Altered platelet serotonin 5-HT2A receptor density but not second messenger inositol trisphosphate levels in drug-free schizophrenic patients

The 5-HT2A receptor binding parameters using [H-3]ketanserine and its intracellular signal inositol 1,4,5 trisphosphate (IP3) concentrations were determined in platelets from schizophrenic patients so as to assess differences with respect to a control group and to a standardized antipsychotic drug treatment. Seventy-five antipsychotic-free patients with a DSM-IV diagnosis of paranoid schizophrenia were included in the study. Blood samples were collected before the onset of antipsychotic treatment (baseline values) and after 3 weeks of treatment. Antipsychotic-free schizophrenic patients showed significantly increased basal 5-HT2A densities in comparison to the control group, together with a significantly increase (23%) in the 5-HT2A binding density in those patients treated with risperidone. These changes could be attributed to an up-regulation of 5-HT2A receptors caused by previous treatment with antipsychotic drugs, which is consistent with the chronic effect of 5-HT2A antagonists to up-regulate the number of binding sites. With regard to second messenger IP3 concentrations, basal concentrations in schizophrenic patients were not significantly different from control values, nor was there any significant difference between basal vs. posttreatment values. These results are possibly related to failure of second messenger systems of 'translating' extracellular messages generated presynaptically into effective neurotransmitter signals in schizophrenic patients. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.