IMPACT OF DIFFERENT ANTIPSYCHOTICS ON CYTOKINES AND TRYPTOPHAN METABOLITES IN STIMULATED CULTURES FROM PATIENTS WITH SCHIZOPHRENIA

Background: An imbalance of tryptophan metabolites plays a role in the pathophysiology of schizophrenia. Also cytokines seem to be involved and are able to enhance the tryptophan metabolism. In this study the impact of cytokines, tryptophan metabolites and antipsychotics was evaluated in schizophrenic patients/ healthy controls and correlated with the psychopathology of schizophrenia. Subjects and methods: This study investigated 12 patients with schizophrenia and 24 matched controls. Peripheral blood mononuclear cell cultures were stimulated in vitro with lipopolysaccharide (LPS) or polyinosine-polycytidylic acid (poly I:C) and different antipsychotics (quetiapine, risperidone, haloperidole and clozapine) were added. The cytokines IL-4, IL-10, IFN-γ and tryptophan metabolites were analysed. Symptom severity was assessed using the positive and negative syndrome scale (PANSS). Results: Peripheral mononuclear cells of schizophrenia patients showed a reduced IFN-γ response to LPS (p=0.008). When quetiapine and risperidone were added this imbalance between patients and controls disappeared. Tryptophan levels were significantly lower in patients’ cells cultures when the cells were stimulated with LPS (p=0.029). A group effect for lower levels in the patients’ cell culture was evaluated for tryptophan and kynurenine (p=0.043; p=0.05). In addition, high tryptophan levels correlated with low PANSS negative scores in patients and higher kynurenine levels resulted in higher PANSS positive scores. Conclusions: Only two atypical antipsychotics were identified to reverse the imbalanced cytokine levels in schizophrenia. The low concentrations of tryptophan and kynurenine in these patients could be a sign of a fast degradation of tryptophan – yet tryptophan metabolites could not be changed by any of the investigated antipsychotics.