Anxiety and Subjective Response to Alcohol: Moderating Effects of Drinking Context and Mediation by Cortisol Response to Alcohol

 描述(由申请人提供)：焦虑症是酒精使用障碍(AUD)的一个危险因素，但风险机制尚不清楚。一种可能性是，酒精对焦虑的人来说更具负面作用。支持这一点的研究表明，焦虑的人报告说，他们对酒精的紧张缓解预期更高，应对饮酒的动机也更高。研究还表明，在压力源之前饮酒可能会大大减轻焦虑的个人的压力反应，但这些结果并不一定适用于在没有迫在眉睫的压力源的情况下饮酒(这可能是大多数现实世界饮酒的特征)。在没有迫在眉睫的压力源的情况下进行的少数研究未能利用足够的安慰剂对照，或没有使用经过验证的酒精反应测量。需要进行符合这些标准的研究，以确定焦虑的人是否会在超出预期的情况下从酒精中获得更大的负面强化。现有的研究也未能解决环境环境的影响，环境环境已被证明影响对酒精的主观反应(例如，在刺激较少的环境中有更大的放松感觉，在群体环境中比在独处环境中有更强的积极主观影响)。如果 低刺激环境有助于焦虑的个体获得更大的负面强化，这将有助于识别出AUDS的最高风险人群(例如，焦虑的单独饮酒者)。最后，了解酒精对焦虑个体的负面强化作用的潜在机制可能有助于确定干预和预防这一人群中酒精使用障碍的关键目标。一种可能的机制是皮质醇对酒精的反应，与血液酒精曲线下降端的少量饮酒者相比，重度饮酒者的皮质醇反应迟钝。与少量饮酒者相比，大量饮酒的人也会感受到更强的积极主观影响和更弱的负面主观影响(这预示着未来的酒精使用和问题)。这表明皮质醇的反应可能会影响对酒精的主观反应，至少在下降的肢体上是这样，在那里这些影响占主导地位。因此，皮质醇反应可能是这种低唤醒主观效应的一个标志(例如，皮质醇升高=低唤醒效应被体验为负面，如眩晕；钝化皮质醇=低唤醒效应被体验为积极，如放松)。如果皮质醇的反应确实影响主观效果， 焦虑的人可能会通过这种机制患上酒精问题，因为他们和酗酒者一样，由于慢性激活而表现出HPA轴调节失调。拟议的研究培训计划将使用安慰剂控制的酒精给药设计来调查以下目的：1)确定焦虑症状是否与相对于安慰剂的主观反应的负面强化有关。2)确定饮酒环境(身体和社会)是否缓和了焦虑症状和酒精反应之间的关系。3)研究皮质醇对酒精的反应作为焦虑症状和对酒精的主观反应之间关系的潜在中介。

 DESCRIPTION (provided by applicant): Anxiety disorders are a risk factor for alcohol use disorders (AUDs), but mechanisms of risk are not well understood. One possibility is that alcohol is more negatively reinforcing for anxious individuals. Supporting this, studies show that anxious individuals report greater tension-reduction expectancies for alcohol and higher coping motives for drinking. Studies also suggest that consuming alcohol prior to a stressor may provide greater reduction of stress response for anxious individuals, but these results do not necessarily generalize to drinking in the absence of an imminent stressor (which likely characterizes most real-world drinking). The few studies conducted in the absence of an imminent stressor have failed to utilize adequate placebo controls or have not used validated measures of alcohol response. Studies meeting these criteria are needed to establish whether anxious individuals receive greater negative reinforcement from alcohol above and beyond expectancies. Existing studies also fail to address effects of environmental context, which has been shown to affect subjective response to alcohol (e.g., greater feelings of relaxation in less stimulating environments, stronger positive subjective effects in groups vs. solitary settings). If low-stimulation contexts facilitate greater negative reinforcement for anxious individuals, this would aid in identifying those at greatest risk for AUDs (e.g., anxious solitary drinkers). Finally understanding mechanisms underlying negatively reinforcing effects of alcohol in anxious individuals may lead to the identification of key targets for intervention and prevention of alcoho use disorders in this population. One possible mechanism is cortisol response to alcohol, which is blunted in heavy drinkers compared to light drinkers on the descending limb of the blood alcohol curve. Heavy drinkers also experience stronger positive and weaker negative subjective effects from alcohol compared to light drinkers (which is predictive of future alcohol use and problems). This suggests that cortisol response may influence subjective response to alcohol, at least on the descending limb, where these effects predominate. So, perhaps cortisol response is a marker of the valence of such low-arousal subjective effects (e.g., elevated cortisol = low-arousal effects experienced as negative, e.g., wooziness; blunted cortisol = low-arousal effects experienced as positive, e.g., relaxation). If cortisol response does influence subjective effects, anxious individuals may be at risk for developing alcohol problems via this mechanism because they, similar to heavy drinkers, show a dysregulated HPA axis due to chronic activation. The proposed research training plan will use a placebo-controlled alcohol administration design to investigate the following aims: 1) Determine whether anxiety symptoms are associated with a negatively reinforcing profile of subjective response relative to placebo. 2) Determine whether drinking context (physical and social) moderates the relationship between anxiety symptoms and alcohol response. 3) Investigate cortisol response to alcohol as a potential mediator of the relationship between anxiety symptoms and subjective response to alcohol.