2012年11月15日 訊 /生物谷BIOON/ --大麻所引發(fā)的個(gè)體不良精神狀況是社會(huì)長(zhǎng)期以來(lái)關(guān)注的一個(gè)問(wèn)題,，青年人使用大麻容易增加其患精神分裂癥風(fēng)險(xiǎn),，近日來(lái)自倫敦大學(xué)國(guó)王學(xué)院精神病學(xué)研究所的研究人員揭示了引發(fā)大麻型精神病相關(guān)的基因突變，研究者發(fā)現(xiàn)在大麻型精神病患者中,，其機(jī)體編碼RAC-α絲氨酸/蘇氨酸蛋白激酶（Akt1）的基因發(fā)生了突變,，這項(xiàng)研究對(duì)于研究類似大麻相關(guān)的精神病非常重要。相關(guān)研究成果刊登于國(guó)際雜志Biological Psychiatry上,。
這項(xiàng)研究中,，研究者發(fā)現(xiàn)，AKT1基因的突變以及大麻的使用可以增加使用者患精神病的風(fēng)險(xiǎn),。研究者Forti說(shuō),，我們研究AKT1，是因?yàn)槠鋮⑴c了多巴胺的信號(hào)路徑,，而在精神病患者機(jī)體中,，該途徑處于異常狀態(tài)。
研究者這項(xiàng)研究包括489名首次發(fā)生精神病的患者以及278名健康個(gè)體,，研究者評(píng)估了這些參與者的大麻使用情況,，發(fā)現(xiàn)AKT1基因型可以影響大麻使用者患精神病的風(fēng)險(xiǎn)，AKT1基因突變的大麻使用者患精神病的風(fēng)險(xiǎn)是正常大麻使用個(gè)體的兩倍,，而且如果其每日使用大麻,，那么患精神病風(fēng)險(xiǎn)可以增加至7倍。
當(dāng)AKT1基因型水平不能達(dá)到臨床診斷為大麻型精神病的風(fēng)險(xiǎn)標(biāo)準(zhǔn),，那么這些風(fēng)險(xiǎn)因子就可以在個(gè)體機(jī)體中進(jìn)行累積,。當(dāng)然，這項(xiàng)研究也揭示了Akt1所介導(dǎo)的引發(fā)大麻型精神病的分子信號(hào)路徑,，這或許為未來(lái)開(kāi)發(fā)大麻型精神病的療法提供幫助,。（生物谷Bioon.com）
編譯自：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.
