Disturbances of Kynurenine Pathway of Trytophan Metabolism in Schizophrenia: A Quantitative RT-PCR Study

In this pilot study, we propose to characterize the pattern of activation of the kynurenine pathway of tryptophan metabolism in peripheral macrophages of patients with schizophrenia. To do this, we will measure the gene expression of several major enzymes in this pathway in macrophages, including the key enzyme involved in tryptophan to kynurenine metabolism, IDO, by means of quantitative reverse-transcription polymerase chain reaction (RT-PCR). The focus on enzyme mRNA expression as opposed to serum or cerebrospinal fluid levels of metabolites provides a possibly more sensitive characterization of the activation of this metabolic pathway.

Primary hypotheses: We hypothesize that patients with schizophrenia will differ in their expression of macrophage IDO mRNA, reflecting activation of this pathway compared to normals. We further hypothesize that patients with deficit syndrome will have higher degrees of enzyme activation.

Secondary hypotheses: Serum tryptophan levels will be lower in patients with schizophrenia compared to controls, and they will correlate with measures of dysphoria. Serum kynurenine levels will be elevated in patients with schizophrenia, particularly in deficit syndrome patients. mRNA expression levels of enzymes downstream from IDO will differ between patients and controls. Measures of immune activation will be influenced by medical disease burden (medical comorbidities).