Journal
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 15, Issue 5, Pages 525-531Publisher
ELSEVIER
DOI: 10.1016/j.euroneuro.2005.02.001
Keywords
GNB3 gene; antipsychotics; schizophrenia; genetics; ethnicity
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G-proteins are composed of alpha, beta and gamma subunits. Once activated, these subunits play a major role in the conversion of external receptor activation into intracellular signals. The functional C825T polymorphism of the beta 3 subunit gene (GNB3) has recently been shown to modulate antidepressant response, with the T-allele conferring an increased signaling and being associated with favorable antidepressant response. We hypothesized that this polymorphism may be associated with response to antipsychotics in a population of 145 chronic schizophrenic patients deriving from two study-samples and being mainly treated with clozapine for up to 6 months. Overall, the C/C genotype was significantly associated with relative clinical improvement as measured by Brief Psychiatric Rating Scale (BPRS) change scores after 6 and 12 weeks (p < 0.01 and p = 0.03, respectively), with estimated effect sizes ranging from 4.8 to 7%. Our results further suggest that this effect is only attributable to Caucasians when compared to African-Americans. Moreover, our findings point to the role of intracellular mechanisms in antipsychotic response. (c) 2005 Elsevier B.V. and ECNP. All rights reserved.
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