Cognitive Behavioral Therapy and Tai Chi Reverse Cellular and Genomic Markers of Inflammation in Late-Life Insomnia: A Randomized Controlled Trial

Abstract

Background Sleep disturbance is associated with activation of systemic and cellular inflammation, as well as pro-inflammatory transcriptional profiles in circulating leukocytes. Whether treatments that target insomnia-related complaints might reverse these markers of inflammation in older adults with insomnia is not known. Methods In this randomized trial, 123 older adults with insomnia were randomly assigned to cognitive behavioral therapy for insomnia (CBT-I), tai chi chih (TCC), or sleep seminar education active control condition (SS) for two hour sessions weekly over 4 months with follow-up at 7- and 16-months. We measured C-reactive protein (CRP) at baseline, month 4 and 16, Toll-like receptor-4 (TLR-4)-activated monocyte production of proinflammatory cytokines at baseline, month 2, 4, 7, and 16, and genome-wide transcriptional profiling at baseline and month 4. Results As compared to SS active control, CBT-I reduced levels of CRP (month 4, 16, P’s<0.05), monocyte production of proinflammatory cytokines (month 2 only, P<0.05), and pro-inflammatory gene expression (month 4, P<0.01). TCC marginally reduced CRP (month 4, P=0.06), and significantly reduced monocyte production of proinflammatory cytokines (month 2, 4, 7, 16, all P’s<0.05) and proinflammatory gene expression (month 4, P<0.001). In CBT and TCC, TELIS promoter-based bioinformatics analyses indicated reduced activity of nuclear factor (NF)-κB and AP1. Conclusions Among older adults with insomnia, CBT-I reduced systemic inflammation, TCC reduced cellular inflammatory responses, and both treatments reduced expression of genes encoding proinflammatory mediators. The findings provide an evidence-based molecular framework to understand the potential salutary effects of insomnia treatment on inflammation, with implications for inflammatory disease risk.

Sleep Disturbance, Daytime Symptoms, and Functional Performance in Patients With Stable Heart Failure

“…For example, cognitive behavioral therapy for insomnia produced large effects on fatigue among HF patients (Redeker et al, 2015), and improved biomarkers of cardiac risk (Carroll et al, 2015; Irwin et al, 2015; Irwin et al, 2014) among a sample of older adults of whom the majority had cardiovascular disorders. Meditation and guided imagery may also be efficacious in improving sleep and sleep-related symptoms among these patients (Kwekkeboom & Bratzke, 2015).…”

Genetic Pathways to Insomnia

“…Positive changes in immune-related genes (i.e., lower expression of inflammatory cytokines, increases in regulatory genes), implication of the ubiquitin pathway (via pathway analysis) and improvement in depression symptoms were all seen in the improved sleep group, providing insight into the molecular changes that occur with successful insomnia interventions. Further, Irwin and colleagues [95] examined the effects of several insomnia interventions (CBT-I, tai chi) on levels of inflammatory markers in a randomized control trial design using older individuals. Both interventions resulted in positive changes.…”

The impact of drugs for multiple sclerosis on sleep

“…Given that both MS and sleep disruption generate pro-inflammatory cytokine profiles, it would be intriguing to assess how co-morbid sleep disturbances affect the cytokine profile, and whether treatment for sleep disorders would be able to modulate the levels of systemic and cellular proinflammatory mediators and the leukocyte expression of pro-inflammatory genes. Interestingly, a recent randomized controlled trial found that CBT and tai chi reversed cellular and genomic markers of inflammation in older adults with insomnia, 51 thus providing an evidence-based molecular framework to understand the potential effects of insomnia treatment on inflammation. Moreover, CBT for insomnia had the additional effect of increasing activity of IFNresponsive transcription factors, 51 consistent with prior findings that CBT increases ex vivo production of IFN.…”

“…Interestingly, a recent randomized controlled trial found that CBT and tai chi reversed cellular and genomic markers of inflammation in older adults with insomnia, 51 thus providing an evidence-based molecular framework to understand the potential effects of insomnia treatment on inflammation. Moreover, CBT for insomnia had the additional effect of increasing activity of IFNresponsive transcription factors, 51 consistent with prior findings that CBT increases ex vivo production of IFN. 52 These findings have potential crucial implications for inflammatory diseases and immuno-mediated CNS disorders, such as MS. Large, prospective, multicenter, cohort studies, using both subjective questionnaire and objective polysomnographic data, are mandatory to address these points.…”