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 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.
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. Electronic address: mirwin1@ucla.edu.
Michael R
MR
Irwin
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience; Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine.
Richard
R
Olmstead
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience; Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine.
Elizabeth C
EC
Breen
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience.
Tuff
T
Witarama
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience.
Carmen
C
Carrillo
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience.
Nina
N
Sadeghi
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.
Jesusa M G
JM
Arevalo
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.
Jeffrey
J
Ma
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience; Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine.
Perry
P
Nicassio
Department of Psychology, University of Arizona, Tucson, Arizona.
Richard
R
Bootzin
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.
Steve
S
Cole
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015928:Cognitive Behavioral Therapy; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D007319:Sleep Initiation and Maintenance Disorders / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000628:therapy*; D026302:Tai Ji; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
Aging; Cognitive-behavioral therapy; Gene expression; Inflammation; Insomnia; Tai chi