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THE -141C Ins/Del POLYMORPHISM IN THE DOPAMINE
D2 RECEPTOR GENE PROMOTER REGION IS ASSOCIATED
WITH ANXIOLYTIC AND ANTIDEPRESSIVE EFFECTS DURING BROMPERIDOL
AND NEMONAPRIDE TREATMENTS IN SCHIZOPHRENIC PATIENTS
Dept. of Neuropsychiatry, Hirosaki Univ. Sch. Med., and *
Dept. of Neuropsychiatry, Yamagata Univ. Sch. Med., Japan
S.Ono, A.Suzuki, T.Kondo, K.Mihara, N.Yasui-Furukori,
M.Ishida, H.Furukori, S.Kaneko, and K.Otani*
Previous studies have shown that the subjects without Del
alleles of the -141C Ins/Del polymorphism in dopamine
D2 receptor (DRD2)
gene promoter region have lower DRD2 density
than those with one or two Del alleles. The present study
was aimed to examine whether the -141C Ins/Del DRD2
promoter polymorphism is related to therapeutic response to
bromperidol and nemonapride, which are selective and potent
DRD2 antagonists, in the treatment of
schizophrenia. Thirty acutely exacerbated schizophrenic inpatients
were randomly allocated to one of the three different doses
of bromperidol, i.e., 6 mg/day (n=11), 12 mg/day (n=11) or 18
mg/day (n=8), while 19 patients were treated with nemonapride
at 18 mg/day. Clinical symptoms were evaluated by the Brief
Psychiatric Rating Scale (BPRS) before and 3 weeks after the
treatment. The -141C Ins/Del DRD2
genotypes, The Ins and Del alleles, were determined
by 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 significantly higher percentage improvement
in anxiety-depression symptoms than those with Del allele
after 3-week treatment while percentage improvement in total
BPRS or other subgouped symptoms (positive, negative, excitement
and cognitive symptoms) were similar between the two genotype
groups. The present results suggest that the -141C Ins/Del
DRD2 polymorphism is associated with anxiolytic
and antidepressive effects of neuroleptic treatment in schizophrenic
patients. |
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