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02-05-2012 | Mental health | Article

Kynurenic acid levels increased in schizophrenia patients

Abstract

Free abstract

MedWire News: Schizophrenia patients show increased levels of kynurenic acid (KYNA) and its precursor kynurenine (KYN) in cerebrospinal fluid, researchers report.

They say that their findings provide further support for the hypothesis that KYNA is involved in the pathophysiology of schizophrenia.

Writing in Schizophrenia Bulletin, Sophie Erhardt (Karolinska Institute, Stockholm, Sweden) and team explain: "KYNA is an endogenous metabolite of tryptophan (TRP) produced in astrocytes and antagonizes N-methyl-D-aspartate and α7 nicotinic receptors."

Because of this activity, it is thought to play an important role in neurophysiologic and neuropathologic processes.

The researchers add that "animal studies show that pharmacologically elevated levels of brain KYNA impair contextual learning and working memory and disrupt prepulse inhibition, a behavioral model measuring sensory motor gating. Interestingly, these domains are affected in patients with schizophrenia."

For the current study, Erhardt and team assessed levels of KYNA and its precursors KYN and TRP in cerebrospinal fluid collected from 16 antipsychotic-treated men with schizophrenia, aged a mean of 36.8 years, and 29 mentally healthy men (controls), aged a mean of 25.4 years, after a fasting period of at least 8 hours.

The researchers found that KYNA levels were significantly increased in schizophrenia patients compared with controls, at 2.03 versus 1.36 nM.

Furthermore, schizophrenia patients showed a two-fold increase in KYN levels compared with controls, at 60.7 versus 28.6 nM.

However, there was no significant difference between schizophrenia patients and controls regarding cerebrospinal fluid levels of TRP, at 1.73 versus 1.80 µM.

The researchers note that there were no significant correlations among cerebrospinal fluid levels of KYNA, KYN, or TRP and Brief Psychiatric Rating scale scores, Global Assessment of Functioning scores, age, antipsychotic dose, or smoking status.

Erhardt and team conclude: "Present results show that cerebrospinal fluid concentrations of KYN and KYNA are elevated in patients with schizophrenia.

"Because the availability of KYN critically determines the formation of KYNA, an elevation of KYN should explain the increased formation of brain KYNA in patients with schizophrenia."

They add: "The precise mechanism responsible for the elevation remains to be revealed; however, present results further support an involvement of metabolites of the KYN pathway in the pathophysiology of schizophrenia."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Mark Cowen

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