Department of Psychology, Yale University, New Haven, Connecticut 06520, USA.
Alcohol Clin Exp Res. 2010 Mar 1;34(3):385-95. doi: 10.1111/j.1530-0277.2009.01103.x. Epub 2009 Dec 17.
Subjective response to alcohol (SR), which reflects individual differences in sensitivity to the pharmacological effects of alcohol, may be an important endophenotype in understanding genetic influences on drinking behavior and alcohol use disorders (AUDs). SR predicts alcohol use and problems and has been found to differ by a range of established risk factors for the development of AUDs (e.g., family history of alcoholism). The exact pattern of SR associated with increased risk for alcohol problems, however, remains unclear. The Low Level of Response Model (LLR) suggests that high-risk individuals experience decreased sensitivity to the full range of alcohol effects, while the Differentiator Model (DM) asserts that high risks status is associated with increased sensitivity to alcohol's positive effects but decreased sensitivity to negative effects.
The current paper (1) reviews two prominent models of subjective response, (2) reviews extant laboratory-based research on subjective response, (3) highlights remaining gaps in our understanding and assessment of subjective response, and (4) encourages collaborative efforts to address these methodological and conceptual concerns.
This paper reviews studies which employed placebo-controlled and non-placebo-controlled alcohol challenge paradigms to assess a range of alcohol effects including impairment, stimulation, and sedation.
The research literature provides at least partial support for both the LLR and DM models. High-risk individuals have been shown to have a reduced response to alcohol with respect to sedative or impairing effects, particularly on the descending limb of the blood alcohol curve (BAC). There is also evidence that ascending limb stimulant effects are more pronounced or operate differently for high-risk individuals.
Despite commendable advances in SR research, important questions remain unanswered. Inconsistent results across studies may be attributable to a combination of an inadequate understanding of the underlying construct and methodological differences across studies (e.g., number and timing of assessments across the BAC, inclusion of a placebo condition). With respect to the underlying construct, existing measures fail to adequately distinguish between cognitive/behavioral impairment and sedation, aspects of which may be perceived positively (e.g., anxiolysis) due to their ability to act as negative reinforcers.
Addressing the concerns raised by the current review will be integral to making meaningful scientific progress in the field of subjective response.
对酒精的主观反应（SR）反映了个体对酒精药理作用的敏感性差异，可能是理解遗传对饮酒行为和酒精使用障碍（AUD）影响的重要表型。SR 预测酒精使用和问题，并且已经发现它与 AUD 发展的一系列既定风险因素（例如，酗酒家族史）不同。然而，与酒精问题风险增加相关的 SR 确切模式仍不清楚。低反应水平模型（LLR）表明，高风险个体对酒精的全面影响的敏感性降低，而差异化模型（DM）则认为高风险状态与对酒精的正效应的敏感性增加但对负效应的敏感性降低有关。
本文（1）综述了两种突出的主观反应模型，（2）综述了现有的基于实验室的主观反应研究，（3）强调了我们对主观反应的理解和评估方面仍然存在的差距，（4）鼓励开展合作努力解决这些方法学和概念性问题。
本文综述了使用安慰剂对照和非安慰剂对照酒精挑战范式来评估一系列酒精效应的研究，包括损害、刺激和镇静。
研究文献至少部分支持了 LLR 和 DM 模型。高风险个体在镇静或损害方面对酒精的反应降低，特别是在血液酒精曲线（BAC）的下降支上。也有证据表明，上升支刺激效应更为明显或对高风险个体的作用方式不同。
尽管在 SR 研究方面取得了可喜的进展，但仍有重要问题未得到解答。研究之间的不一致结果可能归因于对潜在结构的理解不足以及研究之间的方法学差异（例如，BAC 上的评估次数和时间、是否包括安慰剂条件）。就潜在结构而言，现有的测量方法无法充分区分认知/行为损害和镇静，镇静的某些方面可能会被感知为正面（例如，焦虑减轻），因为它们能够作为负强化物。
解决当前综述中提出的问题对于在主观反应领域取得有意义的科学进展至关重要。
