Reduced Glial Cell Density and Neuronal Size in the Anterior Cingulate Cortex in Major Depressive Disorder
Abstract
Background Glial cells are more numerous than neurons in the cortex and are crucial to neuronal function. There is evidence for reduced neuronal size in schizophrenia, with suggestive evidence for reduced glial cell density in mood disorders. In this investigation, we have simultaneously assessed glial cell density and neuronal density and size in the anterior cingulate cortex in schizophrenia, major depressive disorder, and bipolar disorder. Methods We examined tissue from area 24b of the supracallosal anterior cingulate cortex in 60 postmortem brain specimens from 4 groups of 15 subjects, as follows: major depressive disorder, schizophrenia, bipolar disorder, and normal controls. Glial cell density and neuronal size and density were examined in all subjects using the nucleator and the optical disector. Results Glial cell density (22%) (P =.004) and neuronal size (23%) (P =.01) were reduced in layer 6 in major depressive disorder compared with controls. There was some evidence for reduced glial density in layer 6 (20%) (P =.02) in schizophrenia compared with controls, before adjusting for multiple layerwise comparisons, but there were no significant changes in neuronal size. There was no evidence for differences in glial density or neuronal size in bipolar disorder compared with controls. Neuronal density was similar in all groups to that found in controls. Conclusion These findings suggest that there is reduced frontal cortical glial cell density and neuronal size in major…
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In cerebral cortex of mood disorder subjects, glial deficits are greatest in layers III, V, and VI when laminar analysis is used.
“In several reports, the deficits in glia in the cerebral cortex depended upon laminar analysis with the greatest effects in layers III, V, and VI (Cotter et al, 2001a(Cotter et al, , 2002;;Rajkowska et al, 1999Rajkowska et al, , 2001;;Uranova et al, 2004;Vostrikov et al, 2007).”
From Neurocircuitry of Mood Disorders (2010) · cites this paper as Cotter et al, 2001a
Reductions in glial cell counts and density, and/or glia-to-neuron ratios were found in MDD subjects versus controls in the pregenual ACC, dorsal anterolateral PFC, and amygdala.
“Reductions in glial cell counts and density, and/or glia-to-neuron ratios additionally were found in MDD subjects versus controls in the pregenual ACC (pgACC [BA24]) (Cotter et al. 2001a), the dorsal anterolateral PFC (BA9) (Cotter et al. 2002; Uranova et al. 2004) and the amygdala (Bowley et al. 2002; Hamidi et al. 2004).”
From Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression (2008) · cites this paper as Cotter et al. 2001a
The histopathological correlates of these abnormalities include reductions in glial cells with no equivalent loss of neurons, reductions in synapses or synaptic proteins, elevations in neuronal density, and reductions in neuronal size in MDD and/or BD samples.
“The histopathological correlates of these abnormalities included reductions in glial cells with no equivalent loss of neurons, reductions in synapses or synaptic proteins, elevations in neuronal density, and reductions in neuronal size in MDD and/or BD samples”
From Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression (2008) · cites this paper as Cotter et al. 2001a
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- Authors
- Cotter, D., Mackay, D., Landau, S., Kerwin, R., & Everall, I.
- Affiliations
- King's College London (GB)
- Corresponding author
- Cotter, David
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2001-06-01
- Volume
- 58
- Issue
- 6
- Pages
- 545
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2136869363
- Cited by
- 766
- References
- 3
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 16 · 2023: 13 · 2022: 33 · 2021: 55 · 2020: 23 · 2019: 29 · 2018: 32 · 2017: 28 · 2016: 34 · 2015: 38 · 2014: 45 · 2013: 40 · 2012: 45
- FWCI
- 22.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glial cell density, neuron size, anterior cingulate cortex, major depressive disorder, schizophrenia, bipolar disorder, neuronal density, layer 6, postmortem brain, frontal cortex, neuroanatomy
- MeSH terms
- Adult, Age Factors, Bipolar Disorder, Cell Count, Depressive Disorder, Female, Gyrus Cinguli, Humans, Functional Laterality, Male, Middle Aged, Neuroglia, Neurons, Schizophrenia, Prefrontal Cortex, Cell Size
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