Sleep and circadian rhythm phenotypes and mechanisms associated with opioid use disorder treatment outcomes

阿片类药物使用障碍（OUD）是一种迅速升级的公共卫生危机，最近的证据表明， 去年70%的药物过量都与阿片类药物有关。虽然许多人寻求治疗OUD 超过一半的人在维持阿片类药物使用障碍（MOUD）药物治疗的情况下恢复使用， 迫切需要确定与OUD复发相关的因素。长期使用阿片类药物 与睡眠连续性和结构紊乱有关，增加了睡眠呼吸障碍（SDB）的风险， 以及昼夜节律的替代指标异常。然而，对纵向的了解较少。 OUD治疗个体中睡眠/昼夜节律表型与非药物阿片类药物使用的相关性，以及 可能解释这些关联的可塑性通路。这些知识对于为翻译提供信息至关重要 研究和开发新的干预措施，旨在改善睡眠，昼夜节律和OUD 成果。拟议的观察性纵向研究将利用现有的合作， 基于社区的提供者来确定睡眠持续时间、睡眠架构、SDB和代理的关联 治疗期间非法阿片类药物使用的昼夜节律的测量，以及潜在的途径（例如，积极和 负面影响），可能会影响这些关系。受试者（N = 130）将入组丁丙诺啡 或美沙酮治疗，并完成为期6个月的纵向研究，其中他们将完成过夜，在实验室 多导睡眠图（PSG）会话三次以评估睡眠度量随时间的变化（例如，总睡眠 时间、睡眠结构、SDB）。在PSG治疗前后，我们将收集参与者的唾液样本， 来测定皮质醇的昼夜变化参与者还将配备一个腕戴式腕动记录设备， 量化睡眠和昼夜休息活动节律。在基线和每个月的最后一周， 治疗后，参与者将完成为期一周的“数据突发”，其中包括生态瞬时评估 情感渴望和压力参与者将完成尿液毒理学筛查并自我报告其药物 在每个数据突发结束时使用。研究的具体目的是（目的1）确定双向 昼夜RAR和昼夜皮质醇模式与非医疗阿片类药物使用的关联，（目的2）研究 治疗过程中的睡眠持续时间和结构是否与非药物阿片类药物有关 使用，以及（目标3）检查（a）MOUD使用与SDB的关联，以及（B）SDB是否与低 积极的情感和高度的消极情感。我们还将探讨是否有临床意义的睡眠和昼夜节律 节律表型与低积极情感、高消极情感和非医疗阿片类药物使用相关， 情感过程是否介导睡眠/昼夜节律表型和阿片类药物使用的关联。 该项目的发现将增强我们对特定睡眠和昼夜节律参数的理解 参与OUD，以及睡眠表型，情感过程和非医学阿片类药物之间的关系 使用.这项高度严格的研究将阐明未来干预试验的临床相关终点。

Opioid use disorder (OUD) is a rapidly escalating public health crisis with recent evidence suggesting that close to 70% of drug overdoses involved opioids in the last year. Although many individuals seek treatment for OUD over half return to use despite being maintained on a medication for opioid use disorder (MOUD), underscoring the critical need to identify factors that are associated with OUD reoccurrence. Chronic opioid use has been linked to disturbances in sleep continuity and architecture, increased risk of sleep disordered breathing (SDB), and abnormalities in proxy measures of circadian rhythms. However, less is known about the longitudinal association of sleep/circadian phenotypes with non-medical opioid use among individuals in OUD treatment, and malleable pathways that may account for these associations. Such knowledge is critical to informing translational research and the development of novel interventions aimed at improving sleep, circadian rhythms, and OUD outcomes. The proposed observational, longitudinal study will capitalize on existing collaborations with community-based providers to determine the association of sleep duration, sleep architecture, SDB, and proxy measures of circadian rhythms with illicit opioid use during treatment, and potential pathways (e.g., positive and negative affect) that may influence these relationships. Participants (N = 130) will be enrolled in buprenorphine or methadone treatment and complete a 6-month longitudinal study wherein they will complete overnight, in-lab polysomnography (PSG) sessions three times to assess changes over time in sleep metrics (e.g., total sleep time, sleep architecture, SDB). Before and after PSG sessions, we will collect saliva samples from participants to determine diurnal cortisol patterns. Participants will also be fitted with a wrist-worn actigraphy device to further quantify sleep and circadian rest activity rhythms. At baseline and during the final week of each month of treatment, participants will complete a week-long “data burst” that includes ecological momentary assessments of affect, craving, and stress. Participants will complete urine toxicology screens and self-report on their drug use at the end of each data burst. Specific aims of the study are to (Aim 1) determine the bi-directional association of circadian RARs and diurnal cortisol patterns with non-medical opioid use, (Aim 2) investigate whether sleep duration and architecture over the course of treatment are associated with non-medical opioid use, and (Aim 3) examine (a) associations of MOUD use with SDB, and (b) whether SDB is associated with low positive affect and high negative affect. We will also explore whether clinically significant sleep and circadian rhythm phenotypes are associated with low positive affect, high negative affect, and non-medical opioid use, and whether affective processes mediate the association of sleep/circadian rhythm phenotypes and opioid use. Findings from this project will enhance our understanding of specific sleep and circadian rhythms parameters implicated in OUD, and the relationships among sleep phenotypes, affective processes, and non-medical opioid use. This highly rigorous study will shed light on clinically relevant endpoints for future intervention trials.