More than half of rheumatoid arthritis (RA) patients complain of sleep disturbance and this cardinal complaint is associated with fatigue, pain, and depressed mood in patients with this chronic inflammatory disorder. Despite the frequency of this complaint, there is limited effort to evaluate sleep or the psychobiological mechanisms that account for disordered sleep in RA patients. Given evidence that abnormal increases in the expression of proinflammatory cytokines play a key role in the progression of RA, we hypothesize that the cytokine network is one physiological system that is associated with sleep disturbance in RA patients. Proinflammatory cytokines signal the central nervous system and are associated with an integrated syndrome of behavioral changes described as """"""""sickness behaviors"""""""" that include changes in sleep, energy, and pain sensitivity. Preliminary studies suggest that disturbances of sleep are associated with increased symptoms of pain, fatigue, and depressed mood in rheumatic patients. Moreover, sleep loss is coincident with alterations in sympathetic tone, which is thought to contribute to increases of pro- inflammatory cytokine activity.
The specific aims of this study are to: 1) determine the nature and severity of disordered sleep RA patients vs. controls;2) evaluate the effects of sleep, sleep loss, and recovery sleep on symptoms of pain, fatigue, and mood and on measures of sympathovagal balance and proinflammatory cytokine activity in RA patients and controls;3) examine the contribution of cytokines on sleep by administering a TNF antagonist vs. placebo to probe the action of proinflammatory cytokines on sleep in RA patients. Examination of sleep and its consequences for autonomic functioning and proinflammatory cytokine activity within the framework of an observational and experimental research design will have implications for understanding the psycho-biological mechanisms that link sleep and the clinical manifestations of RA. Results from this study will guide the development of interventions that target disordered sleep with potential effects on disability in RA.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079955-04
Application #
7643341
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Twery, Michael
Project Start
2006-05-20
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2009
Total Cost
$749,521
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Bjurström, Martin F; Olmstead, Richard; Irwin, Michael R (2017) Reciprocal Relationship Between Sleep Macrostructure and Evening and Morning Cellular Inflammation in Rheumatoid Arthritis. Psychosom Med 79:24-33
Irwin, Michael R; Opp, Mark R (2017) Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity. Neuropsychopharmacology 42:129-155
Bower, Julienne E; Irwin, Michael R (2016) Mind-body therapies and control of inflammatory biology: A descriptive review. Brain Behav Immun 51:1-11
Irwin, Michael R; Bjurstrom, Martin F; Olmstead, Richard (2016) Polysomnographic measures of sleep in cocaine dependence and alcohol dependence: Implications for age-related loss of slow wave, stage 3 sleep. Addiction 111:1084-92
Bjurstrom, Martin F; Irwin, Michael R (2016) Polysomnographic characteristics in nonmalignant chronic pain populations: A review of controlled studies. Sleep Med Rev 26:74-86
Irwin, Michael R; Olmstead, Richard; Carroll, Judith E (2016) Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation. Biol Psychiatry 80:40-52
Cho, Hyong Jin; Seeman, Teresa E; Kiefe, Catarina I et al. (2015) Sleep disturbance and longitudinal risk of inflammation: Moderating influences of social integration and social isolation in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Brain Behav Immun 46:319-26
Ormseth, Sarah R; Draper, Taylor L; Irwin, Michael R et al. (2015) Multidimensional Model of Disability and Role Functioning in Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 67:1686-92
Irwin, Michael R; Olmstead, Richard; Breen, Elizabeth C et al. (2015) Cognitive behavioral therapy and tai chi reverse cellular and genomic markers of inflammation in late-life insomnia: a randomized controlled trial. Biol Psychiatry 78:721-9
Irwin, Michael R; Witarama, Tuff; Caudill, Marissa et al. (2015) Sleep loss activates cellular inflammation and signal transducer and activator of transcription (STAT) family proteins in humans. Brain Behav Immun 47:86-92

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