2012年11月15日 讯 /生物谷BIOON/ --大麻所引发的个体不良精神状况是社会长期以来关注的一个问题,青年人使用大麻容易增加其患精神分裂症风险,近日来自伦敦大学国王学院精神病学研究所的研究人员揭示了引发大麻型精神病相关的基因突变,研究者发现在大麻型精神病患者中,其机体编码RAC-α丝氨酸/苏氨酸蛋白激酶(Akt1)的基因发生了突变,这项研究对于研究类似大麻相关的精神病非常重要。相关研究成果刊登于国际杂志Biological Psychiatry上。
这项研究中,研究者发现,AKT1基因的突变以及大麻的使用可以增加使用者患精神病的风险。研究者Forti说,我们研究AKT1,是因为其参与了多巴胺的信号路径,而在精神病患者机体中,该途径处于异常状态。
研究者这项研究包括489名首次发生精神病的患者以及278名健康个体,研究者评估了这些参与者的大麻使用情况,发现AKT1基因型可以影响大麻使用者患精神病的风险,AKT1基因突变的大麻使用者患精神病的风险是正常大麻使用个体的两倍,而且如果其每日使用大麻,那么患精神病风险可以增加至7倍。
当AKT1基因型水平不能达到临床诊断为大麻型精神病的风险标准,那么这些风险因子就可以在个体机体中进行累积。当然,这项研究也揭示了Akt1所介导的引发大麻型精神病的分子信号路径,这或许为未来开发大麻型精神病的疗法提供帮助。(生物谷Bioon.com)
编译自:A Risk Gene for Cannabis Psychosis
doi:10.1016/j.biopsych.2012.06.020
PMC:
PMID:
Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users
Di Forti M, Iyegbe C, Sallis H, Kolliakou A, Falcone MA, Paparelli A, Sirianni M, La Cascia C, Stilo SA, Marques TR, Handley R, Mondelli V, Dazzan P, Pariante C, David AS, Morgan C, Powell J, Murray RM.
Background Cannabis use is associated with an increased risk of psychosis. One study has suggested that genetic variation in the AKT1 gene might influence this effect. Methods In a case-control study of 489 first-episode psychosis patients and 278 control subjects, we investigated the interaction between variation at the AKT1 rs2494732 single nucleotide polymorphism and cannabis use in increasing the risk of psychosis. Results The rs2494732 locus was not associated with an increased risk of a psychotic disorder, with lifetime cannabis use, or with frequency of use. We did, however, find that the effect of lifetime cannabis use on risk of psychosis was significantly influenced by the rs2494732 locus (likelihood ratio statistic for the interaction = 8.54; p = .014). Carriers of the C/C genotype with a history of cannabis use showed a greater than twofold increased likelihood of a psychotic disorder (odds ratio = 2.18 [95% confidence interval: 1.12, 4.31]) when compared with users who were T/T carriers. Moreover, the interaction between the rs2494732 genotype and frequency of use was also significant at the 5% level (likelihood ratio = 13.39; p = .010). Among daily users, C/C carriers demonstrated a sevenfold increase in the odds of psychosis compared with T/T carriers (odds ratio = 7.23 [95% confidence interval: 1.37, 38.12]). Conclusions Our findings provide strong support for the initial report that genetic variation at rs2494732 of AKT1 influences the risk of developing a psychotic disorder in cannabis users.