Association analysis of haplotypes and regulatory potential of serotonin receptor genes in patients with schizophrenia and tardive dyskinesia

Association analysis of haplotypes and regulatory potential of serotonin receptor genes in patients with schizophrenia and tardive dyskinesia

 

Authors

 

I.V. Pozhidaev

Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation

S.A. Ivanova

Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation

 

https://doi.org/10.26617/1810-3111-2024-1(122)-27-36

 

Journal: Siberian Herald of Psychiatry and Addiction Psychiatry. 2024; 1 (122):  27-36.

 

Abstract

Background. Tardive dyskinesia (TD) is a severe and potentially irreversible movement disorder that can develop as a side effect of long-term use of antipsychotic medications. Despite the fact that the pathophysiological mechanisms underlying antipsychotic-induced tardive dyskinesia are not yet sufficiently studied, literature data indicates the important role of genetic factors and the possible disruption of the dopaminergic and serotonergic systems. Changes in the genetic regulatory potential of serotonin receptors may play a role in the development of the antipsychotic-induced TD in patients with schizophrenia. Objective: to conduct a haplotype analysis of serotonin receptor genes, to determine the regulatory potential of the study genes in patients with schizophrenia and tardive dyskinesia. Material and Methods. The study was carried out on a sample of 449 patients aged 18-65 years suffering from schizophrenia and undergoing inpatient treatment at Mental Health Research Institute of Tomsk National Research Medical Center, Tomsk Clinical Psychiatric Hospital and Kemerovo Regional Clinical Psychiatric Hospital. Two groups were formed from them: patients meeting the criteria for the presence of tardive dyskinesia (n=121), patients without movement disorders (n=328). Dyskinesia was diagnosed using the standardized Abnormal Involuntary Movement Scale (AIMS). Genotyping 29 single-nucleotide polymorphic variants of 7 serotonin receptor genes was carried out using mass spectrometry on a Sequenom genetic analyzer. The regulatory potential of associations between single nucleotide polymorphisms and gene expression was assessed using the Genotype-Tissue Expression project portal. Results. The analysis demonstrated the association of the CTTTAACC haplotype of the HTR2A gene with the presence of tardive dyskinesia, that was a predisposing factor in the development of this side effect (OR=2.10, p=0.029). The detected association and annotation of the biological pathways of the studied genes confirmed the involvement of serotonergic receptor genes in the pathogenesis of medication-induced tardive dyskinesia under long-therm therapy with antipsychotics.

 

Keywords: schizophrenia, tardive dyskinesia, serotonin receptors, haplotype, haplotype analysis, quantitative trait locus.

 

Article (pdf)

 

Contacts

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Materials 

For citation: Pozhidaev I.V., Ivanova S.A. Association analysis of haplotypes and regulatory potential of serotonin receptor genes in patients with schizophrenia andtardive dyskinesia. Siberian Herald of Psychiatry and Addiction Psychiatry.2024; 1 (122): 27-36. https://doi.org/10.26617/1810-3111-2024-1(122)-27-36

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