Suggestive association between the C825T polymorphism of the G-protein β3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia

Daniel J. Müller, Vincenzo De Luca, Tricia Sicard, Nicole King, Rudi Hwang, Jan Volavka, Pal Czobor, Brian B. Sheitman, Jean Pierre Lindenmayer, Leslie Citrome, Joseph Patrick McEvoy, Jeffrey A. Lieberman, Herbert Y. Meltzer, James L. Kennedy

Research output: Contribution to journalArticle

50 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)525-531
Number of pages7
JournalEuropean Neuropsychopharmacology
Volume15
Issue number5
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Fingerprint

Protein Subunits
GTP-Binding Proteins
Antidepressive Agents
Antipsychotic Agents
Schizophrenia
Brief Psychiatric Rating Scale
Clozapine
African Americans
Genes
Alleles
Genotype
Population

Keywords

  • Antipsychotics
  • Ethnicity
  • GNB3 gene
  • Genetics
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

Suggestive association between the C825T polymorphism of the G-protein β3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia. / Müller, Daniel J.; De Luca, Vincenzo; Sicard, Tricia; King, Nicole; Hwang, Rudi; Volavka, Jan; Czobor, Pal; Sheitman, Brian B.; Lindenmayer, Jean Pierre; Citrome, Leslie; McEvoy, Joseph Patrick; Lieberman, Jeffrey A.; Meltzer, Herbert Y.; Kennedy, James L.

In: European Neuropsychopharmacology, Vol. 15, No. 5, 01.10.2005, p. 525-531.

Research output: Contribution to journalArticle

Müller, DJ, De Luca, V, Sicard, T, King, N, Hwang, R, Volavka, J, Czobor, P, Sheitman, BB, Lindenmayer, JP, Citrome, L, McEvoy, JP, Lieberman, JA, Meltzer, HY & Kennedy, JL 2005, 'Suggestive association between the C825T polymorphism of the G-protein β3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia', European Neuropsychopharmacology, vol. 15, no. 5, pp. 525-531. https://doi.org/10.1016/j.euroneuro.2005.02.001
Müller, Daniel J. ; De Luca, Vincenzo ; Sicard, Tricia ; King, Nicole ; Hwang, Rudi ; Volavka, Jan ; Czobor, Pal ; Sheitman, Brian B. ; Lindenmayer, Jean Pierre ; Citrome, Leslie ; McEvoy, Joseph Patrick ; Lieberman, Jeffrey A. ; Meltzer, Herbert Y. ; Kennedy, James L. / Suggestive association between the C825T polymorphism of the G-protein β3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia. In: European Neuropsychopharmacology. 2005 ; Vol. 15, No. 5. pp. 525-531.
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