Changed signals of blood adenosine and cytokines are associated with parameters of sleep and/or cognition in the patients with chronic insomnia disorder

Ren, Cheng; Rao, Ji-Xian; Zhang, Xiang-Xia; Zhang, Mei; Xia, Lan; Chen, Guihai

doi:10.1016/j.sleep.2021.02.005

Cited by 29 publications

(22 citation statements)

References 70 publications

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“…This discrepancy may be attributable to factors such as the illness duration, the existence of heterogeneity in the current study, sample size, and differences in the severity of insomnia. 53–56 Further studies are needed to reach a definitive conclusion.…”

Section: Discussionmentioning

confidence: 99%

Are Anti-Inflammatory Cytokines Associated with Cognitive Impairment in Patients with Insomnia Comorbid with Depression? A Pilot Study

Chen

et al. 2021

NSS

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Background To distinguish insomnia comorbid with depression (ICD) from chronic insomnia disorder (CID) by exploring the relationship between serum levels of frequently overlooked anti-inflammatory cytokines and cognitive function. Methods A total of 42 ICD patients, 63 CID patients, and 42 healthy control subjects were enrolled in the study. The Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale were used to assess sleep quality and depression severity, respectively. The Chinese-Beijing version of Montreal Cognitive Assessment scale (MoCA-C) and Nine-Box Maze Test (NBMT) were used to assess cognitive function. Serum levels of anti-inflammatory interleukins (IL-1RA, IL-4, IL-5, IL-10, IL-13, and IL-28A), transforming growth factor (TGF)-β1, granulocyte-macrophage colony-stimulating factor, interferon-γ, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES) were measured by enzyme-linked immunosorbent assay. Results The ICD group had significantly more errors in the spatial reference task (H=2.55, P s =0.03) and spatial working memory task (H=5.67, P s <0.01) of the NBMT, as well as lower levels of IL-1RA (H=−2.85, P s =0.01), IL-4 (H=−3.28, P s <0.01), IL-5 (H=−3.35, P s <0.01), IL-10 (H=−4.46, P s <0.01), and IL-28A (H=−2.75, P s =0.02) than control subjects. Compared with the CID group, the ICD group had significantly more errors in the spatial reference memory task (H=−2.84, P s =0.01) of the NBMT, and lower levels of IL-5 (H=3.41, P s <0.01), IL-10 (H=5.30, P s <0.01), IL-13 (H=3.89, P s <0.01), and GM-CSF (H=2.72, P s =0.02). A partial correlation analysis showed that the level of one or more of IL-4, IL-5, IL-10, IL-13, and TGF-β1 was positively correlated with cognitive function (MoCA-C score and/or performance in spatial memory task) in ICD patients. Conclusion ICD is a distinct condition that can be distinguished from CID based on immune dysfunction and specific types of cognitive dysfunction.

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Section: Discussionmentioning

confidence: 99%

Are Anti-Inflammatory Cytokines Associated with Cognitive Impairment in Patients with Insomnia Comorbid with Depression? A Pilot Study

Chen

et al. 2021

NSS

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“…Acutely, sleep deprivation has been shown to result in an increase in proinflammatory cytokines and concurrent decrease in antiinflammatory cytokines (Hirotsu et al, 2012;Taraz et al, 2013). At longer timescales, this trend shifts into an upregulation of both pro-and anti-inflammatory markers (Wright et al, 2015;Ren et al, 2021). In a recent study of 110 individuals with and without chronic insomnia, Ren et al (2021) demonstrated that both TNFα and IL-10 levels were elevated in insomnia patients, with TNFα positively correlating with PSQI score.…”

Section: Poor Sleep Quality Is Associated With Elevation Of Pro-and Anti-inflammatory Cytokines In Mtbi Warfightersmentioning

confidence: 99%

“…At longer timescales, this trend shifts into an upregulation of both pro-and anti-inflammatory markers (Wright et al, 2015;Ren et al, 2021). In a recent study of 110 individuals with and without chronic insomnia, Ren et al (2021) demonstrated that both TNFα and IL-10 levels were elevated in insomnia patients, with TNFα positively correlating with PSQI score. Conversely, adenosine levels were found to be reduced and negatively correlated with PSQI.…”

Section: Poor Sleep Quality Is Associated With Elevation Of Pro-and Anti-inflammatory Cytokines In Mtbi Warfightersmentioning

confidence: 99%

“…Shearer et al (2001) similarly reported that four nights of total sleep deprivation resulted in significant increases in levels of IL-6 and soluble TNFα receptor I in 21 healthy individuals. These inflammatory processes extend into chronic timescales as well, such that IL-6 and TNFα levels are correlated with severity of self-reported sleep dysfunction in otherwise healthy individuals with chronic insomnia (Ren et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Poor Sleep Quality is Linked to Elevated Extracellular Vesicle-Associated Inflammatory Cytokines in Warfighters With Chronic Mild Traumatic Brain Injuries

et al. 2022

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Background: Elevations of inflammatory cytokine levels occur immediately after mild traumatic brain injury (mTBI) and can persist for years. These elevations have been associated with neuropsychological outcomes, including depression and PTSD symptoms. Sleep disorders, another common sequelae of mTBI, are independently associated with inflammation in otherwise healthy individuals. However, whether sleep and inflammation are linked in chronic mTBI has not been reported.Methods: A retrospective cross-sectional cohort of warfighters was used to investigate the hypothesis that inflammation may be linked to sleep quality in chronic mTBI. Clinical history, peripheral blood samples, and sleep quality scores were collected from 182 warfighters (n = 138 mTBI; n = 44 controls) during enrollment in the Chronic Effects of Neurotrauma Consortium study. Biomarkers of inflammation (IL-6, IL-10, TNFα cytokines) from plasma and plasma-derived extracellular vesicles (EVs) were quantified using single molecule array. Relationships between sleep quality and cytokine levels were assessed, controlling for age, sex, and BMI. Using clinical cutoff scores for sleep quality, mTBI patients were then divided into “good” and “poor” sleepers and cytokine levels compared between groups.Results: In mTBI participants, sleep quality was significantly associated with EV levels of IL-10 [ß (SE) = 0.11 (0.04), p = 0.01] and TNFα [ß (SE) = 0.07 (0.03), p < 0.01]. When divided according to “good” versus “poor” sleepers, those reporting poor sleep had significantly elevated EV IL-10 compared to those reporting good sleep [ß (SE) = 0.12 (0.04), p < 0.01]. Plasma-derived associations were not significant. No associations were found between sleep quality and cytokine levels in controls.Conclusion: These results suggest a significant relationship between sleep quality and chronic inflammation in mTBI patients. Clinically, mTBI patients with a high likelihood of sleep disorders demonstrate elevated levels of inflammatory cytokines. Signal from EVs, though smaller in magnitude, may have stronger clinical associations than from plasma. Sleep-focused interventions may also serve to regulate chronic inflammatory processes in these patients. Larger prospective studies are needed to investigate the mechanisms and therapeutic implications of the likely bi-directional relationship between sleep and inflammation following mTBI.

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“…In this study, we used network pharmacology theory and related tools to select the active components and related targets of ZSS and linked them with insomnia-related targets to construct a D-C-G-D visual network, which more intuitively showed the specific relationship between drug components and diseases through 108 consensus genes. The results of PPI analysis showed complex interactions between overlapping genes, and 48 core targets were further screened according to the average node degree between them, such as TNF with a high node degree, meaning that one key to ZSS treatment of insomnia may be the inhibition of inflammation in vivo [ 43 ], which also made our subsequent analysis more prominent.…”

Section: Discussionmentioning

confidence: 99%

Exploration of Ziziphi Spinosae Semen in Treating Insomnia Based on Network Pharmacology Strategy

Gong

Xie

Chen³

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Ziziphi Spinosae Semen (ZSS) is a common natural medicine used to treat insomnia, and to show clearly its method of action, we managed and did an in-depth discussion. Network pharmacology research is very suitable for the analysis of multiple components, multiple targets, and multiple pathways of Traditional Chinese Medicine (TCM). According to the relevant theory, we first carefully collected and screened the active ingredients in ZSS and received 11 active ingredients that may work. The targets going along with these active components were also strongly related to insomnia targets, 108 common genes were identified, and drug-compound-gene symbol-disease visualization network and protein-protein interaction network were constructed. Forty-eight core genes were identified by PPI analysis and subjected to GO functional analysis with KEGG pathway analysis. The results of GO analysis pointed that there were 998 gene ontology items for the treatment of insomnia, including terms of 892 biological processes, 47 cellular components, and 59 molecular functions. It mainly shows the coupling effect and transport mode of some proteins in the biological pathways of ZSS in the treatment of insomnia and explains the mechanism of action through the connection between the target and the cell biomembrane. KEGG enrichment analyzed 19 signaling pathways, which were collectively classified into seven categories. We have identified the potential pathways of ZSS against insomnia and obtained the regulatory relationship between core genes and pathways and know that the same target can be regulated by multiple components at the same time. The results of molecular docking also prove this conclusion. We sought to provide a new analytical approach to explore TCM treatments for diseases using network pharmacology analysis tools.

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Changed signals of blood adenosine and cytokines are associated with parameters of sleep and/or cognition in the patients with chronic insomnia disorder

Cited by 29 publications

References 70 publications

Are Anti-Inflammatory Cytokines Associated with Cognitive Impairment in Patients with Insomnia Comorbid with Depression? A Pilot Study

Are Anti-Inflammatory Cytokines Associated with Cognitive Impairment in Patients with Insomnia Comorbid with Depression? A Pilot Study

Poor Sleep Quality is Linked to Elevated Extracellular Vesicle-Associated Inflammatory Cytokines in Warfighters With Chronic Mild Traumatic Brain Injuries

Exploration of Ziziphi Spinosae Semen in Treating Insomnia Based on Network Pharmacology Strategy

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