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The lack of association between serotonin receptor - 2A and - 2C gene polymorphisms and extrapiramidal side effects in haloperidol-treated patients with schizophrenia

The treatment of schizophrenia with antipsychotics is far from satisfactory in terms of tolerability and side effects. Schizophrenic patients treated particularly with classical antipsychotics, such as haloperidol, often experience extrapyramidal side-effects (EPS), usually related to the dopaminergic system. However, serotonergic mechanisms might be also involved, either by regulatory effects on dopamine release or via serotonergic receptors. Although, serotonin 5-HT2A and 5-HT2C receptors represent molecular targets for some antipsychotics, the association between polymorphic variants of these receptor genes and EPS is unclear. Hence, the aim of the study was to examine the association of 5- HT2A and 5-HT2C receptor gene polymorphisms with the occurrence of EPS in schizophrenic patients, following 2 weeks haloperidol monotherapy. The severity of EPS in schizophrenia-diagnosed patients (DSM-IV criteria) was evaluated using Simpson Angus Rating Scale for Extrapyramidal Side Effects, Barnes Akathisia Rating Scale and Extrapyramidal Symptom Rating Scale. Genomic DNA was extracted from whole blood and genotyping of polymorphisms in 5-HT2A (102T/C ; rs6313) and 5-HT2C (-759C/T ; rs3813929) receptor genes was performed using TaqMan Real-Time allelic discrimination. The results demonstrated no significant differences in the genotype and allele frequencies of 5-HT2A or 5-HT2C receptor gene polymorphisms, between patients with or without EPS and their particular symptoms. Although our results have not provided supporting evidence for the potential involvement of the 5-HT2A and 5-HT2C receptor gene variants in the haloperidol-induced EPS of schizophrenic patients, further studies are needed to investigate the role of serotonergic system and its genes in the development of EPS.

schizophrenia; haloperidol; extrapyramidal side-effects; 5-HT2A and 5-HT2C receptor gene polymorphisms

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