Abstract
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.
Original language | English (US) |
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Pages (from-to) | 248-259 |
Number of pages | 12 |
Journal | European Neuropsychopharmacology |
Volume | 16 |
Issue number | 4 |
DOIs | |
State | Published - May 2006 |
Funding
Funding and grants:1) National Institutes of Health (NIH), 2) Canadian Institutes of Health Research (CIHR), 3) Ontario Mental Health Foundation (OMHF); 4) Ritter Foundation; 5) Warren Foundation; 6) Prentiss Foundation.
Keywords
- Antipsychotics
- Clozapine
- D2
- Dopamine
- Pharmacogenetics
- Response
ASJC Scopus subject areas
- Pharmacology
- Neurology
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry
- Pharmacology (medical)