Role of Kynurenine pathway and its metabolites in mood disorders: A systematic review and meta-analysis of clinical studies

Abstract

Activation of the kynurenine pathway is one of the described mechanisms by which inflammation can induce depression. It involves multiple pathways including interference with the bioavailability of tryptophan central to the synthesis of the neurotransmitter serotonin. In this systematic review, we examine the relationship between kynurenine metabolites (kynurenine, kynurenic acid, tryptophan, quinolinic acid, the ratio of kynurenine and tryptophan) and mood disorders by conducting a meta-analysis. Fifty-six studies were identified, 21 met inclusion criteria and 14 were deemed suitable (9 investigating unipolar depression and 5 bipolar disorder). We found decreased levels of kynurenine in unipolar major depression vs. healthy controls but studies were significantly heterogeneous in nature. No significant differences were found in tryptophan levels or kynurenine/tryptophan ratios. Kynurenine metabolites are likely to play a role in major depression but an exact etiological role in mood disorder seem complex and requires further research.

Keywords: Bipolar disorder; Depression; Inflammation; Kynurenine; Mood disorder; Quinolinic acid; Tryptophan.

Figure 1:

Study flow for the systematic review – Kynurenine Pathway and Mood Disorders

Figure 2:

Meta-analysis output (funnel plot) in the unipolar major depression of circulating levels of kynurenine metabolites