Alcohol Alters the Circadian Response to Light in Humans

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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".