1. ¹Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai, China
2. ²Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
3. ³Shanghai Institute of Mental Health, Shanghai, China
4. ⁴NHGG, Bio-X Center, Shanghai Jiao Tong University, Shanghai, China

Correspondence: Dr L He, Bio-X Life Science Research Center, Shanghai Jiao Tong University, PO Box 501, Hao Ran Building, 1954 Hua Shan Road, Shanghai 200030, China. E-mails: helin@bio-x.cn; Dr Q Xing, Institute for Nutritional Sciences, Shanghai institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China, Tel/Fax: + 00 86 21 62822491; xingginghe@sjtu.edu.cn

Received 10 July 2006; Revised 8 March 2007; Accepted 9 March 2007; Published online 11 April 2007.

Abstract

Previous observations of the anatomical distribution and pharmacological profile of the dopamine D₃ receptor (DRD3) have indicated its potential role in antipsychotic drug action. Risperidone, an effective first-line atypical antipsychotic agent, exhibits a relatively high affinity for this receptor. Recent studies have reported an association of the Ser9Gly polymorphism in the DRD3 gene with therapeutic response to risperidone, but the results were inconsistent. We therefore postulated that the Ser9Gly polymorphism might be in linkage disequilibrium with an undetected variant that exerts a direct influence on risperidone efficacy. The present study genotyped eight single nucleotide polymorphisms (SNPs) distributed throughout the DRD3 gene and examined five of these for association with treatment outcome, following an 8-week period of risperidone monotherapy in 130 schizophrenic patients from mainland China. Clinical symptoms were assessed before and after the treatment period, using the Brief Psychiatry Rating Scale (BPRS). The confounding effects of non-genetic factors were estimated and the baseline symptom score was included as a covariate for adjustment. Neither was any association observed between the five polymorphisms and improvement in total BPRS scores nor was any combined effect of these variants detected in the haplotype analysis. The current results indicate that genetic variations within the DRD3 gene may not contribute significantly to interindividual differences in the therapeutic efficacy of risperidone.