Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies
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Rationale The neurotrophin hypothesis of major depressive disorder (MDD) postulates that this illness results from aberrant neurogenesis in brain regions that regulates emotion and memory. Notwithstanding this theory has primarily implicated BDNF in the neurobiology of MDD. Recent evidence suggests that other trophic factors namely GDNF, VEGF and IGF-1 may also be involved.Purpose The present review aimed to critically summarize evidence regarding changes in GDNF, IGF-1 and VEGF in individuals with MDD compared to healthy controls. In addition, we also evaluated the role of these mediators as potential treatment response biomarkers for MDD.Methods A comprehensive review of original studies studies measuring peripheral, central or mRNA levels of GDNF, IGF-1 or VEGF in patients with MDD was conducted. The PubMed/MEDLINE database was searched for peer-reviewed studies published in English through June 2nd, 2015.Results Most studies reported a reduction in peripheral GDNF and its mRNA levels in MDD patients versus controls. In contrast, IGF-1 levels in MDD patients compared to controls were discrepant across studies. Finally, most studies reported high peripheral VEGF levels and mRNA expression in MDD patients compared to healthy controls.Conclusions GDNF, IGF-1 and VEGF levels and their mRNA expression appear to be differentially altered in MDD patients compared to healthy individuals, indicating that these molecules might play an important role in the pathophysiology of depression and antidepressant action of therapeutic interventions.
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GDNF binds to GFRα1, activating tyrosine kinase signaling.
“It binds to the GDNF-family receptors α1 (GFRα1) activating tyrosine kinase signaling (Sharma et al. 2016).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Sharma et al. 2016
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“It binds to the GDNF-family receptors α1 (GFRα1) activating tyrosine kinase signaling (Sharma et al. 2016).”
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- Authors
- Sharma, A. N., da Costa e Silva, B. F. B., Soares, J. C., Carvalho, A. F., & Quevedo, J.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- ORCID
- Soares, Jair C.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 197
- Pages
- 9-20
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC4837031
- OpenAlex
- W2288312973
- Cited by
- 142
- References
- 74
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 16 · 2020: 18 · 2019: 17 · 2018: 21 · 2017: 17 · 2016: 5
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH085667)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- major depressive disorder, glial cell line-derived neurotrophic factor, insulin-like growth factor I, vascular endothelial growth factor, neurotrophins, neurogenesis, treatment response biomarkers, peripheral biomarkers, mRNA expression, antidepressant action, depression pathophysiology
- MeSH terms
- Antidepressive Agents, Major Depressive Disorder, Female, Humans, Insulin-Like Growth Factor I, Male, Biomarkers, Vascular Endothelial Growth Factor A, Glial Cell Line-Derived Neurotrophic Factor
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