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Making the case for a candidate vulnerability gene in schizophrenia: Convergent evidence for regulator of G-protein signaling 4 (RGS4).

Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee 37203, USA.
Biological Psychiatry (Impact Factor: 10.25). 10/2006; 60(6):534-7. DOI: 10.1016/j.biopsych.2006.04.028
Source: PubMed

ABSTRACT Both genetic and environmental factors have been associated with an increased risk for schizophrenia. These factors are not mutually exclusive; a single gene can be a genetic factor (due to a mutation in the gene sequence) and a target of a physiological response to an environmental stimulus, both with the common endpoint of altered expression of the gene. Regulator of G-protein signaling 4 (RGS4) has been implicated as such a gene from three lines of evidence. First, a subset of genetic studies revealed an association between schizophrenia and non-functional polymorphisms in the RGS4 gene. Second, across the cortical mantle the expression of RGS4 mRNA is decreased in a diagnosis-specific manner in subjects with schizophrenia. Third, neurobiological studies demonstrate that RGS4 is highly responsive to environmental stimuli and capable of modulating the function of G-protein coupled neurotransmitter receptors implicated in schizophrenia. RGS4 is an example of a molecule that may underlie increased vulnerability through either genetic or non-genetic mechanisms, which we suggest may be typical of other genes in a complex, polygenic disorder such as schizophrenia.

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