Study On Relationship Between Somatic Symptoms Of MDD And Changes In Cortisol Rhythm And Immune-metabolism Factors

BackgroundMajor Depressive Disorder(MDD)is a common and complex mental illness characterized by significant and persistent depression,loss of interest and lack of energy.It includes a series of cognitive,emotional and somatic symptoms,with high prevalence,high recurrence rate and high disability rate.The somatic symptoms of depression are very common in patients with MDD,leading to high misdiagnosis rate,inappropriate treatment and waste of medical resources,somatic symptoms are closely related to the severity,course and prognosis of MDD.Disrupted HPA axis,inflammatory response and metabolic abnormality in the pathological mechanism of MDD have received widespread attention,but the research results are often inconsistent,which may be be associated with the heterogeneity of the MDD diagnosis.A growing body of evidence indicates that the disorder of HPA axis and CRP(C reactive protein,CRP)levels are associated with the somatic symptoms of MDD,both biomarkers exhibited stronger relationships with somatic than with cognitive-affective symptoms.This immune inflammation and metabolic disorders may be the biological basis of MDD somatic symptom,and has been further implicated as a potential mechanism through which depression increases the risk of cardiovascular disease,metabolic syndrome and other physical diseases.To our knowledge,such biological systems in somatic depressive symptoms which remains largely unexplored in China.ObjectiveTo analyze the clinical characteristics of MDD patients with somatic symptoms,to investigate the associations of cortisol level and rhythm changes,C-reactive protein and other immune metabolic related indexes with depressive symptom,and to understand the neurobiological mechanism of somatic symptoms of MDD patients from the perspectives of immune regulation,inflammation and metabolism.Methods1.Subjects:Using a case-control study design,based on inclusion and exclusion criteria,Patients who met the diagnosis of major depressive disorder according to the fifth edition of the diagnostic and statistical manual of mental disorders(DSM-5),and had a total score of HAMD-24≥20 were recruited.According to the Patient Health Questionnaire(PHQ-15)score,a total of 73 MDD patients with somatic symptoms whose PHQ-15≥10 were classified as S-MDD group.a total of 70 MDD patients without somatic symptoms whose PHQ-15<5 were classified as NS-MDD group.2.Laboratory indicators:plasma cortisol(COR8,COR16,COR24)at 8,16 and 24points on the same day was detected by electrochemiluminescence.Plasma C-reactive protein(CRP)and plasma interleukin-6(IL-6)were detected by electrochemiluminescence method at 8 o’clock in the morning.Serum uric acid(UA),blood glucose(GLU),blood lipid(TC,TG,HDL,LDL)were detected by Siemens automatic biochemical analyzer.3.Statistical analysis:SPSS20.0 statistical software package was adopted.Enumeration data were represented by frequency,Chi-square test was used for comparison between groups,K-S test was used for measurement data,data of normal distribution were expressed in terms of mean±standard deviation.,independent sample t test was used for comparison between groups,and Pearson correlation analysis was conducted for ages and ages of first onset.Cortisol at three time points was compared between the two groups using repeated measures analysis of variance.COR8,COR16,COR24,area under the curve of cortisol(AUC),the slope of cortisol(COR8-16,COR16-24),CRP,IL-6,and metabolic indexes of the two groups were compared by covariance analysis.Multivariate logistic regression analysis was used for exploring factors influencing somatic symptoms in MDD patients.Results1.Comparison of social demographic data and clinical characteristicsThere were 73 patients in S-MDD group,including 32 males and 41 females,aged from 19 to 65,with an average age of 44.There were 70 patients in NS-MDD group,including 25 males and 45 females,aged from 18 to 65,with an average age of 35.The age of S-MDD group was older than that of NS-MDD group,and the difference was statistically significant(t=-4.044,-3.091,P<0.05).There were no significant difference in gender,years of education,course of disease and total score of HAMD-24 between the two groups(P>0.05).2.Comparison of cortisol levels and rhythm between the two groupsRepeated measures ANOVA showed that the time effect of COR level,the effect between groups and the interaction effect between time and groups were statistically significant(P<0.05).Making age as the covariable,covariance analysis showed that COR16,total Cortisol output/area under the curve(AUC)and the slope of COR8-16in S-MDD group were higher than that in NS-MDD group,and the differences were statistically significant(F=8.971,4.320,8.731,P<0.05).There was no significant difference in COR8,COR24,COR16-24 between the two groups(P>0.05).3.Comparison of CRP,IL-6 and metabolism-related indexes between the two groupsUsing age as covariate,the CRP and UA levels in S-MDD group were higher than those in NS-MDD group,and the differences between the two groups were statistically significant(F=25.436,5.120,P<0.05).There were no statistically significant difference in IL-6,TC,TG,HDL,LDL and Glu between the two groups(P>0.05).4.Comparison of the proportion of patients with high CRP between the two groupsIn S-MDD group,42 patients(58%)had high CRP(CRP≥1mg/L),and 31 patients(42%)had low CRP(CRP<1mg/L).In the NS-MDD group,16 patients(23%)had high CRP and 54 patients(77%)had low CRP.Patients with high CRP in S-MDD group were significantly more than those in NS-MDD group,and the difference was statistically significant(χ~2=17.824,P<0.01).5.Multivariate Logistic regression analysis of somatic symptoms of MDDTaking whether accompanied by somatic symptoms or not as the dependent variable,gender,age,years of education,current course of disease,age of first onset,total score of HAMD-24,COR8,COR16,COR24,AUC,COR8-16,COR16-24,CRP,IL-6,UA,TC,TG,HDL,LDL and GLU as independent variables,multivariate Logistic regression analysis was conducted.The influencing factors of somatic symptoms of MDD were CRP(P<0.001,OR=4.934,95%CI:2.398～10.151),COR8-16(P=0.008,OR=3.451,95%CI:1.380～8.633),age(P=0.003,OR=1.053,95%CI:1.018～1.089),UA(P=0.025,OR=1.008,95%CI:1.001～1.016)and IL-6(P=0.008,OR=0.691,95%CI:0.525～0.909).Conclusions1.Abnormal cortisol levels and rhythms are closely related to the somatic symptoms of MDD.The slope of diurnal cortisol can sensitively reflect the functional changes of HPA axis at the subclinical level.2.After excluding the influence of age as covariable,high CRP and high uric acid were still risk factors for somatic symptoms of MDD,suggesting that immune metabolic dysfunction is also the biological basis of somatic symptoms of MDD.3.The main influencing factors of somatic symptoms of depression were high CRP,flatter slope of diurnal cortisol,aging and high uric acid level.