Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Aug;53(4):857-867.
doi: 10.62641/aep.v53i4.1967.

Serum Brain-derived Neurotrophic Factor Levels as a Biomarker of Treatment Response in Patients With Depression: Systematic Review and Meta-analysis

Yang Li  1 , Jing Ma  1 , Wen-Xiu Zhang  1 , Yan-Li Cao  1 , Chen Lei  2
Affiliations
Meta-Analysis

Serum Brain-derived Neurotrophic Factor Levels as a Biomarker of Treatment Response in Patients With Depression: Systematic Review and Meta-analysis

Yang Li et al. Actas Esp Psiquiatr. 2025 Aug.

Abstract

Background: Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of depression and the mechanism of action of antidepressants. This study aimed to evaluate the changes of BDNF in patients with depression and how it is affected by antidepressant treatment through meta-analysis.

Methods: Multiple databases (including PubMed, Embase and China National Knowledge Infrastructure (CNKI)) were searched for studies on BDNF levels in patients with depression published up to November 15, 2024. Meta-analyses of serum and plasma BDNF levels were performed using RevMan 5.4.1, with the effect sizes expressed as mean differences (MD) and 95% confidence intervals. Heterogeneity was assessed using I2 statistics (random-effects model if I2 ≥ 50%; fixed-effects if I2 < 50%).

Results: Serum BDNF levels in patients with depression were significantly lower than those in healthy controls [MD = -1.54, 95% confidence intervals (CI) (-2.85 to -0.24), p = 0.02]. Antidepressant drug treatment for 6 weeks significantly increased serum BDNF levels [MD = 7.42, 95% CI (1.10-13.74), p = 0.02], but the effect of 4 weeks of treatment was not statistically significant. Plasma BDNF levels showed no statistically significant differences between depressed patients and healthy controls (p > 0.05). Sensitivity analysis indicated that the meta-analysis results were robust and not unduly influenced by any single study.

Conclusion: Serum BDNF levels serve as potential biomarkers in patients with depression, but their sensitivity to short-term antidepressant treatment is limited.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
PRISMA 2020 flow diagram illustrating the study selection process. CNKI, China National Knowledge Infrastructure.
Fig. 2.
Fig. 2.
Cochrane Risk of Bias assessment for the 13 included randomised controlled trials (RCTs).
Fig. 3.
Fig. 3.
Forest plot comparing serum BDNF between the two groups of patients. Note: BDNF, Brain-Derived Neurotrophic Factor. Green squares represent study-specific effect sizes; the black diamond represents the pooled estimate.
Fig. 4.
Fig. 4.
Forest plot comparing plasma BDNF between two patient groups. Note: BDNF, Brain-Derived Neurotrophic Factor. Green squares represent study-specific effect sizes; the black diamond represents the pooled estimate.
Fig. 5.
Fig. 5.
Forest plot of the total effect of serum BDNF levels after antidepressant drug treatment. Note: BDNF, Brain-Derived Neurotrophic Factor. Green squares represent study-specific effect sizes; the black diamond represents the pooled estimate.
Fig. 6.
Fig. 6.
Forest plot of the effect of antidepressants on serum BDNF concentration after 4 weeks of treatment. Note: No statistically significant difference was observed (p > 0.05). BDNF, Brain-Derived Neurotrophic Factor. Green squares represent study-specific effect sizes; the black diamond represents the pooled estimate.
Fig. 7.
Fig. 7.
Forest plot of the effect of antidepressant treatment on serum BDNF levels after 6 weeks. Note: BDNF, Brain-Derived Neurotrophic Factor. Green squares represent study-specific effect sizes; the black diamond represents the pooled estimate.
Fig. 8.
Fig. 8.
Forest map for sensitivity analysis. Note: BDNF, Brain-Derived Neurotrophic Factor. Green squares represent study-specific effect sizes; the black diamond represents the pooled estimate.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron . 2002;34:13–25. doi: 10.1016/s0896-6273(02)00653-0. - DOI - PubMed
    1. Karyotaki E, Efthimiou O, Miguel C, Bermpohl FMG, Furukawa TA, Cuijpers P, et al. Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis. JAMA Psychiatry . 2021;78:361–371. doi: 10.1001/jamapsychiatry.2020.4364. - DOI - PMC - PubMed
    1. Moreno-Agostino D, Wu YT, Daskalopoulou C, Hasan MT, Huisman M, Prina M. Global trends in the prevalence and incidence of depression:a systematic review and meta-analysis. Journal of Affective Disorders . 2021;281:235–243. doi: 10.1016/j.jad.2020.12.035. - DOI - PubMed
    1. Jahromy MH, Baghchesara B, Javanshir S. Effects of Allopurinol as a xanthine oxidase inhibitor on depressive-like behavior of rats and changes in serum BDNF level. IBRO Neuroscience Reports . 2022;13:373–377. doi: 10.1016/j.ibneur.2022.10.004. - DOI - PMC - PubMed
    1. Di Carlo P, Punzi G, Ursini G. Brain-derived neurotrophic factor and schizophrenia. Psychiatric Genetics . 2019;29:200–210. doi: 10.1097/YPG.0000000000000237. - DOI - PMC - PubMed