Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia
Autor: | M Schlafman, A Shelevoy, B. Lerer, L Karagichev, Ronnen H. Segman, B Finkel, A Dorevitch, A Yakir, T Neeman, Uriel Heresco-Levy, A Lerner |
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Rok vydání: | 1999 |
Předmět: |
Adult
Male Psychosis medicine.medical_specialty Dyskinesia Drug-Induced Genotype medicine.medical_treatment Glycine Tardive dyskinesia Cellular and Molecular Neuroscience Dopamine receptor D3 Reference Values Internal medicine medicine Serine Humans Israel Antipsychotic Molecular Biology Allele frequency Receptors Dopamine D2 Receptors Dopamine D3 Middle Aged medicine.disease Abnormal involuntary movement Psychiatry and Mental health Endocrinology Dyskinesia Schizophrenia Jews Female medicine.symptom Psychology Antipsychotic Agents |
Zdroj: | Molecular psychiatry. 4(3) |
ISSN: | 1359-4184 |
Popis: | Dopamine receptor antagonism is a common mechanism underlying the therapeutic efficacy of all classical antipsychotic drugs. It is also thought to underlie the propensity of these agents to induce the movement disorder, tardive dyskinesia (TD), in one fifth of chronically exposed schizophrenia patients. We examined the polymorphic serine to glycine substitution in the first exon of the gene encoding the dopamine D3 receptor (DRD3) inn 53 schizophrenia patients with TD, 63 matched patients with similar antipsychotic exposure but no TD and 117 normal controls. There was a difference in allele frequency that was of borderline significance (P = 0.055), due to an excess of the DRD3gly allele (allele 2) in the schizophrenia patients with TD. The difference in genotype distribution among the groups was highly significant (chi2 = 19.1, d.f. 4, P = 0.0008) due to an excess of the DRD3ser-gly genotype in the schizophrenia patients with TD. The difference between the schizophrenia patients with TD and the controls was highly significant (chi2 = 19.0, d.f. 2, P = 0.00007), even after correction for multiple testing, as was the difference between the combined group of schizophrenia patients and the controls (chi2 = 12.2, d.f. 2, P = 0.002). Comparing the schizophrenia patients with and without TD, genotypes containing the gly allele (DRD3ser-gly and DRD3gly-gly genotypes combined) were significantly associated with dyskinesia (OR = 2.62, 95% CI 1.18-5.59, P = 0.02). DRD3 genotype and age at first antipsychotic treatment contributed significantly to total score on the Abnormal Involuntary Movements Scale (AIMS). The contribution of DRD3 to the variance in AIMS total was 5.2% and the total proportion of the variance accounted for by these two variables together was 11.9%. These results support and extend the report by Steen et al (1997) of an association between DRD3 and TD in schizophrenia patients. |
Databáze: | OpenAIRE |
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