Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation

项目摘要/摘要 美国的阿片类药物流行每年造成超过1.5T美元的损失和超过7.5万人的死亡。未被充分研究的风险因素 对于阿片使用障碍(OUD)及其治疗是睡眠和昼夜节律(CR)的重要性。 阿片类药物以抑制恢复的方式影响睡眠质量，而睡眠仍然是一个关键因素，即使在 患者接受治疗：两种最有效的药物也会导致睡眠问题 这导致了次优的结果。要解决阿片类药物流行的巨大代价，至关重要的是 了解多动症、睡眠不良和负性情绪之间关系的潜在机制 结果。因此，我们的中心假设是对睡眠和昼夜节律表型的检查将有助于 在Moud上确定将从特定干预中受益的个人。双向性的刻画 睡眠行为、睡眠结构、昼夜节律和神经认知测量之间的相互作用 Moud上的个人是确定潜在机制或可修改变量的关键第一步 改善Moud的结果。识别特定类型的睡眠/昼夜节律中断可能会突出显示 解决相关睡眠问题的辅助治疗选择(例如，认知行为治疗 失眠)。此外，霉菌会扰乱睡眠，但尚不清楚这是通过CR或CR的改变实现的 睡眠行为/结构的改变。睡眠/CR科学为分离提供了实验方法 昼夜节律来自睡眠生理学的90分钟一天的形式。先前的工作突出了神经认知 表型，渴望和情绪调节(ER)，这是成功的Moud结果的关键。食欲 既是一种不良症状，也是复发的常见预测指标。睡眠质量可能通过以下途径影响渴望 积极和消极的影响，强调ER是Moud的关键问题，因为患者报告 不能将情绪调节作为使用和复发的主要动机。睡眠不佳与 减少ER。在Moud上的100个人中，我们将1)评估(A)自然发生的睡眠模式，使用 在睡眠实验室通过多导睡眠图记录进行一周的活动监测和(B)睡眠生理学 为跨研究站点的共同目标做出贡献，并提供描述性分析；2)检查睡眠 和昼夜节律表型，使用通过动作图、PSG和90分钟一天方案收集的变量来 检查这些表型与神经认知机制的关系，这些神经认知机制可能会影响OUD的结果 治疗包括渴求和情绪调节；3)采用定性的方法调查 针对特定机制关系的干预措施的可接受性、可行性和感知效用 假设的。总而言之，我们计划对睡眠/昼夜节律之间的新通路进行全面检查 节奏和神经认知因素-渴望和情绪调节-作为推测的穆德成功的关键 支持睡眠质量差和治疗效果不佳之间联系的机制。

Project Summary/Abstract The US opioid epidemic costs over $1.5T and over 75,000 deaths annually. An understudied risk factor for opioid use disorder (OUD) and its treatment is the importance of sleep and circadian rhythms (CR). Opioids impact sleep quality in a fashion that inhibits recovery, and sleep remains a critical factor even when patients enter treatment: the two most efficacious medications for OUD (MOUD) also cause sleep problems that contribute to suboptimal outcomes. To address the enormous costs of the opioid epidemic, it is essential to understand the mechanisms underlying the relationship between MOUD, poor sleep, and negative outcomes. Thus, our central hypothesis is that examination of sleep and circadian phenotypes, will help to identify individuals on MOUD who will benefit from specific interventions. Characterization of the bidirectional interplay between sleep behaviors, sleep architecture, circadian rhythms, and neurocognitive measures in individuals on MOUD is a crucial first step in identifying potential mechanisms or modifiable variables to improve MOUD outcomes. Identifying the specific type of sleep/circadian disruption by MOUD may highlight adjunctive treatment options to address the relevant sleep problem (e.g., cognitive behavioral therapy for insomnia). Moreover, MOUDs disrupt sleep, but it is not known whether this is via alterations of CR or alterations of sleep behavior/architecture. Sleep/CR science provides experimental methods for separating circadian timing from sleep physiology in the form of the 90-minute day. Prior work highlights neurocognitive phenotypes, craving and emotion regulation (ER), that are critical for successful MOUD outcomes. Cravings are both an OUD symptom and frequent predictor of relapse. Sleep quality affects craving possibly through positive and negative affect, emphasizing that ER is of critical concern with MOUD, as patients report an inability to regulate emotions as a primary motivation for use and for relapse. Poor sleep is associated with diminished ER. In 100 individuals on MOUD we will 1) evaluate (a) naturally occurring sleep patterns using activity monitoring for one week and (b) sleep physiology through polysomnographic recording in the sleep lab to contribute to the common aim across research sites and to provide descriptive analyses; 2) examine sleep and circadian phenotypes using variables collected via actigraphy, PSG, and the 90-min day protocol to examine associations of these phenotypes with neurocognitive mechanisms that may impact outcome of OUD treatment including craving and emotion regulation; and 3) use qualitative methods to investigate the acceptability, feasibility, and perceived utility of interventions targeting the specific mechanistic relationships hypothesized. In summary, we plan a comprehensive examination of novel pathways between sleep/circadian rhythms and neurocognitive factors —craving and emotion regulation—critical to success in MOUD as putative mechanisms underpinning the association of poor sleep and suboptimal treatment outcomes.