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Objective Studies in the recent decade have shown that neuropeptide VGF (nonacronymic) may play an important role in the pathogenesis of major depressive disorder (MDD).This study aimed to assess whether serum VGF in MDD patients was abnormal,and how it responded to drug treatment.Methods Serum VGF concentrations were measured in MDD patients before treatment (n =26), after 8 weeks of antidepressant treatment (n =26), and in healthy controls (n =25) using a sandwich ELISA method.The severity of depression was assessed with the 17-item Hamilton Depression Rating Scale (HDRS17).Re.sults Compared to controls, baseline VGF levels were significantly lower in MDD patients (1273.77±229.36 vs 1078.29 ± 201.54, P =0.028), and they were reversed by antidepressant treatment (1441.68±360.47, P <0.001).Either escitalopram or duloxetine could increase the levels of serum VGF in MDD patients (all P <0.001).There was no significant correlation between baseline serum VGF levels and HDRS17 scores in MDD patients (r =-0.032, P =0.889).Furthermore,no significant correlation between the change of VGF levels and the reductive rates of HDRS17 scores in patients after 8 weeks of drug treatment (r =0.151, P =0.512).Moreover,there were no correlations among gender, age, education, episodes, duration of illness as well as VGF levels in MDD patients (all P >0.05).Limitations: This study was carried out on a small number of patients and short-term follow up.Large samples and longitudinal follow up will be needed to overcome these limitations.Concltsions Our findings provide further support to the role of VGF in major depressive disorders and suggest that VGF could be a specific biomarker for the pathogenesis of depression and antidepressant treatment.