TY - JOUR
T1 - Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia
AU - Segman, R. H.
AU - Heresco-Levy, U.
AU - Finkel, B.
AU - Goltser, T.
AU - Shalem, R.
AU - Schlafman, M.
AU - Dorevitch, A.
AU - Yakir, A.
AU - Greenberg, D.
AU - Lerner, A.
AU - Lerer, B.
N1 - Funding Information:
This work was supported in part by grants from the Yisumi Fund of Hadassit Research and Development Corporation and the National Institute for Psychobiology in Israel (to RS) and the India–Israel Human Genome Collaboration (to BL). The Biological Psychiatry Laboratory, Hadassah–Hebrew University Medical Center (http://www.hadassah.org.il/departments/biopsyc/), is supported by the Harry Stern Family Foundation.
PY - 2001
Y1 - 2001
N2 - Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs. We examined the association of three polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility - T102C and his452tyr in the coding region and A-1438G 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% Cl 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 schizophrenia may reflect association of a sub-group of patients with a susceptibility to abnormal involuntary movements related to antipsychotic drug exposure.
AB - Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs. We examined the association of three polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility - T102C and his452tyr in the coding region and A-1438G 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% Cl 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 schizophrenia may reflect association of a sub-group of patients with a susceptibility to abnormal involuntary movements related to antipsychotic drug exposure.
KW - 5-HT2A
KW - Genetic association
KW - Schizophrenia
KW - Serotonin receptors
KW - Tardive dyskinesia
UR - https://www.scopus.com/pages/publications/17744392199
U2 - 10.1038/sj.mp.4000842
DO - 10.1038/sj.mp.4000842
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 11317227
AN - SCOPUS:17744392199
SN - 1359-4184
VL - 6
SP - 225
EP - 229
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 2
ER -