Several lines of evidence suggest that up-regulation of immune response and alterations of
kynurenine pathway function are involved in pathogenesis of
schizophrenia. Correlations among clinical status (using PANNS, SANS and SAPS scales) and blood levels of
kynurenic acid (KYNA),
3-hydroxykynurenine (3-HK) and levels of selected immunoactive molecules, soluble
interleukin-2 receptor (sIL-2R),
interferon-α (IFN-α) and
IL-4 were analyzed in 51 chronic
schizophrenia patients during acute relapse, after four weeks of
therapy and at remission. KYNA levels were significantly lower in comparison with controls (N=45) throughout the study, whereas 3-HK did not differ from controls at admission and during
therapy, but increased at remission. The KYNA/3-HK ratio and
IL-4 levels, but not sIL-2R and IFN-α levels, were consistently decreased in
schizophrenia patients at all analyzed time points. KYNA level and KYNA/3-HK ratio measured at admission correlated negatively with the duration of illness, whereas 3-HK level correlated negatively with the improvement of SANS score at discharge. sIL-2R level before treatment was positively linked with number of relapses. In the subgroup of patients with poor response to
pharmacotherapy, treated with
clozapine later on, initial KYNA level and the ratio KYNA/3-HK correlated negatively with number of relapses. Positive association of sIL-2R level with number of relapses was also evident in this subgroup. Furthermore, among these patients, starting IFN-α level was negatively linked with the improvement of total PANSS score at discharge. Presented here data support the concept of disturbed
kynurenine pathway function in
schizophrenia and suggest that assessment of KYNA and 3-HK levels during acute relapse might be useful in prediction of response to
antipsychotic therapy. Deficit of peripheral KYNA and higher 3-HK levels could be associated with more severe symptoms of
schizophrenia. Further studies with larger samples size are needed to validate our results.