The relationship between the therapeutic response to risperidone and the dopamine D2 receptor polymorphism in Chinese schizophrenia patients

Abstract

Antipsychotic drugs exert both therapeutic and adverse effects through dopamine D2 receptor (DRD2) antagonism. Genetic variants of this receptor may be responsible for individual variations in neuroleptic response and may therefore be useful in predicting response. In this study we evaluated the role of six polymorphisms of the DRD2 gene in 125 risperidone-treated Chinese schizophrenia patients following the hypothesis that variation in the DRD2 gene could affect drug response. Response was categorized as a change of >40% on the Brief Psychiatric Rating Scale (BPRS). Our results show that genotyping A-241G may help to predict the efficacy of risperidone treatment on the basis that patients with the A allele showed greater improvement than those with the G allele on the overall BPRS (chi2=7.19, p=0.007, p=0.031 after correction by the program SNPSpD), while other polymorphisms, including -141C Ins/Del, TaqIB, rs1076562, T939C and TaqIA, did not show any association with the response to risperidone. These data suggest that the DRD2 A-241G polymorphism or, alternatively, another genetic variation that is in linkage disequilibrium, may influence response to risperidone in schizophrenia patients.

Associations betweenDRDs and schizophrenia in a Korean population: multi-stage association analyses

“…While they found no association between rs1799978 of DRD2 and schizophrenia, similar to our present result, this SNP has been given particular attention recently for its relationship to the phenotype of a differential treatment response within a patient group with schizophrenia (Lencz et al, 2006;Xing et al, 2007), suggesting the possibility of an association between this SNP and sub-phenotypes of schizophrenia.…”

“…Despite the negative association results at Stage 2 in our analyses, some of the suggestively associated SNPs in Stage 1 have been studied previously in various neuropsychiatric disorders as well as schizophrenia. Since an association between rs1800955 (-521CT) of DRD4 and schizophrenia was first reported by Okuyama et al (1999), this polymorphism has become one of the most intensively studied SNPs of DRD4 not only for schizophrenia (Mitsuyasu et al, 2001;Jonsson et al, 2003;Xing et al, 2007), but also for other psychiatric illness such as personality disorders (Okuyama et al, 2000;Mitsuyasu et al, 2001;Joyce et al, 2003) and ADHD (Kirley et al, 2004;Bellgrove et al, 2005;Yang et al, 2008). Overall, results are still inconsistent despite extensive investigations, and recent meta-analyses for associations between the SNP and schizophrenia showed significant effects with odds ratios of 1.15 to 1.22 (Jonsson et al, 2003;Allen et al, 2008).…”

The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

“…Individuals with the Ser311Cys polymorphism, the fourth polymorphism of the gene, specifically the Ser/Ser genotype, were prone to respond to Risperidone treatment in a study with 123 Chinese participants [49] and demonstrated a decrease in cAMP synthesis inhibition in a study with 50 Japanese participants [50]. For the A-241G polymorphism, Asian individuals with A allele or A/A genotype showed a positive improvement to Risperidone treatment in a study with 125 Chinese participants [51] and in study with 120 Japanese participants [30]. However, American individuals with the A allele or A/A genotype showed a delayed response to Risperidone treatment in a study with 61 Caucasian and African American participants [44].…”

Genetic variants in the BDNF gene and therapeutic response to risperidone in schizophrenia patients: a pharmacogenetic study

“…[5][6][7][8][9][10] A total of 127 unrelated schizophrenia patients (45 males and 84 females; mean±SD age: 36.1±11.1 years) were recruited from the Shanghai Mental Health Center on the basis of the following inclusion criteria: (1) had no physical complications or other psychiatric disorders; (2) had no history suggesting that antipsychotic treatment would be ineffective; (3) satisfied the DSM-IV criteria for schizophrenia; and (4) had not received any medication for 4-6 weeks before this study. All subjects gave signed, written informed consent through their responsible relatives before the study.…”

“…3,4 Genetic factors are commonly considered to be the main cause of these interindividual differences. [5][6][7][8][9][10] Previous studies have demonstrated that the expression levels of the human brain-derived neurotrophic factor (BDNF) gene in the prefrontal cortex, hippocampus are decreased in schizophrenic patients. 11 Clinical psychopharmacological and animal model-based experiments have also shown that antipsychotics can regulate the expression of BDNF.…”