酗酒和高强度饮酒——与静脉内酒精自我管理和潜在危险因素的关联,Addiction Biology

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酗酒和高强度饮酒——与静脉内酒精自我管理和潜在危险因素的关联
Addiction Biology ( IF 3.4 ) Pub Date : 2022-09-05 , DOI: 10.1111/adb.13228
Martin H Plawecki ₁ , Julian Boes ₂ , Leah Wetherill ₂ , Ann E K Kosobud ₃ , Bethany L Stangl ₄ , Vijay A Ramchandani ₄ , Ulrich S Zimmermann _{5,

6} , John I Nurnberger ₁ , Marc Schuckit ₇ , Howard J Edenberg _{2,

8} , Gayathri Pandey ₉ , Chella Kamarajan ₉ , Bernice Porjesz ₉ , Tatiana Foroud ₂ , Sean O'Connor ₁

Affiliation

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Human Psychopharmacology Laboratory, Division of Intramural Clinical and Biological Research, NIAAA, Bethesda, Maryland, USA.
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus of the Technische Universität Dresden, Dresden, Germany.
Department of Addiction Medicine and Psychotherapy, kbo Isar-Amper-Klinikum Haar/Munich, Munich, Germany.
Department of Psychiatry, University of California San Diego, San Diego, California, USA.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Henri Begleiter Neurodynamics Laboratory, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA.

某些饮酒方式比其他饮酒方式风险更大。酒精暴露的水平和比率如何导致酒精使用障碍的风险增加尚不清楚，但可能取决于酒精浓度的时间进程。我们假设大脑对酒精浓度的变化率很敏感，并且风险较高的人会更快地自我管理。我们开发了一种新颖的静脉内酒精自我管理范式，使参与者能够直接且可重复地控制他们呼出的酒精浓度变化的速度。我们使用饮酒强度和酒精依赖生物学家族史的密度作为风险指标。35 名年龄在 21-28 岁之间的饮酒参与者提供了来自单一、使用我们的计算机辅助酒精输注系统速率控制范例的静脉内酒精自我管理会议。达到 80 mg/dl 的时间较短与暴饮暴食定义的倍数增加有关（p = 0.004），这又与更高密度的酗酒家族史有关（FHD，p = 0.04）。主观反应（中毒和刺激）的速率依赖性变化也与 FHD 相关（每个p = 0.001）。随后，鉴于有限的样本量和 FHD 范围，在酒精中毒遗传学合作研究数据库的分析中复制和扩展了暴饮暴食定义的倍数与 FHD 之间的关联。速率控制范式模拟实验室中的暴饮暴食和高强度饮酒，并提供了一种新方法来检查酒精的药代动力学和药效学之间的关系以及酒精使用障碍发展的潜在风险。

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Binge and high-intensity drinking—Associations with intravenous alcohol self-administration and underlying risk factors

Some styles of alcohol consumption are riskier than others. How the level and rate of alcohol exposure contribute to the increased risk of alcohol use disorder is unclear, but likely depends on the alcohol concentration time course. We hypothesized that the brain is sensitive to the alcohol concentration rate of change and that people at greater risk would self-administer faster. We developed a novel intravenous alcohol self-administration paradigm to allow participants direct and reproducible control over how quickly their breath alcohol concentration changes. We used drinking intensity and the density of biological family history of alcohol dependence as proxies for risk. Thirty-five alcohol drinking participants aged 21–28 years provided analytical data from a single, intravenous alcohol self-administration session using our computer-assisted alcohol infusion system rate control paradigm. A shorter time to reach 80 mg/dl was associated with increasing multiples of the binge drinking definition (p = 0.004), which was in turn related to higher density of family history of alcoholism (FHD, p = 0.04). Rate-dependent changes in subjective response (intoxication and stimulation) were also associated with FHD (each p = 0.001). Subsequently, given the limited sample size and FHD range, associations between multiples of the binge drinking definition and FHD were replicated and extended in analyses of the Collaborative Study on the Genetics of Alcoholism database. The rate control paradigm models binge and high-intensity drinking in the laboratory and provides a novel way to examine the relationship between the pharmacokinetics and pharmacodynamics of alcohol and potentially the risk for the development of alcohol use disorders.

更新日期：2022-09-07

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