Abstract
BackgroundBiomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients.MethodsThis research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment.ResultsThe administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes.A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group.ConclusionsThe DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.
Highlights
Biomarkers are widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research
The dopamine receptor D4 (DRD4) and Serotonin 2A receptor (5HTR2A) genes are co-expressed in peripheral blood mononuclear cells (PBMCs) during antipsychotic administration
Dynamics of the mental state in patients during the administration of antipsychotics Between June 2014 and April 2016, 60 schizophrenic patients with first-episode psychosis were randomly assigned to olanzapine treatment (n = 30) or haloperidol treatment (n = 30 as a comparison [control] group)
Summary
Biomarkers are widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. The dopaminergic hypothesis for schizophrenia is still largely based on the consequences of pharmacologic manipulations of dopamine transmission by either mimicking or reducing the symptoms of schizophrenia [2, 3]. This “dopamine hyperfunction hypothesis” is the dominant theory in schizophrenia and has been supported by molecular, pharmacological and clinical evidence for more than 40 years [4, 5]. Identifying biomarkers that can predict treatment response in patients with schizophrenia will be an important step towards providing personalized medicine that will increase the efficiency and safety of therapy [8, 9]
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