Dopamine D2 receptor gene variants and quantitative measures of positive and negative symptom response following clozapine treatment.
OBJECTIVE
Explore relationships between 12 dopamine D2 gene variants and quantitative measures of positive and negative symptom response following clozapine treatment in two treatment refractory or intolerant populations (Caucasian and African-American).


METHODS
Subjects included 97 Caucasian and 35 African-American DSM-III-R or DSM-IV schizophrenics and were genotyped by 5'-exonuclease fluorescence assays. Genotype, allele +/- and haplotype groups were compared on Brief Psychiatric Rating Scale (BPRS) overall, positive (BPOS) and negative symptom subscales (BNEG) using analysis of variance.


RESULTS
In Caucasians, no significant associations were found for any individual polymorphisms or haplotypes. In African-Americans, the TaqIB B2 (T) allele and rs1125394 allele 1 (A), and a two-marker haplotype containing these two alleles were associated with improvement in overall BPRS and BPOS response.


CONCLUSIONS
Variability in clozapine response is still not fully understood and likely involves multiple factors. This study suggests that D2 receptor gene variants may be among such factors.
Hwang
Rudi
R
Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
Shinkai
Takahiro
T
Deluca
Vincenzo
V
Macciardi
Fabio
F
Potkin
Steven
S
Meltzer
Herbert Y
HY
Kennedy
James L
JL
D000328:Adult; D001741:Black or African American; D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D003710:Demography; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome; D044465:White People
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D003024:Clozapine