Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia.
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.
Müller
Daniel J
DJ
Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada. daniel.mueller@charite.de
De Luca
Vincenzo
V
Sicard
Tricia
T
King
Nicole
N
Hwang
Rudi
R
Volavka
Jan
J
Czobor
Pal
P
Sheitman
Brian B
BB
Lindenmayer
Jean-Pierre
JP
Citrome
Leslie
L
McEvoy
Joseph P
JP
Lieberman
Jeffrey A
JA
Meltzer
Herbert Y
HY
Kennedy
James L
JL
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
D014150:Antipsychotic Agents; C454420:G-protein beta3 subunit; D003596:Cytosine; D020962:Heterotrimeric GTP-Binding Proteins; D013941:Thymine