Elsevier

Biological Psychiatry

Volume 78, Issue 10, 15 November 2015, Pages 721-729
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2015.01.010Get rights and content

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.

Section snippets

Participants

This randomized controlled trial was conducted from April 2006 to August 2011 with University of California, Los Angeles Institutional Review Board approval. As described (25), 123 community-dwelling adults older than 55 years of age who fulfilled criteria for primary insomnia in DSM-IV (53) and for general insomnia in the International Classification of Sleep Disorders (54) were randomly assigned to CBT-I, TCC, or SS (2:2:1). Complete inclusion criteria are provided in Supplement 1.

Interventions

Each group

Baseline Characteristics of the Patients

A total of 294 subjects underwent baseline assessment; 207 were eligible, and 123 completed baseline (Figure S1 in Supplement 1). Treatment groups were comparable with regard to background characteristics (Table 1); none of these variables was included as a covariate. A total of 112 (92%) participants completed the assigned interventions (month 4), and 108 (89%) completed follow-up (month 16). Those who did not complete the intervention were younger (t121 = 2.12; p < .05) and had higher scores

Discussion

Given mounting evidence that insomnia patients are at greater risk for depression, medical comorbidities, and mortality (8); that sleep disturbance is associated with inflammation (6, 8, 20, 21); and that inflammation can lead to increased risk of depression (9, 66), cardiovascular disease (11), diabetes mellitus (14), and certain cancers (67, 68, 69), this study is significant by examining for the first time the efficacy of insomnia treatment on inflammation. These novel results link sleep

Acknowledgments And Disclosures

This work was supported by Grant R01-AG034588 from the National Institute of Aging; other Grant support from the National Institutes of Health to MRI, including R01-CA119159, R01-HL079955, R01 HL095799, P30-AG028748, P30-AG017265, and UL RR 033176; the Cousins Center for Psychoneuroimmunology; and UCLA Claude D. Pepper Older Americans Independence Center. The National Institutes of Health had no role in the design and conduct of the study.

We thank all the study participants for their support

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