Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation

Abstract

Background: Sleep disturbance is associated with inflammatory disease risk and all-cause mortality. Here, we assess global evidence linking sleep disturbance, sleep duration, and inflammation in adult humans.

Methods: A systematic search of English language publications was performed, with inclusion of primary research articles that characterized sleep disturbance and/or sleep duration or performed experimental sleep deprivation and assessed inflammation by levels of circulating markers. Effect sizes (ES) and 95% confidence intervals (CI) were extracted and pooled using a random effect model.

Results: A total of 72 studies (n > 50,000) were analyzed with assessment of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα). Sleep disturbance was associated with higher levels of CRP (ES .12; 95% CI = .05-.19) and IL-6 (ES .20; 95% CI = .08-.31). Shorter sleep duration, but not the extreme of short sleep, was associated with higher levels of CRP (ES .09; 95% CI = .01-.17) but not IL-6 (ES .03; 95% CI: -.09 to .14). The extreme of long sleep duration was associated with higher levels of CRP (ES .17; 95% CI = .01-.34) and IL-6 (ES .11; 95% CI = .02-20). Neither sleep disturbances nor sleep duration was associated with TNFα. Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFα. Some heterogeneity among studies was found, but there was no evidence of publication bias.

Conclusions: Sleep disturbance and long sleep duration, but not short sleep duration, are associated with increases in markers of systemic inflammation.

Keywords: Inflammation; Insomnia; Interleukin-6; Meta-analysis; Sleep deprivation; Sleep disturbance; Sleep duration.

Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Forest plot of sleep disturbance associated with inflammation as indexed by C-reactive. Sleep disturbance is assessed by self-reported symptoms and questionnaires. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).

Figure 2

Forest plot of sleep disturbance associated with inflammation as indexed by circulating levels of interleukin-6. Sleep disturbance is assessed by self-reported symptoms and questionnaires. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).

Figure 3

Forest plot of sleep duration associated with inflammation as indexed by C-reactive. Sleep duration is assessed continuously by subjective and objective measures. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).

Figure 4

Forest plot of sleep duration associated with inflammation as indexed by circulating levels of interleukin-6. Sleep duration is assessed continuously by subjective and objective measures. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).

Figure 5

Forest plot of sleep duration associated with inflammation as indexed by C-reactive. Sleep duration is assessed categorically with normal sleep being defined by sleep duration 7–8 h per night, and short sleep as 8 h per night. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).

Figure 6

Forest plot of sleep duration associated with inflammation as indexed by circulating levels of interleukin-6. Sleep duration is assessed categorically with normal sleep being defined by sleep duration 7–8 h per night, and short sleep as 8 h per night. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).

Figure 7

Forest plot of experimentally shortened sleep duration associated with inflammation as indexed by C-reactive. Sleep duration was shortened by either partial- or total night sleep deprivation for one night or for multiple nights. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).

Figure 8

Forest plot of experimentally shortened sleep duration associated with inflammation as indexed by circulating levels of interleukin-6. Sleep duration was shortened by either partial- or total night sleep deprivation for one night or for multiple nights. Results are expressed as effect sizes (ES) and 95% confidence intervals (95% CI).