Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder.

Objectives: To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID). Methods: Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT). Results: Relative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=-4.169, p<0.001), and lower level of sestrin-2 (Z=-2.438, p=0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=-0.590, p=0.001) and wake time (r=-0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=-0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=-0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=-0.257, p=0.044), pannexin-1 was positively associated with the mean erroneous distance in the BVAT (r=0.270, p=0.033). Conclusions: The CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively.

Effects of Sleep Reactivity on Sleep Macro-Structure, Orderliness, and Cortisol After Stress: A Preliminary Study in Healthy Young Adults.

Purpose: To investigate changes and links of stress and high sleep reactivity (H-SR) on the macro-structure and orderliness of sleep and cortisol levels in good sleepers (GS). Patients and Methods: Sixty-two GS (18-40 years old) were recruited, with 32 in the stress group and 30 in the control group. Each group was further divided into H-SR and low SR subgroups based on the Ford Insomnia Response to Stress Test. All participants completed two nights of polysomnography in a sleep laboratory. Before conducting polysomnography on the second night, the stress group completed the Trier Social Stress Test and saliva was collected. Results: The duration of NREM sleep stages 1, 2 (N1, N2) and rapid eye movement sleep (REM) decreased, and the values of approximate entropy, sample entropy, fuzzy entropy, and multiscale entropy increased under stress and SR effects. Stress increased rapid eye movement density, and H-SR increased cortisol reactivity. Conclusion: Stress can damage the sleep and increase cortisol release in GS, especially those with H-SR. N1, N2 and REM sleep are more easily affected, while NREM sleep stage 3 sleep is relatively stable.

Relationships Between a Range of Inflammatory Biomarkers and Subjective Sleep Quality in Chronic Insomnia Patients: A Clinical Study.

PURPOSE: To examine whether associations exist between chronic insomnia disorder (CID) and overlooked inflammatory factors (Serum amyloid protein A [SAA]), tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], and regulated on activation and normal T cell expressed and presumably secreted [RANTES]). PATIENTS AND METHODS: A total of 65 CID patients and 39 sex- and age-matched good sleeper (GS) controls participated in this study. They completed a baseline survey to collect data on demographics, and were elevated sleep and mood by Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS), 17-item Hamilton Depression Rating Scale (HAMD-17) and 14-item Hamilton Anxiety Rating Scale (HAMA-14), respectively. The blood samples were collected and tested the serum levels of SAA, TNF-α, GM-CSF and RANTES. RESULTS: The CID group had higher serum levels of SAA, TNF-α, and GM-CSF and a lower level of RANTES than the GS group. In the Spearman correlation analysis, SAA and GM-CSF positively correlated with the PSQI and AIS scores. After controlling for sex, HAMD-17 score, and HAMA-14 score, the partial correlation analysis showed that GM-CSF was positively correlated with PSQI score. Further stepwise linear regression analyses showed that GM-CSF was positively associated with the PSQI and AIS scores, while RANTES was negatively associated with them, and SAA was positively associated with just the AIS score. CONCLUSION: The serum levels of inflammatory mediators (SAA, TNF-α, and GM-CSF) were significantly elevated and the level of RANTES was significantly decreased in CID patients and, to some extent, the changes are related to the severity of insomnia. These findings may help us to improve interventions to prevent the biological consequences of CID by inhibiting inflammation, thereby promoting health.