[논문]Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia

Segman, R H; Heresco-Levy, U; Finkel, B; Goltser, T; Shalem, R; Schlafman, M; Dorevitch, A; Yakir, A; Greenberg, D; Lerner, A; Lerer, B

doi:10.1038/sj.mp.4000842

[해외논문] Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia 원문보기

Molecular psychiatry, v.6 no.2, 2001년, pp.225 - 229

Segman, R H (Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah–) , Heresco-Levy, U (Hebrew University Medical Center, Jerusalem, Israel) , Finkel, B (Herzog Hospital, Jerusalem, Israel) , Goltser, T (Lev Hasharon Hospital, Pardessia, Israel) , Shalem, R (Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah–) , Schlafman, M (Hebrew University Medical Center, Jerusalem, Israel) , Dorevitch, A (Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah–) , Yakir, A (Hebrew University Medical Center, Jerusalem, Israel) , Greenberg, D (Kfar Shaul Hospital, Jerusalem, Israel) , Lerner, A (Talbieh Hospital, Jerusalem, Israel) , Lerer, B (Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah–)

Abstract ▼ AI-Helper

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers.1 Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs.2 We examined the association of three polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility—T102C3 and his452tyr4 in the coding region and A-1438G5 in the promoter—in matched schizophrenia patients with (n = 59, SCZ-TD-Y) and without TD (n = 62, SCZ-TD-N) and normal control subjects (n = 96). The T102C and the A-1438G polymorphisms are in complete linkage disequilibrium but not his452tyr. There was a significant excess of 102C and −1438G alleles (62.7%) in the SCZ-TD-Y patients compared to SCZ-TD-N patients (41.1%) and controls (45.9%; χ2 = 12.8, df = 2, P = 0.002; SCZ-TD-Y vs SCZ-TD-N, χ2 = 11.4, df = 1, P = 0.0008, OR 2.41, 95% CI 1.43–3.99) and of 102CC and −1438GG genotypes (SCZ-TD-Y 42.4%, SCZ-TD-N, 16.1%, controls 20.8%, χ2 = 13.3, df = 4, P = 0.01). The 102CC and the −1438GG genotypes were associated with significantly higher AIMS trunk dyskinesia scores (F = 3.9; df = 2, 116; P = 0.02) and more incapacitation (F = 5.0; df = 2, 115; P = 0.006). The his452tyr polymorphism showed no association with TD. These findings suggest that the 5-HT2A receptor gene is significantly associated with susceptibility to TD in patients with chronic schizophrenia. Previously reported association of the T102C and A-1438G polymorphisms with schizophrenia6 may reflect association of a sub-group of patients with a susceptibility to abnormal involuntary movements related to antipsychotic drug exposure.

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