Cognitive behavioral therapy and tai chi reverse cellular and genomic markers of inflammation in late-life insomnia: a randomized controlled trial

Biol Psychiatry. 2015 Nov 15;78(10):721-9. doi: 10.1016/j.biopsych.2015.01.010. Epub 2015 Feb 4.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cognitive Behavioral Therapy*
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation Mediators / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Sleep Initiation and Maintenance Disorders / blood*
  • Sleep Initiation and Maintenance Disorders / complications
  • Sleep Initiation and Maintenance Disorders / genetics
  • Sleep Initiation and Maintenance Disorders / therapy*
  • Tai Ji*
  • Toll-Like Receptor 4 / metabolism
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Biomarkers
  • Inflammation Mediators
  • Interleukin-6
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT00280020