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

青春期后期的昼夜节律调整、奖励功能和饮酒

• 批准号: 8906710
• 负责人: Brant P. Hasler
• 金额: $ 21.47万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-10 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8906710
• 关键词: Adolescence; Adolescent; Affect; Alcohol abuse; Alcohol consumption; Brain; Circadian Dysregulation; Circadian Rhythms; Clinical Research; Conflict (Psychology); Data; Development; Ecological momentary assessment; Esthesia; Functional Magnetic Resonance Imaging; Grant; Health; Laboratories; Light; Measures; Melatonin; Methods; Modeling; National Institute on Alcohol Abuse and Alcoholism; Natural experiment; Pathway interactions; Patient Self-Report; Phase; Polysomnography; Population; Preventive Intervention; Prospective Studies; Public Health; Reporting; Research; Rest; Rewards; Risk; Salivary; Sampling; Scanning; Schedule; Sleep; Sleep Disorders; Staging; Time; actigraphy; alcohol involvement; alcohol use disorder; brain behavior; craving; design; experience; in vivo; innovation; neural correlate; neuroimaging; novel; prospective; relating to nervous system; response; reward circuitry; reward processing; underage drinking; young adult

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.

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会影响青春期和青春期酒精使用障碍(AUD)的发展。这一途径可能是双向的，因为酒精使用(AU)会扰乱睡眠和昼夜节律。然而，睡眠/昼夜节律功能与AU之间关系的确切机制仍不清楚，因此是本应用的重点。具体地说，我们假设青少年睡眠和昼夜节律紊乱导致奖赏功能失调(即，调节控制减弱， 更多的感觉寻求，和/或减少积极的情感)，这反过来导致更多的AU。我们建议的研究将检验睡眠/昼夜节律因素、奖励功能和AU之间的短期因果动态，从而为AUDS的新的预防和干预方法的发展提供信息。特别是，我们提出了一种前瞻性的、混合方法的方法，在32名报告了一系列当前AU的晚期青少年样本中。这种新颖的设计结合了最先进的活体方法(提高生态有效性和精确度，同时限制回忆偏见)和实验室方法(提高科学严谨性)。具体地说，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的客观测量(动作图，唾液褪黑激素)，以及(3)奖励回路功能的fMRI测量。我们的设计利用了工作日-周末睡眠、昼夜节律和AU变化的“自然实验”，进一步增强了有效性。我们将从周末前和周末后的所有三个领域收集数据，使我们能够检查睡眠、昼夜节律或昼夜节律是否在短期内预测AU，反之亦然。周末前后的fMRI扫描将使我们能够评估作为睡眠/昼夜节律因素和AU之间的中介变量的奖励功能的神经关联。具体目的1是研究在自然主义条件下，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绪、渴望和AU。具体目标2是研究在工作日-周末过渡期间睡眠/昼夜节律因素、AU和奖赏神经加工之间的动态联系。具体目标3是检查较晚的昼夜节律(更晚的夜晚)是否会使睡眠/昼夜节律因素与AU之间的有问题的相互作用变得脆弱。这项建议是对PA-12-178(NIAAA)的回应，旨在促进我们对青春期睡眠/昼夜节律功能和酒精使用(AU)之间动态相互作用的理解。这项新颖的研究将证明可行性，有助于改进我们的方法，并为随后的更大规模的拨款提供初步数据。总之，这项初步研究和随后的R01将具有重大影响和公共卫生意义，有可能在关键发展阶段阐明非盟问题的新机制。