Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Institutd'InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. CIBERSAM; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
Eur Neuropsychopharmacol. 2019 Jun;29(6):786-794. doi: 10.1016/j.euroneuro.2019.04.005. Epub 2019 May 7.
Alterations of the endocannabinoid system (ECS) may play an important role in the development of schizophrenia and other psychotic disorders. Cannabis use is one of the environmental factors more repeatedly related to an increase the risk of developing a psychotic episode, while its use modifies the ECS normal function. In the present study we purposed to examine the gene by environment (GxE) interaction between 15 selected single nucleotide polymorphisms (SNPs) related to the ECS and cannabis use in a cohort of 321 patients with a first episode of psychosis (FEP) and 241 matched healthy controls. We found the fatty-acid amide hydrolase (FAAH) rs2295633 SNP genetic polymorphism was associated with a greater risk of presenting a FEP in subjects with relevant cannabis use, but not in subjects without a history of cannabis use. The probability of presenting a FEP was tenfold higher (OR: 10.69) in cannabis users who were homozygote carriers of the T allele of the FAAH rs2295633 SNP, compared to users of cannabis without this genotype. We also found that a higher a proportion of TT carriers of the FAAH rs2295633 SNP with a positive history of cannabis use was treated with high potency antipsychotic. This study has identified a GxE-environment interaction between a genetic polymorphism from the ECS and cannabis use involved in the risk of presenting a FEP. Although this preliminary data should be replicated with independent samples, our results highlight the importance of the pro-psychotic effects of exogenous cannabis use over the ECS in certain subjects.
内源性大麻素系统 (ECS) 的改变可能在精神分裂症和其他精神病性障碍的发展中起重要作用。大麻使用是与增加精神病发作风险相关的环境因素之一，而其使用会改变 ECS 的正常功能。在本研究中，我们旨在检查与 ECS 相关的 15 个单核苷酸多态性 (SNP) 与大麻使用之间的基因-环境 (GxE) 相互作用，该研究纳入了 321 名首发精神病患者 (FEP) 和 241 名匹配的健康对照者。我们发现脂肪酸酰胺水解酶 (FAAH) rs2295633 SNP 遗传多态性与相关大麻使用者中出现 FEP 的风险增加有关，但与无大麻使用史者无关。与无此基因型的大麻使用者相比，携带 FAAH rs2295633 SNP T 等位基因纯合子的大麻使用者出现 FEP 的概率高十倍 (OR：10.69)。我们还发现，FAAH rs2295633 SNP 的 TT 携带者中，有阳性大麻使用史的比例较高，他们接受了高效抗精神病药物治疗。这项研究确定了 ECS 中的遗传多态性与大麻使用之间的 GxE-环境相互作用，与出现 FEP 的风险有关。尽管这些初步数据需要用独立样本进行复制，但我们的结果强调了外源性大麻使用对某些个体的 ECS 产生促精神病作用的重要性。
