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Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins
Open accessAbstract
Background Postmortem studies have provided evidence for abnormalities of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia, including deficits of GABA-containing interneurons. The calcium-binding proteins parvalbumin, calbindin, and calretinin can be used as markers for specific subpopulations of cortical GABAergic interneurons.Methods Following our previous observation of a reduction in the density of parvalbumin- but not calretinin-immunoreactive cells in the prefrontal cortex (Brodmann area 10) in schizophrenia, we have quantified the laminar density of neurons immunoreactive for the calcium-binding proteins parvalbumin, calbindin, and calretinin in a further prefrontal cortical region (Brodmann area 9) in patients with schizophrenia, bipolar disorder, major depression, and in matched control subjects (each group n = 15).Results Initial statistical analysis revealed reductions in the total cortical density of parvalbumin- and calbindin- but not calretinin-immunoreactive neurons in schizophrenia relative to control subjects. Further analysis comparing individual laminar densities between groups indicated that, following correction for multiple comparisons, only a reduction in calbindin-immunoreactive neurons in cortical layer II in the schizophrenic group attained statistical significance.Conclusions These findings suggest that deficits of specific GABAergic neurons, defined by the presence of calcium-binding proteins, are present in schizophrenia. Trends toward similar reductions are observed in bipolar disorder.
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“However, studies investigating PV cell density in schizophrenia have provided mixed results (Beasley et al, 2002;Hashimoto et al, 2003;Tooney and Chahl, 2004;Woo et al, 1997).”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Beasley et al, 2002
In the citing paper
“Before low magnification imaging, a power analysis of the number of cells needed to detect a difference in PV cell density, based on prior findings (Beasley et al, 2002), was used to determine the total number of PV neurons to sample.”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Beasley et al, 2002
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“Thus, prior reports of apparently lower PV cell density (Beasley et al, 2002) are likely due to lower levels of PV protein”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Beasley et al, 2002
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“Under low magnification, the mean (± SD) density of layer 3 PV cells in schizophrenia subjects (2695 ±527 cells per mm 3 ) was 11.7% lower (F 1,27 = 7.54, P = 0.011; Figure 2a) compared with that in comparison subjects (3051 ± 416 cells per mm 3 ), a decrement similar to a previous study (Beasley et al, 2002).”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Beasley et al, 2002
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Metadata
- Authors
- Beasley, C. L., Zhang, Z. J., Patten, I., & Reynolds, G. P.
- Affiliations
- University of Sheffield (GB)
- Corresponding author
- Beasley, Clare L
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 52
- Issue
- 7
- Pages
- 708-715
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1969171865
- Cited by
- 374
- References
- 38
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 16 · 2023: 11 · 2022: 12 · 2021: 11 · 2020: 14 · 2019: 20 · 2018: 14 · 2017: 14 · 2016: 21 · 2015: 23 · 2014: 22 · 2013: 20 · 2012: 19
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- 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 interneurons, prefrontal cortex, calcium-binding proteins, parvalbumin, calbindin, calretinin, bipolar disorder, major depressive disorder, Brodmann area 9, Brodmann area 10
- MeSH terms
- Adult, Calcium-Binding Proteins, Cell Count, Female, gamma-Aminobutyric Acid, Humans, Immunohistochemistry, Interneurons, Male, Middle Aged, Parvalbumins, Schizophrenia, Prefrontal Cortex, Calbindins, S100 Calcium Binding Protein G, Calbindin 2
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