Serum Tryptophan and Kynurenine/Tryptophan Ratio as Markers of Depressive Symptoms in Chronic Obstructive Pulmonary Disease (COPD)

Background and aim Depression is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD). Given the involvement of the tryptophan-kynurenine pathway in depression, this study aimed to investigate the potential clinical value of the serum markers of tryptophan-kynurenine metabolism in COPD-related depressive symptoms. Methods A comparative cross-sectional study was designed. The serum levels of tryptophan and kynurenine were measured by liquid chromatography-mass spectrometry in consecutive adult patients with severe COPD. The tryptophan, kynurenine, and kynurenine-to-tryptophan ratio (KTR) were investigated as potential markers for depressive symptoms, which were classified by the six-item Hamilton Depression subscale (HDS-6). The associations of tryptophan-kynurenine pathway markers with depressive symptoms were assessed using Spearman's correlation and logistic regression models. Results Among the included 102 patients with COPD, 44 (43.1%) had depressive symptoms. Compared to the controls, the patients with depressive symptoms had lower serum levels of tryptophan and a higher kynurenine-to-tryptophan ratio (KTR). The severity of depressive symptoms, as measured by the HDS-6 score, showed a significant negative correlation with tryptophan levels (ρ=-0.478, p<0.001) and a positive correlation with KTR (ρ=0.613, p<0.001). In multivariate logistic analyses, higher serum tryptophan quartiles were associated with a decreasing risk of depressive symptoms, while higher KTR quartiles were associated with an increasing risk (p for trend <0.001 for both). Conclusion In this cohort of COPD patients, lower serum tryptophan and a higher kynurenine-to-tryptophan ratio (KTR) were significantly associated with the presence and severity of depressive symptoms. These findings nominate serum tryptophan and KTR as potential biomarkers for assessing depressive symptoms in COPD, which could improve diagnostic accuracy and guide treatment strategies.