Abstract
G-proteins are composed of α, β and γ 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 β3 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.
Original language | English (US) |
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Pages (from-to) | 525-531 |
Number of pages | 7 |
Journal | European Neuropsychopharmacology |
Volume | 15 |
Issue number | 5 |
DOIs | |
State | Published - Oct 2005 |
Funding
The genetic analyses reported here were supported by a Canadian Institutes of Health Research (CIHR) operating grant to JLK, and a CIHR postdoctoral fellowship award to DJM. NIMH grant (R10 MH53550) provided the principal support for the parent study. Additional support was provided by the UNC-Mental Health and Neuroscience Clinical Research Center (MH MH33127) and the Foundation of Hope, Raleigh North Carolina. We thank Janssen Pharmaceutica Research Foundation, Eli Lilly and Company, Novartis Pharmaceuticals, and Merck and Co., for their generous gifts of medications. Eli Lilly and Company contributed supplemental funding that covered approximately 18% of the total cost of the study. However, overall experimental design, data acquisition, statistical analyses, and interpretation of the results were implemented without any input from any of the pharmaceutical companies. Linda Kline, RN, MS was the chief coordinator of the entire project.
Keywords
- Antipsychotics
- Ethnicity
- GNB3 gene
- Genetics
- Schizophrenia
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Psychiatry and Mental health
- Pharmacology (medical)
- Biological Psychiatry
- Pharmacology