title: Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia.
abstract: 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 beta3 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.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada. daniel.mueller@charite.de
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Tricia
authors.initials: T
authors.lastname: Sicard
authors.forename: Nicole
authors.initials: N
authors.lastname: King
authors.forename: Rudi
authors.initials: R
authors.lastname: Hwang
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
authors.forename: Pal
authors.initials: P
authors.lastname: Czobor
authors.forename: Brian B
authors.initials: BB
authors.lastname: Sheitman
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lindenmayer
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003596:Cytosine; D005260:Female; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D013941:Thymine
chemical_list: D014150:Antipsychotic Agents; C454420:G-protein beta3 subunit; D003596:Cytosine; D020962:Heterotrimeric GTP-Binding Proteins; D013941:Thymine