Relationship between brain-derived neurotrofic factor (Bdnf) and sleep on depression: a critical review
Open accessAbstract
The Brain-Derived Neurotrofic Factor (BDNF) is one of the most important neurotrophins in the brain and it is suggested influences the activity of the serotonergic, noradrenergic and dopaminergic pathways. In the last few years, it has been hypothesized that BDNF level is related with depression and sleep. Several studies show that depressive subjects present low levels of BDNF in the brain. Poor sleep quality is also related with alterations in the BDNF concentration. Some authors argue that most of the cases show that impaired sleep quality increases the stress and, consequently, the vulnerability to depressive disorders, suggesting that there is a relationship between sleep, depression and BDNF levels.
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Reduced peripheral BDNF is consistently observed; although levels often increase with antidepressant treatment, their temporal trajectory does not always parallel symptom improvement.
“Reduced peripheral BDNF is consistently observed; although levels often increase with antidepressant treatment, their temporal trajectory does not always parallel symptom improvement, suggesting complex regulatory mechanisms (Autry and Monteggia, 2012; Monteiro et al., 2017).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Monteiro et al., 2017
The Introduction reports low BDNF levels in unmedicated depressed individuals, and BDNF AND DEPRESSION says antidepressant treatment generally increases BDNF expression. HYPOTHETICAL RELATIONSHIP BETWEEN BDNF AND SLEEP ON DEPRESSION says improvement in serum BDNF does not necessarily coincide with improvement in depressive symptoms. The copy does not establish that reduced *peripheral* BDNF is consistently observed, or describe a measured temporal trajectory of BDNF against symptoms. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHPA-axis dysregulation is a key pathological feature of depression, and PBMC methylation is a potential biomarker.
“supporting HPA-axis dysregulation as a key pathological feature and highlighting PBMC methylation as a potential biomarker (Autry and Monteggia, 2012; Monteiro et al., 2017)”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Monteiro et al., 2017
The section “Hypothetical Relationship Between BDNF and Sleep on Depression” links stress-related HPA-axis activation and cortisol secretion to reduced BDNF in a proposed pathway to depression. It does not establish HPA-axis dysregulation as a key pathological feature, and our copy does not discuss PBMC methylation as a potential biomarker. (LLM, conf=0.80)
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Cites
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Self-citationPhysiology of the Neurotrophins
Lewin, G. R., & Barde, Y. (1996) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.19.030196.001445 · Cited by 1,955 · see citing works
Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression
Shirayama, Y., Chen, A. C.-H., Nakagawa, S., Russell, D. S., & Duman, R. S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03251.2002 · Cited by 1,654 · see citing works
Binder (2004) · doi:10.1080/08977190410001723308 · Cited by 1,481 · see citing works
Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders
Autry, A. E., & Monteggia, L. M. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.005108 · Cited by 1,390 · see citing works
New insights into BDNF function in depression and anxiety
Martinowich, K., Manji, H., & Lu, B. (2007) · Nature Neuroscience · doi:10.1038/nn1971 · Cited by 1,221 · see citing works
Increased hippocampal bdnf immunoreactivity in subjects treated with antidepressant medication
Chen, B., Dowlatshahi, D., MacQueen, G. M., Wang, J.-F., & Young, L. T. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01083-6 · Cited by 1,164 · see citing works
Normal Human Sleep: An Overview
Carskadon, M. A., & Dement, W. C. (2005) · Elsevier eBooks · doi:10.1016/b0-72-160797-7/50009-4 · Cited by 1,161 · see citing works
Shimizu, E., Hashimoto, K., Okamura, N., Koike, K., Komatsu, N., Kumakiri, C., Nakazato, M., Watanabe, H., Shinoda, N., Okada, S.-I., et al. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00181-1 · Cited by 1,151 · see citing works
Antidepressant-like effect of brain-derived neurotrophic factor (BDNF)
Siuciak, J. A., Lewis, D. R., Wiegand, S. J., & Lindsay, R. M. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(96)00169-4 · Cited by 841 · see citing works
BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?
Lü, Y., Christian, K. M., & Lu, B. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.08.018 · Cited by 768 · see citing works
Role of neurotrophic factors in depression
CASTREN, E., VOIKAR, V, & RANTAMAKI, T. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.08.009 · Cited by 667 · see citing works
BDNF in schizophrenia, depression and corresponding animal models
Angelucci, F., Brené, S., & Mathé, A. A. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001637 · Cited by 548 · see citing works
The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment
Lee, B.-H., & Kim, Y. (2010) · Psychiatry Investigation · doi:10.4306/pi.2010.7.4.231 · Cited by 447 · see citing works
Brain-Derived Neurotrophic Factor Is Required for the Maintenance of Cortical Dendrites
Gorski, J. A., Zeiler, S. R., Tamowski, S., & Jones, K. R. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06856.2003 · Cited by 411 · see citing works
Regulation of hippocampal synaptic plasticity by BDNF
Leal, G., Afonso, P. M., Salazar, I. L., & Duarte, C. B. (2015) · Brain Research · doi:10.1016/j.brainres.2014.10.019 · Cited by 410 · see citing works
Is it time to reassess the BDNF hypothesis of depression?
Groves, J. O. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002075 · Cited by 403 · see citing works
Depression: The disorder and the burden
Reddy, M. S. (2010) · Indian Journal of Psychological Medicine · doi:10.4103/0253-7176.70510 · Cited by 392 · see citing works
The Role of BDNF in Depression on the Basis of Its Location in the Neural Circuitry
Yu, H., & Chen, Z.-Y. (2011) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.184 · Cited by 343 · see citing works
Physiological pathways and molecular mechanisms regulating uterine contractility
Aguilar, H. N., & Mitchell, B. F. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmq016 · Cited by 323 · see citing works
Altar, C. A., Whitehead, R. E., Chen, R., Wörtwein, G., & Madsen, T. M. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00073-8 · Cited by 300 · see citing works
Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression
Pezawas, L., Meyer‐Lindenberg, A., Goldman, A. L., Verchinski, B. A., Chen, G., Kolachana, B. S., Egan, M. F., Mattay, V. S., Hariri, A. R., & Weinberger, D. R. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.32 · Cited by 237 · see citing works
Circadian rhythms of liver physiology and disease: experimental and clinical evidence
Tahara, Y., & Shibata, S. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.8 · Cited by 231 · see citing works
Insomnia: prevalence, consequences and effective treatment
Cunnington, D., Junge, M. F., & Fernando, A. T. (2013) · The Medical Journal of Australia · doi:10.5694/mja13.10718 · Cited by 212 · see citing works
Serchov, T., Clement, H.-W., Schwarz, M. K., Iasevoli, F., Tosh, D. K., Idzko, M., Jacobson, K. A., de Bartolomeis, A., Normann, C., Biber, K., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.07.010 · Cited by 210 · see citing works
Serum BDNF levels before treatment predict SSRI response in depression
Wolkowitz, O. M., Wolf, J. S., Shelly, W. B., Rosser, R., Burke, H. M., Lerner, G. K., Reus, V. I., Nelson, J. C., Epel, E. S., & Mellon, S. H. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.06.013 · Cited by 174 · see citing works
Pharmacological interventions for sleepiness and sleep disturbances caused by shift work
Liira, J., Verbeek, J. H. A. M., Costa, G., Driscoll, T., Sallinen, M., Isotalo, L. K., & Ruotsalainen, J. H. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009776.pub2 · Cited by 117 · see citing works
BDNF: an indicator of insomnia?
Giese, M., Unternährer, E., Hüttig, H., Beck, J., Brand, S., Calabrese, P., Holsboer‐Trachsler, E., & Eckert, A. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.10 · Cited by 100 · see citing works
Martinotti, G., Pettorruso, M., Berardis, D. D., Varasano, P. A., Pressanti, G. L., Remigis, V. D., Valchera, A., Ricci, V., Nicola, M. D., Janiri, L., et al. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw003 · Cited by 100 · see citing works
The Interplay of Stress and Sleep Impacts BDNF Level
Giese, M., Unternäehrer, E., Brand, S., Calabrese, P., Holsboer‐Trachsler, E., & Eckert, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076050 · Cited by 99 · see citing works
Torregrossa, M. M., Jutkiewicz, E. M., Mosberg, H. I., Balboni, G., Watson, S. J., & Woods, J. H. (2005) · Brain Research · doi:10.1016/j.brainres.2005.11.005 · Cited by 98 · see citing works
Rusch, H. L., Guardado, P., Baxter, T., Mysliwiec, V., & Gill, J. (2015) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.4770 · Cited by 68 · see citing works
Zou, Y., Wang, Y., Liu, P., Feng, X.-L., Wang, B., Zang, T., Yu, X., Wei, J., Liu, Z., Liu, Y., et al. (2009) · Neuropsychobiology · doi:10.1159/000265132 · Cited by 55 · see citing works
Pharmacological interventions for sleepiness and sleep disturbances caused by shift work
Liira, J., Verbeek, J. H., Costa, G., Driscoll, T. R., Sallinen, M., Isotalo, L. K., & Ruotsalainen, J. H. (2015) · Sao Paulo Medical Journal · doi:10.1590/1516-3180.20151331t1 · Cited by 50 · see citing works
Insomnia and Anxiety: Diagnostic and Management Implications of Complex Interactions.
Glidewell, R., Botts, E. M., & Orr, W. (2015) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2014.11.008 · Cited by 46 · see citing works
del Cid‐Pellitero, E., Plavski, A., Mainville, L., & Jones, B. E. (2017) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2017.00017 · Cited by 39 · see citing works
Rethorst, C. D., GREER, T. L., Toups, M. S. P., Bernstein, I. H., Carmody, T. J., & Trivedi, M. H. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.104 · Cited by 36 · see citing works
The brain derived neurotrophic factor and influences of stress in depression.
Kimpton, J. (2012) · PubMed · Cited by 32 · see citing works
Selective targets for arousal-modifying drugs: implications for the treatment of sleep disorders
Szabadi, E. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.01.001 · Cited by 29 · see citing works
Armodafinil for excessive daytime sleepiness
Nishino, S., & Okuro, M. (2008) · Drugs of today · doi:10.1358/dot.2008.44.6.1223892 · Cited by 26 · see citing works
Armodafinil for excessive daytime sleepiness.
Nishino, S., & Okuro, M. (2008) · PubMed · doi:10.1358/dot.2008.44.6.1195861 · Cited by 23 · see citing works
Schramm, P. J., Poland, R. E., & Rao, U. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.09.007 · Cited by 20 · see citing works
Lamego, M. K., Moura, A. D. S., Paes, F., Rocha, N., Filho, A. S. S., Lattari, E., Rimes, R., Manochio, J., Budde, H., Wegner, M., et al. (2015) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666151111125402 · Cited by 11 · see citing works
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Milic, J., Jovic, S., & Sapic, R. (2025) · Genes · doi:10.3390/genes16050487 · Cited by 19 · see citing works
Lv, L.-Z., Wang, Z.-D., Ren, J.-J., Li, L.-H., Liu, X.-B., Li, J.-L., Zhu, H., Jiang, B., Han, Y.-P., Zhou, X.-M., et al. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2025.1722453 · Cited by 7 · see citing works
- Authors
- Monteiro, B. C., Monteiro, S., Candida, M., Adler, N., Paes, F., Rocha, N., Nardi, A. E., Murillo-Rodriguez, E., & Machado, S.
- Affiliations
- Universidade Federal do Rio de Janeiro (BR)
- Corresponding author
- Machado, Sergio
- Venue
- Clinical Practice & Epidemiology in Mental Health
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2017-11-21
- Volume
- 13
- Issue
- 1
- Pages
- 213-219
- ISSN
- 1745-0179 (ISSN-L)
- PMC
- PMC5725585
- OpenAlex
- W2767816287
- Cited by
- 63
- References
- 43
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 7 · 2023: 9 · 2022: 10 · 2021: 6 · 2020: 7 · 2019: 1 · 2018: 4
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Clinical Practice and Epidemiology in Mental Health (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- brain-derived neurotrophic factor, depression, sleep quality, neurotrophins, serotonergic pathways, noradrenergic pathways, dopaminergic pathways, stress, depression vulnerability
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