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

研究阿片类激动剂治疗 OUD 患者结果的机制：解开睡眠和昼夜节律对渴望和情绪调节的影响

• 批准号: 10784209
• 负责人: Mary A Carskadon
• 金额: $ 118.41万
• 依托单位: EMMA PENDLETON BRADLEY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10784209
• 关键词: Address; Affect; Architecture; Behavior; Buprenorphine; Cessation of life; Characteristics; Circadian Dysregulation; Circadian Rhythms; Cognitive Therapy; Dose; Ecological momentary assessment; Electroencephalography; Emotions; Financial cost; Human; Individual; Intervention; Link; Measures; Melatonin; Methadone; Methods; Monitor; Motivation; Neurocognitive; Opioid; Opioid agonist; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phenotype; Polysomnography; Population; Protocols documentation; Qualitative Methods; Recovery; Relapse; Reporting; Research; Risk Factors; Science; Site; Sleep; Sleep Architecture; Sleep Disorders; Sleep disturbances; Sleeplessness; Symptoms; Treatment outcome; Work; actigraphy; addiction; biological sex; circadian; cost; craving; emotion regulation; improved; insight; medication for opioid use disorder; negative affect; novel; opioid agonist therapy; opioid epidemic; opioid use disorder; poor sleep; relapse prediction; sleep behavior; sleep pattern; sleep physiology; sleep quality; success; targeted treatment; therapy design; therapy development; treatment adherence; Address; Affect; Architecture; Behavior; Buprenorphine; Cessation of life; Characteristics; Circadian Dysregulation; Circadian Rhythms; Cognitive Therapy; Dose; Ecological momentary assessment; Electroencephalography; Emotions; Financial cost; Human; Individual; Intervention; Link; Measures; Melatonin; Methadone; Methods; Monitor; Motivation; Neurocognitive; Opioid; Opioid agonist; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phenotype; Polysomnography; Population; Protocols documentation; Qualitative Methods; Recovery; Relapse; Reporting; Research; Risk Factors; Science; Site; Sleep; Sleep Architecture; Sleep Disorders; Sleep disturbances; Sleeplessness; Symptoms; Treatment outcome; Work; actigraphy; addiction; biological sex; circadian; cost; craving; emotion regulation; improved; insight; medication for opioid use disorder; negative affect; novel; opioid agonist therapy; opioid epidemic; opioid use disorder; poor sleep; relapse prediction; sleep behavior; sleep pattern; sleep physiology; sleep quality; success; targeted treatment; therapy design; therapy development; treatment adherence

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.

项目摘要/摘要 美国阿片类药物流行的费用超过1.5吨，每年造成75,000多人死亡。理解的风险因素 对于卵毒素使用障碍（OUD），其治疗是睡眠和昼夜节律（CR）的重要性。 阿片类药物以抑制康复的方式影响睡眠质量，即使在 患者进入治疗：两种最有效的OUD药物（MOUD）也会引起睡眠问题 这导致了次优的结果。为了解决阿片类药物流行的巨大成本，这是必不可少的 了解穆德，睡眠不良和负面关系之间关系的机制 结果。这是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 确定将从特定干预措施中受益的穆德个人。双向的表征 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 改善穆德的结果。识别穆德的特定类型的睡眠/昼夜节律破坏可能会突出显示 解决相关睡眠问题的辅助治疗方案（例如，认知行为疗法 失眠）。此外，MOUDS破坏了睡眠，但尚不清楚这是通过CR的改变还是 睡眠行为/建筑的改变。睡眠/CR科学提供了分离的实验方法 90分钟一天的形式，睡眠生理学的昼夜节律时间。先前的工作突出了神经认知 表型，渴望和情感调节（ER）对于成功的穆德结果至关重要。渴望 既是OUD症状，又经常预测浮雕。睡眠质量会影响渴望 正面和负面影响，强调ER对MOUD至关重要，因为患者报告了 无法调节情绪作为使用和缓解的主要动机。睡眠不佳与 ER减少。在MOUD上的100个人中，我们将1）评估（a）使用自然发生的睡眠方式 活动监测一周，（b）睡眠生理学通过睡眠实验室中的多疗法记录 为跨研究地点的共同目标做出贡献，并提供描述性分析； 2）检查睡眠 使用通过行动摄影，PSG和90分钟的日期协议收集的变量和昼夜节律表型 检查这些表型与可能影响OUD结果的神经认知机制的关联 包括渴望和情绪调节的治疗； 3）使用定性方法调查 针对特定机械关系的干预措施的可接受性，可行性和可感知的效用 假设。总而言之，我们计划对睡眠/昼夜节律之间的新途径进行全面检查 节奏和神经认知因素 - 渴望和情感调节 - 至关重要的 睡眠不良和次优治疗结果的关联的机制。