The Levels And Clinical Significance Of Endoplasmic Reticulum Stress-related Proteins And Related MicroRNAs In Patients With First-episode Major Depressive Disorder

Purpose:Through the determination of whether there is a difference in levels of the endoplasmic reticulum stress-related proteins,such as GRP78,CHOP,PERK,IRE1α,between patients with first-episode major depressive disorder and healthy populations,and ATF6;The detection of changes in micro RNA(miRNA)expression spectrum in patients with first-episode major depressive disorder;And analysis and research for miRNAs with significant differences in expression and regulation of the endoplasmic reticulum stress-related proteins,to provide a set of biomarkers that can help diagnose the patients with first-episode major depressive disorder.Method:1.According to the criteria of admission and exclusion,38 patients with first-episode major depressive disorder(DSM-5 major depressive disorder diagnostic criteria)are collected,while the control group consists of 21 cases,their age,ethnicity,education level,etc.are matched with the first-episode major depressive disorder group,and they have no bad habits,family history,and physical and mental health disorders,and sign the informed consent.2.When entering the group,the general information of the subjects will be collected,including gender,age,ethnicity,education level,etc..Patients with first-episode major depressive disorder and the healthy control group will be evaluated by the Hamilton Depression Scale(HAMD-17),Hamilton Anxiety Scale(HAMA)and the psychiatric assessment of two psychiatric attending physicians at the time of enrollment.Venous blood will be collected at 7 a.m.8 hours after fasting,the blood samples should be centrifuged,packed and stored in a refrigerator at-80°C for follow-up testing within 2 hours.3.Use enzyme-linked immunosorbent assay(ELISA)to detect the levels of endoplasmic reticulum stress-related proteins GRP78,CHOP,PERK,IRE1α,and ATF6,and analyze the miRNA expression of the first-episode major depressive disorder patients and healthy controls by miRNA sequencing differences,analyze and look for miRNAs that significantly express and regulate ER stress-related proteins and explain their clinical significance.Result:1.Compared with the healthy control group,the levels of GRP78(P<0.001),CHOP(P<0.001),PERK(P=0.004),IRE1α(P=0.001),ATF6(P=0.003)molecules are up-regulated on average in the first-episode major depressive disorder group.2.In the first-episode major depressive disorder group,there is no statistically significant difference in the levels of GRP78,CHOP,PERK,IRE1α,and ATF6 molecules between the male group and the female group(P>0.05).3.In the first-episode major depressive disorder group,compared with the group with depression and anxiety(HAMA≧14 points)and the group without depression and anxiety(HAMA<14 points),there is no statistically significant difference in the levels of GRP78,CHOP,PERK,IRE1α,and ATF6 molecules(P>0.05).4.Through miRNA sequencing analysis,comparing the first-episode major depressive disorder group with the healthy control group,there are statistically significant differences in the expression levels of 223 miRNAs between the two groups(P<0.05).Among them,163 are up-regulated and 60 are down-regulated.In addition,there were 68 significant differences(P value<0.05 and log2(fold change)absolute value>1.5)in expression,including mi R-224_-5p-L-1,which can regulate the levels of GRP78 and CHOP,is down-regulated.Conclusion:1.The serum levels of GRP78,CHOP,PERK,IRE1αand ATF6 in patients with first-episode major depression disorder were elevated,and were not affected by gender and anxiety.2.The expression of mi R-224-5p_-L-1 is down-regulatione,which can regulate the levels of GRP78 and CHOP in patients with first-episode major depressive disorder.3.Endoplasmic reticulum stress-related proteins GRP78,CHOP,ATF6,PERK,IRE1α,and mi R-224-5p_-L-1 as a group biomarker has certain reference value for the diagnosis of patients with major depressive disorder.