Cell atrophy and loss in depression: reversal by antidepressant treatment
Open accessAbstract
Depression is associated with structural alterations in limbic brain regions that control emotion and mood. Studies of chronic stress in animal models and postmortem tissue from depressed subjects demonstrate that these structural alterations result from atrophy and loss of neurons and glial cells. These findings indicate that depression and stress-related mood disorders can be considered mild neurodegenerative disorders. Importantly, there is evidence that these structural alterations can be blocked or even reversed by elimination of stress and by antidepressant treatments. A major focus of current investigations is to characterize the molecular signaling pathways and factors that underlie these effects of stress, depression, and antidepressant treatment. Recent advances in this research area are discussed and potential novel targets for antidepressant development are highlighted.
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Reported mechanisms potentially underlying cell loss include glutamate/glutamine cycling, blunted neurogenesis, decreased neurotrophic factor expression, and upregulation of pro-apoptotic pathways.
“Currently, reported mechanisms potentially underlying cell loss include, but are not limited to, glutamate/glutamine cycling (see section on Molecular and Cellular Mechanisms of Neuroplasticity), blunted neurogenesis, decreased neurotrophic factor expression and upregulation of pro-apoptotic pathways72.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [72]
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Neuroplasticity and the next wave of antidepressant strategies
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Reduced inhibition in depression impairs stimulus processing in human cortical microcircuits
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The dose makes the poison: From glutamate-mediated neurogenesis to neuronal atrophy and depression
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- Authors
- Banasr, M., Dwyer, J. M., & Duman, R. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Duman, Ronald S
- Venue
- Current Opinion in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 23
- Issue
- 6
- Pages
- 730-737
- ISSN
- 0955-0674 (ISSN-L)
- PMC
- PMC3259683
- OpenAlex
- W2077208751
- Cited by
- 201
- References
- 79
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 11 · 2021: 16 · 2020: 13 · 2019: 9 · 2018: 20 · 2017: 14 · 2016: 19 · 2015: 9 · 2014: 17 · 2013: 14 · 2012: 12
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH093897, R01MH045481)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- depression, neuronal atrophy, neurodegeneration, chronic stress, antidepressant treatment, limbic system, molecular pathways, antidepressant targets
- MeSH terms
- Animals, Antidepressive Agents, Atrophy, Brain, Depression, Depressive Disorder, Humans, Neuroglia, Neurons, Mood Disorders
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