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: 10654842
• 负责人: JUN J MAO
• 金额: $ 20.27万
• 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/10654842
• 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; Discipline; Dopamine; Environment; Enzymes; Exhibits; Gastritis; Gene Expression Regulation; General Population; Genetic Polymorphism; Genomics; Genotype; Grant; Health; Homovanillic Acid; Hyperglycemia; Hyperlipidemia; Hypertension; Insulin Resistance; 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; Regulation; 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; anticancer research; antidepressant effect; behavioral phenotyping; cardiometabolism; comparative effectiveness trial; dopamine system; experience; fatty acid metabolism; genomic locus; hypnotic; improved; improvement on sleep; 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.

项目摘要 失眠是常见的，并且在癌症幸存者中衰弱。虽然睡眠对新陈代谢有害 一般人群，其影响很少在癌症幸存者中探索。代谢组学的进步 技术提供了了解系统性代谢健康的新颖策略，该健康具有 揭示环境暴露和基因法规对行为表型的影响。在我们的随机中 对照试验，我们证明了失眠（CBT-I）和针灸的认知行为疗法 导致癌症幸存者的持续和临床有意义的失眠。虽然CBT-I 总体而言，针灸比针灸更有效，针灸更有效 比CBT-I改善了总睡眠时间。最近，我们发现遗传多态性rs4680 儿茶酚-O-甲基转移酶（COMT）与针灸的治疗反应有关，但与 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 针灸相对八周后，多巴胺相关的代谢特征将改变 在失眠的癌症幸存者中对CBT-I进行。利用现有的样本集和我们的 内部代谢组分分析能力，我们将一个多学科的科学家团队汇集在一起 以及行为睡眠研究，代谢组学和生物信息学使用目标代谢组学策略 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，我们将使用非目标的代谢组学方法来捕获其他代谢 与针灸或CBT-I相关的签名（AIM 2）。我们的跨学科工作将确定小说 失眠的综合和行为干预的代谢特征。此外，我们的整合 OMICS科学纳入综合医学代表了向更基于机制的范式转变 针对癌症幸存者的精确睡眠研究。有了有经验的血液样本 多学科团队，以及用于拟议分析的内部设施，这项R21研究是 高度可行的，成功的可能性很大。提出的代谢组分分析可以进一步帮助 发现行为和综合干预措施的潜在机制，以告知更多 有效，高效和个性化的失眠管理，并促进更好的代谢卫生 对癌症幸存者的健康和福祉至关重要。