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Advances in Clinical Medicine
Vol. 12  No. 12 ( 2022 ), Article ID: 59215 , 7 pages
10.12677/ACM.2022.12121629

首发抑郁症伴焦虑特征患者血清脑源性神经因子水平及临床意义

宋京瑶1，王皋茂2*，庞辉1，李振阳1，高贺1，何现萍2

1重庆医科大学附属大学城医院精神科，重庆

2重庆市长寿区第三人民医院精神科，重庆

收稿日期：2022年11月14日；录用日期：2022年12月8日；发布日期：2022年12月16日

摘要

目的：探讨首发抑郁症伴焦虑特征患者的血清脑源性神经营养因子变化水平的关系及临床意义。方法：选取2016年7月至2018年11月就诊于重庆医科大学附属大学城医院门诊和住院的首发抑郁症患者90例(研究组)和体检中心健康人员90例(健康对照组)作为研究对象，将研究组按患者焦虑症状的严重程度分为一般焦虑组(14 < HAMA ≤ 21)和明显焦虑组(HAMA > 21分)，采用酶联免疫吸附法检测血清中BDNF水平，采用HAMD-17、HAMA、CGI评定临床症状及病情严重程度。结果：研究组患者血浆BDNF水平明显低于健康对照组(P < 0.05)。研究组各亚组进一步比较，明显焦虑组年龄低于一般焦虑组(P < 0.05)；明显焦虑组HAMD总分、阻滞因子评分、睡眠障碍因子评分以及CGI-S评分均高于一般焦虑组(P < 0.05)；经Pearson相关分析，基线血清BDNF水平与CGI评分呈负相关(r = −0.221, P = 0.037)。ROC曲线分析显示，BDNF诊断首发伴焦虑症状抑郁症患者的最佳切点值为12.285 ug/L，诊断灵敏度和特异度分别为41.1%和95.6%，ROC曲线下面积为0.747。结论：首发抑郁症伴焦虑特征患者血清BDNF水平与疾病严重程度呈负相关，低年龄、睡眠障碍、阻滞为首发抑郁症患者伴焦虑症状严重程度的尽管，目前大量研究已证实危险因素。

关键词

首发抑郁症，焦虑特征，脑源性神经营养因子

Levels of Serum Brain-Derived Neurothrophic Factor in First-Episode Depression Patients with Anxiety Symptoms and Its Clinical Significance

Jingyao Song1, Gaomao Wang2*, Hui Pang1, Zhenyang Li1, He Gao1, Xianping He2

1Psychiatry Department, University-Town Hospital of Chongqing Medical University, Chongqing

2Psychiatry Department, The Third People’s Hospital of Changshou District in Chongqing, Chongqing

Received: Nov. 14th, 2022; accepted: Dec. 8th, 2022; published: Dec. 16th, 2022

ABSTRACT

Objective: To measured the levers of serum brain-derived neurothrophic factor in first-episode depression patients with anxiety symptoms, and to explore its clinical significance. Methods: From July 2016 to November 2018, 90 first-episode depression patients (research group) treated in University-Town Hospital of Chongqing Medical University and 90 health checkers (health control group) in the physical examination center were selected as the study objects. The research group was divided into general anxiety group (14 < HAMA ≤ 21) and obvious anxiety group (HAMA > 21 points) according to the severity of anxiety symptoms. The levers of BDNF in the serum of the subjects were detected by enzyme-linked immunosorbent assay. We used HAMD-17, HAMA, CGI to assess clinical symptoms and severity of illness. Results: The plasma BDNF level of the study group was significantly lower than that of the healthy control group (P < 0.05). The subgroups of the study group were further compared. The age of the obvious anxiety group was lower than that of the general anxiety group (P < 0.05); the total score of HAMD, block factor score, sleep disorder factor score and CGI-S score of the obvious anxiety group were higher than those of the general anxiety group (P < 0.05); Pearson correlation analysis showed that baseline serum BDNF level was negatively correlated with CGI score (r = −0.221, P = 0.037). ROC curve analysis showed that the best cut-point value of BDNF for diagnosing first-episode depression patients with anxiety symptoms was 12.285 ug/L, the diagnostic sensitivity and specificity were 41.1% and 95.6%, respectively, and the area under the ROC curve was 0.747. Conclusion: The level of serum BDNF in patients with first-onset depression with anxiety symptoms is negatively correlated with the severity of the disease. Low age, sleep disturbance, and blockade are risk factors for the severity of first-on depression with anxiety symptoms.

Keywords:First-Episode Depression, Anxiety Symptoms, Brain-Derived Neurotrophic Factor

Copyright © 2022 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

1. 引言

抑郁症是一种常见的精神障碍，致病因素复杂，异质性高，临床症状多样，导致疾病反复复发，病情迁延不愈。抑郁症多伴随焦虑症状，导致疾病症状更重，以致患者自伤、自杀行为频繁发生，显著增加了治疗难度和疾病负担 [1]。目前，抑郁症的发病机制仍未达成共识，积极探索抑郁症潜在的生物学标志物在预防和诊疗抑郁症中至关重要。如今，“神经营养因子”假说已成为抑郁症的研究热点。现有研究表明，脑源性神经营养因子(Brain-derived neurothrophic factor, BDNF)与抑郁症的发生、发展及病情程度相关 [2] [3] [4]。然而，目前大多数研究主要局限在单纯焦虑或单纯抑郁与神经营养因子相关性的研究 [5]，对焦虑抑郁共病潜在的生物学机制研究匮乏。为此，本研究探讨血清BDNF水平与首发伴焦虑症状抑郁症的相关性，有利于进一步阐明这种共病的起源和潜在的病理生理机制，为神经因子在抑郁症精准医疗中提供新靶点。

2. 资料与方法

2.1. 一般资料

选取2016年7月至2018年11月就诊于重庆医科大学附属大学城医院门诊和住院的首发抑郁症患者。入组标准：1) 符合美国精神障碍诊断与统计手册第5版(Diagnostic and Statistical Manual of Mental Disorders Five Edition, DSM-5)重性抑郁发作的诊断标准；2) 汉密尔顿抑郁量表(HAMD-17)总分 ≥ 17分；汉密尔顿焦虑量表(HAMA)总分 ≥ 14分；3) 首次发作，入组4周内未服用抗抑郁药物；4) 年龄15~60岁。排除标准：1) 其它器质性或药物引起的继发性抑郁症或双相情感障碍；2) 脑器质性疾病或严重躯体疾病；3) 孕妇或哺乳期妇女。另选同期年龄、性别因素与研究组相匹配的体检中心健康体检人员或健康志愿者。入组标准：1) 年龄15~60岁；2) 无精神疾病诊断及重大躯体疾病；3) 入组前4周内未用过任何药物。共纳入180例，研究组和健康对照组各90例，将研究组按患者焦虑症状的严重程度分为一般焦虑组(14 < HAMA ≤ 21)和明显焦虑组(HAMA > 21分)。本研究获得医院伦理委员会批准，所有入组患者或家属自愿签署知情同意书。

2.2. 研究方法

2.2.1. 量表评定

由2名经过严格培训的精神科主治医师采用临床定式检查进行抑郁症诊断。并搜集所有研究对象的一般资料，同时进行HAMD-17、HAMA及CGI-S量表评定。

HAMD-17：共17项，由焦虑/躯体化因子、认知障碍因子、体重因子、阻滞因子、睡眠障碍因子组成，评分越高，提示抑郁症状越重。评分标准；HAMD-17 ≥ 24分，为重度抑郁；17 ≤ HAMD-17 < 24分，为中度抑郁，7 ≤ HAMD-17 < 17分，为轻度抑郁，HAMD-17 ≤ 7分，则没有抑郁 [6]。

HAMA：共14项，由躯体性焦虑因子和精神性焦虑因子组成，评分越高，提示焦虑症状越重。评分标准：14 < HAMA ≤ 21肯定有焦虑；21 < HAMA ≤ 28有明显焦虑；总分 ≥ HAMA分，可能为严重焦虑 [7]。

临床总体印象量表–严重程度量表(CGI-S)：采用0~7分8级评定，评分越高，提示病情越重 [8]。

2.2.2. 血清BDNF检测

受试者于次日清晨采取外周静脉血4 ml，真空采血管采集(非抗凝)。血样本室温静止30 min，以3000 rpm离心10 min，分离出上层血清，放置于−80℃储存。使用酶联免疫吸附法(ELISA)进行检测所有入组患者血清中BDNF水平，试剂盒购自上海沪宇生物科技有限公司，由实验员一次性解冻所有标本，严格按照说明书要求进行操作。

2.3. 统计学方法

采用SPSS 23.0统计软件进行数据分析，符合正态分布的计量资料以均数 ± 标准差( x ¯ ± s )表示，两组间比较采用t检验；计数资料采用卡方检验比较组间的差别。血清BDNF水平与CGI、HAMD等评分的相关性分析采用Pearson相关分析。受试者工作特征(ROC)曲线判断血清BDNF指标的诊断价值。P < 0.05表示差具有统计学意义。

3. 结果

3.1. 研究组和健康对照组人口学及血清BDNF水平比较

研究组患者BDNF水平明显低于健康对照组，差异有统计学意义(P < 0.05)。两组患者在年龄、性别、教育年限上比较，差异无统计学意义(P > 0.05)。见表1：

Table 1. Comparison of demographic and serum BDNF levels between the study group and the healthy control group

表1. 研究组和健康对照组人口学及血清BDNF水平比较

3.2. 研究组各亚组患者人口学、临床量表及血清BDNF水平比较

研究组各亚组进一步比较，明显焦虑组年龄低于一般焦虑组，差异有统计学意义(P < 0.05)；明显焦虑组HAMD总分、阻滞因子评分、睡眠障碍因子评分以及CGI-S评分均高于一般焦虑组，差异有统计学意义(P < 0.05)；两组在性别、文化年限、焦虑/躯体化因子评分、体质量因子评分、认知障碍因子评分以及血清BDNF水平上比较，差异均无统计学意义(P > 0.05)，见表2。

Table 2. Comparison of demographic, clinical scales and serum BDNF and GDNF levels in subgroups of the study group

表2. 研究组各亚组患者人口学、临床量表及血清BDNF、GDNF水平比较

3.3. 研究组血清BDNF水平与临床量表的相关性分析

血清BDNF水平与CGI评分呈负相关(r = −0.221, P = 0.037)，与HAMD、HAMA评分均无相关性。

3.4. 血清BDNF水平诊断首发抑郁症的ROC曲线分析

血清BDNF诊断抑郁症的曲线下面积为(AUC)分别为0.747，血清BDNF诊断抑郁症的最佳临界值为12.285 ug/L，诊断灵敏度和特异度分别为41.1%和95.6%。见图1。

Figure 1. ROC curve of serum BDNF level in diagnosis of first-episode depression

图1. 血清BDNF水平诊断首发抑郁症的ROC曲线

4. 讨论

焦虑抑郁共病是临床常见的一种共病综合征，共病率高达80.3%，临床症状复杂多变，治疗难度大，预后不良，备受精神领域学者的广泛关注 [9]。迄今为止，焦虑抑郁共病潜在的病理生理机制尚未阐明。众多研究表明，焦虑抑郁共病可能与下丘脑–垂体–肾上腺轴功能 [10]、结构和功能脑影像学表现 [11]、炎症标志物 [12] 等方面相关。He C等学者对75例未服药的抑郁症患者和42例认知正常的受试者进行静息功能磁共振成像研究发现，焦虑抑郁共病组患者杏仁核功能连接性普遍降低，尤其在额顶系统和内侧颞叶 [13]。Lin等研究发现，与健康组比较，焦虑抑郁共病组静息状态下的总δ和θ值较低，总β值、低β值和高β值较高，证明此类患者全脑区β活性较高 [14]。Molina等研究发现，5-羟色胺1-A受体基因多态性与焦虑症和抑郁症常见临床表现具有相关性，提示焦虑抑郁共病具有共同的遗传机制 [15]。尽管，目前大量研究已证实，焦虑抑郁共病与不同的神经生理及生物学机制相关，但仍缺乏统一有力证据 [16]。

如今，“神经因子假说”和“神经可塑性假说”一直为抑郁症生物学领域的研究热点。神经营养因子是一种神经元的发育、存活和凋亡起重要作用的蛋白质，是治疗神经损伤等疾病的潜在药物靶标。其中，BDNF是一种参与中枢神经可塑性和神经损伤修复的营养因子，可以提高脑内5-羟色胺浓度水平，防止5-羟色胺神经元退化 [17]。目前，众多研究者认为，在抑郁症急性发作期，血清BDNF水平降低，而且经过抗抑郁药治疗后逐渐恢复 [18]。但关于焦虑抑郁共病的研究相对匮乏。本研究结果显示，研究组BDNF水平均低于健康对照组。统计结果还表明血清BDNF水平诊断抑郁症的ROC曲线面积为0.747，诊断抑郁症的最佳临界值为12.285 ug/L，诊断灵敏度和特异度分别为41.1%和95.6%。因此，BDNF水平可能是首发抑郁症共病焦虑症发病的致病因素之一，对抑郁症诊断具有较高价值。

本研究结果显示，血清BDNF水平与CGI呈负相关，与HAMD、HAMA评分均无相关性，表明血清BDNF水平越低，首发伴焦虑症状的抑郁症患者疾病严重程度越重，而与单纯的焦虑、抑郁症状无相关性。既往研究显示，血清BDNF水平与抑郁症患者的HAMD、HAMA评分呈负相关 [19] [20]。与本研究结论不一致的结论原因可能在于本研究入组对象为首发抑郁症伴焦虑症状的患者，其临床症状复杂，疾病的严重程度不能以单纯的焦虑、抑郁症状进行评价。同时，本研究进一步对研究组不同程度焦虑症状患者的BDNF水平进行比较，发现明显焦虑症状组与一般焦虑症状组在BDNF水平上比较，差异无统计学意义(P > 0.05)，表明首发抑郁症患者血清BDNF水平与共病焦虑症状的严重程度无相关性。

Haberling等 [20] 将126名青少年抑郁症的研究发现，焦虑抑郁共病组比单纯抑郁组病情及临床症状更重，尤其在抑郁症状、睡眠问题及躯体症状，而且疾病复发率高。本研究也同样发现，明显焦虑组HAMD评分、阻滞因子评分、睡眠障碍因子评分及CGI评分均高于一般焦虑组(P < 0.05)，表明首发抑郁症患者伴焦虑程度越重，患者的病情越重，可表现出更严重的抑郁症状，尤其在睡眠障碍、阻滞方面突出，提示对于首发伴焦虑症状抑郁症患者临床上尤其要关注患者的睡眠质量、抑郁情绪等。Dold等 [21] 学者对1346例合并焦虑症和不合并焦虑症的MDD患者的人口学和临床资料进行了比较，其中共病任何焦虑障碍及社交恐惧症均与年龄较小具有相关性。Wu Z等 [22] 研究发现，抑郁障碍共病阈下核心焦虑症状和焦虑症的患者年龄均较非共病组较小，且共病组存在明显的恶劣情绪及更高的自杀风险。本研究也同样发现，明显焦虑组患者的平均年龄低于一般焦虑组，表明首发抑郁症患者的年龄越低，共病的焦虑症状越重。

综上所述，首发伴焦虑症状抑郁症患者血清BDNF水平与疾病严重程度呈负相关，低年龄、睡眠障碍、阻滞为首发抑郁症伴焦虑症状严重程度的危险因素。但本研究仍存在一定局限性，研究样本数量较少，未动态追踪治疗后血清BDNF水平的变化，今后需进一步深入研究。

基金项目

重庆市卫生与计划生育委员会面上项目(2016MSXM061)；重庆市长寿区科技计项目(cskj2022037)。

文章引用

宋京瑶,王皋茂,庞 辉,李振阳,高 贺,何现萍. 首发抑郁症伴焦虑特征患者血清脑源性神经因子水平及临床意义
Levels of Serum Brain-Derived Neurothrophic Factor in First-Episode Depression Patients with Anxiety Symptoms and Its Clinical Significance[J]. 临床医学进展, 2022, 12(12): 11304-11310. https://doi.org/10.12677/ACM.2022.12121629

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    23. NOTES

    *通讯作者。

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