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Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia

Abstract

Complex defects in neuronal signaling may underlie the dysfunctions that characterize schizophrenia. Using cDNA microarrays, we discovered that the transcript encoding regulator of G-protein signaling 4 (RGS4) was the most consistently and significantly decreased in the prefrontal cortex of all schizophrenic subjects examined. The expression levels of ten other RGS family members represented on the microarrays were unchanged and hierarchical data analysis revealed that as a group, 274 genes associated with G-protein signaling were unchanged. Quantitative in situ hybridization verified the microarray RGS4 data, and demonstrated highly correlated decreases in RGS4 expression across three cortical areas of ten subjects with schizophrenia. RGS4 expression was not altered in the prefrontal cortex of subjects with major depressive disorder or in monkeys treated chronically with haloperidol. Interestingly, targets for 70 genes mapped to the major schizophrenia susceptibility locus 1q21–22 were present on the microarrays, of which only RGS4 gene expression was consistently altered. The combined data indicate that a decrease in RGS4 expression may be a common and specific feature of schizophrenia, which could be due either to genetic factors or a disease- specific adaptation, both of which could affect neuronal signaling.

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Acknowledgements

We are grateful to the colleagues who read and commented on earlier versions of this manuscript, as well as Dr J Pierri for his involvement in the chronic haloperidol treatment of monkeys. The research was supported by projects 1 (DAL) and 2 (PL, KM) of NIMH Center Grant MH45156 (DAL), an endowment fund from the RK Mellon Foundation (PL) and NIMH training grant T32 MH18273 (FM).

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Mirnics, K., Middleton, F., Stanwood, G. et al. Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry 6, 293–301 (2001). https://doi.org/10.1038/sj.mp.4000866

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  • DOI: https://doi.org/10.1038/sj.mp.4000866

Keywords

  • schizophrenia
  • major depression
  • antipsychotic
  • haloperidol
  • gene expression
  • regulator of G-protein signaling
  • RGS4
  • microarray
  • prefrontal
  • cerebral cortex
  • susceptibility gene
  • 1q21–22

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