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

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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.

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Acknowledgements

Dr. Stefano Comai and Dr. Marta Bosia are funded by the Italian Ministry of Health (Grant No. GR-2019-12369523) and Dr. Stefano Comai is also funded by the Department of Pharmaceutical and Pharmacological Sciences, University of Padova (Grant No. PRID-J 2021). Prof. Gilles J. Guillemin is funded by the National Health and Medical Research Council (NHMRC) and Macquarie University.

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The authors did not receive support from any organization for the submitted work. No funding was received to assist with the preparation of this manuscript. No funding was received for conducting this study. No funds, grants, or other support was received.

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  1. Stefano Comai and Marta Bosia have contributed equally to this work.

Authors and Affiliations

  1. IRCCS San Raffaele Scientific Institute, Milan, Italy

    Jacopo Sapienza, Marco Spangaro, Stefano Comai & Marta Bosia

  2. Neuroinflammation Group, Macquarie Medicine School, Macquarie University, Sydney, NSW, Australia

    Gilles J. Guillemin

  3. Department of Psychiatry, McGill University, Montreal, QC, Canada

    Stefano Comai

  4. Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy

    Stefano Comai

  5. Department of Biomedical Sciences, University of Padua, Padua, Italy

    Stefano Comai

  6. School of Medicine, Vita Salute San Raffaele University, Milan, Italy

    Marta Bosia

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Sapienza, J., Spangaro, M., Guillemin, G.J. et al. Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies. Eur Arch Psychiatry Clin Neurosci 273, 1317–1328 (2023). https://doi.org/10.1007/s00406-022-01519-0

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  • DOI: https://doi.org/10.1007/s00406-022-01519-0

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