Oklahoma Family Health Patterns: A Study Across Generations

描述(由申请人提供)：俄克拉荷马州家庭健康模式项目是对有酗酒家族史(FH+)的健康年轻人的心理、行为和应激反应特征的深入研究，目的是确定将这些人置于疾病风险增加的特征。我们最近发现，早期生活不良经历(ELA)，包括身体和性虐待以及与父母分离，在FH+中发生的影响不成比例，我们已经表明，ELA导致应激反应减弱、行为冲动和情绪调节不良，所有这些都是酒精和其他物质使用障碍的危险因素。考虑到FH+和ELA之间已知的正反馈，ELA在FH+群体中的影响需要在基因x环境交互作用中进一步研究。我们的目标是通过对我们的FH x ELA进行基因分型，并检查基因对目前正在研究的广泛个人特征的影响，来进行G x E交互作用研究。目的1.通过扩大志愿者样本，检验ELA对FH+组和FH-组的心理和行为特征的不同影响。目的2.使用我们更大的样本进行基因x环境分析，以测试强烈怀疑会影响大脑激励系统活动的特定等位基因，扩展了我们与NIAAA启动的工作，这要归功于本R01(AA012207-S1)的补充。目的3.测试气质的特定方面，作为将FH和ELA与行为、认知和应激反应联系起来的内在表型，作为个人表型的方面。目标4.通过在第二个地点-圣安东尼奥的德克萨斯大学HSC筛选和测试志愿者来扩大我们的招募基础，我们目前在那里进行神经成像研究。酗酒是一种代价高昂的社会负担，但人们对酗酒的风险因素知之甚少。绝大多数研究集中在酗酒患者身上，但无法从饮酒史的影响中理清先前存在的影响。我们的高风险研究设计可以通过对比FH+和FH-在环境因素和导致行为风险因素的遗传脆弱性方面的差异而具有价值。

DESCRIPTION (provided by applicant): The Oklahoma Family Health Patterns project is an intensive study of psychological, behavioral, and stress reactivity characteristics in healthy young adults with a family history of alcoholism (FH+) with a goal of identifying characteristics that place these persons at elevated risk for the disorder. We have recently identified early life adverse experience (ELA), including physical and sexual abuse and separation from parents, as occurring with disproportionate impact in FH+, and we have shown that ELA accounts for diminished stress reactivity, behavioral impulsivity, and poor mood regulation, all of which are risk factors for alcohol and other substance use disorders. The impact of ELA in the FH+ population demands to be studied further in a Gene x Environment interaction given the known positive feedbacks between FH+ and ELA. Our goal is to carry out a G x E interaction study by genotyping our FH x ELA and examining the impact of genotype on the broad range of personal characteristics currently under study in this project. Aim 1. Examine the differential impact of ELA on psychological and behavioral characteristics of FH+ vs. FH- groups using an expanded sample of volunteers. Aim 2. Use our larger sample to carry out a Gene x Environment analysis to test specific alleles that are strongly suspected of influencing activity in brain motivational systems, expanding on work we initiated with NIAAA thanks to a supplement to this R01 (AA012207-S1). Aim 3. Test specific aspects of temperament as endophenotypes linking FH and ELA to behavioral, cognitive, and stress reactivity as aspects of the person's phenotype. Aim 4. Increase our recruitment base by screening and testing volunteers at a second site, the University of Texas HSC, San Antonio, where we currently conduct our neuroimaging studies. Alcoholism is a costly burden to society, but risk factors for alcoholism are poorly understood. The vast majorities of studies focuses on alcoholic patients but are unable to disentangle preexisting influences from the effects of alcohol intake history. Our high-risk study design can be of value by contrasting FH+ and FH- with regard to environmental contributors and genetic vulnerabilities that contribute to behavioral risk factors.