Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies

Jacopo Sapienza, Marco Spangaro, Gilles J. Guillemin, Stefano Comai*, Marta Bosia

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)

Abstract

Schizophrenia is a chronic psychotic disease burdened by cognitive deficits which hamper daily functioning causing disability and costs for society. Biological determinants underlying cognitive impairment are only partially understood and there are no convincing pharmacological targets able to improve cognitive outcome. Mounting evidence has shown the involvement of the kynurenine pathway in the pathophysiology of schizophrenia, also concerning cognitive symptoms. Therefore, the action of specific metabolites of kynurenine could affects cognition in schizophrenia. To evaluate the impact of the metabolites of kynurenine pathway on cognitive functions in schizophrenia spectrum disorders, with a focus on the modulating role of gender, to identify predictors of cognitive functioning and hypothetical pharmacological targets able to resize disability by improving cognition, thus functioning and quality of life. A systematic review was performed in PubMed/MEDLINE and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. All studies measuring the direct impact of kynurenine metabolites on cognitive performances in living individuals with schizophrenia spectrum disorders were included in the review. Six studies were included. The activation of the kynurenine pathway resulted associated with greater cognitive deficits in patients with schizophrenia and both elevations and reduction of metabolites seemed able to affect cognitive outcome. No modulating role of sex emerged. This systematic review provides evidence that the activation of the kynurenine pathway affects cognition in patients with schizophrenia and highlights this pathway as a possible future target for developing novel drugs toward this still unmet clinical need. However, evidence is still limited and future studies are needed to further clarify the relationship between kynurenine pathway and cognition in schizophrenia.

Original languageEnglish
Pages (from-to)1317-1328
Number of pages12
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
Volume273
Issue number6
Early online date2 Dec 2022
DOIs
Publication statusPublished - Sept 2023

Keywords

  • Cytokines
  • Inflammation
  • Kynurenic acid
  • Psychosis
  • Quinolinic acid
  • Tryptophan

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