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

焦虑和对酒精的主观反应：饮酒环境的调节作用和皮质醇对酒精反应的调节

• 批准号: 9285594
• 负责人: Kyle Menary
• 金额: $ 4.4万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2018-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9285594
• 关键词: Address; Affect; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Anxiety; Anxiety Disorders; Arousal; Beverages; Blood; Chronic; Development; Disease; Environment; Etiology; Euphoria; Expectancy; Feeling; Future; Home environment; Hydrocortisone; Individual Differences; Intervention; Laboratories; Lead; Light; Limb structure; Literature; Measures; Mediating; Mediation; Mediator of activation protein; Negative Reinforcements; Pharmacology; Physiological; Placebo Control; Placebos; Population; Positive Valence; Prevention; Preventive Intervention; Prospective Studies; Relaxation; Reporting; Research Training; Risk; Risk Factors; Role; Salivary; Wit; alcohol abuse therapy; alcohol effect; alcohol expectancy; alcohol reinforcement; alcohol response; alcohol risk; alcohol use disorder; anxiety symptoms; anxious; anxious individuals; associated symptom; biological adaptation to stress; coping; design; drinking; experience; high risk; meetings; negative affect; novel; prospective; public health relevance; response; social; stressor

 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.

 描述（由申请人提供）：焦虑症是酒精使用障碍（AUD）的一个风险因素，但风险机制尚不清楚。一种可能性是，酒精对焦虑的人有更大的负面强化作用。支持这一点，研究表明，焦虑的人报告更大的紧张减少预期酒精和更高的应对饮酒的动机。研究还表明，在压力源之前饮酒可能会更大程度地减少焦虑个体的压力反应，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有效的酒精反应措施。需要进行符合这些标准的研究，以确定焦虑的个体是否会从酒精中获得超出预期的更大的负强化。现有的研究也未能解决环境背景的影响，这已被证明会影响对酒精的主观反应（例如，在刺激性较低的环境中有更大的放松感，在群体与孤独环境中有更强的积极主观效果）。如果 低刺激环境促进焦虑个体的更大负强化，这将有助于识别AUD风险最大的个体（例如，孤独的饮酒者（最后，了解酒精在焦虑个体中的负强化作用的机制可能会导致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，在血液酒精曲线的下降段，重度饮酒者的皮质醇反应比轻度饮酒者的反应迟钝。与轻度饮酒者相比，重度饮酒者也会经历更强的积极和更弱的消极主观影响（这是未来酒精使用和问题的预测）。这表明皮质醇反应可能会影响对酒精的主观反应，至少在下降肢体上，这些影响占主导地位。所以，也许皮质醇反应是这种低唤醒主观效应的效价的标志（例如，皮质醇升高=低唤醒效应被认为是负面的，例如，头晕;皮质醇减弱=低唤醒效应被认为是积极的，例如，松弛）。如果皮质醇反应确实影响主观效果， 焦虑的个体可能有通过这种机制发展酒精问题的风险，因为他们与重度饮酒者相似，由于慢性激活而显示出失调的HPA轴。拟定的研究培训计划将使用安慰剂对照酒精给药设计，以研究以下目的：1）确定焦虑症状是否与相对于安慰剂的主观反应的负强化特征相关。2)确定饮酒环境（身体和社会）是否调节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。