伴有焦虑症状双相抑郁患者认知功能损害与GRIN2B基因启动子区DNA甲基化相关性研究
The correlation between cognitive impairment and DNA methylation in the GRIN2B gene promoter region in bipolar depression patients with anxiety symptom
余浩 1王丞基 2吴瑶 2邹韶红2
作者信息
- 1. 新疆医科大学(乌鲁木齐 830000);新疆维吾尔自治区人民医院临床心理科
- 2. 新疆维吾尔自治区人民医院临床心理科
- 折叠
摘要
目的 探索伴有焦虑症状双相抑郁患者认知功能与N-甲基-D-天冬氨酸受体2B亚基(glutamate iono-tropic receptor NMDA type subunit 2B,GRIN2B)基因启动子区各CpG位点甲基化水平的相关性.方法 根据汉密尔顿焦虑量表(14-item Hamilton anxiety rating scale,HAMA)评分将31例双相抑郁患者分为焦虑组15例和非焦虑组16例,同期选取16名健康对照.采用蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA)、数值广度测验(digital span test,DST)、连线测试A部分(trail making test A,TMT-A)、斯特鲁普色词测验(Stroop color and word test,SCWT)评估3组总体认知功能、注意力及执行控制、信息处理速度、执行功能等认知功能维度,采用Massarray质谱法检测所有受试者外周血GRIN2B基因启动子区各CpG位点的DNA甲基化水平.结果 3组GRIN2B基因启动子区DNA甲基化水平差异性位点为CpG3、CpG5、CpG7、CpG10、CpG12(P<0.05),其中,焦虑组CpG12甲基化水平低于非焦虑组(36.23%±16.41%vs.50.20%±19.79%,P<0.05).偏相关分析显示,焦虑组患者中较差的命名能力与GRIN2B基因CpG4低甲基化水平相关(r=0.670,P=0.034),较差的执行功能与CpG6低甲基化水平相关(r=0.926,P<0.001),较差的注意力与GRIN2B基因CpG8高甲基化水平相关(r=-0.810,P=0.025),较差的言语记忆与CpG9高甲基化水平相关(r=-0.810,P<0.001),较差的抽象能力与CpG10高甲基化水平相关(r=-0.756,P=0.011).结论GRIN2B基因启动子区DNA甲基化水平与伴有焦虑症状双相抑郁患者认知功能损害可能有关联,与双相抑郁患者焦虑症状的产生也可能有关联.
Abstract
Objective To explore the correlation between cognitive function and methylation levels of various CpG sites in the promoter region of the glutamate ionotropic receptor NMDA type subunit 2B(GRIN2B)gene in patients with bipolar depression accompanied by anxiety symptoms.Methods According to the 14-item Hamilton anxiety rating scale(HAMA)score,31 bipolar depression patients were divided into a group of 15 with anxiety symptoms and a group of 16 without anxiety symptoms.Sixteen healthy individuals were selected as controls during the same period.The Montreal cognitive assessment(MoCA),digital span test(DST),trail making test A(TMT-A),and Stroop color and word test(SCWT)were used to measure cognitive areas such as global cognitive function,attention and executive control,information processing speed,executive function in three groups.The DNA methylation levels of the CpG site in the GRIN2B gene promoter region in the peripheral blood of all participants were measured using Massarray spectrometry.Results The CpG sites showing differences in DNA methylation levels among the three groups were CpG3,CpG5,CpG7,CpG10,and CpG12(P<0.05),and the level of CpG12 methylation was lower in the group with anxiety than in the group without anxiety(36.23%±16.41%vs.50.20%±19.79%,P<0.05).Partial correlation analysis showed that,in the group with anxiety,poor naming ability was correlated with the lower methylation level of GRIN2B gene's CpG4(r=0.670,P=0.034),poor executive function was correlated with the lower CpG6 methylation level(r=0.926,P<0.001),poor attention was correlated with the higher CpG8 methylation level(r=-0.810,P=0.025),poor verbal memory was correlated with the higher CpG9 methylation level(r=-0.810,P<0.001),and poor abstract ability was correlated with the higher CpG10 methylation level(r=-0.756,P=0.011).Conclusion The DNA methylation level in the promoter region of the GRIN2B gene may be associated with cognitive impairment and anxiety symptoms in patients with bipolar depression.
关键词
DNA甲基化/双相障碍/抑郁发作/认知功能/焦虑症状/N-甲基-D-天冬氨酸受体2B亚基Key words
DNA methylation/Bipolar disorder/Depressive episode/Cognition/Anxiety symptoms/N-methyl-D-aspartate receptor 2B subunit引用本文复制引用
基金项目
新疆维吾尔自治区自然科学基金(2022D01C606)
天山创新团队计划(2022D14011)
出版年
2024
NETL
NSTL
万方数据