| Depression is a state of low mood and demotivated condition that affects a person's feelings,cognition and behaviors.According to the survey of WHO in 2017,there were about 322 million people suffering from depression worldwide,and over 90 million people in China.The prevalence of depression was as high as 4.3%in the world,about6%in the developed countries and about 4.2%in China.Depression is a great burden on individuals and the society,which is one of the major diseases leading to human disability and severe depression has been recognized as a high risk factor of suicide.Thus,evaluating the severity of depression is crucial for treatment.Though the prevalence of depression showed an increasing trend year by year,it is up to 30%of depressive patients who are not clearly diagnosed and are less likely to be treated in time.The main reason lies in the diagnosis of depression which mainly depends on the subjective evaluation for lack of experimental diagnosis,so it is of great importance to explore the biomarkers for the diagnosis and evaluation of depression.Nesfatin-1,first discovered in 2006,is a polypeptide derived from nucleobindin-2?NUCB2?,which is widely distributed in the central system and surrounding tissues.Some previous studies have reported that nesfatin-1 protein played a role in integrating feeding,glucose homeostasis,and energy expenditure.Furthermore,the role of nesfatin-1 protein in the regulation of emotional states including depression and anxiety has also been found.Recent experiments suggested that nesfatin-1 protein may induce depressive behavior by activating the HPA axis which was proposed to be among the causal factors for triggering depressive episodes.Clinical studies have shown that the plasma level of nesfatin-1 protein in depressive patients was significantly higher than that of healthy controls.Because of the dysfunction of the HPA axes,with the important role of nesfatin-1 protein in the pathophysiology of depression,we hypothesized that the plasma nesfatin-1 level may be associated with depression severity,which was expected to be a new indicator for the diagnosis and evaluation of depression.Nucb2 mRNA is translated to NUCB2 which is the precursor of nesfatin-1 protein.Nucb2 mRNA is widely distributed in the central system and surrounding tissues.Animal experiments showed that the HPA axis of rats was activated under stress and both hypothalamus Nucb2 mRNA and plasma nesfatin-1 protein levels were significantly increased,suggesting that hypothalamus Nucb2 mRNA may enter the peripheral blood through the blood-brain barrier.Currently,there are few reports on human Nucb2 mRNA,but a large number of studies have confirmed the existence of various mRNAs in peripheral blood which are significantly correlated with depression.The level of TNFAIP3 mRNA in peripheral blood was closely related to the severity of depression.TLR4 mRNA level was associated with anxiety,weight loss and other symptoms.SLC6A4 mRNA level can be used as a clinical marker to predict the existence of suicide attempt in patients with major depression.5-HTT mRNA level can be used as a potential marker to predict the efficacy of anti-depression.However,it is not clear whether Nucb2 mRNA exists in peripheral blood and whether Nucb2 mRNA expression can be used as a diagnostic indicator of depression.We intended to explore the clinical value of Nucb2 mRNA in the diagnosis and prognosis of depression by dectecting the expression level of Nucb2 mRNA in peripheral blood.Aim To explore the clinical values of Nesfatin-1 protein and Nucb2 mRNA expression in diagnosis and evaluation of depression.Methods A total of 103 depressive patients and 32 healthy subjects were assessed.According to HAMD-17 scores,patients with depression were divided into three groups:mild,moderate and severe.Nesfatin-1 protein was determined by the ELISA method.Nucb2 mRNA was detected by fluorescence quantitative RT-qPCR.The serum level of TSH,FT3 and FT4 were detected with Electroluminescence methord.The level of FBG,TC,TG,HDL-C and LDL-C were detected with enzymatic reaction.Differences between groups were compared and associations between Nesfatin-1 protein,Nucb2mRNA and other variables were analyzed.Results1.Compared with healthy controls?8.11±3.31ng/mL?,the plasma level of nesfatin-1protein significantly increased in the depressive patients?17.52±9.79ng/mL?.Theplasma level of nesfatin-1 protein was significantly positively correlated withHAMD-17 score?r=0.651?,and HAMD-17 score??=0.715?was one of theindependent factors influencing nesfatin-1 protein.2.According to HAMD-17 scores,patients with depression were divided into threegroups:mild,moderate and severe.The level of nesfatin-1 protein were11.17±3.58ng/mL,16.33±8.78ng/mL and 27.65±8.26ng/mL,respectively.Therewere significant differences among the groups?P<0.01?.The average level ofnesfatin-1 protein gradually increased with the aggravation of depression.Plasmanesfatin-1 level?Odds ratio[OR]=1.269,P=0.001?was an independent indicatorfor severe depression.3.Based on the ROC curve analysis,nesfatin-1 protein cut-off point of 8.905ng/mLshowed 84.5%sensitivity and 75.0%specificity,and with the Area under Curve?AUC?0.837?95%CI 0.760–0.914?was the optimal cut-off point for identificationof depression.Nesfatin-1 protein cut-off point of 20.25 ng/mL showed 82.4%sensitivity and 91.3%specificity,and with AUC 0.903?95%CI 0.835–0.971?wasthe optimal cut-off point for identification of severe depression.4.Nucb2 mRNA expression existed in peripheral blood of healthy controls and thesevere depressive patients.Compared with healthy controls(1.25±1.05(2-??CT)),Nucb2 mRNA expression significantly increased in the severe depressive patients(2.81±1.44(2-??CT)).5.In severe depressive patients,Nucb2 mRNA expression was siginificant positivelycorrelated with the level of nesfatin-1protein?r=0.726?,duration of depression?r=0.545?and HAMD-17 score?r=0.461?,and negatively correlated with age?r=-0.347?.6.Based on the ROC curve analysis,Nucb2 mRNA cut-off point of 1.465(2-??CT)showed 94.1%sensitivity and 71.9%specificity,and with AUC 0.803?95%CI0.693–0.913?was the optimal cut-off point for identification of severe depression.Conclusions1.The plasma level of nesfatin-1 protein was significant positively correlated with theseverity of depression in depressive patients which was an independent indicatorfor severe depression.The plasma level of nesfatin-1 protein may be a potentialindicator for depression severity.2.Nucb2 mRNA was found in human peripheral blood.Nucb2 mRNA expression wassignificantly increased in patients with severe depression,which was positivelycorrelated with the level of nesfatin-1 protein and HAMD-17 score.Nucb2 mRNAexpression may be a marker for clinical diagnosis of severe depression. |
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