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

K. Mirnics, F. A. Middleton, G. D. Stanwood, D. A. Lewis, P. Levitt

Research output: Contribution to journalArticle

365 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)293-301
Number of pages9
JournalMolecular Psychiatry
Volume6
Issue number3
DOIs
StatePublished - Apr 18 2001

Fingerprint

GTP-Binding Protein Regulators
Schizophrenia
Prefrontal Cortex
Major Depressive Disorder
Haloperidol
Oligonucleotide Array Sequence Analysis
GTP-Binding Proteins
Genes
Haplorhini
In Situ Hybridization
Gene Expression

Keywords

  • 1q21-22
  • Antipsychotic
  • Cerebral cortex
  • Gene expression
  • Haloperidol
  • Major depression
  • Microarray
  • Prefrontal
  • RGS4
  • Regulator of G-protein signaling
  • Schizophrenia
  • Susceptibility gene

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. / Mirnics, K.; Middleton, F. A.; Stanwood, G. D.; Lewis, D. A.; Levitt, P.

In: Molecular Psychiatry, Vol. 6, No. 3, 18.04.2001, p. 293-301.

Research output: Contribution to journalArticle

Mirnics, K. ; Middleton, F. A. ; Stanwood, G. D. ; Lewis, D. A. ; Levitt, P. / Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. In: Molecular Psychiatry. 2001 ; Vol. 6, No. 3. pp. 293-301.
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