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

描述（由申请人提供）：拟议研究的主要目的是解决遗传和认知机制，通过这些机制，压力生活事件（SLEs）和酒精相关认知与酒精中毒有关。研究已经确定了酒精相关认知（酒精预期和饮酒动机）是酗酒的危险因素，但关于调节这种关联的遗传、心理和环境过程，还有很多有待研究。此外，尽管经验证据表明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很多有待了解。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增加了随后酒精消费量增加的风险；(2) SLEs与遗传因素相互作用增加成人酒精中毒风险；(3)紧张缓解动机调节了SLEs与酒精中毒的关系；(4)遗传因素是酒精相关认知的个体差异的基础。本研究将从两个纵向社区双胞胎样本中提取信息，以检验这些假设：(1)成年双胞胎（n= 9249），他们几乎都经历了患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，因为他们从早期饮酒经历过渡（9-17岁）。潜在差异评分结构方程模型将用于检验成人SLEs和酒精中毒的时间关系。适度的双变量双胞胎模型将用于测试潜在饮酒动机的遗传因素是否与SLEs相互作用以增加成人酒精中毒的风险。测量的基因型将用于测试SLEs是否与血清素转运体变异相互作用，从而增加成人酒精中毒的风险。最后，将使用纵向双变量双胞胎模型来检查青少年开始饮酒之前和之后存在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：酒精中毒的风险因素包括遗传易感性、对生活压力事件的饮酒反应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结合和相互作用的了解仍然存在很大差距。这项研究将利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，对这些病因机制的更多了解将指导制定更有效的策略来预防酒精中毒的发生和发展。

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.