Combination of dopamine D2 receptor gene polymorphisms as a possible predictor of treatment-resistance to dopamine antagonists in schizophrenic patients

Both the A1 allele carriers of TaqI A and Del allele noncarriers of -141C Ins/Del for dopamine D(2) receptor (DRD(2)) gene polymorphisms have been reported to have a lowered DRD(2) density. The present study aimed to examine whether the combinations of these two DRD(2) gene polymorphisms predict treatment response to antidopaminergic agents in schizophrenic patients. Subjects consisted of 49 acutely exacerbated schizophrenic inpatients treated with bromperidol (30 cases, mean dose+/-S.D.: 11.4+/-4.8 mg/day) or nemonapride (19 cases, 18 mg/day). Clinical symptoms were evaluated using Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. DRD(2) genotypes were determined using a polymerase chain reaction method. The A1 noncarriers with a Del allele showed poorer percentage improvement in anxiety-depression symptom after 3-week treatment (n=9, 7.3+/-42.9%) than A1 carriers without Del alleles (n=25, 62.4+/-38.0%) or A1 noncarriers without Del alleles (n=10, 65.4+/-29.2%). However, these preliminary results should be replicated in further research with a larger number of the subjects in each haplotype subgroup.