AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers.
AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers.
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DOI：
10.1038/tp.2015.219
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发表时间：
2016-02-16
影响因子：
6.8
通讯作者：
Curran HV
中科院分区：
文献类型：
--
作者：
Morgan CJ;Freeman TP;Powell J;Curran HV
每天吸食大麻使个人患精神病的风险增加一倍，但具体脆弱性的指标在很大程度上难以确定。遗传变异是一种潜在的风险调节因子。AKT 1和儿茶酚-O-甲基转移酶（COMT）基因中的单核苷酸多态性与大麻，精神病和认知之间的相互作用有关，但没有研究考察它们对个体对吸食大麻的急性反应的影响。共有442名健康的年轻大麻使用者在被自己的大麻中毒时进行了测试-分析了δ-9-四氢大麻酚（THC）和大麻二酚含量-并且在无药物时相隔±7天。拟精神症状和工作记忆进行了评估的两个会议。AKT 1基因的rs 2494732位点的变异预测了大麻沿着的急性精神病反应，以及对药物的依赖和基线典型症状。大麻急性工作记忆在女性中更差，一些建议COMT多态性对工作记忆的影响时，药物自由。这些发现首次证明AKT 1介导了健康个体对大麻的急性反应，并暗示AKT 1通路可能是预防和治疗大麻精神病的靶点。
Smoking cannabis daily doubles an individual's risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual's acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis—which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content—and also ±7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.