Expression of Dopamine D1-4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia

Adam Wysokiński; Elżbieta Kozłowska; Ewa Szczepocka; Anna Łucka; Justyna Agier; Ewa Brzezińska-Błaszczyk; Katarzyna Sobierajska

doi:10.3389/fpsyt.2021.645081

Expression of Dopamine D_1-4 and Serotonin 5-HT_1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia

Front Psychiatry. 2021 Mar 10:12:645081. doi: 10.3389/fpsyt.2021.645081. eCollection 2021.

Authors

Adam Wysokiński¹, Elżbieta Kozłowska², Ewa Szczepocka¹, Anna Łucka¹, Justyna Agier², Ewa Brzezińska-Błaszczyk², Katarzyna Sobierajska³

Affiliations

¹ Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
² Department of Experimental Immunology, Medical University of Lodz, Lodz, Poland.
³ Department of Molecular Cell Mechanisms, Medical University of Lodz, Lodz, Poland.

Abstract

Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D₁, D₂, D₃, D₄ 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 IC₅₀, half of IC₅₀, and one-quarter of IC₅₀ concentrations. Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D₁, D₂ and D₄ 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 D₁ lost its significance, while that of D₃, 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.

Keywords: PBMCs; Schizophrenia; biomarkers; dopamine receptors; serotonin receptors.