Expression of Dopamine D(1−4) and Serotonin 5-HT(1A-3A) Receptors in Blood Mononuclear Cells in Schizophrenia

Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D(1), D(2), D(3), D(4) and serotonin 5-HT(1A), 5-HT(2A), and 5-HT(3A) receptors in peripheral blood mononuclear cells (PBMCs) in schizophrenia and the in vitro effect of antipsychotics on the expression of these receptors in PBMCs of healthy subjects. Materials and Methods: Twenty-seven patients with schizophrenia and 29 healthy controls were recruited for the study. All study subjects underwent thorough clinical assessment, including anthropometric and body composition measurements. The expression of mRNA for dopamine D(1−4) and serotonin 5-HT(1A−3A) receptors was measured using quantitative RT-PCR in peripheral blood mononuclear cells. In vitro mRNA and protein expression of these receptors was measured using quantitative RT-PCR and Western Blotting in PBMCs cultured with quetiapine, haloperidol, aripiprazole, risperidone, olanzapine or clozapine at IC(50), half of IC(50), and one-quarter of IC(50) concentrations. Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D(1), D(2) and D(4) receptors (p < 0.001), and significantly lower mRNA expression of 5-HT(3A) receptors (p < 0.01). After adjusting for smoking, the mRNA expression of D(1) lost its significance, while that of D(3), 5-HT(1A), 5-HT(2A) became significant (all three were lower in the schizophrenia group). These receptors also demonstrated different ratios of mRNA expression in the schizophrenia group. The in vitro experiments showed that high concentrations of antipsychotics influenced the mRNA and protein expression of all studied receptors. Conclusion: Schizophrenia patients display a distinctive pattern of dopamine and serotonin receptor mRNA expression in blood mononuclear cells. This expression is little affected by antipsychotic treatment and it may therefore serve as a useful diagnostic biomarker for schizophrenia.