Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia
Open accessAbstract
OBJECTIVE: Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. METHOD: Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. RESULTS: Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the alpha 1 and delta subunits of GABA(A) receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. CONCLUSIONS: Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.
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GABA-related functional deficits are seen even in the visual cortex of schizophrenia patients.
“and GABA-related functional deficits are seen even in their visual cortex (68–71).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [70]
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- Authors
- Hashimoto, T., Bazmi, H. H., Mirnics, K., Wu, Q., Sampson, A. R., & Lewis, D. A.
- Affiliations
- University of Pittsburgh (US)
- Venue
- American Journal of Psychiatry
- Published
- 2008-04
- Volume
- 165
- Issue
- 4
- Pages
- 479-489
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC2894608
- OpenAlex
- W2085848150
- Cited by
- 457
- References
- 50
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 13 · 2023: 23 · 2022: 11 · 2021: 13 · 2020: 53 · 2019: 19 · 2018: 17 · 2017: 18 · 2016: 29 · 2015: 39 · 2014: 30 · 2013: 32 · 2012: 37
- FWCI
- 24.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH043784, MH-067234, MH-045156, R01MH067234, P50MH045156, R37MH043784, MH043784)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD015052)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, GABAergic neurotransmission, neocortex, gene expression, dorsolateral prefrontal cortex, anterior cingulate cortex, primary motor cortex, primary visual cortex, somatostatin, parvalbumin, glutamic acid decarboxylase, GABA transporter 1, GABAA receptor, calretinin, cortical dysfunction
- MeSH terms
- Adult, Aged, Cause of Death, Female, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Gyrus Cinguli, Humans, Male, Middle Aged, Motor Cortex, Synaptic Transmission, Parvalbumins, Receptors, GABA-A, Schizophrenia, Somatostatin, Tissue Distribution, Polymerase Chain Reaction, Prefrontal Cortex, Neocortex, Gene Expression Profiling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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