Colizzi Marco, Iyegbe Conrad, Powell John, Ursini Gianluca, Porcelli Annamaria, Bonvino Aurora, Taurisano Paolo, Romano Raffaella, Masellis Rita, Blasi Giuseppe, Morgan Craig, Aitchison Katherine, Mondelli Valeria, Luzi Sonija, Kolliakou Anna, David Anthony, Murray Robin M, Bertolino Alessandro, Di Forti Marta
Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
Schizophr Bull. 2015 Sep;41(5):1171-82. doi: 10.1093/schbul/sbv032. Epub 2015 Mar 31.
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.
大麻使用和多巴胺受体（DRD2）基因都与精神分裂症、类精神病体验及认知有关。然而，尚无已发表的数据研究DRD2多巴胺能信号的基因决定变异是否可能在个体对大麻相关精神病的易感性中起作用。我们对272例首次发作精神病患者和234例对照进行了病例对照研究，并对252名健康受试者的样本进行了基因分型，检测DRD2的功能性变异rs1076560。通过施用大麻体验问卷收集了所有研究对象的大麻使用史数据。在健康受试者样本中，我们还使用分裂型人格问卷和n-back工作记忆任务收集了关于分裂型特质和认知表现的数据。在病例对照研究中，我们发现DRD2基因rs1076560基因型与大麻使用之间在影响精神病性障碍发生可能性方面存在显著交互作用。在大麻使用者中，DRD2基因rs1076560的T等位基因携带者患精神病性障碍的概率比GG携带者高3倍（比值比[OR]=3.07；95%置信区间[CI]：1.22-7.63）。在每日使用者中，携带T等位基因的受试者患精神病的几率比GG携带者高5倍（OR=4.82；95%CI：1.39-16.71）。在健康受试者中，携带T等位基因的大麻使用者与携带T等位基因的未使用过大麻的受试者、GG基因型大麻使用者以及GG基因型未使用过大麻的受试者相比，分裂型特质增加（所有P≤0.025）。携带T等位基因的大麻使用者与其他组相比，工作记忆准确性降低（所有P≤0.008）。因此，DRD2基因rs1076560基因型的变异可能调节大麻使用的致精神病作用。
