Characteristics of Somatic Symptoms and Their Correlations with Brain-derived Neurotrophic Factor and Inflammatory Cytokinesin Patients with Major Depressive Disorder

doi:10.12114/j.issn.1007-9572.2022.0652

Chinese General Practice ›› 2023, Vol. 26 ›› Issue (12): 1463-1471.DOI: 10.12114/j.issn.1007-9572.2022.0652

Special Issue: 精神卫生最新文章合辑；心理健康最新文章合辑；脑健康最新研究合辑；营养最新文章合辑

• Original Research • Previous Articles Next Articles

Characteristics of Somatic Symptoms and Their Correlations with Brain-derived Neurotrophic Factor and Inflammatory Cytokinesin Patients with Major Depressive Disorder

¹Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, China
²Department of Psychiatry, Children's Hospital of Shanxi/Women Health Center of Shanxi, Taiyuan 030001, China
³School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China
The first author, DU Yeming, currently works at Songjiang District Mental Health Center, Shanghai

Received:2022-10-09 Revised:2022-12-11 Published:2023-04-20 Online:2022-12-30
Contact: WANG Yanfang

重性抑郁障碍患者躯体症状与脑源性神经营养因子和炎性因子的相关性研究

¹030001　山西省太原市，山西医科大学第一医院精神卫生科
²030001　山西省太原市，山西省儿童医院　山西省妇幼保健院精神卫生科
³030001　山西省太原市，山西医科大学基础医学院
第一作者都业铭现工作单位是：上海市松江区精神卫生中心

通讯作者: 王彦芳
作者简介:
作者贡献：都业铭、王彦芳进行文章的构思与设计、研究的实施与可行性分析、文章的质量控制及审校和论文修订；都业铭、张云巧、王宗琦、闵雪、崔雅莲进行数据收集和数据整理；都业铭负责统计学处理、结果分析与解释、撰写论文；王彦芳对文章整体负责，监督管理。
基金资助:
山西省卫健委科研基金项目(2022140); 山西省136兴医工程项目(Y2022136012); 山西省自然科学基金资助项目(201801D121345); 国家重点研发计划(2016YFC1307103)

Abstract

Abstract:

Background

Considerable evidence suggests that people with depressive disorder are at higher risk for somatic symptoms than normal people, but the mechanisms of susceptibility are unclear. Some studies suggest that the levels of precursor of brain-derived neurotrophic factor (ProBDNF) and inflammatory cytokines in depressive disorder patients are higher, but it is still unclear whether this is related to the accompanying somatic symptoms.

Objective

To explore the characteristics of somatic symptoms, and their correlations with BDNF and inflammatory cytokines in patients with major depressive disorder (MDD) .

Methods

A total of 59 MDD outpatients and inpatients from Mental Health Department, First Hospital of Shanxi Medical University and 32 healthy volunteers from the community were recruited from February 2019 to December 2020. Somatic symptoms were diagnosed using the Somatic Self-rating Scale (SSS, SSS score >36 and SSS score ≤36 were defined as with somatic symptoms or without, respectively) . Depression was assessed using the Hamilton Depression Rating Scale (HAMD-17) . Clinical data were collected, including gender, age, years of education, HAMD-17 score, SSS score, absorbance of ProBDNF and BDNF, and inflammatory cytokines (CRP, IL-4, IL-10, IL-18, IL-23a, HMGB1, IL-6, TNF-α, IFN-α) . Spearman's rank correlation analysis was used to investigate the correlation of somatic symptoms (including dizziness and headache, frequent and urgency of urination, cardiovascular symptoms, muscle soreness, gastrointestinal symptoms, tingling and twitching of hands and feet, choking and sighing, blurred vision, and discomfort of the throat) , SSS-S factor score and HAMD-17 score with ProBDNF and BDNF, and inflammatory cytokines.

Results

MDD patients with somatic symptoms had higher total HAMD-17 score than those without (P<0.001) . Both MDD patients with and without somatic symptoms had higher total HAMD-17 score than healthy volunteers (P<0.001) . MDD patients with somatic symptoms had higher total SSS score and SSS-S factor score than those without (P<0.001) . And they also had higher total SSS score and SSS-S factor score than healthy volunteers (P<0.001) . MDD patients with somatic symptoms had higher BDNF than those without (P<0.05) . The IFN-α in healthy volunteers was lower than of MDD patients with or without somatic symptoms (P<0.001) . ProBDNF was negatively correlated with muscle soreness (r_s=-0.262, P<0.05) . CRP was negatively correlated with tingling and twitching of hands and feet (r_s=-0.386, P<0.01) . IL-4 had a negative correlation with gastrointestinal symptoms (r_s=-0.336, P<0.01) . IL-10 had a positivecorrelation with blurred vision (r_s=0.286, P<0.05) . BDNF was positively correlated with dizziness and headache (r=0.339, P<0.01) , cardiovascular symptoms (r_s=0.309, P<0.05) , gastrointestinal symptoms (r_s=0.278, P<0.05) , muscle soreness (r_s=0.419, P<0.01) , tingling and twitching of hands and feet (r_s=0.286, P<0.05) , choking and sighing (r_s=0.372, P<0.01) , discomfort of the throat (r_s=0.392, P<0.01) and SSS-S factor score (r_s=0.418, P<0.01) . IL-6 was positively correlated with cardiovascular symptoms (r_s=0.283, P<0.05) and choking and sighing (r_s=0.374, P<0.01) . TNF-α was negatively correlated with muscle soreness (r_s=-0.299, P<0.05) . IFN-α showed a negative correlation with blurred vision (r_s=-0.267, P<0.05) .

Conclusion

The peripheral blood IFN-α of MDD patients was lower than that of normal people. The severity of depression and BDNF level were higher in MDD patients with somatic symptoms than those without. The elevation of multiple inflammatory cytokines was correlated with the increase in the risk of somatic symptoms, suggesting that patients with MDD may be prone to somatic symptoms and adverse outcomes, requiring early intervention.

Key words: Depression, Major depressive disorder, Inflammatory factor, Brain-derived neurotrophic factor, Somatic symptoms

摘要：

背景

大量证据表明抑郁障碍患者的躯体症状的风险比正常人高，但躯体易感性的机制尚不明确。部分研究认为前者脑源性神经营养因子前体（ProBDNF）、炎性因子水平比正常人高，而这是否与伴随的躯体症状有关还没有明确的结论。

目的

探讨重性抑郁障碍（MDD）患者躯体症状与脑源性神经营养因子（BDNF）、炎性因子的特征及其相关性。

方法

选取2019年2月至2020年12月山西医科大学第一医院精神卫生科门诊或住院部MDD患者59例与同期社区招募的健康志愿者32例作为研究对象。根据躯体化症状自评量表（SSS）将MDD患者分为伴躯体症状抑郁障碍（SD）组37例（SSS总分>36分）和不伴躯体症状抑郁障碍（NSD）组22例（SSS总分≤36分），32例健康志愿者为健康对照组（HC组）。收集临床资料，包括性别、年龄、受教育年限、17项汉密尔顿抑郁量表（HAMD-17）评分、SSS评分、BDNF、ProBDNF与炎性因子〔C反应蛋白（CRP）、白介素4（IL-4）、白介素6（IL-6）、白介素10（IL-10）、白介素18（IL-18）、白介素23a（IL-23a）、高迁移率族蛋白B1（HMGB1）、肿瘤坏死因子α（TNF-α）、α干扰素（IFN-α）〕的吸光度。采用SSS评估躯体化症状、HAMD-17评估抑郁障碍症状。采用Spearman秩相关分析探讨SSS中躯体症状（包括头晕头痛、尿频尿急、心血管症状、肌肉酸痛、胃肠道症状、手脚发麻抽搐、憋闷叹气、视物模糊、咽部不适）得分、躯体化症状自评量表-躯体化因子（SSS-S）总分、HAMD-17总分与BDNF、炎性因子的相关性。

结果

SD组HAMD-17总分高于NSD组、HC组（P<0.001）；NSD组HAMD-17总分高于HC组（P<0.001）。SD组SSS总分、SSS-S总分高于NSD组、HC组（P<0.001）。SD组BDNF高于NSD组（P<0.05）。SD组、NSD组的IFN-α低于HC组（P<0.001）。ProBDNF与肌肉酸痛呈负相关（r_s=-0.262，P<0.05），CRP与手脚发麻抽搐呈负相关（r_s=-0.386，P<0.01），IL-4与胃肠道症状呈负相关（r_s=-0.336，P<0.01），IL-10与视物模糊（r_s=0.286，P<0.05）呈正相关，BDNF与头晕头痛（r_s=0.339，P<0.01）、心血管症状（r_s=0.309，P<0.05）、胃肠道症状（r_s=0.278，P<0.05）、肌肉酸痛（r_s=0.419，P<0.01）、手脚发麻抽搐（r_s=0.286，P<0.05）、憋闷叹气（r_s=0.372，P<0.01）、咽部不适（r_s=0.392，P<0.01）、SSS-S总分（r_s=0.418，P<0.01）呈正相关。IL-6与心血管症状（r_s=0.283，P<0.05）、憋闷叹气（r_s=0.374，P<0.01）呈正相关。TNF-α与肌肉酸痛（r_s=-0.299，P<0.05）呈负相关。IFN-α与视物模糊（r_s=-0.267，P<0.05）呈负相关。

结论

MDD患者外周血IFN-α较正常人低，SD患者抑郁严重程度比NSD患者高，SD患者BDNF比NSD患者高，多种炎性因子水平与躯体症状呈正相关，或许提示抑郁患者可出现躯体症状及不良转归，需尽早干预。

关键词: 抑郁, 重性抑郁障碍, 炎性因子, 脑源性神经营养因子, 躯体症状

DU Yeming,ZHANG Yunqiao,WANG Zongqi, et al. Characteristics of Somatic Symptoms and Their Correlations with Brain-derived Neurotrophic Factor and Inflammatory Cytokinesin Patients with Major Depressive Disorder[J]. Chinese General Practice, 2023, 26(12): 1463-1471. DOI: 10.12114/j.issn.1007-9572.2022.0652.
都业铭,张云巧,王宗琦等. 重性抑郁障碍患者躯体症状与脑源性神经营养因子和炎性因子的相关性研究[J]. 中国全科医学, 2023, 26(12): 1463-1471. DOI: 10.12114/j.issn.1007-9572.2022.0652.

Figures/Tables 3

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组别	例数	性别〔n（%）〕		年龄〔M（P₂₅，P₇₅），岁〕	受教育年限〔M（P₂₅，P₇₅），年〕	HAMD-17总分〔M（P₂₅，P₇₅），分〕	SSS总分〔M（P₂₅，P₇₅），分〕	SSS-S总分〔M（P₂₅，P₇₅），分〕
组别	例数	男	女	年龄〔M（P₂₅，P₇₅），岁〕	受教育年限〔M（P₂₅，P₇₅），年〕	HAMD-17总分〔M（P₂₅，P₇₅），分〕	SSS总分〔M（P₂₅，P₇₅），分〕	SSS-S总分〔M（P₂₅，P₇₅），分〕
SD组	37	10（27.0）	27（73.0）	27（22，39）	14（11，15）	21（19，24）	50（42，58）	18（16，23）
NSD组	22	10（45.5）	12（54.5）	33（22，49）	15（15，15）	17（17，18）^a	33（28，34）^a	12（10，13）^a
HC组	32	16（50.0）	16（50.0）	31（26，33）	15（14，15）	1（1，3）^ab	24（21，28）^a	10（9，12）^a
H（χ²）值		4.029^c		3.340	8.210	70.931	60.536	44.615
P值		0.122		0.188	0.017	<0.001	<0.001	<0.001

组别	例数	性别〔n（%）〕		年龄〔M（P₂₅，P₇₅），岁〕	受教育年限〔M（P₂₅，P₇₅），年〕	HAMD-17总分〔M（P₂₅，P₇₅），分〕	SSS总分〔M（P₂₅，P₇₅），分〕	SSS-S总分〔M（P₂₅，P₇₅），分〕
组别	例数	男	女	年龄〔M（P₂₅，P₇₅），岁〕	受教育年限〔M（P₂₅，P₇₅），年〕	HAMD-17总分〔M（P₂₅，P₇₅），分〕	SSS总分〔M（P₂₅，P₇₅），分〕	SSS-S总分〔M（P₂₅，P₇₅），分〕
SD组	37	10（27.0）	27（73.0）	27（22，39）	14（11，15）	21（19，24）	50（42，58）	18（16，23）
NSD组	22	10（45.5）	12（54.5）	33（22，49）	15（15，15）	17（17，18）^a	33（28，34）^a	12（10，13）^a
HC组	32	16（50.0）	16（50.0）	31（26，33）	15（14，15）	1（1，3）^ab	24（21，28）^a	10（9，12）^a
H（χ²）值		4.029^c		3.340	8.210	70.931	60.536	44.615
P值		0.122		0.188	0.017	<0.001	<0.001	<0.001

组别	例数	BDNF	ProBDNF	CRP	IL-4	IL-6
SD组	37	0.422（0.328，0.534）	0.187（0.180，0.217）	0.238（0.213，0.257）	0.089（0.077，0.094）	0.054（0.051，0.059）
NSD组	22	0.301（0.275，0.449）^a	0.207（0.098，0.212）	0.242（0.070，0.268）	0.083（0.080，0.093）	0.053（0.051，0.061）
HC组	32	0.341（0.276，0.422）	0.184（0.074，0.215）	0.216（0.153，0.242）	0.088（0.080，0.097）	0.056（0.052，0.074）
H值		8.110	1.955	4.216	0.353	1.823
P值		0.017	0.376	0.121	0.838	0.402
组别	IL-10	IL-18	IL-23a	HMGB1	TNF-α	IFN-α
SD组	0.082（0.079，0.085）	0.106（0.098，0.127）	0.033（0.030，0.035）	0.231（0.190，0.287）	0.082（0.079，0.083）	0.128（0.124，0.135）
NSD组	0.080（0.079，0.083）	0.099（0.095，0.119）	0.035（0.030，0.035）	0.214（0.198，0.262）	0.082（0.080，0.084）	0.134（0.125，0.139）
HC组	0.081（0.079，0.084）	0.107（0.095，0.117）	0.033（0.031，0.036）	0.246（0.204，0.273）	0.081（0.079，0.082）	0.142（0.137，0.145）^ab
H值	1.519	1.245	0.726	2.608	3.816	31.708
P值	0.468	0.537	0.696	0.271	0.148	<0.001

组别	例数	BDNF	ProBDNF	CRP	IL-4	IL-6
SD组	37	0.422（0.328，0.534）	0.187（0.180，0.217）	0.238（0.213，0.257）	0.089（0.077，0.094）	0.054（0.051，0.059）
NSD组	22	0.301（0.275，0.449）^a	0.207（0.098，0.212）	0.242（0.070，0.268）	0.083（0.080，0.093）	0.053（0.051，0.061）
HC组	32	0.341（0.276，0.422）	0.184（0.074，0.215）	0.216（0.153，0.242）	0.088（0.080，0.097）	0.056（0.052，0.074）
H值		8.110	1.955	4.216	0.353	1.823
P值		0.017	0.376	0.121	0.838	0.402
组别	IL-10	IL-18	IL-23a	HMGB1	TNF-α	IFN-α
SD组	0.082（0.079，0.085）	0.106（0.098，0.127）	0.033（0.030，0.035）	0.231（0.190，0.287）	0.082（0.079，0.083）	0.128（0.124，0.135）
NSD组	0.080（0.079，0.083）	0.099（0.095，0.119）	0.035（0.030，0.035）	0.214（0.198，0.262）	0.082（0.080，0.084）	0.134（0.125，0.139）
HC组	0.081（0.079，0.084）	0.107（0.095，0.117）	0.033（0.031，0.036）	0.246（0.204，0.273）	0.081（0.079，0.082）	0.142（0.137，0.145）^ab
H值	1.519	1.245	0.726	2.608	3.816	31.708
P值	0.468	0.537	0.696	0.271	0.148	<0.001

项目	BDNF	ProBDNF	CRP	IL-4	IL-10	IL-18	IL-23a	HMGB1	IL-6	TNF-α	IFN-α
HAMD-17总分	0.020	0.096	0.229	-0.073	0.008	-0.007	-0.117	0.253	-0.024	-0.192	-0.075
头晕头痛	0.339^a	-0.157	0.059	0.015	0.135	0.121	-0.183	0.040	0.106	-0.115	-0.176
心血管症状	0.309^a	-0.245	-0.092	0.168	0.208	0.072	0.009	0.115	0.283^b	-0.042	-0.212
胃肠道症状	0.278^a	-0.068	-0.119	-0.336^a	-0.092	0.056	0.166	0.176	-0.013	-0.201	-0.238
肌肉酸痛	0.419^a	-0.262^a	-0.207	0.141	0.197	0.247	-0.117	0.044	0.052	-0.299^a	-0.159
手脚发麻抽搐	0.286^a	-0.125	-0.386^a	-0.181	-0.027	0.018	-0.159	-0.065	-0.001	-0.025	-0.147
视物模糊	0.186	-0.141	-0.061	0.083	0.286^a	-0.096	-0.209	0.093	0.028	-0.215	-0.267^b
憋闷叹气	0.372^a	-0.020	-0.142	-0.008	0.014	0.161	-0.113	-0.024	0.374^a	-0.035	-0.232
咽部不适	0.392^a	-0.138	-0.066	-0.156	-0.154	0.196	-0.107	-0.017	-0.151	-0.029	-0.062
尿频尿急	-0.172	-0.190	-0.182	0.047	0.083	-0.196	-0.058	0.003	0.131	-0.191	0.006
SSS-S总分	0.418^a	-0.150	-0.181	-0.059	0.054	0.123	-0.119	0.037	0.162	-0.164	-0.243

Characteristics of Somatic Symptoms and Their Correlations with Brain-derived Neurotrophic Factor and Inflammatory Cytokinesin Patients with Major Depressive Disorder

重性抑郁障碍患者躯体症状与脑源性神经营养因子和炎性因子的相关性研究

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