Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.

This research sought to investigate the relationship between cognitive impairment and kynurenine pathway metabolites in individuals diagnosed with major depressive disorder (MDD). A total of 67 patients diagnosed with MDD and 61 healthy controls (HC) were enrolled in this study. Cognitive function w...

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Main Authors: Yingying Pan, Peiwei Xu, Xueli Sun
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0328886
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author Yingying Pan
Peiwei Xu
Xueli Sun
author_facet Yingying Pan
Peiwei Xu
Xueli Sun
author_sort Yingying Pan
collection DOAJ
description This research sought to investigate the relationship between cognitive impairment and kynurenine pathway metabolites in individuals diagnosed with major depressive disorder (MDD). A total of 67 patients diagnosed with MDD and 61 healthy controls (HC) were enrolled in this study. Cognitive function was assessed utilizing the MATRICS Consensus Cognitive Battery. Plasma levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were quantified by liquid chromatography-tandem mass spectrometry. Subsequently, we examined the potential associations between metabolites of the KYN pathway and cognitive dysfunction. MDD patients exhibited significantly poorer performance across all cognitive domains, including processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem-solving, and social cognition. Inter-group comparisons indicated that levels of KYN, QUIN, and the KYN/TRP ratio in MDD patients were significantly lower than those in HC, whereas KYNA and the KYNA/QUIN ratio were significantly higher. In MDD patients, a negative correlation was observed between KYN levels and working memory (r = -0.302, p = 0.020), and the KYN/TRP ratio was also negatively correlated with working memory (r = -0.307, p = 0.018). Our findings indicate that impaired working memory in MDD is correlated with increased KYN levels and KYN/TRP ratio. This suggests that the KYN pathway may play a role in the pathological mechanisms underlying neurocognitive dysfunction, particularly working memory deficits, in MDD.
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spelling doaj-art-a73628b828504c7fbdba3b5ccb60eb6a2025-08-23T05:32:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01208e032888610.1371/journal.pone.0328886Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.Yingying PanPeiwei XuXueli SunThis research sought to investigate the relationship between cognitive impairment and kynurenine pathway metabolites in individuals diagnosed with major depressive disorder (MDD). A total of 67 patients diagnosed with MDD and 61 healthy controls (HC) were enrolled in this study. Cognitive function was assessed utilizing the MATRICS Consensus Cognitive Battery. Plasma levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were quantified by liquid chromatography-tandem mass spectrometry. Subsequently, we examined the potential associations between metabolites of the KYN pathway and cognitive dysfunction. MDD patients exhibited significantly poorer performance across all cognitive domains, including processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem-solving, and social cognition. Inter-group comparisons indicated that levels of KYN, QUIN, and the KYN/TRP ratio in MDD patients were significantly lower than those in HC, whereas KYNA and the KYNA/QUIN ratio were significantly higher. In MDD patients, a negative correlation was observed between KYN levels and working memory (r = -0.302, p = 0.020), and the KYN/TRP ratio was also negatively correlated with working memory (r = -0.307, p = 0.018). Our findings indicate that impaired working memory in MDD is correlated with increased KYN levels and KYN/TRP ratio. This suggests that the KYN pathway may play a role in the pathological mechanisms underlying neurocognitive dysfunction, particularly working memory deficits, in MDD.https://doi.org/10.1371/journal.pone.0328886
spellingShingle Yingying Pan
Peiwei Xu
Xueli Sun
Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.
PLoS ONE
title Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.
title_full Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.
title_fullStr Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.
title_full_unstemmed Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.
title_short Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.
title_sort associations between kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder
url https://doi.org/10.1371/journal.pone.0328886
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