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

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

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

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 precur_(s)or 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,Fir_(s)t Hospital of Shanxi Medical Univer_(s)ity and 32 healthy volunteer_(s) 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≤36were 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,year_(s) 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 volunteer_(s)(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 volunteer_(s)(P<0.001).MDD patients with somatic symptoms had higher BDNF than those without(P<0.05).The IFN-αin healthy volunteer_(s) 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-αwas negatively correlated with muscle soreness(r_(s)=-0.299,P<0.05).IFN-αshowed a negative correlation with blurred vision(r_(s)=-0.267,P<0.05).Conclusion The peripheral blood IFN-αof 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 adver_(s)e outcomes,requiring early intervention.