Alcohol Alters the Circadian Response to Light in Humans

酒精改变人类对光的昼夜节律反应

• 批准号: 8580814
• 负责人: Helen Julia Burgess
• 金额: $ 18.17万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8580814
• 关键词: Address; Adult; Adverse effects; Affect; Alcohol consumption; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Biological Clocks; Blood Circulation; Budgets; Cardiovascular Diseases; Cardiovascular system; Circadian Rhythms; Clinical Trials; Congresses; Data; Diabetes Mellitus; Disease; Dose; Exhibits; Exploratory/Developmental Grant; Exposure to; Foundations; Future; Goals; Health; Healthcare; Heavy Drinking; Hour; Human; Inflammation; Injury; Intervention; Knowledge; Lead; Light; Liver diseases; Malignant Neoplasms; Measures; Melatonin; Mental Depression; Mental Health; Metabolic; National Institute on Alcohol Abuse and Alcoholism; Obesity; Pathology; Pathway interactions; Performance; Personal Satisfaction; Phase; Placebos; Population; Productivity; Property; Protocols documentation; Public Health; Recording of previous events; Relapse; Reporting; Research; Research Design; Risk; Rodent; Sleep; Sleep Disorders; Sleep disturbances; System; Testing; Time; Tissues; Translating; United States National Institutes of Health; Woman; alcohol effect; alcohol related problem; circadian pacemaker; cost; design; drinking; improved; lifestyle factors; light treatment; men; novel; physical conditioning; problem drinker; public health relevance; response; social

DESCRIPTION (provided by applicant): Excessive alcohol consumption is a significant public health burden that affects 30% of the population at some point in their lives, contributes to multiple diseases including liver disease, cardiovascular disease, obesity, diabetes and cancer, and is estimated to cost $24.6 billion in health care and $161.3 billion in lost productivity annually. Even the social drinking that 50-70% of the adult US population engages in is associated with health risks. One causative pathway between heavier alcohol consumption and disease may be circadian misalignment because excessive alcohol consumption delays circadian rhythms, leading to sleep disturbance, and worse physical (inflammation, metabolic, cardiovascular) and mental health (depression, performance). Precisely how excessive alcohol consumption leads to circadian misalignment remains to be determined. Studies in rodents have demonstrated that alcohol directly impacts the central circadian pacemaker's response to light. However, the effect of alcohol on the circadian response to light in humans is not known. We propose two novel within-subjects design studies to determine if alcohol alters phase shifts to light in humans. Specific Aim 1 is to determine if alcohol alters circadian phase delays in response to late night light in healthy humans (n=15). Specific Aim 2 is to determine if alcohol alters circadian phase advances in response to morning light in healthy humans (n=15). An exploratory aim is to determine if the effect of alcohol on phase shifts to light is different in mn versus women. Our preliminary data suggests that a single dose of alcohol can alter phase shifts to light in humans. These studies will provide a critically needed mechanistic understanding of how alcohol may produce circadian misalignment in humans. The results will also provide an important foundation for future clinical trials which can (1) determine if phase shifts to light in abstinent alcoholics are abnormal and (2) test nonaddictive, affordable and accessible chronobiological treatments (evening exogenous melatonin and/or enhanced morning light exposure) to reduce circadian misalignment and improve health. This R21 application answers PA-11-179 Circadian Rhythms and Alcohol Induced Tissue Injury which calls for "exploratory/developmental grant applications that propose to conduct mechanistic studies of circadian rhythms...appropriate topics include alcohol's effects on circadian rhythms". This research also addresses goals set forth in the recent 2011 NIH Sleep Disorders Research Plan to "advance the understanding of circadian functions and basic circadian mechanisms...identify lifestyle factors [e.g. alcohol] contributing to the risk of circadian disturbances". Finally, this research directly addresses a goal of the NIAAA as outlined in the FY 2013 NIAAA Budget Justification to Congress to: "reduce alcohol-related problems focus on identification of mechanisms by which alcohol causes pathologies".

描述（由申请人提供）：过量饮酒是一项重大的公共健康负担，在一生中的某个阶段影响着 30% 的人口，导致多种疾病，包括肝病、心血管疾病、肥胖、糖尿病和癌症，据估计每年医疗保健费用为 246 亿美元，生产力损失为 1,613 亿美元。即使 50-70% 的美国成年人参与的社交饮酒也与健康风险有关。大量饮酒与疾病之间的原因之一可能是昼夜节律失调，因为过量饮酒会延迟昼夜节律，导致睡眠障碍，以及身体（炎症、代谢、心血管）和心理健康（抑郁、表现）恶化。过量饮酒究竟如何导致昼夜节律失调仍有待确定。对啮齿动物的研究表明，酒精直接影响中央昼夜节律起搏器对光的反应。然而，酒精对人类对光的昼夜节律反应的影响尚不清楚。我们提出了两项​​新颖的受试者内设计研究，以确定酒精是否会改变人类对光的相移。具体目标 1 是确定酒精是否会改变健康人 (n=15) 对深夜光的反应的昼夜节律相位延迟。具体目标 2 是确定酒精是否会改变健康人 (n=15) 对晨光的昼夜节律提前。一个探索性的目的是确定酒精对光相移的影响在男性和女性中是否不同。我们的初步数据表明，单剂量的酒精可以改变人类对光的相移。这些研究将为酒精如何导致人类昼夜节律失调提供迫切需要的机制理解。这些结果还将为未来的临床试验提供重要基础，这些临床试验可以（1）确定戒酒者向光的相移是否异常，以及（2）测试非成瘾性、负担得起且易于使用的时间生物学治疗（晚上外源性褪黑激素和/或增强晨光）暴露）以减少昼夜节律失调并改善健康。此 R21 申请回答了 PA-11-179 昼夜节律和酒精引起的组织损伤，该申请呼吁“提出对昼夜节律进行机械研究的探索性/发展性拨款申请……适当的主题包括酒精对昼夜节律的影响”。这项研究还涉及最近 2011 年 NIH 睡眠障碍研究计划中提出的目标，即“增进对昼夜节律功能和基本昼夜节律机制的理解……确定导致昼夜节律紊乱风险的生活方式因素（例如酒精）”。最后，这项研究直接解决了 NIAAA 的目标，如 2013 财年 NIAAA 向国会提交的预算理由中概述的那样：“减少与酒精相关的问题，重点是确定酒精引起病理的机制”。