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

Pat Levitt, Philip Ebert, Karoly Mirnics, Vishwajit L. Nimgaonkar, David A. Lewis

Research output: Contribution to journalReview article

75 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)534-537
Number of pages4
JournalBiological Psychiatry
Issue number6
Publication statusPublished - Sep 15 2006



  • RGS proteins
  • Synaptic function
  • gene-environment
  • neurodevelopment
  • schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

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