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.