Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone

Y. Yamanouchi, Nakao Iwata, T. Suzuki, Tsuyoshi Kitajima, Masashi Ikeda, N. Ozaki

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Six candidate polymorphisms (HTR2A -1438G>A, 102T>C, H452Y; DRD2 -141delC, Taq I A; COMT V158M) were genotyped. The diplotype configuration for each individual was estimated by the maximum-likelihood method. Multiple linear regressions were used to analyze the effects of these haplotypes/genotype and other prognostic factors on PANSS scale performance. After adjustment for the effects of patient-related variables, HTR2A diplotype and COMT genotype, as well as other potential prognostic factors, did not significantly influence the clinical performance. A DRD2 haplotype tended to correlate with better clinical performance. Compared with patients who had Ins-A2/Ins-A2 diplotype (n=25), PANSS total scores of patients with Ins-A2/ Del-A1 diplotype (n=10) showed 40% greater improvement (P=0.03). The PANSS total scores of patients with HTR2A A-T/A-T diplotype (n=22) tended to show 15% worse improvement compared with A-T/G-C diplotype (n=33) (P-0.06). These results should be treated with caution because of limitations due to small sample size, heterogeneity of patients with respect to past antipsychotic use history, and no correction for multiple corrections. However, the present findings generate important hypotheses in a sample of Japanese schizophrenia patients that may lay the foundation for future pharmacogenomics investigations in other populations.

Original languageEnglish
Pages (from-to)356-361
Number of pages6
JournalPharmacogenomics Journal
Volume3
Issue number6
DOIs
Publication statusPublished - 01-12-2003

Fingerprint

Risperidone
Antipsychotic Agents
Genes
varespladib methyl
Haplotypes
Schizophrenia
Genotype
Pharmacogenetics
Sample Size
Linear Models
History
Population

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

@article{9d2940602d4f4bab87f824e318f72e01,
title = "Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone",
abstract = "Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Six candidate polymorphisms (HTR2A -1438G>A, 102T>C, H452Y; DRD2 -141delC, Taq I A; COMT V158M) were genotyped. The diplotype configuration for each individual was estimated by the maximum-likelihood method. Multiple linear regressions were used to analyze the effects of these haplotypes/genotype and other prognostic factors on PANSS scale performance. After adjustment for the effects of patient-related variables, HTR2A diplotype and COMT genotype, as well as other potential prognostic factors, did not significantly influence the clinical performance. A DRD2 haplotype tended to correlate with better clinical performance. Compared with patients who had Ins-A2/Ins-A2 diplotype (n=25), PANSS total scores of patients with Ins-A2/ Del-A1 diplotype (n=10) showed 40{\%} greater improvement (P=0.03). The PANSS total scores of patients with HTR2A A-T/A-T diplotype (n=22) tended to show 15{\%} worse improvement compared with A-T/G-C diplotype (n=33) (P-0.06). These results should be treated with caution because of limitations due to small sample size, heterogeneity of patients with respect to past antipsychotic use history, and no correction for multiple corrections. However, the present findings generate important hypotheses in a sample of Japanese schizophrenia patients that may lay the foundation for future pharmacogenomics investigations in other populations.",
author = "Y. Yamanouchi and Nakao Iwata and T. Suzuki and Tsuyoshi Kitajima and Masashi Ikeda and N. Ozaki",
year = "2003",
month = "12",
day = "1",
doi = "10.1038/sj.tpj.6500211",
language = "English",
volume = "3",
pages = "356--361",
journal = "Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
number = "6",

}

Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone. / Yamanouchi, Y.; Iwata, Nakao; Suzuki, T.; Kitajima, Tsuyoshi; Ikeda, Masashi; Ozaki, N.

In: Pharmacogenomics Journal, Vol. 3, No. 6, 01.12.2003, p. 356-361.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone

AU - Yamanouchi, Y.

AU - Iwata, Nakao

AU - Suzuki, T.

AU - Kitajima, Tsuyoshi

AU - Ikeda, Masashi

AU - Ozaki, N.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Six candidate polymorphisms (HTR2A -1438G>A, 102T>C, H452Y; DRD2 -141delC, Taq I A; COMT V158M) were genotyped. The diplotype configuration for each individual was estimated by the maximum-likelihood method. Multiple linear regressions were used to analyze the effects of these haplotypes/genotype and other prognostic factors on PANSS scale performance. After adjustment for the effects of patient-related variables, HTR2A diplotype and COMT genotype, as well as other potential prognostic factors, did not significantly influence the clinical performance. A DRD2 haplotype tended to correlate with better clinical performance. Compared with patients who had Ins-A2/Ins-A2 diplotype (n=25), PANSS total scores of patients with Ins-A2/ Del-A1 diplotype (n=10) showed 40% greater improvement (P=0.03). The PANSS total scores of patients with HTR2A A-T/A-T diplotype (n=22) tended to show 15% worse improvement compared with A-T/G-C diplotype (n=33) (P-0.06). These results should be treated with caution because of limitations due to small sample size, heterogeneity of patients with respect to past antipsychotic use history, and no correction for multiple corrections. However, the present findings generate important hypotheses in a sample of Japanese schizophrenia patients that may lay the foundation for future pharmacogenomics investigations in other populations.

AB - Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Six candidate polymorphisms (HTR2A -1438G>A, 102T>C, H452Y; DRD2 -141delC, Taq I A; COMT V158M) were genotyped. The diplotype configuration for each individual was estimated by the maximum-likelihood method. Multiple linear regressions were used to analyze the effects of these haplotypes/genotype and other prognostic factors on PANSS scale performance. After adjustment for the effects of patient-related variables, HTR2A diplotype and COMT genotype, as well as other potential prognostic factors, did not significantly influence the clinical performance. A DRD2 haplotype tended to correlate with better clinical performance. Compared with patients who had Ins-A2/Ins-A2 diplotype (n=25), PANSS total scores of patients with Ins-A2/ Del-A1 diplotype (n=10) showed 40% greater improvement (P=0.03). The PANSS total scores of patients with HTR2A A-T/A-T diplotype (n=22) tended to show 15% worse improvement compared with A-T/G-C diplotype (n=33) (P-0.06). These results should be treated with caution because of limitations due to small sample size, heterogeneity of patients with respect to past antipsychotic use history, and no correction for multiple corrections. However, the present findings generate important hypotheses in a sample of Japanese schizophrenia patients that may lay the foundation for future pharmacogenomics investigations in other populations.

UR - http://www.scopus.com/inward/record.url?scp=0346025677&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346025677&partnerID=8YFLogxK

U2 - 10.1038/sj.tpj.6500211

DO - 10.1038/sj.tpj.6500211

M3 - Article

C2 - 14610521

AN - SCOPUS:0346025677

VL - 3

SP - 356

EP - 361

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

SN - 1470-269X

IS - 6

ER -