Isoforms of soluble vascular endothelial growth factor in stress-related mental disorders: a cross-sectional study
Open accessAbstract
Vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of stress-related mental disorders. However, VEGF levels have seldom been compared across mental disorders and never by isoforms. Pathophysiological processes involving leakage of astrocyte-derived extracellular vesicles (EVs) across the blood–brain barrier could be associated with VEGF levels in patients with stress-related mental disorders. This cross-sectional study compared plasma levels of VEGF 121, VEGF 165, and VEGF 121 + VEGF 165 (VEGF total) in patients with stress-induced exhaustion disorder (SED) (n = 31), patients with major depressive disorder (MDD) (n = 31), and healthy controls (n = 61). It also analyzed the correlation between VEGF and astrocyte-derived EVs in plasma. An enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF 121 and VEGF 165 in citrate plasma, and flow cytometry was used to measure astrocyte-derived EVs in plasma. The mean concentration of soluble VEGF 121 (sVEGF 121) was significantly higher in patients with SED than healthy controls (P = 0.043). Mean sVEGF 165 was significantly lower in patients with MDD than patients with SED (P = 0.004) or healthy controls (P = 0.037). Mean sVEGF total was significantly higher in patients with SED than in patients with MDD (P = 0.021) and also higher in patients with SED than healthy controls (P = 0.040). Levels of sVEGF 121 were positively correlated with levels of astrocyte-derived EVs only in patients with SED (P = 0.0128). The same was true of levels of sVEGF total and astrocyte-derived EVs (P = 0.0046). Differing levels of VEGF isoforms may reflect different pathophysiological mechanisms in SED and MDD. Further research is needed to better understand the potential roles of VEGF isoforms and astrocyte-derived EVs in mental disorders.
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There is an ongoing debate as to whether ENTS should be considered a disorder on its own or whether it should be a part of depression.
“There is an ongoing debate as to whether ENTS should be considered a disorder on its own or whether it should be a part of depression, with diverging evidence currently supporting both positions [26–32].”
From Psychological Treatment of Exhaustion Due to Persistent Non-Traumatic Stress: A Scoping Review. (2024) · cites this paper as [30]
The Introduction (page unavailable) says stress-induced exhaustion disorder is classified as a disorder in Sweden but is sometimes classified as a kind of depression elsewhere. That supports differing views of its status, but the paper does not describe an ongoing debate or present evidence supporting both positions. The paper uses “SED”; it does not identify the citing sentence’s term “ENTS.” (LLM, conf=0.79)
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- Authors
- Wallensten, J., Mobarrez, F., Åsberg, M., Borg, K., Beser, A., Wilczek, A., & Nager, A.
- Affiliations
- Region Stockholm (SE)
- Uppsala University (SE)
- Danderyds sjukhus (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Wallensten, Johanna
- Venue
- Scientific Reports
- Published
- 2021-08-17
- Volume
- 11
- Issue
- 1
- Pages
- 16693-16693
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8370974
- OpenAlex
- W3196021382
- Cited by
- 19
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 4
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-06-23)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- the Network Health Care (Nätverkssjukvård) project
- Skandia
- the Foundation for Rehabilitation and Medical Research, Karolinska Institutet
- Region Stockholm, including the Department of Rehabilitation Medicine at Danderyd University Hospital
- Söderström Königska Foundation
- Karolinska Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- vascular endothelial growth factor, VEGF isoforms, VEGF121, VEGF165, stress-related disorders, major depressive disorder, blood-brain barrier, plasma biomarkers
- MeSH terms
- Burnout, Psychological, Adult, Cross-Sectional Studies, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Protein Isoforms, Vascular Endothelial Growth Factor A
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