Dopamine Metabolism and Nonpharmacologic Insomnia Interventions Among Cancer Survivors

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.