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

Mol Psychiatry. 2001 May;6(3):293-301. doi: 10.1038/sj.mp.4000866.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Antipsychotic Agents / therapeutic use
  • Chromosomes, Human, Pair 1*
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / metabolism
  • Family Health
  • Female
  • GTP-Binding Proteins / metabolism*
  • Gene Expression / physiology
  • Genetic Predisposition to Disease
  • Haloperidol / therapeutic use
  • Humans
  • Macaca fascicularis
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Prefrontal Cortex / physiology
  • RGS Proteins / genetics*
  • RGS Proteins / metabolism*
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism


  • Antipsychotic Agents
  • RGS Proteins
  • RGS4 protein
  • GTP-Binding Proteins
  • Haloperidol

Associated data

  • GENBANK/U27768