Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Abstract

Aim Tryptophan is the sole precursor of both peripherally and centrally produced serotonin and kynurenine. In depressed patients, tryptophan, serotonin, kynurenine, and their metabolite levels remain unclear. Therefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC). Methods Fasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (serotonin, its precursor 5‐hydroxytryptophan and its metabolite 5‐hydroxyindoleacetic acid), and kynurenine pathway (kynurenine and six of its metabolites: anthranilic acid, kynurenic acid, nicotinamide, picolinic acid, xanthurenic acid, and 3‐hydroxyanthranilic acid). Results Sixty (34.7%) patients were antidepressant‐drug free. Tryptophan levels did not differ between MDE patients and HC. Serotonin and its precursor (5‐hydroxytryptophan) levels were lower in MDE patients than in HC, whereas, its metabolite (5‐hydroxyindoleacetic acid) levels were within the standard range. Kynurenine and four of its metabolites (kynurenic acid, nicotinamide, picolinic acid, and xanthurenic acid) were lower in MDE patients. Conclusion Whilst the results of this study demonstrate an association between the metabolites studied and depression, conclusions about causality cannot be made. This study uses the largest ever sample of MDE patients, with an extensive assessment of peripheral tryptophan metabolism in plasma. These findings provide new insights into the peripheral signature of MDE. The reasons for these changes should be further investigated. These results might suggest new antidepressant therapeutic strategies.

Postpartum corticosterone and fluoxetine shift the tryptophan-kynurenine pathway in dams

“…Higher levels of IL-1β can also upregulate TKP (reviewed in Maes et al, 2011), so this may have contributed to the current findings. Maternal postpartum FLX decreased plasma XA concentration, which is consistent with data in individuals with MDD (Colle et al, 2020). XA has not been specifically described as either neuroprotective or neurotoxic, but its downstream effects on the glutaminergic system have been implicated in psychiatric diseases (reviewed Fazio et al, 2018).…”

“…CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.11.430473 doi: bioRxiv preprint concentration, which is consistent with data in individuals with MDD (Colle et al, 2020). XA has not been specifically described as either neuroprotective or neurotoxic, but its downstream effects on the glutaminergic system have been implicated in psychiatric diseases (reviewed Fazio et al, 2018).…”

Studies on the Changes of Pharmacokinetics Behaviors of Phytochemicals and the Influence on Endogenous Metabolites After the Combination of Radix Bupleuri and Radix Paeoniae Alba Based on Multi-Component Pharmacokinetics and Metabolomics

“…Furthermore, as well as clinically, decreased plasma picolinic acid levels have been demonstrated in depressed patients (Ryan et al, 2020), and picolinic acid has also been shown to produce significant antidepressant effects in a typical depression (Davidson et al, 2003). Our study demonstrated that the five phytochemicals with improved bioavailability after combination (saikogenin F, saikogenin G, albiflorin, methyl gallate, paeonimetabolin II) were significantly positively correlated with picolinic acid, a metabolite that was significantly downregulated in depressed patients (Colle et al, 2020). Besides, chronic stress can cause imbalances in the kynurenine metabolic pathway and excessively produce the "↓" or "↑" means the metabolite significantly decreased or increased in 3 h group compared with 0 h group.…”

Multivariate Analysis of Amino Acids and Health Beneficial Properties of Cantaloupe Varieties Grown in Six Locations in the United States

“…Similarly, HT-IG (100.28 ± 5.35 µg/g) and TT-DV (109.29 ± 11.08 µg/g) fruits showed higher Thr contents in AZ samples compared to other states. Trp is the precursor of serotonins, which regulate human mood, anxiety, appetite, and sleep [ 49 ]. Among the analyzed samples, HT-IG and the commercial local variety (CAR) harvested from CA showed significant higher contents of Trp at 71.82 ± 1.73 µg/g and 58.82 ± 2.04 µg/g, respectively, while TT-DV fruits grown in AZ had higher levels of Trp (68.67 ± 10.75 µg/g) compared to other locations and varieties.…”