Dopamine Metabolism and Nonpharmacologic Insomnia Interventions Among Cancer Survivors

项目摘要 失眠在癌症幸存者中很常见，令人虚弱。虽然睡眠对人体的新陈代谢有不利影响 在普通人群中，它的影响很少在癌症幸存者中被探索。代谢组学研究进展 科技为理解系统代谢健康提供了新的策略，它具有以下能力 揭示环境暴露和基因调控对行为表型的影响。在我们随机化的 对照试验，我们证明了认知行为疗法(CBT-I)和针灸都可以治疗失眠 导致癌症幸存者失眠的持续和有临床意义的改善。尽管CBT-I 在降低失眠严重程度方面总体上比针灸更有效，针灸更有效 在改善总睡眠时间方面优于CBT-I。最近，我们发现猪的遗传多态rs4680 儿茶酚-O-甲基转移酶(COMT)与针灸疗效相关，但与针灸疗效无关 CBT-I。由于COMT是决定多巴胺分解代谢效率的关键酶，我们假设 针灸治疗8周后，与多巴胺相关的代谢特征将发生改变 对患有失眠的癌症幸存者进行CBT-I。利用现有的样本集合和我们的 内部代谢分析能力，我们汇聚了一支多学科的科学家团队 以及行为睡眠研究、代谢组学和生物信息学，以使用定向代谢组学策略来 评价针刺与CBT-I对多巴胺系统下游代谢变化的影响 (目标1)。此外，我们将使用非靶向代谢组学方法来获取更多的代谢 与针灸或CBT-I相关的信号(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 组学科学进入综合医学代表着一种范式的转变，即更多地基于机制和 针对癌症幸存者的精确睡眠研究。有了现成的血液样本，经验丰富的 多学科团队，以及非常便于进行拟议分析的内部设施，这项R21研究是 非常可行，成功的可能性很大。建议的新陈代谢分析可以进一步帮助 揭示行为干预和综合干预的潜在机制，为制定更多 有效、高效和个性化地管理失眠，促进更好的新陈代谢健康，这是 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.