Gene-Environment Interations Underlying Alcoholism Vulne

儿童时期的逆境往往早于反社会行为等外化行为和抑郁等内化行为，这两者都是问题饮酒和酗酒的危险因素。我们使用了来自雅芳父母和儿童纵向研究的大约7000名高加索女孩和男孩的父母和教师自我报告问卷的数据。母亲是在怀孕早期招募的，他们的孩子一直到8岁。我们已经对儿童S的DNA进行了基因分型，以检测三个基因的功能多态：单胺氧化酶A、5-羟色胺转运体和儿茶酚-O-甲基转移酶。我们正在研究基因-环境相互作用对酒精中毒易感性障碍发展的纵向影响。 我们发现，0？2岁儿童经历的母性精神病理对行为、多动症和ADHD有显著影响，这些影响至少会持续到8岁。在同一时间段经历的应激生活事件也有相同的影响，尽管影响不那么强大。我们发现，在男孩和女孩中，MAOA VNTR变体与行为方面的生活事件之间存在交互作用，特别是多动症。进一步的分析正在进行中。对HTT启动子多态性、HTTLPR和生活事件之间相互作用的初步分析表明，HTT启动子的多态对情绪性有影响。相比之下，对COMT Val158Met与生活事件相互作用的初步分析表明，对儿童情绪性没有影响。

Childhood adversity often pre-dates externalizing behaviors such as antisocial behavior and internalizing behaviors such as depression, both of which are risk factors for problem drinking and alcoholism. We are using data derived from parental and teacher self-report questionnaires in a cohort of approximately 7000 Caucasian girls and boys from the Avon Longitudinal Study of Parents and Children (ALSPAC), U.K. Mothers were recruited in early pregnancy and data is available on their children up to age 8. We have genotyped the children?s DNA for functional polymorphisms in three genes: monoamine oxidase A (MAOA), serotonin transporter (HTT) and catechol-O-methyltransferase (COMT). We are looking at the longitudinal influence of gene-environment interactions on the development of alcoholism vulnerability disorders. We have found that maternal psychopathology experienced by children at age 0 ? 2 years has a significant effect on conduct, hyperactivity and ADHD that persists at least until age 8. Stressful life events experienced during the same time frame has the same, although less powerful, influence. We have found an interaction between the MAOA VNTR variant and life events on behavior, particularly hyperactivity, in both boys and girls. Further analyses are underway. Preliminary analyses on the interaction between the HTT promoter polymorphism, HTTLPR, and life events indicate an influence on emotionality. In contrast, preliminary analyses of the interaction of the COMT Val158Met and life events indicate no influence on childhood emotionality.