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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RGS4 levels are greatly reduced in the PFC of patients with schizophrenia, and there is evidence of genetic alterations in RGS4 in some families with schizophrenia or bipolar disorder.
“RGS4 levels are greatly reduced in the PFC of patients with schizophrenia134,135, and there is evidence of genetic alterations in RGS4 in some families with schizophrenia or bipolar disorder136,137.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [134]
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- Authors
- Mirnics, K., Middleton, F. A., Stanwood, G. D., Lewis, D. A., & Levitt, P.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Mirnics, K
- Venue
- Molecular Psychiatry
- Published
- 2001-04-27
- Volume
- 6
- Issue
- 3
- Pages
- 293-301
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W1991503782
- Cited by
- 446
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 10 · 2017: 6 · 2016: 11 · 2015: 11 · 2014: 6 · 2013: 9 · 2012: 13
- FWCI
- 22.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Andrew W. Mellon Foundation
- National Institute of Mental Health (T32 MH18273, MH 45156, T32MH018273, P50MH045156)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- schizophrenia, RGS4, regulator of G protein signaling, prefrontal cortex, gene expression, G protein signaling, major depressive disorder, haloperidol, neuronal signaling, transcriptome
- MeSH terms
- Adult, Animals, Chromosomes, Human, Pair 1, Major Depressive Disorder, Family Health, Female, Haloperidol, Humans, Macaca fascicularis, Male, Middle Aged, Molecular Sequence Data, Schizophrenia, Antipsychotic Agents, Gene Expression, Prefrontal Cortex, GTP-Binding Proteins, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, RGS Proteins
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