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 pro-inflammatory 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 pro-inflammatory 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.
Key words:
Insomnia, Inflammation, Cognitive behavioral therapy, Tai Chi, Gene expression, Aging
