抑郁症患者躯体症状与皮质醇节律改变的关系

Relationship between somatic symptoms of major depressive disorder and cortisol rhythm change

目的:探讨抑郁症躯体症状与皮质醇(cortisol,COR)节律改变及其他免疫代谢相关指标之间的关系,从内分泌及免疫调节角度了解其发生机制。方法:采用病例对照研究,以符合DSM-5诊断标准的抑郁症住院患者为研究对象,根据患者健康问卷(patient health questionnaire,PHQ-15),将PHQ-15≥10分定为伴躯体症状的抑郁症组(S-MDD组),共纳入73例;将PHQ-15<5分定为不伴躯体症状的抑郁症组(NS-MDD组),共纳入70例。检测患者同日8:00、16:00及24:00血浆皮质醇(COR8、COR16、COR24)及同日8∶00时的C反应蛋白(C-reactive protein,CRP)、白介素6(interleukin-6,IL-6)水平,血清尿酸(UA)、血糖(GLU)、血脂(TC、TG、HDL、LDL)水平;采用独立样本t检验、非参数检验、卡方检验、重复测量方差分析、协方差分析及多因素Logistic回归分析进行数据处理。结果:①采用重复测量方差分析,发现COR水平的时间效应、组间效应及时间与组间的交互效应均有统计学意义(P<0.05)。以年龄为协变量,采用协方差分析发现,S-MDD组的COR16、皮质醇分泌总量(total cortisol output/area under the curve,AUC)及COR8-16斜率[(90.50±40.57)μg/L、(1425.12±564.78)、(-6.43±5.76)]大于NS-MDD组[(68.74±31.51)μg/L、(1251.57±456.61)、(-8.77±5.48)],差异有统计学意义(F=8.971,4.320,8.731,P<0.05)。②S-MDD组CRP水平[(1.41±1.06)mg/L]高于NS-MDD组[(0.61±0.53)mg/L],差异有统计学意义(F=25.436,P<0.05)。S-MDD组高CRP(CRP≥1 mg/L)患者人数比例(58%)高于NS-MDD组(23%),差异有统计学意义(χ^2=17.824,P<0.01)。③多因素Logistic回归分析发现,CRP(OR=4.953,95%CI:2.407~10.193)、COR8-16(OR=3.451,95%CI:1.380~8.633)是抑郁症躯体症状的主要危险因素。结论:日间皮质醇节律紊乱及高CRP水平可能是抑郁症患者躯体症状产生的神经生物学基础。

Objective:To explore the relationship between somatic symptoms of major depressive disorder(MDD)and cortisol(COR)rhythm,C-reactive protein(CRP)and other immune-metabolism-related indicators,and understand its mechanism from the perspective of endocrine and immune regulation.Methods:A case-control study was conducted in hospitalized patients with MDD who met DSM-5 diagnostic criteria.According to the Patient Health Questionnaire(PHQ-15),PHQ-15≥10 were classified as the somatic major depressive disorder group(S-MDD group)and 73 patients were enrolled.PHQ-15<5 was classified as the non-somatic depressive disorder group(NS-MDD group)and 70 patients were enrolled.Plasma cortisol(COR8,COR16 and COR24)levels were measured at 8∶00,16∶00 and 24∶00 on the same day,plasma CRP and interleukin-6(IL-6)level,serum uric acid(UA),blood glucose(GLU),blood lipid(TC,TG,HDL,LDL)level were detected at 8∶00.Independent sample t test,non-parametric test,chi-square test,repeated ANOVA,covariance analysis,and multivariate Logistic regression were used for statistical analysis.Results:①Time effect,grouping effect and the interaction effect of the time and grouping in the level of COR were statistically significant(P<0.05).Covariance analysis excluded age as an influential factor,COR16,AUC(total cortisol output/area under the curve,AUC)and COR8-16 in S-MDD group((90.50±40.57)μg/L,(1425.12±564.78),(-6.43±5.76))were higher than those in NS-MDD group((68.74±31.51)μg/L,(1251.57±456.61),(-8.77±5.48)),and the difference was statistically significant(F=8.971,4.320,8.731,P<0.05).②CRP in S-MDD group((1.41±1.06)mg/L)were higher than that in NS-MDD group((0.61±0.53)mg/L),and the difference was statistically significant(F=25.436,P<0.05).The proportion of patients with higher CRP level(CRP≥1 mg/L)in S-MDD group(58%)was higher than that in NS-MDD group(23%),and the difference was statistically significant(χ^2=17.824,P<0.01).③Multivariate logistic regression analysis found that CRP(OR=4.953,95%CI:2.407-10.193),COR8-16(OR=3.451,95%CI:1.380-8.633)were main risk factors of somatic symptoms of MDD(P<0.05).Conclusion:Cortisol rhythm disturbance and high CRP level may be the biological basis of somatic symptoms in patients with MDD.