The regulator of
G protein signaling (RGS) molecules are a class of
proteins that modulate the signaling activity of
G-protein coupled receptors. Regulator of
G protein signaling 4 (RGS4) is of particular interest in
schizophrenia since it is associated with the
dopamine (DA) receptor, its expression is altered in affected CNS tissue, and polymorphisms in the RGS4 gene are being examined as risk factors for the disease (Morris et al.2004, Am J Med Genet B Neuropsychiatr Genet 125:50-53; Prasad et al.2005, Mol Psychiatry 10:213-219; Williams et al.2004, Biol Psychiatry 55:192-195). To further test for the involvement of RGS4 expression in
schizophrenia, we examined a selection of different cortical and subcortical regions in human brain for alterations in RGS4
mRNA and
protein expression. To evaluate the effect of
antipsychotic medication on RGS4 expression levels, we compared a subset of treated and untreated cases that were off
antipsychotic medication for at least 3 months prior to death. We report a significant decrease in RGS4
mRNA levels in the cingulate gyrus, superior frontal gyrus, and the insular cortex of all
schizophrenia cases when compared with controls. A decrease in RGS4
mRNA was also observed in the caudate, but only in the medicated
schizophrenia cases. Measurement of
protein levels using Western blot demonstrated that
RGS4 protein is decreased in the frontal cortex of
schizophrenia cases.