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


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.


CONCLUSIONS
These data suggest that the SNPs in DRD2 and AKT1 may influence the treatment response to risperidone in schizophrenia patients.
Ikeda
Masashi
M
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. ikeda-ma@fujita-hu.ac.jp
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Kitajima
Tsuyoshi
T
Yoshimura
Reiji
R
Hashimoto
Shuji
S
O'Donovan
Michael C
MC
Nakamura
Jun
J
Ozaki
Norio
N
Iwata
Nakao
N
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004298:Dopamine / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007564:Japan / Q000208:ethnology; D016014:Linear Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D011985:Receptors, Serotonin / Q000235:genetics*; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D018967:Risperidone; D004298:Dopamine