Dopamine Metabolism and Nonpharmacologic Insomnia Interventions Among Cancer Survivors

癌症幸存者的多巴胺代谢和非药物性失眠干预

• 批准号: 10512800
• 负责人: JUN J MAO
• 金额: $ 24.82万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10512800
• 关键词: 3,4-Dihydroxyphenylacetic Acid; Acupuncture Therapy; Address; Affect; Alleles; Amino Acids; Animals; Aromatic Amino Acids; Behavior Therapy; Behavioral; Behavioral Mechanisms; Binding; Bioinformatics; Biological; Blood specimen; Brain; Branched-Chain Amino Acids; Cancer Survivor; Catabolism; Catechol O-Methyltransferase; Chronic stress; Clinical; Cognitive Therapy; Development; Dopamine; Environment; Enzymes; Exhibits; Gastritis; Gene Expression Regulation; General Population; Genetic Polymorphism; Genomics; Genotype; Gold; Grant; Health; Homovanillic Acid; Hyperglycemia; Hyperlipidemia; Hypertension; Insulin; Integrative Medicine; Intervention; Link; Lipids; Literature; Maintenance; Menopause; Mental Depression; Metabolic; Metabolic syndrome; Metabolism; Methylation; Molecular; Neurobiology; Nonpharmacologic Therapy; Norepinephrine; Pathway interactions; Patients; Personal Satisfaction; Phenotype; Phenylalanine; Physiological; Plasma; Play; Population; Process; Proteins; Psychiatry; Quality of life; Randomized Controlled Trials; Research; Research Personnel; Risk; Role; Sampling; Schizophrenia; Science; Scientist; Serotonin; Severities; Shapes; Sleep; Sleep Wake Cycle; Sleep disturbances; Sleeplessness; Synapses; Techniques; Technology; Therapeutic Effect; Time; Tryptophan; Tyrosine; United States; Variant; Work; Yang; anticancer research; antidepressant effect; base; behavioral phenotyping; cardiometabolism; comparative effectiveness trial; dopamine system; experience; fatty acid metabolism; genomic locus; hypnotic; improved; innovation; insight; member; metabolic profile; metabolome; metabolomics; multidisciplinary; neurotransmission; new technology; novel; novel strategies; personalized management; poor sleep; response; sample collection; success; systematic review; treatment response; tumor metabolism; uptake

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.

项目概要 失眠在癌症幸存者中很常见并且使人衰弱。虽然睡眠对新陈代谢有不利影响 对于一般人群来说，其对癌症幸存者的影响很少被探讨。代谢组学的进展 技术提供了了解全身代谢健康的新策略，它有能力 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，我们证明了失眠认知行为疗法（CBT-I）和针灸 导致癌症幸存者的失眠得到持续且具有临床意义的改善。虽然 CBT-I 总体而言，对于减轻失眠严重程度，针灸比针灸更有效 比 CBT-I 更能改善总睡眠时间。最近，我们发现rs4680基因多态性 儿茶酚邻甲基转移酶（COMT）与针灸治疗反应相关，但与针灸治疗反应无​​关。 CBT-I。由于 COMT 是决定多巴胺分解代谢效率的关键酶，因此我们假设 经过八周的针灸治疗后，与多巴胺相关的代谢特征将发生改变 在患有失眠症的癌症幸存者中进行 CBT-I。利用现有的样本集合和我们的 内部代谢组分析能力，我们汇集了多学科的科学家团队进行综合分析 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 评估针灸与 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捕获额外的代谢 与针灸或 CBT-I 相关的特征（目标 2）。我们的跨学科工作将发现新颖的 失眠综合和行为干预的代谢特征。此外，我们的整合 组学科学向综合医学的转变代表着一种范式转变，转向更加基于机制和 针对癌症幸存者的精准睡眠研究。经验丰富的人员可提供即用型血液样本 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 研究是 高度可行，成功的可能性很大。所提出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，为更多的发展提供信息 有效、高效、个性化地管理失眠，促进更好的代谢健康，这是 对癌症幸存者的健康和福祉至关重要。