Dopamine Metabolism and Nonpharmacologic Insomnia Interventions Among Cancer Survivors

项目摘要 在癌症幸存者中，虚弱是常见的，并且使人衰弱。虽然睡眠对新陈代谢有不利影响， 在一般人群中，很少在癌症幸存者中探索其影响。代谢组学研究进展 技术提供了新的战略，以了解系统的代谢健康，这拥有的权力， 揭示环境暴露和基因调控对行为表型的影响。在我们的随机 对照试验，我们证明了失眠的认知行为疗法（CBT-I）和针灸 在癌症幸存者中持续和临床上有意义的失眠改善。虽然CBT-I 总体而言，在减轻失眠严重程度方面， 比CBT-I改善总睡眠时间。最近，我们发现，rs 4680的遗传多态性， 儿茶酚-O-甲基转移酶（COMT）与针刺治疗反应相关，但与 CBT-I因为COMT是决定多巴胺催化效率的关键酶，我们假设， 针刺治疗8周后，多巴胺相关的代谢特征将发生改变， CBT-I在患有失眠症的癌症幸存者中的应用利用现有的样本收集和我们的 内部代谢组学分析能力，我们汇集了一个多学科的科学家团队， 和行为睡眠研究，代谢组学和生物信息学，使用有针对性的代谢组学策略， 评价针刺与CBT-I对多巴胺系统下游代谢变化的影响 (Aim 1）。此外，我们将使用非靶向代谢组学方法来捕获额外的代谢产物。 与针灸或CBT-I相关的特征（目标2）。我们的跨学科工作将确定新的 失眠综合和行为干预的代谢特征。此外，我们的整合 将组学科学纳入综合医学代表了一种范式转变， 针对癌症幸存者的精准睡眠研究有了现成的血液样本， 多学科团队，以及用于拟议分析的极其方便的内部设施，这项R21研究 非常可行，成功的可能性很大。拟议的代谢组学分析可以进一步帮助 揭示行为和综合干预的潜在机制，以告知更多的发展 有效，高效和个性化的失眠管理，促进更好的代谢健康， 对癌症幸存者的健康和福祉至关重要。

Project Summary Insomnia is common and debilitating in cancer survivors. While sleep has detrimental effects on metabolism in the general population, its impact has rarely been explored in cancer survivors. Advances in metabolomics technology offers novel strategies to understand systemic metabolic health, which possesses the power to reveal the effect of environment exposures and gene regulations on behavioral phenotypes. In our randomized controlled trial, we demonstrated that both cognitive behavioral therapy for insomnia (CBT-I) and acupuncture led to sustained and clinically meaningful insomnia improvements among cancer survivors. Although CBT-I was overall more effective than acupuncture for reducing insomnia severity, acupuncture was more effective than CBT-I for improving total sleep time. Recently, we found that the genetic polymorphism rs4680 of catechol-o-methyltransferase (COMT) was associated with treatment response for acupuncture but not for CBT-I. Because COMT is a key enzyme that determines dopamine catabolism efficiency, we hypothesize that the dopamine-related metabolic signatures will be altered after eight weeks of acupuncture treatment relative to CBT-I among cancer survivors with insomnia. Taking advantage of existing collections of samples and our in-house metabolomic analysis capacity, we bring together a multidiscipline team of scientists in integrative and behavioral sleep research, metabolomics, and bioinformatics to use a targeted metabolomics strategy to evaluate the effects of acupuncture versus CBT-I on downstream metabolic changes in the dopamine system (Aim 1). Additionally, we will use a non-targeted metabolomics approach to capture additional metabolic signatures associated with acupuncture or CBT-I (Aim 2). Our interdisciplinary work will identify novel metabolic signatures of integrative and behavioral interventions for insomnia. In addition, our integration of omics science into integrative medicine represents a paradigm shift towards more mechanism-based and precision-focused sleep research for cancer survivors. With ready-to-use blood samples, an experienced multidisciplinary team, and extremely accessible in-house facilities for the proposed analysis, this R21 study is highly feasible with a strong likelihood of success. The proposed metabolomic analysis can further help uncover underlying mechanisms of behavioral and integrative interventions to inform the development of more effective, efficient, and personalized management of insomnia, and promote better metabolic heath , which is critical to the health and wellbeing of cancer survivors.