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

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.