Abstract
BACKGROUND: The tryptophan-kynurenine (TRP-KYN) pathway may be implicated in the pathophysiology of cognitive impairment and pain severity in major depressive disorder (MDD); however, few studies have explored the intricacies of their interaction. AIM: To investigate the relationship between the TRP-KYN pathway and cognitive function in MDD patients with and without painful physical symptoms (PPS). METHODS: Seventy patients with MDD were recruited, including 33 and 37 with and without PSS, respectively. The Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Short-form of McGill pain questionnaire (SFMPQ) were used to assess clinical symptoms. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB) score. TRP-KYN pathway metabolites' serum levels were measured using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: The with PPS group exhibited significantly higher TRP-KYN ratios than did the without PPS group; in the former, the SFMPQ scores positively and negatively correlated with the TRP-KYN ratio and total MCCB score, respectively. Regression analysis indicated that body mass index and SFMPQ scores were significantly associated with the TRP-KYN ratio, predicting 30% of the variance. CONCLUSION: The TRP-KYN ratio is a potential biomarker for identifying patients with depression accompanied by pain symptoms, and targeting it may represent a novel therapeutic strategy for managing pain in these individuals. Further elucidation of the biological mechanisms underlying cognitive impairment in MDD patients with PPS is warranted.