Changed nocturnal levels of stress-related hormones couple with sleep-wake states in the patients with chronic insomnia disorder: A clinical pilot study.

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.

Research on the correlation of immunity in patients with chronic insomnia.

Purpose: To investigate the changes in immunity and clinical infection events among patients with chronic insomnia. Materials and methods: Forty-two patients with chronic insomnia (age = 64.44 ± 10.53) and 47 normal controls (age = 67.08 ± 7.822) were selected to determine differences in data, such as complete blood counts (CBCs), biochemical indices, lymphocyte subsets, immunoglobulin (Ig), complement C3 and C4 and interleukin-6 (IL-6), as well as to compare the incidence of clinical infection between the two groups. Results: There were significant differences in erythrocyte, hemoglobin, hematocrit, albumin, globulin, creatinine, IgG, IgG/IgM ratio, CD4+ T-lymphocytes, CD19-lymphocytes, CD4+/CD8+ ratio, platelet/lymphocyte ratio, CD19/CD3 ratio, and clinical infection events between the chronic insomnia group and the control group (p < 0.05). There was no significant difference in neutrophil, lymphocyte, monocyte, and platelet counts; lymphocyte subsets CD8+ T and CD56+; platelet-to-lymphocyte ratio (PLR); neutrophil-to-lymphocyte ratio (NLR); complement C3; complement C4; IgM; IgA; and IL-6 between the experimental group and their controls (p > 0.05). The systolic and diastolic blood pressures of the chronic insomnia group did not vary widely from those of the controls (p > 0.05). Conclusion: Patients with chronic insomnia have immunological abnormalities, characterized by a higher incidence of clinical infection.

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

OBJECTIVES: This study aimed to investigate whether plasma levels of adenosine, adenosine deaminase (ADA), and certain cytokines change in patients with chronic insomnia disorder (CID), and if so, whether these alterations are associated with poor sleep quality and cognitive dysfunction. METHODS: Fifty-five CID patients were selected for the study, along with fifty-five healthy controls (HC) matched to the patients according to their basic data. All subjects completed sleep, emotion, and cognition assessments, with some CID patients also completing an overnight polysomnography. The plasma level of adenosine was measured using liquid chromatography-tandem mass spectrometry, while ADA level was quantified using a quantitative sandwich enzyme-linked immunosorbent assay. Levels of cytokines, including IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ, were measured using Luminex liquid chip technology. RESULTS: CID patients had a lower adenosine level, and higher levels of ADA and some of the cytokines (IL-1ß, IL-2, IL-6, IL-10 and TNF-α) compared with controls. In the CID group, plasma concentrations of adenosine were negatively correlated with Pittsburgh Sleep Quality Index scores, while concentrations of IL-1ß, IL-6 and TNF-α were positively correlated with these scores. Concentrations of IL-1ß and TNF-α were negatively correlated with scores on the Chinese-Beijing Version of the Montreal Cognitive Assessment. Moreover, levels of IL-1ß, TNF-α, IL-6, and IL-2 were positively correlated with memory test errors by CID patients after controlling for confounding factors. CONCLUSIONS: The reduced adenosine and elevated cytokine levels of CID patients were associated with the severity of insomnia and/or cognitive dysfunction.

Astroglial Mechanisms Underlying Chronic Insomnia Disorder: A Clinical Study.

PURPOSE: The objective of this study was to investigate whether the serum biomarkers S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) change in patients with chronic insomnia disorder (CID), and if this is the case, whether the altered levels of these serum biomarkers are associated with poor sleep quality and cognitive decline in CID. PATIENTS AND METHODS: Fifty-seven CID outpatients constituted the CID group; thirty healthy controls (HC) were also enrolled. Questionnaires, polysomnography, Chinese-Beijing Version of Montreal Cognitive Assessment (MoCA-C) and Nine Box Maze Test (NBMT) were used to assess their sleep and neuropsychological function. Serum S100B, GFAP, BDNF, and GDNF were evaluated using enzyme-linked immunosorbent assay. RESULTS: The CID group had higher levels of S100B and GFAP and lower levels of BDNF and GDNF than the HC group. Spearman correlation analysis revealed that poor sleep quality, assessed by subjective and objective measures, was positively correlated with S100B level and negatively correlated with BDNF level. GFAP level correlated positively with poor subjective sleep quality. Moreover, S100B and GFAP levels correlated negatively with general cognitive function assessed using MoCA-C. GFAP level correlated positively with poor spatial working memory (SWM) in the NBMT; BDNF level was linked to poor SWM and object recognition memory (ORcM) in the NBMT. However, principal component analysis revealed that serum S100B level was positively linked to the errors in object working memories, BDNF and GDNF concentrations were negatively linked with errors in ORcM, and GFAP concentration was positively correlated with the errors in the SWM and spatial reference memories. CONCLUSION: Serum S100B, GFAP, BDNF, and GDNF levels were altered in patients with CID, indicating astrocyte damage, and were associated with insomnia severity or/and cognitive dysfunction.