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遗传和认知机制，通过该机制，压力生活事件（SLEs）和酒精相关认知与酗酒相关。研究已经确立了酒精相关的认知（酒精预期和饮酒动机）作为酗酒的危险因素，但仍有很多关于遗传，心理和环境过程，调节这种关联。此外，尽管有经验证据表明SLE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很多东西需要了解。拟议的研究将使用创新的统计方法来测试以下假设：（1）严重的SLE增加了随后增加酒精消费的风险;（2）SLE与遗传因素相互作用，增加了成年人酗酒的风险;（3）SLE和酗酒之间的关联受到紧张减轻动机的调节;（4）遗传因素是酒精相关认知的个体差异的基础。这项研究将从两个纵向的基于社区的双胞胎样本中抽取，这些样本为检验这些假设提供了信息：（1）成年双胞胎（n= 9，249），他们几乎都经历了发展AD的风险期;（2）青少年双胞胎（N=1219），他们正在接受前瞻性评估，因为他们正在经历早期酒精体验（9-17岁）。潜差得分结构方程模型将被用来检查SLE和酗酒的时间关系的成年人。适度双变量双胞胎模型将被用来测试是否遗传因素潜在的饮酒动机与SLE相互作用，以增加成年人酗酒的风险。测量的基因型将用于测试SLE是否与5-羟色胺转运体变异相互作用，以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查存在之前和之后的青少年开始饮酒的酒精预期的个体差异。该项目通过应用新方法分析当前数据集，直接解决了NIAAA的研究重点。公共卫生相关性：酒精中毒的危险因素包括遗传倾向，对压力生活事件的饮酒反应，以及对酒精影响的积极期望。然而，在我们对这些风险因素如何联合收割机结合和相互作用的了解方面，仍然存在很大的差距。本研究将使用两个遗传信息样本来解决这些差距，以阐明这些复杂的过程。最终，更多地了解这些病因机制将指导更有效的策略，以防止酗酒的发展和进展的发展。

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.