Making the Case for a Candidate Vulnerability Gene in Schizophrenia: Convergent Evidence for Regulator of G-Protein Signaling 4 (RGS4)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Biological Psychiatry (Impact Factor: 10.26). 10/2006; 60(6):534-7. DOI: 10.1016/j.biopsych.2006.04.028
Source: PubMed


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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    • "Thus, breakdown in the functional segregation of these pathways might lead to aberrant modulation and dysregulation of cellular activity. Indeed, mutations in RGS4 have been linked to neuropsychiatric disorders such as schizophrenia (Levitt et al., 2006). Future studies are necessary to investigate the interactions of RGS4 and neuromodulatory signaling in disease. "
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    • "Rgs4 is implicated in intestinal inflammation [6], [7], [59], [60], cardiovascular diseases [61]–[63] and psychiatric disorders [4], [8]–[12]. However, the regulatory mechanism of Rgs4 expression has not been well understood. "
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