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健康危机，最近的证据表明 去年，70%的药物过量涉及阿片类药物。尽管许多人寻求治疗OUD 超过一半的人尽管继续服用阿片类药物使用障碍(Moud)，但仍恢复使用，强调 迫切需要确定与OUD复发相关的因素。慢性阿片类药物的使用 与睡眠连续性和睡眠结构障碍有关，增加睡眠呼吸紊乱(SDB)的风险， 以及昼夜节律的替代测量中的异常。然而，对于纵向的 在OUD治疗的个体中，睡眠/昼夜节律表型与非医用阿片类药物使用的相关性 可以解释这些关联的延展性路径。这样的知识对于告知翻译是至关重要的 研究和开发旨在改善睡眠、昼夜节律和OUD的新型干预措施 结果。拟议的观察性纵向研究将利用现有的与 基于社区的提供商，以确定睡眠持续时间、睡眠架构、SDB和代理之间的关联 衡量治疗期间非法使用阿片类药物的昼夜节律，以及可能的途径(例如，积极和 负面影响)，这可能会影响这些关系。参与者(N=130)将参加丁丙诺啡 或美沙酮治疗，并完成为期6个月的纵向研究，在此研究中，他们将在实验室过夜完成 多导睡眠图(PSG)三次，以评估睡眠指标随时间的变化(例如，总睡眠 时间、睡眠架构、SDB)。在PSG会议之前和之后，我们将收集参与者的唾液样本 以确定皮质醇的昼夜模式。参赛者还将佩戴手腕上的动作记录仪，以进一步 量化睡眠和昼夜休息活动节律。在每个月的基线和最后一周 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。参与者将完成尿毒学筛查和药物自我报告 在每个数据突发的末尾使用。研究的具体目标是(目标1)确定双向 昼夜RARs和昼夜皮质醇模式与非医用阿片类药物使用的关系，(目标2)调查 睡眠时间和治疗过程中的结构是否与非医用阿片类药物有关 使用，并(目标3)检查(A)使用Moud与SDB的关联，以及(B)SDB是否与Low相关联 积极情感和高度消极情感。我们还将探索临床上有意义的睡眠和昼夜节律 节律表型与低积极情绪、高负面情绪和非药物阿片类药物使用有关，以及 情感过程是否在睡眠/昼夜节律表型和阿片类药物使用之间起中介作用。 这个项目的发现将加强我们对特定睡眠和昼夜节律参数的理解 与OUD有关，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。这项高度严谨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.