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

  • Michael R. Irwin
    Correspondence
    Address correspondence to: Michael R. Irwin, M.D., Cousins Center for Psychoneuroimmunology, UCLA Semel Institute, 300 UCLA Medical Plaza, Room 3130, Los Angeles, CA 90095-7076.
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine

    Department of Psychology, University of California, Los Angeles
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  • Richard Olmstead
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine
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  • Elizabeth C. Breen
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine
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  • Tuff Witarama
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience
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  • Carmen Carrillo
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience
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  • Nina Sadeghi
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience
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  • Jesusa M.G. Arevalo
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine

    Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California
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  • Jeffrey Ma
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine

    Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California
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  • Perry Nicassio
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine
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  • Richard Bootzin
    Affiliations
    Department of Psychology, University of Arizona, Tucson, Arizona
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  • Steve Cole
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine

    Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California
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Published:February 04, 2015DOI:https://doi.org/10.1016/j.biopsych.2015.01.010

      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.

      Keywords

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      Linked Article

      • Behavioral Interventions Produce Robust Beneficial Biological Alterations
        Biological PsychiatryVol. 78Issue 10
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          Irwin et al. (1) demonstrate in a randomized controlled trial that cognitive-behavioral therapy for insomnia and tai chi chih, a westernized variant of tai chi, produce robust reductions of inflammatory markers in participants >55 years old with insomnia. Although the temporal persistence of the effects varies, and the specific molecular outcome measures differ to some extent, both interventions show beneficial biological changes immediately after the 4-month intervention and persistence of some of these effects up to 1 year after completion of the intervention.
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