English
Pages (from-to)	1171-1182
Number of pages	12
Journal	Schizophrenia Bulletin
Volume	41
Issue number	5
Early online date	31 Mar 2015
DOIs	https://doi.org/10.1093/schbul/sbv032
Publication status	Published - 1 Sept 2015

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Interaction Between Functional Genetic Variation_MORGAN_Publishedonline31March2015_GREEN AAMAccepted author manuscript, 213 KB

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Colizzi, M., Iyegbe, C., Powell, J., Ursini, G., Porcelli, A., Bonvino, A., Taurisano, P., Romano, R., Masellis, R., Blasi, G., Morgan, C., Aitchison, K., Mondelli, V., Luzi, S., Kolliakou, A., David, A., Murray, R. M., Bertolino, A., & Forti, M. D. (2015). Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis. Schizophrenia Bulletin, 41(5), 1171-1182. https://doi.org/10.1093/schbul/sbv032

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title = "Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis",

abstract = "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-na{\"i}ve subjects, GG cannabis users, and GG cannabis-na{\"i}ve 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.",

author = "Marco Colizzi and Conrad Iyegbe and John 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 Aitchison and Valeria Mondelli and Sonija Luzi and Anna Kolliakou and Anthony David and Murray, {Robin M} and Alessandro Bertolino and Forti, {Marta Di}",

year = "2015",

month = sep,

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doi = "10.1093/schbul/sbv032",

language = "English",

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Colizzi, M , Iyegbe, C , Powell, J, Ursini, G, Porcelli, A, Bonvino, A, Taurisano, P, Romano, R, Masellis, R, Blasi, G, Morgan, C , Aitchison, K , Mondelli, V , Luzi, S , Kolliakou, A , David, A , Murray, RM, Bertolino, A & Forti, MD 2015, 'Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis', Schizophrenia Bulletin, vol. 41, no. 5, pp. 1171-1182. https://doi.org/10.1093/schbul/sbv032

TY - JOUR

T1 - Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis

AU - Colizzi, Marco

AU - Iyegbe, Conrad

AU - Powell, John

AU - Ursini, Gianluca

AU - Porcelli, Annamaria

AU - Bonvino, Aurora

AU - Taurisano, Paolo

AU - Romano, Raffaella

AU - Masellis, Rita

AU - Blasi, Giuseppe

AU - Morgan, Craig

AU - Aitchison, Katherine

AU - Mondelli, Valeria

AU - Luzi, Sonija

AU - Kolliakou, Anna

AU - David, Anthony

AU - Murray, Robin M

AU - Bertolino, Alessandro

AU - Forti, Marta Di

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

U2 - 10.1093/schbul/sbv032

DO - 10.1093/schbul/sbv032

M3 - Article

C2 - 25829376

SN - 0586-7614

VL - 41

SP - 1171

EP - 1182

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

IS - 5

ER -

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

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