The role of the kynurenine pathway and quinolinic acid in adolescent major depressive disorder.

BACKGROUND

The biological mechanisms underlying major depressive disorder (MDD) are not yet sufficiently understood. The kynurenine pathway has been proposed to play a key role between peripheral inflammation and alterations in the central nervous system. This is because of reduced usability of tryptophan (TRP) and production of oxygen radicals and highly potent neurotoxic agents in this pathway.

OBJECTIVE

In this study, we aimed to compare the metabolites of the serum kynurenine pathway (tryptophan, kynurenine, quinolinic acid and kynurenic acid) and IFN-γ, IL-6, IL-1β and high-sensitivity C-reactive protein (hsCRP) levels in patients with major depressive disorder and in healthy controls and to evaluate the relationship between cytokine levels and the functioning of the kynurenine pathway.

METHODS

Clinical and biochemical data from the patients were obtained and assessed in a cross-sectional design. Serum samples were analysed for IL-6, IL-1β, interferon (IFN)-γ, tryptophan (TRP), quinolinic acid (QUIN), kynurenic acid (KYNA) and kynurenine (Kyn) levels by the enzyme-linked immunosorbent assay. hsCRP test was analysed by the immunoturbidimetric method.

RESULTS

In total, 48 adolescent patients with major depressive disorder (no drug use) and 31 healthy controls were included in the study. TRP levels were observed to be significantly lower in patients with MDD than in healthy controls (P = .046); the Kyn/TRP ratio was significantly higher in patients with MDD than in healthy controls (P = .032); the levels of QUIN were significantly higher in patients with MDD than in healthy controls (P = .003). No significant difference was found between the groups in terms of other kynurenine metabolites and cytokines levels.

CONCLUSION

These results suggest that the Kyn and related molecular pathways may play a role in the pathophysiology of MDD. The most important finding was the increased level of QUIN, which has a neurotoxic effect, in the kynurenine pathway.