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Dopamine D 2 receptor gene polymorphisms predict well the response to dopamine antagonists at therapeutic dosages in patients with schizophrenia
Author(s) -
SAKUMOTO NOBORU,
KONDO TSUYOSHI,
MIHARA KAZUO,
SUZUKI AKIHITO,
YASUIFURUKORI NORIO
Publication year - 2007
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/j.1440-1819.2007.01633.x
Subject(s) - brief psychiatric rating scale , medicine , dopamine receptor , dopamine , dopaminergic , dopamine transporter , schizophrenia (object oriented programming) , haloperidol , psychology , extrapyramidal symptoms , dopamine receptor d2 , pharmacogenetics , endocrinology , antipsychotic , psychosis , genotype , psychiatry , biology , genetics , gene
Abstract Previous reports have shown that both A1 allele carriers of Taq I A and Del allele non‐carriers of −141C Ins / Del for dopamine D 2 receptor ( DRD 2 ) gene polymorphisms have a better antipsychotic drug response. The present study aimed to examine the validity of a combination of these two DRD 2 polymorphisms as predictors for response to DRD 2 antagonists. The subjects consisted of 49 acutely exacerbated inpatients with schizophrenia treated with bromperidol (30 cases, 6–18 mg/day) or nemonapride (19 cases, 18 mg/day) for 3 weeks. Brief Psychiatric Rating Scale and Udvalg for Kliniske Undersøgelser side‐effects rating scale were used for clinical assessments. DRD 2 genotypes were determined using a polymerase chain reaction method. In the overall 49 subjects, combined DRD 2 polymorphisms weakly predicted the response to DRD 2 antagonists (Fisher exact test, P = 0.049), that is, good response in A1 (+) or Del (–) subjects and poor response in A1 (–) plus Del (+) subjects. In the former subjects, non‐responders with A1 (+) or Del (–) showed higher scores of psychic, extrapyramidal and total side‐effects. At therapeutic doses (6–8 mg/day haloperidol equivalent dose) in 30 subjects, the predictability of response was greatly increased (Fisher exact test, P < 0.0045) with higher positive and negative predictive values (78.3% and 85.7%, respectively). These findings suggest that combined DRD 2 polymorphisms can be used as a pretreatment marker for response to DRD 2 antagonists at therapeutic doses, and that A1 (+) or Del (–) subjects are highly sensitive to DRD 2 antagonists, expressed as either treatment responders or non‐responders vulnerable to extrapyramidal symptoms.