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

描述（由申请人提供）：各种证据表明，睡眠、昼夜节律和昼夜节律调整影响青春期和青年期酒精使用障碍（AUD）的发展。这条通路可能是双向的，因为饮酒（Au）会扰乱睡眠和昼夜节律。然而，睡眠/昼夜节律功能和Au之间关系的确切机制仍然未知，因此是本申请的焦点。具体来说，我们假设青少年睡眠和昼夜节律紊乱导致奖励功能失调（即，减少监管控制， 增加的感觉寻求和/或减少的积极影响），这又导致增加的Au。 我们提出的研究将检查睡眠/昼夜因素，奖励功能和Au之间的短期因果动态，从而为AUD的新的预防和干预方法的发展提供信息。特别是，我们提出了一个前瞻性的，混合方法的方法，在一个样本的32晚青少年报告一系列当前Au。新的设计结合了最先进的体内方法（以提高生态有效性和精度，同时限制回忆偏差）和实验室方法（以提高科学严谨性）。具体而言，我们将收集（1）14天的生态瞬时评估（自我报告的影响，冲动和Au），（2）睡眠和内源性昼夜节律计时的客观测量（活动记录仪，唾液褪黑激素），（3）奖励电路功能的fMRI测量。我们的设计利用了“自然实验”，即睡眠、昼夜节律和Au的工作日-周末变化，进一步提高了有效性。我们将收集周末前和周末后所有三个领域的数据，使我们能够检查睡眠，昼夜节律相位或昼夜节律调整是否在短期内预测Au，反之亦然。周末前后的功能磁共振成像扫描将使我们能够评估奖励功能的神经相关性，作为睡眠/昼夜节律因素和Au之间的干预变量。具体目标1是研究在自然条件下，工作日睡眠/昼夜节律因素是否能预测周末自我报告的积极情感、渴望和Au。具体目标2是研究睡眠/昼夜因素，Au，和神经处理的奖励在工作日-周末过渡之间的动态关联。具体目标3是检查较晚的昼夜节律定时（更大的晚上度）是否赋予睡眠/昼夜节律因素和Au之间的有问题的相互作用的脆弱性。 该提案是对PA-12-178（NIAAA）的回应，旨在促进我们对青春期睡眠/昼夜节律功能与酒精使用（Au）之间动态相互作用的理解。这项新的研究将证明可行性，帮助改进我们的方法，并为随后的更大资助提供初步数据。总之，这项初步研究和随后的R 01将产生重大影响和公共卫生意义，有可能阐明Au问题在关键发展阶段的新机制。

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.