Association between brain-derived neurotrophic factor (BDNF) and depressive disorder: a literature review




Brain-derived neurotrophic factor; Neuronal plasticity; Depressive disorder; Antidepressive agents.


Objectives: This study aimed to gather and systematize the main available studies, which would clarify the close relationship between the levels of Brain Derived Neurotrophic Factor (BDNF) with depressive disorder. Methodology: 30 articles related to BDNF and depressive disorder from indexing platforms, published between 2017 and 2021, were selected, and the focus was on articles that presented contributions to the theme by associating the two conditions. Results and Discussion: Several studies linking BDNF to depressive disorder demonstrate a relationship between decreased levels of this polypeptide in patients with the pathology when compared to healthy individuals, even serving as a biomarker of the disease, in addition, there was an increase in the levels of this factor when performed specific treatments for depression. Other authors relate the increase in BDNF levels with the performance of physical activities and caloric restriction and suggest the possibility of such activity being considered as an adjuvant treatment to the conventional one. Finally, other studies focus on genetic and epigenetic alterations traceable through genomic analysis that can interfere with BDNF expression and serve as increased risk factors for the development of neuropsychiatric disorders. Conclusion: There is enough evidence to support the statement that BDNF is related and may be a promising tool for the diagnosis and future approaches to the pathology, but further studies are needed to consolidate the findings already demonstrated above, as well as to determine the levels of BDNF to be considered as predictors of disease.


Ai, M.., Wang, J., Chen, J., Wang, W., Xu, X., Gan, Y., Li, X., Gou, X., Cao, J., Lv, Z., Chen, X., Wang, H., Ma, Q., & Kuang, L. (2019). Plasma brain-derived neurotrophic factor (BDNF) concentration and the BDNF Val66Met polymorphism in suicide: a prospective study in patients with depressive disorder. Pharmacogenomics and personalized medicine. (12). p.97-106 DOI:

Aldoghachi, A. F., Tor, Y. S., Redzun, S. Z., Lokman, K. A. B., Razaq, N. A. A., Shahbudin, A. F., Badamasi, I. M., Cheah, P-S., Stanslas, J., Veerakumarasivam, A., Rosli, R., Ibrahim, N., Lye, M. S., & Ling, K-H. (2019). Screening of brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms and plasma BDNF levels among Malaysian major depressive disorder patients. PLoS ONE. 14(1). p. e0211241. DOI: pone.0211241.

Arosio, B., Guerini, F. R., Voshaar, R. C., & Aprahamian, I. (2021). Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression: Do We Have a Translational Perspective?. Front Behav Neurosci. 626906(15) DOI: 10.3389/fnbeh.2021.626906

Associação Psiquiátrica Americana. (2014). Manual Diagnóstico e Estatístico de Transtornos Mentais (5ª ed.). Arlington, VA: American Psychiatric Publishing

Bassi, S., Costa, L., Lesik, L., Faccioli, J., Finkelsztein, C., & Cajal, A. (2018). Interaction between polymorphisms in SLC6A4 and BDNF on major depressive disorder in a sample of the argentinean population. Rev. Hosp. Ital. 38(1), p. 5-10.

Capibaribe, V. C. C. (2018). Potencial antidepressivo do timol: efeitos sobre os níveis do fator neurotrófico derivado do cérebro (BDNF) no modelo de estresse crônico induzido por corticosterona em camundongos. Dissertação de mestrado. Universidade Federal do Ceará (UFC), Fortaleza, CE, Brasil.

Chiou, Y. J., & Huang, T. L. (2017). Serum Brain-Derived Neurotrophic Factors in Taiwanese Patients with Drug-Naïve First-Episode Major Depressive Disorder: Effects of Antidepressants. International Journal of Neuropsychopharmacology. 20(3). p. 213–218. DOI: doi:10.1093/ijnp/pyw096

Chiou, Y. J., & Huang, T. L. (2019). Accuracy of brain-derived neurotrophic factor levels for differentiating between Taiwanese patients with major depressive disorder or schizophrenia and healthy controls. PLoS ONE. 14(2): e0212373. DOI:

Colaço, C. S. (2018). Avaliação do potencial antidepressivo da ayahuasca em ratos: comportamento, quantificação de monoaminas e do fator neurotrófico derivado do cérebro (BDNF). Dissertação de mestrado, Universidade de Brasília (UnB), Brasília, DF, Brasil.

Colucci-D’Amato, L., Speranza, L., & Volpicelli, F. (2020). Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. Int. J. Mol. Sci. 21(7777). DOI:

Diniz, D. M., Calabrese, F., Brivio, P., Riva, M. A., Grandjean, J., & Homberg, J. R. (2021). BDNF overexpression in the ventral hippocampus promotes antidepressant- and anxiolytic-like activity in serotonin transporter knockout rats. Int. J. Mol. Sci. 22(5040). DOI:

Emon, P. Z., Das, R., Nishuty, N. L., Qusar, M. M. A. S., Bhuiyan, M. A., & Islam, R. (2020). Reduced serum BDNF levels are associated with the increased risk for developing MDD: a case–control study with or without antidepressant therapy. BMC Res Notes. 13(83). DOI:

Ferrer, A., Labad, J., Salvat-Pujo, N., Barrachina, M., Costas, J., Urretavizcaya, M., Arriba-Arnau, A., Crespo, J. M., Soriano-Mas, C., Carracedo, Á., Menchón, J. M., & Soria, V. (2019). BDNF genetic variants and methylation: effects on cognition in major depressive disorder. Translational Psychiatry. 9(265). DOI:

Galvão, T. F., Pansan, T., & Harrad, D. (2015). Principais itens para relatar Revisões sistemáticas e Meta-análises: A recomendação PRISMA. Epidemiol. Serv. Saúde. 24 (2)

Gökçe, E., Güneş, E., & Nalçaci, E. (2019). Effect of exercise on major depressive disorder and schizophrenia: a BDNF focused approach. Arch Neuropsychiatry. 2019(56). p. 302−310. DOI:

Guerra, T. R. B., & Mesquita, E. T. (2020). Visão metabolômica envolvendo depressão e insuficiência cardíaca: uma análise reflexiva. Research, Society and Development. 9(8). p. e455986035. DOI:

Guerrera, C.S., Furneri, G., Grasso, M., Caruso, G., Castellano, S., Drago, F., Di Nuovo, S., & Caraci, F. (2020). Antidepressant Drugs and Physical Activity: A Possible Synergism in the Treatment of Major Depression? Front. Psychol. 857(11). DOI:

Khan, M. S., Wu, G. W. Y., Reus, V. I., Hough C. M. Lindqvist, D., Westrinc, A., Nier, B. M., Wolkowitz, O. M., & Mellond, S. H. (2019). Low serum brain-derived neurotrophic factor is associated with suicidal ideation in major depressive disorder. Psychiatry Research. 273. p. 108-113. DOI:

Kishi, T., Yoshimura, R., Ikuta, T., & Iwata, N. (2018). Brain-Derived Neurotrophic Factor and Major Depressive Disorder: Evidence from Meta-Analyses. Frontiers in Psychiatry. 8 (308). DOI: 10.3389/fpsyt.2017.00308

Kurdi, F. N., & Flora, R. (2019). Physical Exercise Increased Brain-Derived Neurotrophic Factor in Elderly Population with Depression. Open access Macedonian journal of medical sciences. 13(7). p.2057–2061. DOI:

Lin, C-C., & Huang, T-L. (2020). Brain-derived neurotrophic factor and mental disorders. biomedical journal. 43. p. 134-142. DOI:

Mizoguchi, Y., Yao, H., Imamura, Y., Hashimoto, M., & Monji, A. (2020). Lower brain‑derived neurotrophic factor levels are associated with age‑related memory impairment in community‑dwelling older adults: the Sefuri study. Nature Scientific Reports. 10 (16442). DOI:

Oh, H., Piantadosi, S. C., Rocco, B. R., Lewis, D. A., Watkins, S. C., & Sibille, E. (2019). The Role of Dendritic Brain-Derived Neurotrophic Factor Transcripts on Altered Inhibitory Circuitry in Depression. Biological psychiatry, 85(6), 517–526. DOI:

Park, Y. M., & Lee, B. H. (2018). Alterations in Serum BDNF and GDNF Levels after 12 Weeks of Antidepressant Treatment in Female Outpatients with Major Depressive Disorder. Psychiatry investigation. 8(15). p.818-823. DOI:

Pastori, T. A. N. (2020). Depressão: uma epidemia? Dissertação de mestrado. Fundação Oswaldo Cruz (Escola Nacional de Saúde Pública Sergio Arouca), Rio de Janeiro, RJ, Brasil.

Perito, M. E. S., & Fortunato, J. J. (2012). Marcadores biológicos da depressão: uma revisão sobre a expressão de fatores neurotróficos. Rev Neurocienc. 20(4). p. 597-603.

Phillips, C. (2017). Brain-derived neurotrophic factor, depression, and physical activity: making the neuroplastic connection. Neural Plasticity. 2017(7260130). p. 17. DOI:

Rafa-Zablocka, K., kreiner, G., baginska, M., & Nalepa, I. (2018). Selective Depletion of CREB in Serotonergic Neurons Affects the Upregulation of Brain-Derived Neurotrophic Factor Evoked by Chronic Fluoxetine Treatment. Frontiers in Neuroscience. 12 (637). DOI:

Ritter, O. M. S., Allonço, M., & Lima, F. (2021). Content analysis as a methodology in Qualis-CAPES A1 journals in Science Education. Research, Society and Development. Research Society and Development. 10(3), p. e43110313378

Rossetti, A. C., Paladini, M. S., Trepci, A., Mallien, A., Riva, M. A., Gass, P., & Molteni, R. (2019). Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF. Frontiers in Molecular Neuroscience. 12 (166). DOI: 10.3389/fnmol.2019.00166

Sartori, C. R. (2010). Efeito antidepressivo e cognitivo da atividade física associado a alterações pós-traducionais do Fator Neurotrófico Derivado do Cérebro (BDNF). Tese de doutorado, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil.

Shan, D., Zheng, YD., & Froud, K. (2021). Brain-derived neurotrophic factor as a clinical biomarker in predicting the development of post-stroke depression: a review of evidence. Cureus. 13(6). p. e15662. DOI:

Syafrita, Y., Amir, D., Susanti, R., & Fadhilah, I. (2020). Relationship of brain-derived neurotrophic factor, malondialdehyde, and 8-Hydroxy 2-Deoxyguanosine with post-ischemic stroke depression. Dement Neuropsychol. 14(1) p. 41-46. DOI:

Teng, Z., Wang, L., Li, S., Tan, Y., Qiu, Y., Wu, C., Jin, K., Chen, J., Huang, J., Tang, H., Xiang, H., Wang, B., Yuan, H., & Wu, H. (2021). Low BDNF levels in serum are associated with cognitive impairments in medication-naïve patients with current depressive episode in BD II and MDD. Journal of Affective Disorders. 293. p. 90-9. DOI:

Troyan, A. S., & Levada, O. A. (2020). The diagnostic value of the combination of serum brain-derived neurotrophic factor and insulin-like growth factor-1 for major depressive disorder diagnosis and treatment efficacy. Front. Psychiatry. 11(800). DOI:

World Health Organization - WHO. (2017). Depression and other common mental disorders. Global health estimates. Documento técnico. World Health Organization, Genebra, Suíça.

Xu, W., Yao, X., Zhao, F., Zhao, H., Cheng, Z., Yang, W., Cui, R., Xu, S., & Li, B. (2020). Changes in hippocampal plasticity in depression and therapeutic approaches influencing these changes. Neural Plasticity. 2020(8861903). p. 16. DOI:

Yang, T., Nie, Z., Shu, H., Kuang, Y., Chen, X., Cheng, J., Yu, S., & Liu H. (2020). The Role of BDNF on Neural Plasticity in Depression. Front Cell Neurosci. 82(14). DOI: 10.3389/fncel.2020.00082. PMID: 32351365; PMCID: PMC7174655.

Youssef, M. M., Underwood, M. D., Huang, Y-Y., Hsiung, S-c., Liu, Y., Simpson, N. R., Bakalian, M. J., Rosoklija, G. B., Dwork, A. J., Arango, V., & Mann, J. J. (2018). Association of BDNF Val66Met polymorphism and brain BDNF levels with major depression and suicide. International Journal of Neuropsychopharmacology. 21(6). p. 528–538. DOI:

Zheng, W., Zhou, Y. L., Wang, C. Y., Lan, X. F., Zhang, B., Zhou, S. M., Yan, S., & Ning, Y. P. (2021). Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression. PeerJ. 10989 (9). DOI:

Zhong, F., Liu, L., Wei, J. L., Hu, Z. L., Li, L., Wang, S., Xu, J. M., Zhou, X. F., Li, C. Q., Yang, Z. Y., & Dai, R. P. (2019). Brain-Derived Neurotrophic Factor Precursor in the Hippocampus Regulates Both Depressive and Anxiety-Like Behaviors in Rats. Front. Psychiatry. 9 (776). DOI: doi: 10.3389/fpsyt.2018.00776

Zhou, C., Zhong, J., Zou, B., Fang, L., Chen, J., Deng, X., Zhang, L., Zhao, X., Qu, Z., Lei, Y., & Lei, T. (2017). Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression. PLoS ONE. 12(2): e0172270. DOI: doi:10.1371/journal.pone.0172270



How to Cite

SANTOS, T. B. dos .; SOUZA, V. H. S. de .; LOPES, N. C. G. .; FERREIRA, F. A. .; LEITE, C. Q. .; SILVA, M. G. S. da; SANTOS, B. F. dos . Association between brain-derived neurotrophic factor (BDNF) and depressive disorder: a literature review. Research, Society and Development, [S. l.], v. 10, n. 10, p. e461101019139, 2021. DOI: 10.33448/rsd-v10i10.19139. Disponível em: Acesso em: 18 oct. 2021.



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