Serum Metabolic Profiles of the Tryptophan-Kynurenine Pathway in the high risk subjects of major depressive disorder
Serum Metabolic Profiles of the Tryptophan-Kynurenine Pathway in the high risk subjects of major depressive disorder
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DOI：
10.1038/s41598-020-58806-w
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发表时间：
2020-02-06
影响因子：
4.6
通讯作者：
Saito, Kuniaki
中科院分区：
文献类型：
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作者：
Sakurai, Masashi;Yamamoto, Yasuko;Saito, Kuniaki
此前的报告表明，在慢性炎症期间，色氨酸（TRP）-犬尿氨酸（KYN）途径在抑郁症的发病中发挥着关键作用。本研究的目的是调查的特点，血清TRP-KYN通路代谢产物谱的重性抑郁症（HRMDD）的抑郁评分定义的高危受试者。在来自HRMDD、慢性疼痛障碍患者和健康对照的血清中评估TRP-KYN途径代谢物{TRP、KYN、3-羟基邻氨基苯甲酸（3 HAA）、3-羟基犬尿氨酸（3 HK）、犬尿氨酸（KYNA）和邻氨基苯甲酸（AA）}的浓度。在HRMDD的血清中，观察到AA水平升高和TRP水平降低，但其他代谢产物的水平没有变化。此外，AA（第2）/AA（第1）比值在从健康进展的受试者中的变化。y状态到抑郁状态与CES-D评分的增加相关。IL-1受体拮抗剂（IL-1 RA）水平与AA水平呈负相关。有趣的是，我们证实AA是抑郁症相关症状的可能生物标志物，因为慢性疼痛障碍组和慢性不可预测的轻度应激模型小鼠的代谢产物谱与HRMDD中的代谢产物谱相似。这些结果表明AA可能是HRMDD的有效标志物。
Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA(2nd)/AA(1st) ratio in subjects who progressed from a health. y state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD.