Changed Serum Levels Of Glial Cell Markers And Their Correlations With Sleep And Cognition In The Patients With Chronic Insomnia

Background Insomnia is the most common sleep-wake disorder,which is characterized by difficulty in falling and maintaining sleep,waking up early,or both.It has a significant adverse effect on the cognitive functions,such as attention,memory,executive function and so on.The prevalence of chronic insomnia disorder(CID)is about 6% to 20%.Unfortunately,the mechanism of CID and causes of its cognitive impairment remain unclear.Previous studies have suggested that CID patients have brain microstructural damage.However,the focuses on the astrocytes are still rare.Objectives To investigate whether the serum levels of astrocytic biomarkers,including S100 calcium binding protein B(S100B),glial fibrillary acidic protein(GFAP),brain-derived neurotrophic factor(BDNF)and glial derived neurotrophic factor(GDNF)change,and if it is case,whether the changes are correlated with the poor sleep quality and cognitive impairment in the CID patients.Methods Forty-nine CID patients and 32 healthy controls were enrolled in this study.The Chinese-Beijing Version of Montreal Cognitive Assessment(Mo CA-C),Pittsburgh Sleep Quality Index(PSQI),Hamilton depression rating scale-sleep(HAMD-S),the 17 items of Hamilton depression rating scale(HAMD-17)and the 14 items of Hamilton anxiety scale(HAMA-14)were used to evaluate the cognitive function,subjective sleep quality and emotion."Nine-box maze" test was used to evaluate the spatial working memory,object working memory,spatial reference memory,object reference memory and object recognition memory.The polysomnogram in one night was used to evaluatethe objective sleep quality in some subjects,including: total sleep time(TST),sleep onset latency,sleep efficiency(SE),the structure of non-REM sleep(the duration and percentage of N1,N2,N3 sleep in total sleep time)and the structure of REM sleep(the duration and the percentage of REM sleep in total sleep time).The fasting venous blood at 8: 00 to 10: 00 a.m.was obtained to detect the serum levels of astrocytic biomarkers(S100B,GFAP,BDNF and GDNF)using ELISA.Results 1.Subjective sleep quality.The CID group had significantly higher scores of PSQI and HAMD-S than the healthy control group(P < 0.05).2.General cognitive and special memory functions.Compared to the controls,the Mo CA-C score in the CID group was significantly lower,and the number of errors in the SWM,OWM and ORc M were significantly higher(P < 0.05).3.The levels of serum astrocyte biomarkers.Compared to the controls,the serum levels of S100 B and GFAP in the CID group were significantly higher,while the serum levels of BDNF and GDNF were significantly lower(P < 0.05).4.Correlations between serum biomarkers of astroglia and sleep quality,cognitive function.Sleep quality.In the CID group,serum levels of S100 B and GFAP positively correlated with PSQI scores,respectively(r = 0.476,P = 0.002;r = 0.461,P = 0.002)and S100 B level negatively correlated with TST and SE,respectively(r =-0.481,P = 0.043;r =-0.541,P = 0.020).Serum BDNF and GDNF negatively correlated with PSQI scores,respectively(r =-0.394,P = 0.007;r =-0.502,P < 0.001).Cognitive function.S100 B and GFAP negatively correlated with Mo CA-C scores,respectively(r =-0.475,P = 0.002;r =-0.406,P = 0.006).GFAP positively correlated with the errors in the spatial working memory and object recognition memory(r = 0.352,P = 0.022;r = 0.369,P = 0.015).Serum BDNF and GDNF positively correlated with Mo CA-C scores,respectively(r = 0.301,P = 0.045;r = 0.415,P = 0.005),andnegatively correlated with the errors of spatial working memory,respectively(r =-0.317,P = 0.038;r =-0.377,P = 0.013).Serum GDNF also negatively correlated with the error number of object recognition memory(r =-0.299,P = 0.049).6.ROC analysis.the AUCs of serum S100 B,GFAP,GDNF and BDNF were larger than 0.70,respectively,suggesting that these biomarkers could better distinguish the CID patients with the healthy controls.The optimal cut-off values for them were 347.7 pg/ml,622.0 pg/ml,53.7 pg/ml and 29.6 ng/ml,respectively.Conclusion The CID patients had enhanced serum levels of S100 B and GFAP,and decreased serum levels of BDNF and GDNF.These changed markers might be linked to the severity of insomnia and cognitive impairment.