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. 2012 May;38(3):426-32.
doi: 10.1093/schbul/sbq086. Epub 2010 Aug 20.

Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia

Klas R Linderholm  1 , Elisabeth Skogh, Sara K Olsson, Marja-Liisa Dahl, Maria Holtze, Göran Engberg, Martin Samuelsson, Sophie Erhardt
Affiliations

Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia

Klas R Linderholm et al. Schizophr Bull. 2012 May.

Abstract

Background: The kynurenic acid (KYNA) hypothesis for schizophrenia is partly based on studies showing increased brain levels of KYNA in patients. KYNA is an endogenous metabolite of tryptophan (TRP) produced in astrocytes and antagonizes N-methyl-D-aspartate and α7* nicotinic receptors.

Methods: The formation of KYNA is determined by the availability of substrate, and hence, we analyzed KYNA and its precursors, kynurenine (KYN) and TRP, in the cerebrospinal fluid (CSF) of patients with schizophrenia. CSF from male patients with schizophrenia on olanzapine treatment (n = 16) was compared with healthy male volunteers (n = 29).

Results: KYN and KYNA concentrations were higher in patients with schizophrenia (60.7 ± 4.37 nM and 2.03 ± 0.23 nM, respectively) compared with healthy volunteers (28.6 ± 1.44 nM and 1.36 ± 0.08 nM, respectively), whereas TRP did not differ between the groups. In all subjects, KYN positively correlated to KYNA.

Conclusion: Our results demonstrate increased levels of CSF KYN and KYNA in patients with schizophrenia and further support the hypothesis that KYNA is involved in the pathophysiology of schizophrenia.

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Figures

Fig. 1.
Fig. 1.
Kynurenic acid, kynurenine, and tryptophan in cerebrospinal fluid (CSF) of healthy male volunteers and male patients with schizophrenia. Each point represents the concentration in a single CSF sample and the horizontal line the mean for each group. Statistics: **P < .01, ***P < .001 (Mann-Whitney U test).
Fig. 2.
Fig. 2.
Correlation between cerebrospinal fluid (CSF) kynurenine and CSF kynurenic acid (n = 45) in all subjects. Statistics: P < .05, Spearman's r = 0.360.
See this image and copyright information in PMC

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