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Randomized Controlled Trial
. 2017 Dec 8;17(1):394.
doi: 10.1186/s12888-017-1562-1.

Potential diagnostic markers of olanzapine efficiency for acute psychosis: a focus on peripheral biogenic amines

A E Taraskina  1   2   3 , R F Nasyrova  1 , A M Zabotina  4   5 , D N Sosin  1 , К А Sosina  1 , E E Ershov  6 , M N Grunina  3 , E M Krupitsky  1   2
Affiliations
Randomized Controlled Trial

Potential diagnostic markers of olanzapine efficiency for acute psychosis: a focus on peripheral biogenic amines

A E Taraskina et al. BMC Psychiatry. .

Abstract

Background: Biomarkers 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.

Methods: This 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.

Results: The 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.

Conclusions: The 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.

Keywords: Acute psychosis; Antipsychotic treatment; Dopamine D4 receptor; Olanzapine; Peripheral blood mononuclear cells; Schizophrenia; Serotonin 2A (5-HT2A) receptor; Serum dopamine levels.

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Conflict of interest statement

Ethics approval and consent to participate

The Ethical and Scientific Committee of V.M. Bekhterev Psychoneurological Research Institute approved the project under the n° EC-1361 and all patients signed a consent form.

Consent for publication

Non applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Dynamics of the mean total scores according to the PANSS scale
Fig. 2
Fig. 2
Expression levels of dopamine D4 receptor and 5-HT receptor subtype mRNA in PBMCs from schizophrenic patients during the administration of antipsychotics
Fig. 3
Fig. 3
Association between 5HTR2A and DRD4 mRNA levels during the administration of antipsychotics (olanzapine (a) and haloperidol (b) monotherapy) in schizophrenic patients before treatment and at day 14 and 28 post-administration. Spearman’s correlation analysis was chosen to identify the significant association between the mRNA levels of 5HTR2A and DRD4, which was significant at the level of 0.01
Fig. 4
Fig. 4
Dopamine serum levels from schizophrenic patients during the administration of antipsychotics
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