Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia

Pharmacogenomics. 2008 Oct;9(10):1437-43. doi: 10.2217/14622416.9.10.1437.

Abstract

Aims: Abnormalities in dopaminergic and serotonergic transmission systems are thought to be involved in the pathophysiology of schizophrenia and the mechanisms underlying the therapeutic effects of antipsychotics. We conducted a pharmacogenetic study to evaluate whether variants in dopamine-related genes (DRD1-DRD5, AKT1 and GSK3beta) and serotonin receptor genes (HTR1A, HTR1B, HTR1D, HTR2A, HTR2C, HTR6 and HTR7) can be used to predict the efficacy of risperidone treatment for schizophrenia.

Materials & methods: A total of 120 first-episode neuroleptic-naive schizophrenia patients were treated with risperidone monotherapy for 8 weeks and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale.

Results: Among the 30 variants that we examined, two SNPs in DRD2 (-241A>G [rs1799978] and TaqIA [rs1800497]) and two SNPs in AKT1 (AKT1-SNP1 [rs3803300] and AKT1-SNP5 [rs2494732]) were significant predictors of treatment response to risperidone.

Conclusion: These data suggest that the SNPs in DRD2 and AKT1 may influence the treatment response to risperidone in schizophrenia patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Dopamine / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Genetic Variation
  • Genotype
  • Heterozygote
  • Humans
  • Japan / ethnology
  • Linear Models
  • Male
  • Polymorphism, Single Nucleotide
  • Predictive Value of Tests
  • Psychiatric Status Rating Scales
  • Receptors, Serotonin / genetics*
  • Risperidone / pharmacology
  • Risperidone / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / genetics*
  • Time Factors
  • Young Adult

Substances

  • Antipsychotic Agents
  • Receptors, Serotonin
  • Risperidone
  • Dopamine