DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION

Introduction. Despite the evolution of antipsychotic drugs, the problem of the therapy effectiveness and safety of schizophrenia spectrum disorders and comorbid conditions is very acute. The dopamine receptor D2 gene (DRD2) is one of the key targets of modern pharmacogenetic studies of mental disord...

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Main Authors: M. N. Grunina, A. M. Zabotina, A. S. Zhuravlev, M. M. Pchelina, E. V. Volkova, R. F. Nasyrova, A. E. Taraskina, E. M. Krupitsky
Format: Article
Language:Russian
Published: Academician I.P. Pavlov First St. Petersburg State Medical University 2020-05-01
Series:Учёные записки Санкт-Петербургского государственного медицинского университета им. Акад. И.П. Павлова
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Online Access:https://www.sci-notes.ru/jour/article/view/657
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author M. N. Grunina
A. M. Zabotina
A. S. Zhuravlev
M. M. Pchelina
E. V. Volkova
R. F. Nasyrova
A. E. Taraskina
E. M. Krupitsky
author_facet M. N. Grunina
A. M. Zabotina
A. S. Zhuravlev
M. M. Pchelina
E. V. Volkova
R. F. Nasyrova
A. E. Taraskina
E. M. Krupitsky
author_sort M. N. Grunina
collection DOAJ
description Introduction. Despite the evolution of antipsychotic drugs, the problem of the therapy effectiveness and safety of schizophrenia spectrum disorders and comorbid conditions is very acute. The dopamine receptor D2 gene (DRD2) is one of the key targets of modern pharmacogenetic studies of mental disorders.The objective of the study was to analyze the DRD2 mRNA level in peripheral blood lymphocytes and to identify genetic variations of –141С Ins/Del as potential biomarkers for antipsychotic therapy prognosis.Methods and materials. The study included 112 patients with mental disorders: 61 – with a diagnosis of schizophrenia spectrum disorder, 51 – with a comorbid disease course with alcohol dependence syndrome, and 112 people as a control group. Psychometric evaluation was carried out using PANSS scale. The material was peripheral blood lymphocytes (PBLs). The DRD2 mRNA level was determined by real-time polymerase chain reaction with TaqMan probe. Genotyping –141С Ins/Del was performed by the restriction fragment length polymorphism assay.Results. –141C Ins/Del DRD2 genetic variations are not associated with a risk of mental disorder development, and they did not affect the DRD2 mRNA level in PBLs. There were no significant differences in the gene expression of DRD2 in the control group and patients (p=0.194). Despite the improvement of the mental state in all patients included in the study, the studied DRD2 parameters did not affect either the mental disorder symptoms or the normalization of the patient status against the background of antipsychotic therapy. Ins/Ins genetic variation of –141C Ins/Del was significantly associated with an increase weight gain of more than 7 % on the 28th day of antipsychotic therapy.Conclusion. Ins/Ins genetic variation of –141C Ins/Del can be considered as a biomarker for the prognosis of antipsychotic-induced weight gain.
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series Учёные записки Санкт-Петербургского государственного медицинского университета им. Акад. И.П. Павлова
spelling doaj.art-bbecc772a537442189ea31fb117d1a482025-03-02T11:44:15ZrusAcademician I.P. Pavlov First St. Petersburg State Medical UniversityУчёные записки Санкт-Петербургского государственного медицинского университета им. Акад. И.П. Павлова1607-41812541-88072020-05-01271455610.24884/1607-4181-2020-27-1-45-56478DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATIONM. N. Grunina0A. M. Zabotina1A. S. Zhuravlev2M. M. Pchelina3E. V. Volkova4R. F. Nasyrova5A. E. Taraskina6E. M. Krupitsky7National Research Centre «Kurchatov Institute»Kurchatov Institute; Pavlov UniversityNational Research Centre «Kurchatov Institute»Pavlov UniversityPavlov UniversityBekhterev National Medical Research Center for Psychiatry and NeurologyKurchatov Institute; Pavlov University; Bekhterev National Medical Research Center for Psychiatry and NeurologyBekhterev National Medical Research Center for Psychiatry and Neurology; Pavlov UniversityIntroduction. Despite the evolution of antipsychotic drugs, the problem of the therapy effectiveness and safety of schizophrenia spectrum disorders and comorbid conditions is very acute. The dopamine receptor D2 gene (DRD2) is one of the key targets of modern pharmacogenetic studies of mental disorders.The objective of the study was to analyze the DRD2 mRNA level in peripheral blood lymphocytes and to identify genetic variations of –141С Ins/Del as potential biomarkers for antipsychotic therapy prognosis.Methods and materials. The study included 112 patients with mental disorders: 61 – with a diagnosis of schizophrenia spectrum disorder, 51 – with a comorbid disease course with alcohol dependence syndrome, and 112 people as a control group. Psychometric evaluation was carried out using PANSS scale. The material was peripheral blood lymphocytes (PBLs). The DRD2 mRNA level was determined by real-time polymerase chain reaction with TaqMan probe. Genotyping –141С Ins/Del was performed by the restriction fragment length polymorphism assay.Results. –141C Ins/Del DRD2 genetic variations are not associated with a risk of mental disorder development, and they did not affect the DRD2 mRNA level in PBLs. There were no significant differences in the gene expression of DRD2 in the control group and patients (p=0.194). Despite the improvement of the mental state in all patients included in the study, the studied DRD2 parameters did not affect either the mental disorder symptoms or the normalization of the patient status against the background of antipsychotic therapy. Ins/Ins genetic variation of –141C Ins/Del was significantly associated with an increase weight gain of more than 7 % on the 28th day of antipsychotic therapy.Conclusion. Ins/Ins genetic variation of –141C Ins/Del can be considered as a biomarker for the prognosis of antipsychotic-induced weight gain.https://www.sci-notes.ru/jour/article/view/657drd2 genemrna levels–141с ins/delschizophrenia spectrum disorderscomorbidityalcohol dependence syndromeantipsychotic drugsperipheral blood lymphocytesantipsychotic-induced weight gain
spellingShingle M. N. Grunina
A. M. Zabotina
A. S. Zhuravlev
M. M. Pchelina
E. V. Volkova
R. F. Nasyrova
A. E. Taraskina
E. M. Krupitsky
DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION
Учёные записки Санкт-Петербургского государственного медицинского университета им. Акад. И.П. Павлова
drd2 gene
mrna levels
–141с ins/del
schizophrenia spectrum disorders
comorbidity
alcohol dependence syndrome
antipsychotic drugs
peripheral blood lymphocytes
antipsychotic-induced weight gain
title DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION
title_full DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION
title_fullStr DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION
title_full_unstemmed DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION
title_short DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION
title_sort dopamine receptor d2 drd2 in peripheral blood lymphocytes as biomarker of response to antipsychotic medication
topic drd2 gene
mrna levels
–141с ins/del
schizophrenia spectrum disorders
comorbidity
alcohol dependence syndrome
antipsychotic drugs
peripheral blood lymphocytes
antipsychotic-induced weight gain
url https://www.sci-notes.ru/jour/article/view/657
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