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
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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

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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。

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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。

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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。

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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

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