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Int J Tryptophan Res. 2014 Sep 16;7:15-22. doi: 10.4137/IJTR.S16800. eCollection 2014.

Imbalanced kynurenine pathway in schizophrenia.

Author information

1
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
2
AstraZeneca, Research and Development, Innovative Medicines, Personalised Healthcare and Biomarkers, Translational Science Centre, Science for Life Laboratory, Solna, Sweden. ; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
3
Department of Clinical and Experimental Medicine, Section of Psychiatry, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
4
Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
5
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract

Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

KEYWORDS:

NMDA receptor; cerebrospinal fluid; inflammation; kynurenic acid; psychosis; quinolinic acid

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