国际精神病学杂志--大牛智慧平台

• 文章 •

双相抑郁患者失眠相关执行功能损害与NR2B基因启动子区甲基化水平的关系

余浩,肖玉新,邹韶红

* 通信作者：邹韶红， 单位：新疆维吾尔自治区人民医院 830000

摘要

【摘要】：
目的探讨N-甲基-D-天冬氨酸受体2B亚基（NR2B）基因启动子区甲基化水平与双相抑郁患者失眠相关执行功能损害的相关性，为双相抑郁患者的早期诊断及临床治疗提供理论依据。

方法本研究为病例对照研究，收集双相抑郁患者31例及健康对照16例，根据临床上有无失眠症状及匹兹堡睡眠质量指数（PSQI）分值将双相抑郁患者分为失眠组（PSQI≥7分）及非失眠组（PSQI＜7分）。测定所有受试者外周血NR2B基因启动子区甲基化水平，采用偏相关分析其与双相抑郁患者失眠相关执行功能损害的相关性以及先单后多因素Logistics回归分析其与双相抑郁患者失眠症状的关联。

结果非失眠组、失眠组CpG3及CpG10甲基化率高于健康对照组；失眠组CpG7甲基化率低于健康对照组，CpG9甲基化率高于非失眠组（P<0.05）。偏相关分析显示，CpG10甲基化率与斯特鲁普色词测验（Stroop Color and Word Test，SCWT）单词个数（r＝0.569）及颜色个数（r＝0.526）呈中度正相关（P＜0.05），CpG6甲基化率与SWCT色词个数呈中度正相关（r＝0.558，P＜0.05）。汉密尔顿抑郁量表（HAMD）评分（P＝0.034，OR＝0.729，95％CI：0.544～0.976）与位点CpG9甲基化水平的升高（OR＝0.814，95％CI：0.677～0.978，P＝0.028）为双相抑郁患者失眠症状的独立危险因素。

结论 NR2B基因启动子区甲基化水平异常可能介导双相抑郁患者失眠症状的产生并与失眠相关执行功能受损有关。

关键词：双相抑郁；N-甲基-D-天冬氨酸受体 2B 亚基；DNA甲基化；失眠；执行功能；

ABSTRACT

【Abstract】
Objective To explore the relationship between methylation in the promoter region of N-methyl-D-aspartate receptor 2B subunit (NR2B) gene and insomnia-related executive function impairment in patients with bipolar depression and provide theoretical basis for early diagnosis and clinical treatment of patients with bipolar depression.

Methods This study was a case-control study. 31 patients with bipolar depression and 16 healthy controls were collected. Patients with bipolar depression were divided into insomnia group (PSQI≥7 points) and non-insomnia group (PSQI < 7 points) according to the clinical symptoms of insomnia and the Pittsburgh Sleep Quality index (PSQI) score. The methylation level of NR2B gene promoter in peripheral blood of all subjects was measured. Partial correlation analysis was used to analyze its correlation with insomnia-related executive function impairment in patients with bipolar depression, and its association with insomnia symptoms in patients with bipolar depression was analyzed by Logistics regression.

Results The methylation rates of CpG3 and CpG10 in non-insomnia group and insomnia group were higher than those in healthy control group. The methylation rate of CpG7 in insomnia group was lower than that in healthy control group, and the methylation rate of CpG9 was higher than that in non-insomnia group (P<0.05). Partial correlation analysis showed that the CpG10 methylation rate was moderately positively correlated with the number of words （r＝0.569，P＜0.05）and colors（r＝0.526，P＜0.05）in the Stroop Color words Test (SCWT), and the CpG6 methylation rate was moderately positively correlated with the number of color words in SWCT（r＝0.558，P＜0.05）.Multifactor Logistics regression showed that the increased Hamilton Depression Scale (HAMD) score (P = 0.034, OR = 0.729, 95%CI: 0.544 ~ 0.976) and methylation level of CpG9 (OR = 0.814, 95%CI: 0.677 ~ 0.978, P = 0.028) were independent risk factors for insomnia in patients with bipolar depression.

Conclusion Aberrant methylation in the promoter region of NR2B gene may mediate insomnia in patients with bipolar depression and may be related to the impairment of executive function related to insomnia.

Key words: 【Key words】Bipolar depression; N-methyl-D-aspartate receptor 2B subunit; DNA methylation; insomnia; executive function；

引用本文 / How to Cite This Article

余浩,肖玉新,邹韶红.双相抑郁患者失眠相关执行功能损害与NR2B基因启动子区甲基化水平的关系[J]. 国际精神病学杂志, 2026, 53(1): 73-76

参考文献

[1] 1． Choi J, Kang J, Kim T, et al. Sleep, mood disorders, and the ketogenic diet: potential therapeutic targets for bipolar disorder and schizophrenia[J][J]. Front Psychiatry, 2024, 15(): 1358578-.

[2] 3． Pearson O, Uglik-Marucha N, Miskowiak K W, et al. The relationship between sleep disturbance and cognitive impairment in mood disorders: A systematic review[J][J]. J Affect Disord, 2023, 327(): 207-216.

[3] 4． Carrier J, Semba K, Deurveilher S, et al. Sex differences in age-related changes in the sleep-wake cycle[J][J]. Front Neuroendocrinol, 2017, 47(): 66-85.

[4] 5． Nakamura T J, Nakamura W, Yamazaki S, et al. Age-related decline in circadian output[J][J]. J Neurosci, 2011, 31(28): 10201-10205.

[5] 6． Biello S M, Bonsall D R, Atkinson L A, et al. Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice[J][J]. Neurobiol Aging, 2018, 66(): 75-84.

[6] 7． Steponenaite A, Biello S M, Lall G S. Aging clocks: disrupted circadian rhythms[J][J]. Aging (Albany NY), 2018, 10(11): 3065-3066.

[7] 8．余浩, 邹韶红. N-甲基-D-天冬氨酸受体2B亚基基因遗传与认知功能损害关系的研究进展[J][J]. 神经疾病与精神卫生, 2023, 23(09): 676-680.

[8] 9． Zhao Q, Che R, Zhang Z, et al. Positive association between GRIN2B gene and bipolar disorder in the Chinese Han Population[J][J]. Psychiatry Res, 2011, 185(1-2): 290-292.

[9] 10．Berk M, Berk L, Davey C G, et al. Treatment of bipolar depression[J][J]. Med J Aust, 2013, 199(S6): S32-S35.

[10] 11．Dalkner N, Bengesser S A, Birner A, et al. Metabolic Syndrome Impairs Executive Function in Bipolar Disorder[J][J]. Front Neurosci, 2021, 15(): 717824-.

[11] 12．Ludwig B, Dwivedi Y. Dissecting bipolar disorder complexity through epigenomic approach[J][J]. Mol Psychiatry, 2016, 21(11): 1490-1498.

[12] 13．Gaine M E, Seifuddin F, Sabunciyan S, et al. Differentially methylated regions in bipolar disorder and suicide[J][J]. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2019, 180(7): 496-507.

[13] 14．Fries G R, Li Q, McAlpin B, et al. The role of DNA methylation in the pathophysiology and treatment of bipolar disorder[J][J]. Neurosci Biobehav Rev, 2016, 68(): 474-488.

[14] 15．Fries G R, Quevedo J, Zeni C P, et al. Integrated transcriptome and methylome analysis in youth at high risk for bipolar disorder: a preliminary analysis[J][J]. Transl Psychiatry, 2017, 7(3): e1059-.

[15] 16．Fries G R, Bauer I E, Scaini G, et al. Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder[J][J]. Transl Psychiatry, 2017, 7(12): 1283-.

[16] 17．李宁, 刘紫阳, 詹向红, 等. 长期负性情绪应激对D-gal大鼠认知功能及海马NR2B基因甲基化表达的影响[J][J]. 中国中西医结合杂志, 2019, 39(06): 702-707.

[17] 19．Xu F, Zhao X, Liu H, et al. Misaligned Feeding May Aggravate Pain by Disruption of Sleep-Awake Rhythm[J][J]. Anesth Analg, 2018, 127(1): 255-262.

[18] 20．Li Y, Xiao X, Wang L, et al. Comparison effects of chronic sleep deprivation on juvenile and young adult mice[J][J]. J Sleep Res, 2022, 31(1): e13399-.

[19] 21．梁小敏, 李玮, 张园, 等. 快速眼动期睡眠剥夺对大鼠学习记忆和海马NR2B含量的影响[J][J]. 中华临床医师杂志(电子版), 2013, 7(08): 3471-3474.

[20] 22．Kopp C, Longordo F, Nicholson J R, et al. Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function[J][J]. J Neurosci, 2006, 26(48): 12456-12465.

[21] 23．Kopp C, Longordo F, Luthi A. Experience-dependent changes in NMDA receptor composition at mature central synapses[J][J]. Neuropharmacology, 2007, 53(1): 1-9.

[22] 24．Mukherjee D, Krishnamurthy V B, Millett C E, et al. Total sleep time and kynurenine metabolism associated with mood symptom severity in bipolar disorder[J][J]. Bipolar Disord, 2018, 20(1): 27-34.

[23] 25．Palagini L, Cipollone G, Masci I, et al. Insomnia symptoms predict emotional dysregulation, impulsivity and suicidality in depressive bipolar II patients with mixed features[J][J]. Compr Psychiatry, 2019, 89(): 46-51.

标题作者
文章摘要
参考文献
引用本文
相关文章

PDF 全文下载

浏览量

1529

PDF下载量