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Dopaminergic changes in the subgenual cingulate cortex in dementia with lewy bodies associates with presence of depression
Lina Gliaudelytė, Steven Rushton, Rolando Berlinguer Palmini, Alan J. Thomas, Christopher M. Morris. Translational Psychiatry, 2025-03-20
Topic: Brain proteins, microglia and lab models
In addition to the core clinical features of fluctuating cognition, visual hallucinations, and parkinsonism, individuals with dementia with Lewy bodies (DLB) frequently experience chronic and debilitating major depression. Treatment of depression in DLB is hampered by a lack of available effective therapies and standard serotonergic medication for major depressive disorder (MDD) is typically ineffective. Dysfunction of dopaminergic neurotransmission contributing to anhedonia and loss of motivation has been described in MDD. The subgenual anterior cingulate cortex (sgACC) is important in mood regulation and in the symptomatic expression of depression, displaying structural, functional and metabolic abnormalities in MDD. To assess dopaminergic and serotonergic synaptic changes in DLB, post mortem sgACC tissue from DLB donors with and without depression was investigated using high-resolution stimulated emission depletion (STED) microscopy, as well as Western and dot blotting techniques. STED imaging demonstrated the presence of α-synuclein within individual dopaminergic terminals in the sgACC, α-synuclein presence showing a significant positive correlation with increased synaptosomal associated protein 25 kDa (SNAP25) volumes in depressed DLB cases. A reduction in dopaminergic innervation in the sgACC was observed in DLB cases with depression compared to controls (p < 0.001), but not in non-depressed DLB donors, along with reduced levels of multiple dopaminergic markers and receptors. Limited alterations were observed in serotonergic markers. Our work demonstrates a role for dopaminergic neurotransmission in the aetiology of depression in DLB. Careful and selective targeting of dopaminergic systems in the sgACC may be a therapeutic option for treatment of depression in DLB.
Key findings
- STED imaging demonstrated the presence of α-synuclein within individual dopaminergic terminals in the sgACC, α-synuclein presence showing a significant positive correlation with increased synaptosomal associated protein 25 kDa (SNAP25) volumes in depressed DLB cases.
- A reduction in dopaminergic innervation in the sgACC was observed in DLB cases with depression compared to controls (p < 0.001), but not in non-depressed DLB donors, along with reduced levels of multiple dopaminergic markers and receptors.
Why it matters
In post-mortem brain tissue, this study found reduced dopaminergic innervation in the subgenual anterior cingulate cortex of dementia with Lewy bodies cases with depression compared to controls, but not in non-depressed cases. This links dopaminergic changes to depression in this disease but does not test any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Translational Psychiatry) |
| Journal's citation record | 2 / 4 | Translational Psychiatry: journal h-index 180 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Christopher M. Morris: h-index 69 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Newcastle University: institution h-index 932 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40113786) |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41398-025-03298-3
- PubMed: 40113786
- Original source →
- Free full text: Translational Psychiatry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Gliaudelytė, L., Rushton, S., Palmini, R. B., Thomas, A. J., & Morris, C. M. (2025). Dopaminergic changes in the subgenual cingulate cortex in dementia with lewy bodies associates with presence of depression. Translational Psychiatry. https://doi.org/10.1038/s41398-025-03298-3
Vancouver
Gliaudelytė L, Rushton S, Palmini RB, Thomas AJ, Morris CM. Dopaminergic changes in the subgenual cingulate cortex in dementia with lewy bodies associates with presence of depression. Translational Psychiatry. 2025. doi:10.1038/s41398-025-03298-3. PMID: 40113786.
BibTeX
@article{gliaudelyte2025-40113786,
author = {Gliaudelytė, Lina and Rushton, Steven and Palmini, Rolando Berlinguer and Thomas, Alan J. and Morris, Christopher M.},
title = {{Dopaminergic changes in the subgenual cingulate cortex in dementia with lewy bodies associates with presence of depression}},
journal = {Translational Psychiatry},
year = {2025},
doi = {10.1038/s41398-025-03298-3},
pmid = {40113786},
url = {https://doi.org/10.1038/s41398-025-03298-3}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.