Genetic Links to the Reinforcing Effects of Alcohol in a Social Context

描述（由申请人提供）：人们对酒精的反应不同，这种反应变化已被证明可预测发生酒精使用障碍（AUD）的风险增加。例如，在社会交往中经历更多酒精奖励效应的人可能特别容易滥用酒精。研究人员一直有兴趣确定遗传变异和酒精反应之间的联系，但这一目标已被证明具有挑战性。不一致的结果可能是由于使用小样本量和研究人员倾向于研究个人对酒精的反应，而他们是孤立的。社会因素在AUD中起着重要作用，但研究人员很少研究酒精在群体环境中的影响。拟议的项目将系统地测量酒精对积极和消极影响的影响（使用Ekman等人。的（2002）面部动作编码系统）。自我报告的情绪，社会联系，言语行为和主观中毒水平也将进行评估。该研究将确定基因多态性变异与AUD风险增加相关的人[即，编码血清素转运体、多巴胺D2和D4受体以及γ-氨基丁酸（GABA）受体的基因]在社交环境中对酒精的奖励效应更敏感。社交饮酒者（n= 720）将被分成240个3人组，并将在30分钟内饮用中等剂量的酒精（男性：0.82 g/kg;女性：0.74 g/kg）、安慰剂或非酒精对照饮料。这组饮酒时间将使用数字控制系统进行记录，该系统可以精确分析面部表情随着时间的推移而展开的持续时间和顺序。拟议的项目将是第一个有足够的力量结合联合收割机人类遗传学的观点，社会心理学理论，并在系统测量观察到的行为，以确定在社会背景下的酒精反应变异的遗传联系的最新进展。 酒精使用障碍与多种不良健康后果有关，每年夺去10万多人的生命。发生AUD的风险变异性中约有一半是遗传性的。研究的首要任务是识别出患有AUD的易感性增加的个体，因为这些信息将为预防和治疗策略提供重要信息。通过将人类基因分型与社会背景下酒精强化效应的全面多维评估相结合，可以阐明遗传因素影响男性和女性饮酒结果的机制。这些信息将极大地为饮酒和酗酒理论提供信息，并有助于预测谁可能有饮酒问题的风险。

DESCRIPTION (provided by applicant): People respond to alcohol differently, and this response variation has been shown to predict increased risk to develop alcohol use disorders (AUD). For instance, individuals who experience more rewarding effects of alcohol during social interactions may be especially likely to misuse alcohol. Researchers have been interested in identifying links between genetic variation and alcohol response, but this objective has proved challenging. Inconsistent findings likely result from the use of small sample sizes and the tendency of researchers to study individuals' response to alcohol while they are in isolation. Social factors play a major role in AUD, yet researchers rarely study the effects of alcohol in a group setting. The proposed project will systematically measure the effects of alcohol on positive and negative affect (using Ekman et al.'s (2002) Facial Action Coding System) during a group interaction. Self-reported mood, social bonding, speech behavior, and subjective intoxication levels will also be assessed. The study will determine if persons with polymorphic variation in genes associated with increased risk for AUD [i.e., genes encoding the serotonin transporter, dopamine D2 and D4 receptors, and the receptor for gamma-aminobutyric acid (GABA)] are more sensitive to alcohol's rewarding effects in a social setting. Social drinkers (n= 720) will be assembled into 240 3-person groups and will drink over 30-min a moderate dose of alcohol (males: 0.82 g/kg; females: 0.74 g/kg), a placebo, or a nonalcoholic control drink. This group drinking period will be recorded using a digital control system that enables precise analysis of the duration and sequence of facial expressions as they unfold over time. The proposed project will be the first with sufficient power to combine human genetic perspectives, social psychological theory, and recent advances in the systematic measurement of observed behavior to determine the genetic links to alcohol response variation in a social context. Alcohol use disorders are associated with multiple adverse health consequences and claim the lives of over 100,000 people each year. Approximately half of the variability in risk to develop AUD is genetic. It is a research priority to identify individuals with increased susceptibility to develop AUD, as such information would greatly inform prevention and treatment strategies. By combining human genotyping with a comprehensive multi-dimensional assessment of alcohol's reinforcing effects in a social context, the mechanisms through which genetic factors influence drinking outcomes in men and women may be elucidated. This information will greatly inform theories of drinking and alcoholism and will help to predict who may be at risk of developing drinking problems.