慢性失眠患者血清神经营养因子改变及其与睡眠质量和认知功能的关系

Changed serum levels of neurotrophic factors and their correlations with sleep and cognition in patients with chronic insomnia disorder

目的探讨慢性失眠患者血清脑源性神经营养因子(BDNF)和胶质源性神经营养因子(GDNF)水平的变化及其与睡眠质量和认知功能间的关系。方法纳入2017年5月至2018年7月安徽医科大学附属巢湖医院睡眠障碍科就诊的慢性失眠患者57例,以同期本院健康体检中心的30名健康体检者作为对照。采用匹兹堡睡眠质量指数(PSQI)评估受试者的失眠程度(部分慢性失眠患者接受整夜多导睡眠监测),采用蒙特利尔认知评估量表(MoCA)评估总体认知功能,采用九盒迷宫评估特殊记忆功能,ELISA检测受试者的血清BDNF和GDNF水平。结果慢性失眠患者的PSQI得分显著高于对照组[慢性失眠组(14.0±2.2)分,对照组(3.9±1.1)分;t=28.093,P<0.01],MoCA评分显著低于对照组[慢性失眠组(24.5±3.6)分,对照组(26.5±0.9)分;t=-2.985,P<0.01],同时物体工作[慢性失眠组1.0(0,1.0),对照组0(0,0.3)]、空间工作[慢性失眠组3.0(2.0,4.0),对照组1.0(1.0,2.0)]、物体再认记忆[慢性失眠组0(0,0),对照组0(0,0)]错误数高于对照组(Z=-2.896、-5.007、-2.306,均P<0.05)。慢性失眠患者血清BDNF[慢性失眠组(19.48±7.50)ng/ml,对照组(46.49±13.33)ng/ml]和GDNF[慢性失眠组(32.76±14.04)pg/ml,对照组(59.63±20.30)pg/ml]水平显著低于对照组(t=-10.274、-7.240,均P<0.01),与PSQI得分呈负相关(r=-0.293、-0.320,均P<0.05),与MoCA评分呈正相关(r=0.331、0.295,均P<0.05)。BDNF还与病程和空间工作记忆错误数呈负相关(r=-0.319、-0.393,均P<0.05),GDNF与多导睡眠监测中总睡眠时间呈正相关(r=0.520,P<0.05)。结论慢性失眠患者的血清BDNF和GDNF水平较正常人降低,并与其睡眠质量和认知功能损害相关。

Objective To explore serum levels of brain-derived neurotrophic factor(BDNF)and glial-derived neurotrophic factor(GDNF),and whether changes of BDNF and GDNF are correlated with sleep quality and cognitive function in patients with chronic insomnia disorder(CID).Methods Fifty-seven CID patients in the Department of Sleep Disorders,Chaohu Hospital of Anhui Medical University and 30 healthy controls were enrolled from May 2017 to July 2018.Pittsburgh Sleep Quality Index(PSQI)was used to assess the degree of insomnia severity(some CID patients were monitored by overnight polysomnography).Montreal Cognitive Assessment(MoCA)scale and Nine-Box Maze were used to assess general cognitive function and specific memory function,respectively.The serum levels of BDNF and GDNF were detected using ELISA.Results Compared to the controls,CID patients had significantly higher PSQI scores(CID patients:14.0±2.2,healthy controls:3.9±1.1;t=28.093,P<0.01),lower MoCA scores(CID patients:24.5±3.6,healthy controls:26.5±0.9;t=-2.985,P<0.01),more errors in object working memory(CID patients:1.0(0,1.0),healthy controls:0(0,0.3)),spatial working memory(CID patients:3.0(2.0,4.0),healthy controls:1.0(1.0,2.0))and object recognition memory(CID patients:0(0,0),healthy controls:0(0,0);Z=-2.896、-5.007、-2.306,P<0.05),and lower serum BDNF(CID patients:(19.48±7.50)ng/ml,healthy controls:(46.49±13.33)ng/ml;t=-10.274,P<0.01)and GDNF(CID patients:(32.76±14.04)pg/ml,healthy controls:(59.63±20.30)pg/ml;t=-7.240,P<0.01).The partial correlation analysis showed that in the CID patients,the levels of BDNF and GDNF were correlated with PSQI scores negatively(r=-0.293,-0.320,P<0.05)and MoCA scores positively(r=0.331,0.295,P<0.05).The BDNF level was also correlated with the duration of disease and the errors in the spatial working memory test negatively(r=-0.319,-0.393,P<0.05),and the GDNF level was correlated with the total sleep time detected with polysomnogram positively(r=0.520,P<0.05).Conclusion Serum BDNF and GDNF levels in CID patients were lower than those in healthy controls,and correlated with sleep quality and cognitive impairment.