血清miRNAs对SSRIs治疗巩固期停药抑郁症患者复发的影响

彭玲; 陈莹; 陈晶

doi:10.16766/j.cnki.issn.1674-4152.003589

血清miRNAs对SSRIs治疗巩固期停药抑郁症患者复发的影响

doi: 10.16766/j.cnki.issn.1674-4152.003589

绍兴市第七人民医院焦虑障碍科，浙江绍兴 312000

基金项目:

浙江省医药卫生科技计划项目 2023KY1272

绍兴市卫生健康科技计划项目 2022KY056

详细信息

通讯作者:
彭玲，E-mail：PL363089259@163.com

中图分类号: R749.05 R446
计量
- 文章访问数: 17
- HTML全文浏览量: 9
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2024-01-09
- 网络出版日期: 2024-09-05

The effect of serum miRNAs on the recurrence of depression in patients with SSRIs withdrawal during consolidation period

Department of Anxiety Disorders, Shaoxing Seventh People' s Hospital, Shaoxing, Zhejiang 312000, China

摘要

摘要: 目的基于微小核糖核酸-134(miR-134)、微小核糖核酸-16(miR-16)参与抑郁症基因调控过程理论，分析血清中2种因子对5-羟色胺再摄取抑制剂(5-selective serotonin reuptake inhibitors, SSRIs)治疗巩固期内停药的首发抑郁症患者1年期复发风险的影响。方法选取绍兴市第七人民医院2021年10月—2022年5月5-羟色胺再摄取抑制剂治疗并于巩固期停药的首发抑郁症患者125例。采用Kaplan-Meier生存分析和Cox风险比例回归模型评估血清miR-134、miR-16对停药1年期复发的影响。结果 Kaplan-Meie生存分析结果显示，血清高水平miR-134、miR-16患者“非复发状态”时间为(11.01±0.27)个月和(11.14±0.29)个月，较血清低水平miR-134[(9.32±0.42)个月]、miR-16[(9.59±0.36)个月]患者“非复发状态”时间均显著延长(P＜0.05)。Cox分析显示，患者1年期复发的危险因素为抑郁家族史(HR=2.219)；保护因素为用药时间延长(HR=0.759)、血清miR-134(HR=0.005)、miR-16(HR＜0.001)水平升高以及联合物理治疗(HR=0.188)。结论血清miR-134、miR-16表达水平升高对巩固期内停药的SSRIs治疗首发抑郁症患者1年期复发具有良好的预防与保护作用。
- 首发抑郁症 /
- 血清微小核糖核酸-134 /
- 血清微小核糖核酸-16 /
- 5-羟色胺再摄取抑制剂 /
- 巩固期停药 /
- 复发
Abstract: Objective Based on the theory that microRNA-134 (miR-134) and microRNA-16 (miR-16) are involved in the gene regulation process of depression, this paper analyzes the effects of two factors in serum on the one-year recurrence risk of patients with first-episode depression who stopped taking selective serotonin reuptake inhibitors (SSRIs) during the consolidation period. Methods A total of 125 patients with first-episode depression who were treated with 5-hydroxytryptamine reuptake inhibitors and stopped during the consolidation period from October 2021 to May 2022 in Shaoxing Seventh People ' s Hospital were selected. Kaplan-Meier survival analysis and Cox proportional hazard regression model were used to evaluate the effect of serum miR-134 and miR-16 on one-year recurrence after withdrawal. Results K-M survival analysis showed that the distribution of the "non-recurrent state" in patients with high serum miR-134 and miR-16 levels was (11.01±0.27) months and (11.14±0.29) months, respectively. This was significantly longer than that in patients with low serum miR-134 [(9.32±0.42) months] and miR-16 [(9.59±0.36) months, with P < 0.05]. Cox analysis showed that family history of depression was the risk factor for one-year recurrence (HR=2.219). The protective factors included prolonged medication time (HR=0.759), elevated serum level of miR-134 (HR=0.005), elevated level of miR-16 (HR < 0.001), and combined physical therapy (HR=0.188). Conclusion The expression levels of serum miR-134 and miR-16 have a good preventive and protective effect on the recurrence of first-episode depression patients after stopping SSRIs for one year in consolidation period.
- First-episode depression /
- Serum microRNA-134 /
- Serum microRNA-134 /
- Selective serotonin reuptake inhibitors /
- Consolidation period withdrawal /
- Recurrence

HTML全文

图 1 血清miR-134表达水平对首发抑郁症患者停药1年期复发的Kaplan-Meier生存曲线

Figure 1. Kaplan-Meier survival curve for 1-year recurrence of first-episode depression patients after drug withdrawal, based on serum miR-134 expression

下载: 全尺寸图片幻灯片

图 2 血清miR-16表达水平对首发抑郁症患者停药1年期复发的Kaplan-Meier生存曲线

Figure 2. Kaplan-Meier survival curve for 1-year recurrence of first-episode depression patients after drug withdrawal, based on serum miR-16 expression

下载: 全尺寸图片幻灯片

图 3 SSRIs治疗巩固期内停药的首发抑郁症患者追踪期“非复发状态”的变化趋势图

Figure 3. Trend of 'non-relapse' status during follow-up for first-episode depression patients who discontinued SSRIs during the consolidation period

下载: 全尺寸图片幻灯片

表 1 2组首发抑郁症患者人口学指标比较

Table 1. Comparison of demographic indicators between two groups of patients with first-episode depression

组别	例数	性别[例(%)]		年龄 (x±s, 岁)	受教育程度[例(%)]			抑郁家族史[例(%)]		BMI (x±s)
组别	例数	男性	女性	年龄 (x±s, 岁)	初中以下	高中/中专	大专以上	是	否	BMI (x±s)
复发组	42	13(30.95)	29(69.05)	31.43±7.44	17(40.48)	17(40.48)	8(19.04)	24(57.14)	18(42.86)	22.38±2.43
非复发组	83	41(49.40)	42(50.60)	29.88±6.06	16(19.28)	46(55.42)	21(25.30)	32(38.55)	51(61.45)	23.13±2.38
统计量		3.867^a		1.248^b	-2.074^c			3.897^a		-1.645^b
P值		0.049		0.214	0.038			0.048		0.102
注：^a为χ²值，^b为t值，^c为Z值。

下载: 导出CSV

表 2 2组首发抑郁症患者伴发慢性疾病及血清miRNAs指标比较

Table 2. Comparison of chronic diseases and serum miRNAs between two groups in patients with first-episode depression

组别	例数	高血压[例(%)]		糖尿病[例(%)]		高血脂[例(%)]		miR-134 (x±s)	miR-16 [M(P₂₅, P₇₅)]
组别	例数	是	否	是	否	是	否	miR-134 (x±s)	miR-16 [M(P₂₅, P₇₅)]
复发组	42	12(28.57)	30(71.43)	10(23.81)	32(76.19)	9(21.43)	33(78.57)	0.35±0.11	0.03(0.02, 0.04)
非复发组	83	21(25.30)	62(74.70)	17(20.48)	66(79.52)	15(18.07)	68(81.93)	0.41±0.09	0.04(0.03, 0.05)
统计量		0.153^a		0.182^a		0.202^a		3.672^b	-4.094^c
P值		0.695		0.669		0.653		＜0.001	＜0.001
注：^a为χ²值，^b为t值，^c为Z值。

下载: 导出CSV

表 3 2组首发抑郁症患者抑郁状态、治疗指标比较

Table 3. Comparison of depression status and treatment indicators between two groups of patients with first-episode depression

组别	例数	抑郁严重程度[例(%)]		用药时间 [M(P₂₅, P₇₅), 月]	联合用药[例(%)]		物理治疗[例(%)]		心理治疗[例(%)]		中医治疗[例(%)]
组别	例数	轻中度	重度	用药时间 [M(P₂₅, P₇₅), 月]	是	否	是	否	是	否	是	否
复发组	42	24(57.14)	18(42.86)	4.00(3.00, 6.00)	5(11.90)	37(88.10)	2(4.76)	40(95.24)	8(19.05)	34(80.95)	2(4.76)	40(95.24)
非复发组	83	63(75.90)	20(24.10)	6.00(4.00, 7.00)	7(8.43)	76(91.57)	15(18.07)	68(81.93)	17(20.48)	66(79.52)	13(15.66)	70(84.34)
统计量		4.639^a		-2.527^b	0.387^a		4.205^a		0.036^a		3.138^a
P值		0.031		0.012	0.534		0.040		0.850		0.076
注：^a为χ²值，^b为Z值。

下载: 导出CSV

表 4 首发抑郁症患者停药1年期复发的多因素Cox风险比例回归模型分析

Table 4. Multivariate Cox proportional hazards regression model analysis of 1-year relapse in patients with first-episode depression after drug withdrawal

变量	B	SE	Waldχ²	P值	HR值	95% CI
抑郁家族史	0.797	0.350	5.175	0.023	2.219	1.117~4.409
用药时间	-0.276	0.103	7.245	0.007	0.759	0.620~0.928
miR-134	-5.404	2.052	6.935	0.008	0.005	＜0.001~0.251
miR-16	-26.942	12.112	4.948	0.026	＜0.001	＜0.001~0.041
物理治疗	-1.674	0.779	4.615	0.032	0.188	0.041~0.864

下载: 导出CSV

参考文献(20)

[1]	中华医学会行为医学分会, 中华医学会行为医学分会认知应对治疗学组. 抑郁症治疗与管理的专家推荐意见(2022年)[J]. 中华行为医学与脑科学杂志, 2023, 32(3): 193-202. doi: 10.3760/cma.j.cn371468-20220921-00563 Chinese Society of Behavioral Medicine; ognitive Coping Therapy Group, Chinese Society of Behavioral Medicine. Expert recommendations on the treatment and management of major depressive disorder(2022)[J]. Chinese Journal of Behavioral Medicine and Brain Science, 2023, 32(3): 193-202. doi: 10.3760/cma.j.cn371468-20220921-00563
[2]	陈寿林, 朱生芝, 于畅, 等. 老年抑郁症患者血清指标与认知功能的相关性研究[J]. 中华全科医学, 2022, 20(3): 450-453. doi: 10.16766/j.cnki.issn.1674-4152.002375 CHEN S L, ZHU S Z, YU C, et al. Correlation between serum indexes and cognitive function in elderly patients with depression[J]. Chinese Journal of General Practice, 2022, 20(3): 450-453. doi: 10.16766/j.cnki.issn.1674-4152.002375
[3]	康丽君, 张楠, 王薇, 等. 抑郁症复发与脑功能及结构变化的关系研究进展[J]. 神经损伤与功能重建, 2022, 17(4): 225-227. https://www.cnki.com.cn/Article/CJFDTOTAL-GWKF202204011.htm KANG L J, ZHANG N, WANG W, et al. Research progress on the relationship between recurrence of depression and changes of brain function and structure[J]. Neural Injury and Functional Reconstruction, 2022, 17(4): 225-227. https://www.cnki.com.cn/Article/CJFDTOTAL-GWKF202204011.htm
[4]	胡园园, 丁研, 林鹏, 等. miRNA-16在常见头颈部恶性肿瘤中的研究进展[J]. 现代肿瘤医学, 2023, 31(6): 1166-1169. https://www.cnki.com.cn/Article/CJFDTOTAL-SXZL202306037.htm HU Y Y, DING Y, LIN P, et al. The research progress of miRNA-16 in common head and neck tumors[J]. Journal of Modern Oncology, 2023, 31(6): 1166-1169. https://www.cnki.com.cn/Article/CJFDTOTAL-SXZL202306037.htm
[5]	宋晋, 梁婷, 王强, 等. miR-134/CREB/BDNF通路在低频重复经颅磁刺激影响癫痫大鼠抑郁、焦虑样行为中的作用[J]. 中国老年学杂志, 2022, 42(14): 3562-3565. doi: 10.3969/j.issn.1005-9202.2022.14.052 SONG J, LIANG T, WANG Q, et al. The role of miR-134/ CREB / BDNF pathway in the effect of low-frequency repetitive transcranial magnetic stimulation on depression and anxiety-like behavior in epileptic rats[J]. Chinese Journal of Gerontology, 2022, 42(14): 3562-3565. doi: 10.3969/j.issn.1005-9202.2022.14.052
[6]	顾峰, 周岩, 韦培培. 乳腺癌患者外周血miRNA-134表达及化疗耐药的机制[J]. 重庆医学, 2018, 47(6): 779-782, 785. doi: 10.3969/j.issn.1671-8348.2018.06.018 GU F, ZHOU Y, WEI P P. Expression of peripheral blood miRNA-134 in patients with breast cancer and mechanism of chemotherapy drug resistance[J]. Chongqing medicine, 2018, 47(6): 779-782, 785. doi: 10.3969/j.issn.1671-8348.2018.06.018
[7]	过伟峰, 曹晓岚, 盛蕾, 等. 抑郁症中西医结合诊疗专家共识[J]. 中国中西医结合杂志, 2020, 40(2): 141-148. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ202002006.htm GUO W F, CAO X L, SHENG L, et al. Expert Consensus on Diagnosis and Treatment of Major Depressive Disorder by Integrated Chinese and Western Medicine[J]. Chinese Journal of Integrated Traditional and Western Medicine, 2020, 40(2): 141-148. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ202002006.htm
[8]	高舒展, 张宁. 从临床治愈到临床缓解: 抑郁障碍Remission的认识亟需转变[J]. 临床精神医学杂志, 2022, 32(1): 1-4. doi: 10.3969/j.issn.1005-3220.2022.01.001 GAO S Z, ZHANG N. From clinical cure to clinical remission: the understanding of remission in major depressive disorder urgently needs to be changed[J]. Journal of Clinical Psychiatry, 2022, 32(1): 1-4. doi: 10.3969/j.issn.1005-3220.2022.01.001
[9]	高敏, 高长越. 经颅磁刺激对中枢神经系统胶质细胞的影响及其研究进展[J]. 中华全科医学, 2022, 20(7): 1207-1210, 1239. doi: 10.16766/j.cnki.issn.1674-4152.002559 GAO M, GAO C Y. Effects and research progress of transcranial magnetic stimulation on glial cells in the central nervous system[J]. Chinese Journal of General Practice, 2022, 20(7): 1207-1210, 1239. doi: 10.16766/j.cnki.issn.1674-4152.002559
[10]	尹一淑, 刘军莲, 王佳平, 等. 抑郁症相关发病机制研究进展[J]. 医学综述, 2022, 28(12): 2368-2372. doi: 10.3969/j.issn.1006-2084.2022.12.014 YIN Y S, LIU J L, WANG J P, et al. Research progress in pathogenesis of depression[J]. Medical Recapitulate, 2022, 28(12): 2368-2372. doi: 10.3969/j.issn.1006-2084.2022.12.014
[11]	朱秀芝. miRNA-134调控神经结构可塑性参与抑郁症发病的机制研究[D]. 济南: 山东大学, 2017. ZHU X Z. The mechanism of miRNA-134 regulating neural structural plasticity involved in the pathogenesis of depression[D]. Jinan: Shandong University, 2017.
[12]	曾志涌, 黄玉玲, 黎云鹏. miRNA-134对缺氧缺血性脑病动物模型的调控作用及机制探讨[J]. 中华神经医学杂志, 2018, 17(9): 925-928. ZENG Z Y, HUANG Y L, LI Y P. Regulatory and mechanism of miRNA-134 in animal models of hypoxic ischemic encephalopathy[J]. Chinese Journal of Neuromedicine, 2018, 17(9): 2018, 17(9): 925-928.
[13]	胡雅坤, 王志强, 梁家辉. 微小RNA-134靶向调控环腺苷酸应答元件结合蛋白/脑源性神经营养因子通路对脑卒中后抑郁海马神经细胞的影响[J]. 临床神经病学杂志, 2022, 35(1): 56-60. https://www.cnki.com.cn/Article/CJFDTOTAL-LCSJ202201011.htm HU Y K, WANG Z Q, LIANG J H. Effect of microRNA-134 targeting cyclic AMP response element binding protein 1/brain derived neurotrophic factor pathway on hippocampal neurons of post-stroke depression[J]. Journal of Clinical Neurology, 2022, 35(1): 56-60. https://www.cnki.com.cn/Article/CJFDTOTAL-LCSJ202201011.htm
[14]	郝冉, 王翼鹏, 王永剑, 等. 非编码RNA在抑郁症中的研究进展[J]. 生命科学, 2022, 34(12): 1493-1505. https://www.cnki.com.cn/Article/CJFDTOTAL-SMKX202212004.htm HAO R, WANG Y P, WANG Y J, et al. Research progress of non-coding RNA in depression [J]. Chinese Bulletin of Life Sciences, 2022, 34(12): 1493-1505. https://www.cnki.com.cn/Article/CJFDTOTAL-SMKX202212004.htm
[15]	钱时兴, 房圆, 孙琳, 等. 西酞普兰对抑郁症患者外周血miRNA-16/5-羟色胺转运体通路的影响[J]. 上海交通大学学报(医学版), 2020, 40(6): 814-819. doi: 10.3969/j.issn.1674-8115.2020.06.017 QIAN S X, FANG Y, SUN L, et al. Effect of citalopram on miRNA-16/serotonin transporter pathway in peripheral blood of patients with depression[J]. Journal of Shanghai Jiao tong University: Medical Science, 2020, 40(6): 814-819. doi: 10.3969/j.issn.1674-8115.2020.06.017
[16]	赵俊, 田会玲, 李昱颉, 等. 电针对抑郁模型大鼠不同脑区miRNA-16及5-羟色胺转运体的影响[J]. 针灸临床杂志, 2019, 35(11): 69-74. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJLC201911018.htm ZHAO J, TIAN H L, LI Y J, et al. Effect of electroacupuncture on miRNA-16 and 5-HT transporter in different brain regions of depression model rats[J]. Journal of Clinical Acupuncture and Moxibustion, 2019, 35(11): 69-74. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJLC201911018.htm
[17]	查倩倩, 徐莲英, 孔晓明, 等. 老年抑郁症住院患者复发影响因素的回顾性分析[J]. 中国健康心理学杂志, 2022, 30(3): 326-329. https://www.cnki.com.cn/Article/CJFDTOTAL-JKXL202203002.htm ZHA Q Q, XU L Y, KONG X M, et al. Influencing factors of relapse in late-life depression[J]. China Journal of Health Psychology, 2022, 30(3): 326-329. https://www.cnki.com.cn/Article/CJFDTOTAL-JKXL202203002.htm
[18]	吴婷婷, 娄永翱, 沈翠珍. 老年抑郁症患者复发影响因素分析[J]. 中国医药导报, 2022, 19(29): 77-80. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202229017.htm WU T T, LOU Y A, SHEN C Z. Analysis of influencing factors of recurrence in elderly patients with depression[J]. China Medical Herald, 2022, 19(29): 77-80. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202229017.htm
[19]	李桂萍, 宋明芬, 李静, 等. 降低脑脊液miR-16的水平对大鼠抑郁样行为的影响[J]. 中国病理生理杂志, 2020, 36(10): 1875-1880. https://www.cnki.com.cn/Article/CJFDTOTAL-ZBLS202010020.htm LI G P, SONG M F, LI J, et al. Effects of decreasing miR-16 in cerebrospinal fluid on depression-like behaviors in rats[J]. Chinese Journal of Pathophysiology, 2020, 36(10): 1875-1880. https://www.cnki.com.cn/Article/CJFDTOTAL-ZBLS202010020.htm
[20]	马燕妮, 张程程. 精神分裂症、双相情感障碍和抑郁症的跨疾病miRNA分子标记研究进展[J]. 中华医学遗传学杂志, 2022, 39(5): 548-554. MA Y N, ZHANG C C. Research progress of cross-disease miRNA molecular markers in schizophrenia, bipolar disorder and depression[J]. Chinese Journal of Medical Genetics, 2022, 39(5): 548-554.