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Cited by 822Treatment of Major DepressionStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

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Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells

Rajkowska, Grazyna·2000·Biological Psychiatry
DOI 10.1016/s0006-3223(00)00950-1
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Abstract

The influence of stress and glucocorticoids on neuronal pathology has been demonstrated in animal and clinical studies. It has been proposed that stress-induced changes in the hippocampus may be central to the development of depression in genetically vulnerable individuals. New evidence implicates the prefrontal cortex (PFC) in addition to the hippocampus as a site of neuropathology in depression. The PFC may be involved in stress-mediated neurotoxicity because stress alters PFC functions and glucocorticoid receptors, the PFC is directly interconnected with the hippocampus, and metabolic alterations are present in the PFC in depressed patients. Postmortem studies in major depression and bipolar disorder provide the first evidence for specific neuronal and glial histopathology in mood disorders. Three patterns of morphometric cellular changes are noted: cell loss (subgenual PFC), cell atrophy (dorsolateral PFC and orbitofrontal cortex), and increased numbers of cells (hypothalamus, dorsal raphe nucleus). The relevance of cellular changes in mood disorders to stress and prolonged PFC development and a role of neurotrophic/neuroprotective factors are suggested, and a link between cellular changes and the action of therapeutic drugs is discussed. The precise anatomic localization of dysfunctional neurons and glia in mood disorders may reveal cortical targets for novel antidepressants and mood stabilizers.

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Metadata

Authors
Rajkowska, G.
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2000-10
Volume
48
Issue
8
Pages
766-777
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/s0006-3223(00)00950-1
OpenAlex
W2087955490
Cited by
822
References
10
Citations by year
2026: 7 · 2025: 12 · 2024: 14 · 2023: 15 · 2022: 20 · 2021: 49 · 2020: 17 · 2019: 28 · 2018: 24 · 2017: 27 · 2016: 40 · 2015: 30 · 2014: 44 · 2013: 30 · 2012: 34
FWCI
28.24
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Public Health Service (55872)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
mood disorders, major depressive disorder, bipolar disorder, postmortem brain, glial cells, prefrontal cortex, hippocampus, stress, glucocorticoids, glucocorticoid receptor, neurotoxicity, subgenual prefrontal cortex, dorsolateral prefrontal cortex, orbitofrontal cortex, hypothalamus, dorsal raphe nucleus, cell loss, neurotrophic factors, antidepressants, mood stabilizers
MeSH terms
Atrophy, Glial Fibrillary Acidic Protein, Humans, Neuroglia, Neurons, Stress, Psychological, Brain-Derived Neurotrophic Factor, Mood Disorders

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