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


CONCLUSIONS
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.
Linderholm
Klas R
KR
Department of Physiology and Pharmacology, Nanna Svartz väg 2, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Skogh
Elisabeth
E
Olsson
Sara K
SK
Dahl
Marja-Liisa
ML
Holtze
Maria
M
Engberg
Göran
G
Samuelsson
Martin
M
Erhardt
Sophie
S
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D006801:Humans; D007736:Kynurenic Acid / Q000134:cerebrospinal fluid*; D007737:Kynurenine / Q000096:biosynthesis / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D012559:Schizophrenia / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D014364:Tryptophan / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D007737:Kynurenine; D014364:Tryptophan; D007736:Kynurenic Acid; D000077152:Olanzapine