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

Тараскина, А. Е.; Насырова, Р. Ф.; Zabotina, A. M.; Сосин, Д. Н.; Sosina, K.A.; Ershov, E.; Grunina, M.N.; Krupitsky, Evgeny

doi:10.1186/s12888-017-1562-1

Cited by 9 publications

(5 citation statements)

References 37 publications

(39 reference statements)

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“…Finally, our findings suggest that there is no significant effect of antipsychotic treatment on COMT, 5-HTR2A , and SLC6A4 mRNA expressions. Several previous studies found that there are prominent alterations in these genes expressions after antipsychotic treatment, but with exactly opposite effects ( 26 , 41 , 50 ). Furthermore, some studies reported these genes' expressions existing region-specific alterations along with antipsychotic treatment ( 51 – 53 ).…”

Section: Discussionmentioning

confidence: 90%

COMT, 5-HTR2A, and SLC6A4 mRNA Expressions in First-Episode Antipsychotic-Naïve Schizophrenia and Association With Treatment Outcomes

Han

Zhou

et al. 2018

Front. Psychiatry

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Background: Dopaminergic and serotonergic systems play crucial roles in the pathophysiology of schizophrenia and modulate response to antipsychotic treatment. However, previous studies of dopaminergic and serotonergic genes expression are sparse, and their results have been inconsistent. In this longitudinal study, we aim to investigate the expressions of Catechol-O-methyltransferase (COMT), serotonin 2A receptor (5-HTR2A), and serotonin transporter gene (SLC6A4) mRNA in first-episode antipsychotic-naïve schizophrenia and to test if these mRNA expressions are associated with cognitive deficits and treatment outcomes or not.Method: We measured COMT, 5-HTR2A, and SLC6A4 mRNA expressions in 45 drug-naive first-episode schizophrenia patients and 38 health controls at baseline, and repeated mRNA measurements in all patients at the 8-week follow up. Furthermore, we also assessed antipsychotic response and cognitive improvement after 8 weeks of risperidone monotherapy.Results: Patients were divided into responders (N = 20) and non-responders groups (N = 25) according to the Remission criteria of the Schizophrenia Working Group. Both patient groups have significantly higher COMT mRNA expression and lower SLC6A4 mRNA expression when compared with healthy controls. Interestingly, responder patients have significantly higher levels of COMT and 5-HTR2A mRNA expressions than non-responder patients at baseline. However, antipsychotic treatment has no significant effect on the expressions of COMT, 5-HTR2A, and SLC6A4 mRNA over 8-week follow up.Conclusion: Our findings suggest that dysregulated COMT and SLC6A4 mRNA expressions may implicate in the pathophysiology of schizophrenia, and that COMT and 5-HTR2A mRNA may be potential biomarkers to predict antipsychotic response.

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Section: Discussionmentioning

confidence: 90%

COMT, 5-HTR2A, and SLC6A4 mRNA Expressions in First-Episode Antipsychotic-Naïve Schizophrenia and Association With Treatment Outcomes

Han

Zhou

et al. 2018

Front. Psychiatry

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“…Regarding the effect on receptors, some studies suggest that antipsychotics might affect gene expression in PBMCs and that differences exist between antipsychotic classes or types: for example, 5-HT 3A gene expression is significantly increased by olanzapine, but not haloperidol ( 21 ). However, Taraskina et al did not identify significant changes in the expression of 5-HT 2A or D 4 genes in PBMCs after 28 days of treatment with haloperidol or olanzapine ( 53 ). Also, successful treatment with risperidone has recently been found to increase the 5-HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that the 5-HT3A receptor may be involved in the mechanism of risperidone effect ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…The BNMRCPN (Saint Petersburg) performed a study in patients with acute psychosis treated with olanzapine or haloperidol and found no evidence that mRNA levels of the dopamine D4 receptor and serotonin 2A receptor in peripheral blood mononuclear cells are biomarkers of treatment response [70]. Another study in patients with SZ performed at the IBG (Ufa) showed that polymorphism in genes of the serotoninergic and dopaminergic systems affects individual sensitivity to haloperidol [71].…”

Section: The Modern Landscape Of Psychiatric Genetics In the Russian mentioning

confidence: 99%

Opening up new horizons for psychiatric genetics in the Russian Federation: moving toward a national consortium

et al. 2019

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We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.

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

Cited by 9 publications

References 37 publications

COMT, 5-HTR2A, and SLC6A4 mRNA Expressions in First-Episode Antipsychotic-Naïve Schizophrenia and Association With Treatment Outcomes

COMT, 5-HTR2A, and SLC6A4 mRNA Expressions in First-Episode Antipsychotic-Naïve Schizophrenia and Association With Treatment Outcomes

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

Opening up new horizons for psychiatric genetics in the Russian Federation: moving toward a national consortium

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