5-Hydroxytryptamine Receptors and Tardive Dyskinesia in Schizophrenia

Abstract

Background: Tardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia. Methods: A set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4. Results: Statistically significant associations of rs1928040 of HTR2A gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results. Conclusion: We found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest

Genetic Factors Associated With Tardive Dyskinesia: From Pre-clinical Models to Clinical Studies

“…Lastly, there are three studies that focused on HTR6 rs1805054. No association with TD was reported in Japanese, Ashkenazi, non-Ashkenazi and Caucasian schizophrenia patients ( Ohmori et al, 2002 ; Segman et al, 2003 ; Pozhidaev et al, 2020 ). All of the studies are presented in this chaptercan be found in the Supplementary Table S2 .…”

“…Other HTR2C polymorphisms were studied, such as rs569959, rs17326429, rs12858300, rs4911871, rs5946189, rs1801412 ( Bakker et al, 2012 ), and rs3813929 ( Zhang et al, 2002a ; Koning et al, 2012 ), but no association with TD was recorded. However, HTR2C rs1801412 was significantly associated with the orofacial type of TD in women ( Pozhidaev et al, 2020 ).…”

“…The haplotype analysis of the HTR2A rs6313 and HTR2A rs6314 showed significant associations with TD ( Lerer et al, 2005 ). Finally, HTR2A rs1928040 was associated with the orofacial type of TD ( Pozhidaev et al, 2020 ).…”

Pharmacodynamic Gene Testing in Prader-Willi Syndrome

“…Increased risk for movement disorder, such as tardive dyskinesia, which is an adverse effect associated with the use of antipsychotic medications, is increased among those with the G allele of −1438G > A (rs6311) and the C allele of 102T/C (rs6313) (Lattuada et al, 2004). These two polymorphisms are in strong linkage disequilibrium with rs1928040, another polymorphism of HTR2A associated with the orofacial type of tardive dyskinesia particularly among females (Pozhidaev et al, 2020).…”

Genetic Polymorphisms of 5-HT Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia

“…Studying the association of functional genetic variants with specific clinical phenomena can be applied to elucidate their mechanistic background [ 40 ]. We applied this investigational method several times in attempts to clarify a possible role of 5-HT neurotransmission in the mechanism of two side effects of (atypical) antipsychotic drugs: dyskinesia [ 41 , 42 , 43 , 44 ] and hyperprolactinemia [ 45 ]. Therefore, studying the contribution of 5-HT neurotransmission in the mechanisms of MetS can be considered a logical next step.…”