Tryptophan Catabolites as Diagnostic Biomarkers of Major Depression in Coronary Artery Patients

Abstract

Background: Major depression is common in patients with coronary artery disease (CAD) and it is associated with adverse cardiovascular outcomes, but remains frequently underdiagnosed. The kynurenine pathway (KP) of tryptophan metabolism, activated by chronic inflammation, produces neuroactive metabolites that may link CAD to depression. This study evaluated whether tryptophan catabolites (TRYCATs) can differentiate depressed from non-depressed CAD patients. Methods: A total of 135 participants were enrolled: 45 healthy controls, 38 CAD patients without depression, and 52 CAD patients with clinical depression. Serum levels of tryptophan, kynurenine, 3-hydroxykynurenine (3-HK), kynurenic acid (KYNA), quinolinic acid (QA), and anthranilic acid (AA) were measured. ROC curve analysis determined the diagnostic performance of each biomarker.Results: CAD patients with depression exhibited significantly lower tryptophan and KYNA, and higher kynurenine, 3-HK, QA, AA, and KYN/TRP ratio compared to both controls and non-depressed CAD patients (all p≤0.011). The KYNA/KYN ratio was markedly reduced in the depressed CAD group (p<0.001). White blood cell count and neutrophil-to-lymphocyte ratio were highest in the CAD with depression group. ROC analysis showed that tryptophan had the best discriminatory ability for differentiating depressed from non-depressed CAD patients, with an area under the curve of 0.77 (95% CI: 0.67–0.87, p<0.001) and a cut-off value of ≤45.07 µM (sensitivity 68.9%, specificity 66.4%). 3-HK (AUC=0.71) and KYNA (AUC=0.69) also showed moderate diagnostic performance. Conclusions: Depression in CAD patients is characterized by a distinct TRYCAT signature of reduced neuroprotective KYNA and elevated neurotoxic metabolites. Tryptophan, 3-HK, and KYNA demonstrate moderate diagnostic accuracy for identifying depression in CAD patients; although these biomarkers are not ready for standalone clinical use, they could serve as adjunctive screening tools.