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). Experimental procedures: 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.