Molecular Psychiatry (2020): The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies

Abstract

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry.

We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls.

We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges’ g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included.

Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ.

Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

https://www.nature.com/articles/s41380-020-00951-9

 

just a thought would nutrition effect the results of this paper in a significant confounding manner or rather the papers they have selected for analyses .

 

Good questions. I don't think nutrition plays a role here. To alter the kynurenine pathway you'd would need to be on a weird mix of amino acids which you can't achieve eating normal food. Most people in those studies are probably eating something more or less akin to the standard Western diet. Given that they found significant differences between the two mood disorders and schizophrenia it seems more likely that this is due to metabolic differences between those conditions. Do people with depression, bipolar disorder and schizophrenia eat a radically different diet from each other? I don't know, I doubt it. They might be eating worse than healthy controls.

Regarding the selection of papers, they've done a systematic review and meta-analysis which is an approach that's less prone to bias (though far from perfect of course) than doing a selective narrative review where you cherry-pick papers that support your hypothesis.