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Cited by 254Treatment of Major DepressionStress Responses and CortisolNeuroscience and Neuropharmacology Research

Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder

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Cobb, J.A., O’Neill, K., Milner, J., Mahajan, G.J., Lawrence, T.J., May, W.L., Miguel-Hidalgo, J., Rajkowska, G. +1 more·2016·Neuroscience
DOI 10.1016/j.neuroscience.2015.12.044PMC PMC4836620
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Abstract

Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness. Pathology in astrocytes may contribute significantly to this reduced volume and to the involvement of the hippocampus in MDD. Postmortem hippocampal tissues were collected from 17 subjects with MDD and 17 psychiatrically-normal control subjects. Sections from the body of the hippocampus were immunostained for glial fibrillary acidic protein (GFAP), a marker of intermediate filament protein expressed in astrocytes. The density of GFAP-immunoreactive astrocytes was measured in the hippocampus using 3-dimensional cell counting. Hippocampal subfields were also assessed for GFAP-immunoreactive area fraction. In CA1, there was a significant positive correlation between age and either density or area fraction in MDD. The density of astrocytes in the hilus, but not CA1 or CA2/3, was significantly decreased only in depressed subjects not taking an antidepressant drug, but not for depressed subjects taking an antidepressant drug. The area fraction of GFAP-immunoreactivity was significantly decreased in the dentate gyrus in women but not men with depression. In CA2/3, the area fraction of GFAP-immunoreactivity was inversely correlated with the duration of depression in suicide victims. Astrocyte contributions to neuronal function in the hilus may be compromised in depressed subjects not taking antidepressant medication. Due to the cross-sectional nature of the present study of postmortem brain tissue, it remains to be determined whether antidepressant drug treatment prevented a decrease in GFAP-immunoreactive astrocyte density or restored cell density to normal levels.

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  • Accompanied by decreased astrocyte density, levels of GFAP and the GFAP intermediate filament domain are reduced in brain samples from patients with MDD.

    “Accompanied by a decreased astrocyte density, the levels of GFAP and the GFAP intermediate filament domain are also reduced in brain samples from patients with MDD. 167”

    From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [167]

    The Results (§3.1; page unavailable) report decreased GFAP-immunoreactive astrocyte density in the hippocampal hilus only among MDD subjects without detected antidepressant use. The Introduction (§1; page unavailable) reports lower GFAP protein levels in certain brain regions and patient subgroups, but the paper does not report reduced levels of a separately measured GFAP intermediate filament domain. The sentence also omits the regional and treatment-related limits on the density finding. (LLM, conf=0.87)

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  • The expression of neural cell marker proteins Cx30/43, GFAP, AQP4, and S100B is all decreased under MDD pathological conditions.

    “The expression of neural cell marker proteins in neural cells, including Cx30/43, 162 GFAP, 167 AQP4, 172 and S100B, 177 are all decreased under MDD pathological conditions.”

    From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [167]

    The citation is attached to GFAP, not to Cx30/43, AQP4, or S100B. The Introduction reports reduced GFAP protein expression in some MDD brain regions, but the Discussion describes region-, age-, and treatment-dependent findings; this does not support an unqualified decrease in GFAP expression under all MDD conditions. (LLM, conf=0.86)

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  • Postmortem studies have confirmed a reduced density of GFAP-immunoreactive astrocytes in brain tissues of patients with a history of MDD or who have completed suicide compared to controls.

    “Similarly, postmortem studies have confirmed a reduced density of GFAP-immunoreactive astrocytes in brain tissues of patients with a history of MDD or who have completed suicide compared to controls (97).”

    From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [97]

    Results §3.1 reports a 26% lower density of GFAP-immunoreactive astrocytes in the hippocampal hilus of MDD subjects without detected antidepressant use, compared with controls. The claim is broader than that finding: density was not lower in the other hippocampal regions examined, and the study found no density difference between MDD subjects who died by suicide and those who did not. Page numbers were not supplied for these passages. (LLM, conf=0.88)

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Research works printed but not linked: 2

  1. Amaral D Lavenex P 2007 Hippocampal neuroanatomy The hippocampus book Andersen P Morris R Amaral D Bliss T O’Keefe J 37 114 New York Oxford University Press
  2. First M Spitzer R Gibbon M Williams J 1995 Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID Patient Edition), version 2.0 New York, NY New York State Psychiatric Institute

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Authors
Cobb, J. A., O’Neill, K., Milner, J., Mahajan, G. J., Lawrence, T. J., May, W. L., Miguel-Hidalgo, J., Rajkowska, G., & Stockmeier, C. A.
Affiliations
University of Mississippi Medical Center (US)
Corresponding author
Stockmeier, C.A.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2016-03
Volume
316
Pages
209-220
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2015.12.044
PMC
PMC4836620
OpenAlex
W2199203598
Cited by
254
References
89
Citations by year
2026: 14 · 2025: 29 · 2024: 37 · 2023: 33 · 2022: 20 · 2021: 31 · 2020: 23 · 2019: 17 · 2018: 19 · 2017: 20 · 2016: 11
FWCI
12.03
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • The National Institute of Mental Health (MH67996)
  • The National Institute of General Medical Sciences (P30 GM103328)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
major depressive disorder, astrocytes, glial fibrillary acidic protein, hippocampus, astrocyte density, hippocampal subfields, CA1, hilus, dentate gyrus, CA2/3, disease duration, antidepressant treatment, suicide, sex differences, postmortem brain
MeSH terms
Adolescent, Adult, Age Factors, Aged, Astrocytes, Major Depressive Disorder, Depressive Disorder, Major, Female, Glial Fibrillary Acidic Protein, Hippocampus, Humans, Functional Laterality, Male, Middle Aged, Postmortem Changes, Statistics, Nonparametric, Young Adult

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