Comparison of serum kynurenine pathway metabolites between patients with first-episode and recurrent major depressive disorder / 四川精神卫生

ABSTRACT

BackgroundThe pathogenesis of depression remains not fully understood， and previous studies have suggested that the kynurenine pathway （KP） plays an important role in the pathogenesis of major depressive disorder. ObjectiveTo study the difference in serum KP metabolites level between patients with first-episode and recurrent major depressive disorder， and to testify the correlation between KP metabolites level with the severity of depressive symptoms， so as to provide references for the prevention of recurrence. MethodsA total of 136 patients with major depressive disorder who attended the outpatient clinics of the Affiliated Brain Hospital of Guangzhou Medical University from November 2016 to December 2018 and met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria were included， including 62 patients in the first-episode group and 74 patients in the recurrent group. Meanwhile， 60 healthy subjects were included as control group. All patients were assessed by Hamilton Depression Scale-17 item （HAMD-17）， and serum concentrations of tryptophan （TRP）， kynurenine （KYN） and kynurenic acid （KYNA） were measured by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Then the correlation of HAMD-17 total score and individual item scores with the levels of KP metabolites was tested using partial correlation coefficient. ResultsCompared with the control group， the first-episode group and recurrent group showed a marked decline in TRP concentration （t=-3.044， -4.477， P<0.05 or 0.01） and an increase in KYN/TRP ratio （t=2.343， 3.644， P<0.05 or 0.01）， with significant differences. The KYNA concentrations （t=2.490， 2.636， P<0.05 or 0.01） and KYNA/KYN ratio （t=2.894， 2.616， P<0.01） in first-episode group and control group were notably elevated compared to recurrent group， with statistical difference. Partial correlation analysis in patients with first-episode major depressive disorder demonstrated that KYN/TRP ratio was positively correlated with the HAMD-17 anxiety/somatization factor score （r=0.261， P<0.05）， and KYNA/KYN ratio was negatively correlated with HAMD-17 total score and block factor score （r=-0.286， -0.282， P<0.05）. In patients with recurrent major depressive disorder， KYN/TRP ratio was positively correlated with HAMD-17 anxiety/somatization factor score （r=0.280， P<0.05）. ConclusionKP metabolites in serum differ between first-episode and recurrent major depressive disorder patients， and patients with recurrent episodes experience severe KP metabolite abnormalities. Therefore， KP metabolites are considered to be potential biomarker candidates to assist clinicians in the diagnosis and recurrent prediction of major depressive disorder. ［Funded by National Key Research and Development Program Precision Medicine Research Project （number， 2016YFC0906300）］