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Previous studies have demonstrated a lower density of dopamine D2 receptor (DRD2) in subjects without Del alleles of the −141C Ins/ Del polymorphism in DRD2 gene promoter region than in those with one or two Del alleles. The present study aimed to examine whether the −141C Ins/ DelDRD2 promoter polymorphism is related to therapeutic response to selective DRD2 antagonists in the treatment of schizophrenia. Subjects consisted of 49 acutely exacerbated schizophrenic inpatients treated with bromperidol (30 cases, mean dose ± SD: 11.4 ± 4.8 mg/day) or nemonapride (19 cases, 18 mg/day). Clinical symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. The −141C Ins/ DelDRD2 genotypes, the Ins and Del alleles, were determined by a polymerase chain reaction method. Thirty-five patients were homozygous for the Ins allele and 14 were heterozygous for the Del and Ins alleles. The patients without Del allele showed a higher percentage of improvement in anxiety–depression symptoms than those with Del allele (58.5 ± 44.5% versus 24.1 ± 48.2%) after 3 weeks of treatment while percentage improvement in total BPRS or other subgrouped symptoms (positive, negative, excitement and cognitive symptoms) was similar between the two genotype groups. The present results suggest that the −141C Ins/ DelDRD2 polymorphism is associated with anxiolytic and antidepressive effects of neuroleptic treatment in schizophrenic patients.