Kynurenic acid and schizophrenia.
Advances in experimental medicine and biology January 1, 2003 Sophie Erhardt, Lilly Schwieler, Göran Engberg
Schizophrenia may involve a glutamate deficiency, with the endogenous glutamate antagonist kynurenic acid (KYNA) playing a role. In anesthetized rats, pharmacologically elevated KYNA increased firing and burst activity of midbrain dopamine neurons, similar to effects of psychotomimetics PCP and ketamine. Cerebrospinal fluid KYNA was higher in 28 male first-episode schizophrenia patients (1.67 ± 0.27 nM) than in 17 male healthy controls (0.97 ± 0.07 nM). Elevated KYNA also reversed clozapine's excitatory effect on rat dopamine neurons to inhibition. The study suggests KYNA contributes to schizophrenia pathogenesis, linking dopamine and glutamate hypotheses.