Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2C ser and DRD3 gly alleles to susceptibility
| Autor: | Bernard Lerer, Michael Schlafman, Abe Dorevitch, A Yakir, Uriel Heresco-Levy, Ronnen H. Segman, Aida Shelevoy, T Goltser, Roi Inbar, Tal Neeman, Arturo G. Lerner, Boris Finkel |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male medicine.medical_specialty Psychosis Adolescent Genotype medicine.drug_class Atypical antipsychotic Tardive dyskinesia Gene Frequency Dopamine receptor D3 Internal medicine Receptor Serotonin 5-HT2C medicine Humans Genetic Predisposition to Disease Allele frequency Alleles Aged Pharmacology Analysis of Variance Polymorphism Genetic Receptors Dopamine D2 Receptors Dopamine D3 Middle Aged medicine.disease Genotype frequency Endocrinology Dyskinesia Receptors Serotonin Chronic Disease Schizophrenia Female medicine.symptom Psychology Akathisia Drug-Induced |
| Zdroj: | Psychopharmacology. 152:408-413 |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s002130000521 |
| Popis: | Rationale: Tardive dyskinesia (TD) is a long-term adverse effect of dopamine receptor blockers. The dopamine D3 receptor gene (DRD3) ser9gly polymorphism has been previously associated with susceptibility to TD. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs. Objectives: To examine the association of a functional polymorphism in the 5-HT2C receptor gene (HT2CR) with TD and the joint contribution of HT2CR and DRD3 to susceptibility. Methods: Case control association analysis of allele and genotype frequencies among schizophrenia patients with (n=55) and without TD (n=60), matched for antipsychotic drug exposure and other relevant variables, and normal control subjects (n=97). Parametric analyses of the contribution of 5-HT2Cser and DRD3gly alleles to dyskinesia scores. Results: We found a significant excess of 5-HT2Cser alleles in schizophrenia patients with TD (27.2%) compared to patients without TD (14.6%) and normal controls (14.2%; χ2=6.4, df 2, P=0.03) which was due to the female patients (χ2=8.6, df 2, P=0.01). Among the female TD patients there was an excess of cys-ser and ser-ser genotypes (χ2=11.9, df 4, P=0.02). Analysis of covariance (ANCOVA), controlling for age at first antipsychotic treatment, revealed a significant effect of 5-HT2C genotype on orofacial dyskinesia (OFD) scores (F=3.47, df 2, P=.03). In a stepwise multiple regression analysis, 5-HT2C and DRD3 genotype (5-HT2Cser and DRD3gly allele carriage) respectively contributed 4.2% and 4.7% to the variance in OFD scores. Conclusions: These findings support a small but significant contribution of the HT2CR and DRD3 to susceptibility to TD, which is additive in nature. |
| Databáze: | OpenAIRE |
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