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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 healthy 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. More than 300 million people suffered from major depressive disorder (MDD) in 2017, and the number is increasing year by year 1. Several theories of MDD onset have been proposed 2. The monoamine hypothesis, the chronic inflammation hypothesis, and the abnormalities in the hypothalamus-pituitary-adrenal (HPA) system hypothesis are the predominant hypotheses regarding the pathogenesis of MDD 3. Among these hypotheses, the chronic inflammation hypothesis is closely associated with the kynurenine (KYN) pathway 4. The KYN pathway is one of several tryptophan (TRP) metabolism pathways, and it is the main pathway involved in TRP metabolism 5,6. Inflammatory cytokines such as IFN-γ induce the expression of indoleamine 2,3-dioxygenase (IDO1), which is a

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