Interaction of Genes, Stress, and Cognitions in the Development of Alcoholism

描述(由申请人提供)：拟议研究的广泛目标是解决应激性生活事件(SLEs)和与酒精相关的认知与酒精中毒相关的遗传和认知机制。研究已经确定与酒精相关的认知(酒精预期和饮酒动机)是酒精中毒的危险因素，但关于缓和这种联系的遗传、心理和环境过程仍有许多需要了解。此外，尽管有经验证据表明SLEs与酒精中毒的发展有关，但关于这种联系背后的认知和生物学机制仍有许多需要了解。这项拟议的研究将使用创新的统计方法来检验以下假设：(1)严重的SLEs会增加随后饮酒的风险；(2)SLEs与遗传因素相互作用，增加成年人酗酒的风险；(3)SLEs和酒精中毒之间的联系受到降压动机的调节；以及(4)遗传因素是与酒精相关的认知的个体差异的基础。这项研究将从两个以社区为基础的纵向双胞胎样本中提取，这两个样本对检验这些假设是有信息的：(1)成年双胞胎(n=9,249)，他们几乎都处于阿尔茨海默病的风险期；(2)青春期双胞胎(N=1219)，他们正在接受前瞻性评估，因为他们正在通过早期饮酒经历(从9-17岁)过渡。潜在差异分数结构方程模型将被用来检验SLEs和酒精中毒在成人中的时间关系。缓和的双变量双胞胎模型将被用来测试潜在的饮酒动机的遗传因素是否与SLES相互作用，从而增加成年人酗酒的风险。测量的基因类型将被用来测试SLEs是否与5-羟色胺转运体变体的变异相互作用，从而增加成年人酗酒的风险。最后，纵向双变量双胞胎模型将被用来检验青少年在开始饮酒之前和之后的酒精预期的个体差异。该项目通过应用新的方法来分析当前的数据集，直接处理NIAAA的研究优先事项。公共卫生相关性：酗酒的风险因素包括遗传易感性、因应应激性生活事件而饮酒以及对酒精影响的积极预期。然而，我们对这些风险因素如何组合和相互作用的认识仍然存在很大差距。这项研究将使用两个具有遗传信息的样本来解决这些差距，以阐明这些复杂的过程。最终，对这些病因机制的更多了解将指导制定更有效的策略来防止酒精中毒的发展和进展。

DESCRIPTION (provided by applicant): The broad objective of the proposed research is to address the genetic and cognitive mechanisms through which stressful life events (SLEs) and alcohol-related cognitions are associated with alcoholism. Research has established alcohol-related cognitions (alcohol expectancies and drinking motives) as risk factors for alcoholism, yet much remains to be learned about the genetic, psychological, and environmental processes that moderate this association. In addition, despite empirical evidence demonstrating the association of SLEs with the development of alcoholism, there remains a great deal to be learned about the cognitive and biological mechanisms underlying this association. The proposed research will use innovative statistical methodologies to test the following hypotheses: (1) severe SLEs increase risk for subsequent increases in alcohol consumption; (2) SLEs interact with genetic factors to increase risk for alcoholism in adults; (3) the association between SLEs and alcoholism is moderated by tension-reduction motives; and (4) genetic factors underlie individual differences in alcohol-related cognitions. This study will draw from two longitudinal community-based twin samples who are informative for testing these hypotheses: (1) adult twins (n=9,249) who are nearly all through the risk period for developing AD; and (2) adolescent twins (N=1219) who are being assessed prospectively as they transition through early experiences with alcohol (from ages 9-17). Latent difference score structural equation models will be used to examine the temporal relation of SLEs and alcoholism in adults. Moderated bivariate twin models will be used to test whether genetic factors underlying drinking motives interact with SLEs to increase risk for alcoholism in adults. Measured genotypes will be used to test whether SLEs interact with variations in the serotonin transporter variant to increase risk for alcoholism in adults. Finally, longitudinal bivariate twin models will be used to examine individual differences in alcohol expectancies that exist both prior and subsequent to the initiation of drinking in adolescents. This project directly addresses NIAAA research priorities by applying new approaches to analyze current data sets. Public Health Relevance: Risk factors for alcoholism include genetic predisposition, drinking in response to stressful life events, and positive expectations about alcohol's effects. However, substantial gaps remain in our knowledge about how these risk factors combine and interact. This study will address these gaps using two genetically informative samples to shed light on these complex processes. Ultimately, greater knowledge about these etiological mechanisms will guide the development of more effective strategies to prevent the development and progression of alcoholism.