The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death
Open accessAbstract
A number of studies indicate that prolonged, major depression is associated with a selective loss of hippocampal volume that persists long after the depression has resolved. This review is prompted by two ideas. The first is that overt neuron loss may be a contributing factor to the decrease in hippocampal volume. As such, the first half of this article reviews current knowledge about how hippocampal neurons die during insults, focusing on issues related to the trafficking of glutamate and calcium, glutamate receptor subtypes, oxygen radical generation, programmed cell death, and neuronal defenses. This is meant to orient the reader toward the biology that is likely to underlie any such instances of neuron loss in major depression. The second idea is that glucocorticoids, the adrenal steroids secreted during stress, may play a contributing role to any such neuron loss. The subtypes of depression associated with the hippocampal atrophy typically involve significant hypersecretion of glucocorticoids, and the steroid has a variety of adverse effects in the hippocampus, including causing overt neuron loss. The second half of this article reviews the steps in this cascade of hippocampal neuron death that are regulated by glucocorticoids.
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Many health practitioners in primary and secondary care do not routinely enquire about intimate partner violence in routine health care consultations, nor do they all know how to respond safely to disclosures.
“Many health practitioners in primary and secondary care do not routinely enquire about intimate partner violence in routine health care consultations, nor do they all know how to respond safely to disclosures. 458-460”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [460]
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- Authors
- Sapolsky, R. M.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Sapolsky, Robert M
- ORCID
- Sapolsky, Robert M
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 48
- Issue
- 8
- Pages
- 755-765
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1995671210
- Cited by
- 699
- References
- 86
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 12 · 2023: 14 · 2022: 20 · 2021: 23 · 2020: 21 · 2019: 15 · 2018: 25 · 2017: 24 · 2016: 25 · 2015: 32 · 2014: 34 · 2013: 25 · 2012: 36
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biological Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- major depressive disorder, hippocampal neurotoxicity, neuronal cell death, hippocampal atrophy, glutamate, calcium signaling, glutamate receptor subtypes, oxygen free radicals, programmed cell death, glucocorticoids
- MeSH terms
- Calcium, Major Depressive Disorder, Glucocorticoids, Hippocampus, Humans, Neurons, Synapses, Cell Death, Receptors, Glutamate, Glutamic Acid
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