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

Abstract

Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D1, D2, D3, D4 and serotonin 5-HT1A, 5-HT2A, and 5-HT3A 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 D1−4 and serotonin 5-HT1A−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-HT3A receptors (p < 0.01). After adjusting for smoking, the mRNA expression of D1 lost its significance, while that of D3, 5-HT1A, 5-HT2A 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.

Risperidone Decreases Expression of Serotonin Receptor-2A (5-HT2A) and Serotonin Transporter (SERT) but Not Dopamine Receptors and Dopamine Transporter (DAT) in PBMCs from Patients with Schizophrenia

“…However, evidence indicates that clozapine consumption increases D 3 mRNA levels in CD4 T cells of patients compared to HV [ 27 ]. As for the effect of risperidone on D 3 expression, the evidence demonstrates that PBMCs from medicated patients or cells incubated with risperidone in vitro do not show changes in D 3 expression when compared with HV [ 72 ].…”

Methylome-wide and meQTL analysis helps to distinguish treatment response from non-response and pathogenesis markers in schizophrenia

“…Viable cells were plated at a density of 2 * 10 6 /ml in a 6-well plate and cultured for 72 hours at 37°C and 5% CO 2 with different concentrations of the following antipsychotic drugs (Sigma): haloperidol (12 μM, 6 μM, and 3 μM), olanzapine (3.2 μM, 1.6 μM, and 0.8 μM), clozapine (8 μM, 4 μM, and 2 μM), and risperidone (4 μM, 2 μM, and 1 μM). The concentration of antipsychotic medicine used for the drug treatment was based on an earlier study ( 56 ). The drugs were dissolved in dimethyl sulfoxide (DMSO), and 0.1% DMSO-treated cells were used as the assay control in our study.…”

Antipsychotic-induced bone loss: the role of dopamine, serotonin and adrenergic receptor signalling

“… Antagonism and inverse agonism are indicated by blue, agonism by green and partial agonism by yellow. Data taken from ( 34 , 64 , 140 – 142 , 147 – 184 ). Binding affinity for receptors: + = week association (Ki value 100–1,000); ++ = Moderate association ( 10 – 91 ); +++ = strong association ( Howes et al, 2009 ; De Hert et al, 2011 ; Patel et al, 2014 ; Fraser et al, 2015 ; Lally and MacCabe, 2015 ; Hálfdánarson et al, 2017 ; Haddad and Correll, 2018 ; Wang et al, 2021a ; Australian Institute of Health and Welfare, 2022 ; Azimi Manavi et al, 2023 ); ++++ = very strong association (Ki < 1); ?…”