Relationship between the tryptophan-kynurenine pathway and painful physical symptoms in patients with major depressive disorder

Objectives: To investigate the relationship between the tryptophan-kynurenine (TRP-KYN) pathway and painful physical symptoms (PPS) in major depressive disorder (MDD).Methods: Eighty-four patients with MDD (40 patients with PPS and 44 without PPS) and forty-six healthy controls (HC) were recruited. The serum levels of tryptophan (TRP), kynurenine(KYN), kynurenic acid (KA), quinolinic acid (QA), 3-hydroxy-kynurenine (3-HK), serotonin (5-HT) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Depression, anxiety and pain were assessed using Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Short-form McGill pain questionnaire (SFMPQ) respectively.Results: Patients in the MDD group exhibited significantly lower KA and 5-HT levels than HC, whereas MDD patients with PPS showed higher KYN and QA levels, and a higher KYN/TRP ratio than those without. There was a positive correlation between the scores of SFMPQ and QA levels and a negative correlation between the scores of SFMPQ and TRP levels or KA/QA ratios in MDD patients with PPS group. Stepwise multiple regression analysis showed that the KYN/TRP ratios, the KA/QA ratios, and the HAMD scores were significant predictor factors for SFMPQ scores.Conclusions: These results demonstrated that the TRP-KYN pathway may play a role in the pathophysiology of pain in patients with major depressive disorder, suggesting that further studies of this pathway as a potential biomarker or therapeutic target are required.

Automated summary

The study found a relationship between the tryptophan-kynurenine pathway and painful physical symptoms in major depressive disorder. Patients with painful physical symptoms showed higher levels of kynurenine and quinolinic acid, and a higher kynurenine/tryptophan ratio. There was a positive correlation between the scores of the Short-form McGill pain questionnaire and quinolinic acid levels, and a negative correlation with tryptophan levels or the kynurenic acid/quinolinic acid ratio. Regression analysis identified the kynurenine/tryptophan ratio, the kynurenic acid/quinolinic acid ratio, and the Hamilton Depression Scale scores as significant predictors of the Short-form McGill pain questionnaire scores.