| Background:Insomnia disorder is a persistent difficulty with sleep initiation, duration,consolidation, or quality with some forms of impairments in daytime function, despite adequate opportunity and circumstances for sleep. Insomnia is a remarkably prevalent disorder. There are about 6% to 20% of people suffer from insomnia in the world, which about 50% of the patients were chronic insomnia disorder(CID). Despite the CID can impair cognitive functions, such as attention, memory, executive function, it remains to be a matter that whether CID causes the changes in proteins of biomarkers linked to brain structure damage and whether the changed levels of proteins are associated with functions, including subjective and objective sleep quality, and cognitive functions.Objectives: The aim of this study was to explore the serum levels of neurofilament heavy chains(Nf H), neuron-specific enolase(NSE) and S100 calcium binding protein B(S100B) in the patients with CID and the correlations between the serum proteins levels and impaired functions, including reduced sleep quality and cognitive functions.Methods: Forty insomniac outpatients were categorized into free-therapy CID group(ft-CID, n = 40) and among forty insomniac outpatients, twenty-four patients were selected after six months treatment as re-visiting CID group(rv-CID, n = 24). Twenty demographically similar healthy subjects who accompanied the patients or had a medical examination were selected as negative controls(HC). All subjects were enrolled in the Clinic of Sleep and Memory Disorders in the First Affiliated Hospital of Anhui Medical University. They completed a series of questionnaires assessing sleep and neuropsychological function, including the Pittsburgh Sleep Quality Index(PSQI), the17-item Hamilton Depression Scale(HAMD-17) with the Hamilton Depression Scale-Sleep(HAMD-S), the 14-item Hamilton Anxiety Scale(HAMA-14) with the Hamilton Anxiety Scale-Sleep(HAMA-S) and the Montreal Cognitive Assessment(Mo CA). The special memory was evaluated with the Nine Box Maze Test, including spatial working memory(SWM), object working memory(OWM), spatial reference memory(SRM), object reference memory(ORM) and object recognition memory(ORc M). Some subjects were assessed with the polysomnography(PSG) for one night,and the sleep parameters included: total sleep time(TST), sleep onset latency(SOL),sleep efficiency(SE); NREM sleep structure, i.e., the duration of the stage 1(N1), 2(N2)and 3(N3) and their percentage(%), and REM sleep structure: duration of REM,percentage of REM period in total sleep time(REM %). Serum Nf H, NSE and S100 B levels were quantified with a quantitative sandwich enzyme-linked immunosorbent assay(ELISA).Results: 1 Background information:There were no significant difference among the groups with regard to gender, age, education(P > 0.05). The HAMD-17 and HAMA-14 scores were significantly higher in the ft-CID and rv-CID group compared to the HC group. The rv-CID group had lower HAMD-17 and HAMA-14 scores than the ft-CID group(P < 0.05).2Sleep quality: Compared to the HC group, the PSQI, HAMD-S and HAMA-S scores were significantly higher, and the SOL was significantly longer in the ft-CID and rv-CID groups. Compared to the ft-CID group, the PSQI, HAMD-S and HAMA-S scores was significantly lower, the SOL was significantly shorter, the SE was significantly higher in the rv-CID group(Ps < 0.05).3General cognitive and memory functions: Compared to the HC controls, the Mo CA scores were significantly lower, and the error numbers of ORc M, OWM and SWM were significantly higher in the ft-CID and rv-CID group. Compared to the ft-CID group, the Mo CA scores higher, and the error numbers of ORc M, OWM and SWM were significantly lower in the rv-CID group(Ps < 0.05).4 Changes of Nf H, S100 B and NSE: There were significant differences among the groups with regard to the serum levels of Nf H, S100 B and NSE(P < 0.001). The ft-CID group and the rv-CID group had higher serum levels of Nf H and S100 B than the HC group. Furthermore, the rv-CID patients had lower serum levels of Nf H and NSE than the ft-CID patients, but there was no significant difference in the S100 B concentration between the ft-CID and rv-CID groups, and there was no significant difference in the NSE concentrations between the rv-CID and HC groups.5The relationship between the proteins levels and sleep quality and cognitive functions:In the ft-CID group, there was a positive correlation between the serum levels of Nf H/S100B/NSE and the errors of SRM(r = 0.234, P = 0.032; r = 0.240, P = 0.028; r =0.300, P = 0.006, respectively). The S100 B and NSE concentrations positively correlated with the PSQI scares(r = 0.442, P = 0.004; r = 0.426, P = 0.006,respectively). The S100 B concentration positively correlated with the TST, SE, REMT and REM%(r =-0.464, P = 0.007; r =-0.680, P < 0.001, r =-0.611, P < 0.001; r =-0.644, P < 0.001, respectively). The S100 B concentration negatively correlated with the SOL(r = 0.434, P = 0.005). The Mo CA score negatively correlated with the Nf H and S100 B concentrations(r =-0.372, P = 0.018; r =-0.326, P = 0.040, respectively).6ROC analysis(Suitability of Serum Indexes as Diagnostic Biomarkers for CID): the AUCs of Nf H, Nf L, S100 B and NSE were larger than 0.90, respectively, which were great for predicting ft-CID compared to the HC. The optimal cut-off values for them were 404.7 pg/ml, 3.6 ng/ml, 514.0 pg/ml and 35.0 ng/ml, respectively.Conclusion: The CID patients had elevated serum levels of Nf H, S100 B and NSE that were associated with the severity of insomnia and dysfunction, indicating that insomnia could damage the microstructure of brain. Effective therapy only could suppress the increment of Nf H and NSE concentrations(neuronal damage biomarker), but not reduce the elevated S100 B concentration(astrocytic damage biomarker). Detecting the level of biomarkers might be useful for the diagnosis and prognosis assessment in the CID patients. |
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