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一项对有酗酒家族史（FH+）的健康年轻人的心理、行为和压力反应特征的深入研究，目的是确定这些人患这种疾病的风险升高的特征。我们最近确定了早期生活不良经历（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，我们已经证明ELA导致压力反应性降低，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风险因素。ELA在FH+群体中的影响需要在基因x环境相互作用中进一步研究，因为FH+和ELA之间存在已知的正反馈。我们的目标是通过对FH x ELA进行基因分型，并研究基因型对本项目目前正在研究的广泛的个人特征的影响，来进行G x E相互作用研究。目标1.使用扩大的志愿者样本检查ELA对FH+与FH-组的心理和行为特征的差异影响。目标二。使用我们更大的样本进行基因x环境分析，以测试强烈怀疑影响大脑动机系统活动的特定等位基因，扩展我们在NIAAA中启动的工作，这要归功于对R 01（AA 012207-S1）的补充。目标3.测试特定方面的气质作为内在表型连接FH和ELA的行为，认知和压力反应作为人的表型的方面。目标4。通过在第二个地点筛选和测试志愿者来增加我们的招募基础，德克萨斯大学HSC，圣安东尼奥，我们目前在那里进行神经影像学研究。酗酒对社会来说是一个昂贵的负担，但人们对酗酒的风险因素知之甚少。绝大多数的研究都集中在酗酒患者身上，但无法将先前存在的影响与饮酒史的影响分开。我们的高风险研究设计可以通过比较FH+和FH-在环境因素和遗传脆弱性，有助于行为风险因素的价值。

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.