首发与复发抑郁症患者血清犬尿氨酸途径代谢物水平比较

Comparison of serum kynurenine pathway metabolites between patients with first-episode and recurrent major depressive disorder

背景抑郁症发病机制至今尚未完全清楚,既往研究表明,犬尿氨酸途径(KP)在抑郁症发病中具有重要作用。目的探讨首发和复发抑郁症患者血清KP代谢物水平的差异,并分析血清KP代谢物水平与抑郁症状严重程度的关系,为预防抑郁症复发提供参考。方法连续纳入2016年11月-2018年12月在广州医科大学附属脑科医院门诊就诊的符合《精神障碍诊断与统计手册(第5版)》(DSM-5)诊断标准的136例抑郁障碍患者为研究组,其中首发组62例,复发组74例。同时纳入60例健康被试作为对照组。所有患者均接受汉密尔顿抑郁量表17项版(HAMD-17)评定。采用液相色谱串联质谱(LC-MS/MS)法检测抑郁障碍患者和对照组血清色氨酸(TRP)、犬尿氨酸(KYN)以及犬尿喹啉酸(KYNA)水平。采用偏相关分析考查抑郁症患者HAMD-17各因子评分及总评分与KP代谢物水平的关系。结果与对照组相比,首发组和复发组TRP水平更低(t=-3.044、-4.477,P<0.05或0.01),KYN/TRP更高(t=2.343、3.644,P<0.05或0.01),差异均有统计学意义。与复发组相比,首发组和对照组KYNA水平更高(t=2.490、2.636,P<0.05或0.01),KYNA/KYN更高(t=2.894、2.616,P均<0.01),差异均有统计学意义。偏相关分析显示,首发抑郁症患者KYN/TRP与HAMD-17的焦虑/躯体化因子评分呈正相关(r=0.261,P<0.05),KYNA/KYN与HAMD-17总评分及阻滞评分均呈负相关(r=-0.286、-0.282,P均<0.05);复发抑郁症患者KYN/TRP与焦虑/躯体化评分呈正相关(r=0.280,P<0.05)。结论首发和复发抑郁症患者血清KP代谢物水平存在差异,且复发患者KP代谢物水平异常更明显,KP代谢物可能是抑郁症辅助诊断及判断复发的潜在生物标志物。

Background The 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.Objective To 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.Methods A 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.Results Compared 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).Conclusion KP 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.