A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression
Open accessAbstract
Several clinical studies on major depressive disorder (MDD) have shown that blood brain-derived neurotrophic factor (BDNF) - a factor used to index neuroplasticity - is associated with depression response; however, the results are mixed. The purpose of our study was to evaluate whether BDNF levels are correlated with improvement of depression. We performed a systematic review and meta-analysis of the literature, searching Medline, Cochrane Central, SciELO databases and reference lists from retrieved articles for clinical studies comparing mean BDNF blood levels in depressed patients pre- and post-antidepressant treatments or comparing depressed patients with healthy controls. Two reviewers independently searched for eligible studies and extracted outcome data using a structured form previously elaborated. Twenty articles, including 1504 subjects, met our inclusion criteria. The results showed that BDNF levels increased significantly after antidepressant treatment (effect size 0.62, 95% CI 0.36-0.88, random effects model). In addition, there was a significant correlation between changes in BDNF level and depression scores changes (p=0.02). Moreover, the results were robust according to the sensitivity analysis and Begg's funnel plot results did not suggest publication bias. Finally, there was a difference between pre-treatment patients and healthy controls (effect size 0.91, 95% CI 0.70-1.11) and a small but significant difference between treated patients and healthy controls (effect size 0.34, 95% CI 0.02-0.66). Our results show that BDNF levels are associated with clinical changes in depression; supporting the notion that depression improvement is associated with neuroplastic changes.
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BDNF levels are diminished in pathological populations suffering from anxiety, depression, and addiction.
“Interestingly, studies have shown that BDNF levels are diminished in pathological populations suffering from anxiety, depression, and addiction (33).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [33]
Evidence suggests that there is a positive relation between clinical improvement and improved neuroplasticity.
“evidence suggests that there is a positive relation with clinical improvement being linked with improved neuroplasticity (33).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [33]
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“Serum BDNF is a potential biomarker of psychiatric illness and is reflective of brain-tissue BDNF levels [27], with increases in BDNF associated with improved depressive symptoms [28].”
Mechanisms of Action in the Treatment of Social Anxiety Disorder
Otto, M. W., Safren, S. A., & Hearon, B. A. (2014) · Social Anxiety · doi:10.1016/b978-0-12-394427-6.00027-3 · Cited by 5 · see citing works
Cazzella, T., Fortaner‐Uyà, L., Paolini, M., Percaccioli, C., Colombo, F., Venturelli, E., Colombo, C., Zanardi, R., Spadini, S., Lorenzi, C., et al. (2026) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.70144
- Authors
- Brunoni, A. R., Lopes, M., & Fregni, F.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Fregni, Felipe
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-12
- Volume
- 11
- Issue
- 8
- Pages
- 1169-1180
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2166347822
- Cited by
- 972
- References
- 9
- Citations by year
- 2026: 30 · 2025: 42 · 2024: 42 · 2023: 52 · 2022: 49 · 2021: 68 · 2020: 49 · 2019: 64 · 2018: 53 · 2017: 48 · 2016: 67 · 2015: 74 · 2014: 76 · 2013: 64 · 2012: 62
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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, brain-derived neurotrophic factor, antidepressant response, neuroplasticity, blood biomarkers
- MeSH terms
- Adolescent, Adult, Aged, Data Interpretation, Statistical, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Neuronal Plasticity, Quality Control, Brain-Derived Neurotrophic Factor, Young Adult
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