Morphometric analysis of neuronal and glial cell pathology in the dorsolateral prefrontal cortex in late-life depression
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Background: Late-life depression has been associated with cerebrovascular disease and especially with ischaemic white matter hyperintensities on magnetic resonance imaging. Neuroimaging and morphometric studies have identified abnormalities in the dorsolateral prefrontal cortex. Aims: To examine glial and neuronal density and neuronal volume in the dorsolateral prefrontal cortex in late-life major depression. Method: We used the disector and nucleator methods to estimate neuronal density and volume and glial density of cells in the dorsolateral prefrontal cortex in a post-mortem study of 17 individuals with late-life major depression and 10 age-matched controls. Results: We found a reduction in the volume of pyramidal neurones in the whole cortex, which was also present in layer 3 and more markedly in layer 5. There were no comparable changes in non-pyramidal neurones and no glial differences. Conclusions: Overall, we found a decrease in pyramidal neuronal size in the dorsolateral prefrontal cortex in late-life depression.
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The enhanced susceptibility of medial prefrontal cortex layer V neurons likely resulted from the relatively greater neuroanatomic distances neuronal projections must traverse to subcortical areas.
“This likely resulted from the relatively greater neuroanatomic distances neuronal projections must traverse to subcortical areas. 34”
From High vulnerability of medial prefrontal pyramidal neurons in post-stroke, vascular, Alzheimer's disease, and aging-related dementias (2026) · cites this paper as [34]
The Discussion says layer 5 neurons in the dorsolateral prefrontal cortex project to the caudate and may be vulnerable to ischaemic damage as their axons traverse white matter; the Results report a more pronounced layer 5 change. The paper does not study the medial prefrontal cortex or attribute vulnerability specifically to greater projection distance. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPatients with depression and related mental illnesses have lower BDNF and/or TRKB mRNA levels, reduced cortical neuron size, lower synaptic protein levels, decreased mTOR signaling, and fewer dendritic spines/synapses in the PFC.
“Postmortem studies have demonstrated that patients with depression and related mental illnesses have lower BDNF and/or TRKB mRNA levels (75–77), reduced cortical neuron size (75, 78, 79), lower synaptic protein levels (80), decreased mTOR signaling (81), and fewer dendritic spines/synapses (82, 83) in the PFC.”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [75]
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“14,34 Neuronal densities (in cells/mm 3 ) were measured from raw cell counts obtained within an optical disector box, and overall densities were then calculated using the following equation: 35 Nv = ∑ p − Q − P ⋅ V where: Nv = numerical density, p − = disector samples, Q − = number…”
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- Authors
- Khundakar, A., Morris, C., Oakley, A., McMeekin, W., & Thomas, A. J.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Thomas, Alan J.
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2009-08
- Volume
- 195
- Issue
- 2
- Pages
- 163-169
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2172113254
- Cited by
- 71
- References
- 25
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 7 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 7
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Teesside University Research Portal (Teesside University) (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Medical Research Council (G0400074, G0900652)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- geriatric depression, dorsolateral prefrontal cortex, neuronal density, glial density, neuronal volume, pyramidal neurons, white matter hyperintensities, cerebrovascular disease, postmortem brain
- MeSH terms
- Aged, Autopsy, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Neuroglia, Neurons, Case-Control Studies, Prefrontal Cortex, Age of Onset
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