Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: Longitudinal evidence of a gene X environment interaction
Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: Longitudinal evidence of a gene X environment interaction
复制标题
DOI：
10.1016/j.biopsych.2005.01.026
复制
发表时间：
2005-05-15
影响因子：
10.6
通讯作者：
Craig, IW
中科院分区：
文献类型：
--
作者：
Caspi, A;Moffitt, TE;Craig, IW
背景资料：最近的证据表明，年轻人使用大麻是成年期精神病症状的一个适度的统计风险因素，如幻觉和妄想，以及临床上显著的精神分裂症。绝大多数的大麻使用者不发展精神病，然而，促使其假设，有些人在遗传上容易受到大麻的有害影响。方法：在一项纵向研究中，一个代表性的出生队列随后到成年，我们测试了为什么大麻的使用与精神病的出现在少数用户，而不是在其他人。结果：儿茶酚-O-甲基转移酶（COMT）基因的功能多态性调节了青少年大麻使用对成人精神病的影响。COMT缬氨酸（158）等位基因携带者最有可能表现出精神病症状，并发展为精神分裂症样障碍，如果他们使用大麻。大麻使用坏没有这样的不利影响，个人与两个副本的蛋氨酸allele.Conclusions：这些研究结果提供了证据的基因X环境相互作用，并建议一些易感基因的作用是影响环境病原体的脆弱性。
Background: Recent evidence documents that cannabis use by young people is a modest statistical risk factor for psychotic symptoms in adulthood, such as hallucinations and delusions, as well as clinically significant schizophrenia. The vast majority of cannabis users do not develop psychosis, however, prompting its to hypothesize that some people are genetically vulnerable to the deleterious effects of cannabis.Methods: In a longitudinal study of a representative birth cohort followed to adulthood, we tested why cannabis use is associated with the emergence of psychosis in a minority of users, but not in others.Results: A functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent cannabis use on developing adult psychosis. Carriers of the COMT valine(158) allele were most likely to exhibit psychotic symptoms and to develop schizophreniform disorder if they used cannabis. Cannabis use bad no such adverse influence on individuals with two copies of the methionine allele.Conclusions: These findings provide evidence of a gene X environment interaction and suggest that a role of some susceptibility genes is to influence vulnerability to environmental pathogens.