Circadian alignment, reward function, and alcohol use during late adolescence

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DESCRIPTION (provided by applicant): A variety of evidence suggests that sleep, circadian rhythms, and circadian alignment influence the development of alcohol use disorders (AUDs) during adolescence and young adulthood. This pathway is likely bidirectional, given that alcohol use (AU) can disrupt sleep and circadian rhythms. However, the precise mechanisms underlying the relationships between sleep/circadian function and AU remain unknown, and thus are the focus of this application. Specifically, we hypothesize that adolescent sleep and circadian disturbances result in dysregulated reward function (i.e., diminished regulatory control, increased sensation seeking, and/or reduced positive affect), which in turn leads to increased AU. Our proposed study will examine the short-term causal dynamics between sleep/circadian factors, reward function, and AU, thereby informing the development of novel prevention and intervention approaches for AUDs. In particular, we propose a prospective, mixed-methods approach in a sample of 32 late adolescents reporting a range of current AU. The novel design combines state-of-the-art in vivo methods (to enhance ecological validity and precision, while limiting recall bias) and laboratory methods (to enhance scientific rigor). Specifically, we will collect (1) 14 days of ecological momentary assessment (self-reported affect, urges, and AU), (2) objective measurements of sleep and endogenous circadian timing (actigraphy, salivary melatonin), and (3) fMRI measures of reward circuitry function. Our design capitalizes on the "natural experiment" of weekday-weekend changes in sleep, circadian rhythms, and AU, further enhancing validity. We will collect data from all three domains both pre- and post-weekend, enabling us to examine whether sleep, circadian phase, or circadian alignment prospectively predict AU over the short term, and vice versa. The pre- and post-weekend fMRI scans will allow us to evaluate the neural correlates of reward function as an intervening variable between sleep/circadian factors and AU. Specific Aim 1 is to examine whether weekday sleep/circadian factors predict self-reported positive affect, craving, and AU on the weekend under naturalistic conditions. Specific Aim 2 is to examine the dynamic associations between sleep/circadian factors, AU, and neural processing of reward over the weekday-weekend transition. Specific Aim 3 is to examine whether later circadian timing (greater eveningness) confers vulnerability to problematic interactions between sleep/circadian factors and AU. This proposal, in response to PA-12-178 (NIAAA), aims to advance our understanding of the dynamic interactions between sleep/circadian function and alcohol use (AU) during adolescence. This novel study will demonstrate feasibility, help refine our methods, and provide preliminary data for a subsequent larger grant. Together, this preliminary study and the subsequent R01 will have substantial impact and public health significance, with the potential to elucidate novel mechanisms of AU problems at a key developmental stage.