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 proinflammatory 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 for 2-hour sessions weekly over 4 months with follow-up at 7 and 16 months. We measured C-reactive protein (CRP) at baseline and months 4 and 16; toll-like receptor-4 activated monocyte production of proinflammatory cytokines at baseline and months 2, 4, 7, and 16; and genome-wide transcriptional profiling at baseline and month 4.

Results: As compared with sleep seminar education active control condition, CBT-I reduced levels of CRP (months 4 and 16, ps < .05), monocyte production of proinflammatory cytokines (month 2 only, p < .05), and proinflammatory gene expression (month 4, p < .01). TCC marginally reduced CRP (month 4, p = .06) and significantly reduced monocyte production of proinflammatory cytokines (months 2, 4, 7, and 16; all ps < .05) and proinflammatory gene expression (month 4, p < .001). In CBT-I and TCC, TELiS promoter-based bioinformatics analyses indicated reduced activity of nuclear factor-κB and AP-1.

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.

Trial registration: ClinicalTrials.gov NCT00280020.

Keywords: Aging; Cognitive-behavioral therapy; Gene expression; Inflammation; Insomnia; Tai chi.

Figure 1

Circulating Levels of CRP from Baseline to Month 16, by Treatment Group. Values are mean (SEM). Shaded area indicates period of administration of intervention following baseline assessment. Significant pairwise comparisons: *CBT vs SS P=0.02; +TCC vs SS P=0.06, #CBT vs TCC P=0.08

Figure 2

Toll-like 4 Receptor Stimulated Monocytic Production from Baseline to Month 16, by Treatment Group. Values are mean (SEM) percentage of monocytes producing IL-6 (A), TNF(B); or both IL-6 and TNF(C). Shaded area indicates period of administration of intervention following baseline assessment. Significant pairwise comparisons: *CBT vs SS P<0.05; +TCC vs SS P<0.05, #CBT vs TCC P<0.05

Figure 3

Transcription factor activity as measured by TELiS promoter-based bioinformatic analyses of genes at 4 months (post-intervention), showing differential change in gene expression for comparisons of CBT vs. SS, and TCC vs. SS