Serum levels of brain-derived neurotrophic factor in major depressive disorder: state–trait issues, clinical features and pharmacological treatment
Open accessAbstract
Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression, whether BDNF levels are related to the clinical features of depression and whether distinct antidepressants affect BDNF levels equally. We addressed these questions and investigated serum BDNF levels in 962 depressed patients, 700 fully remitted persons (≥6 months) and 382 healthy controls. We found serum BDNF levels to be low in antidepressant-free depressed patients relative to controls (P=0.007) and to depressed patients who were treated with an antidepressant (P=0.001). BDNF levels of fully remitted persons (whether unmedicated or treated with an antidepressant) were comparable to those of controls. Analyzing the sample of antidepressant-free depressed patients showed that BDNF levels were unrelated to the core clinical features of depression such as its severity or first versus a recurrent episode. The antidepressant associated upregulation of serum BDNF in depressed patients was confined to selective serotonin reuptake inhibitors (SSRIs) (P=0.003) and St John's wort (P=0.03). Our results suggest that low serum levels of BDNF are a state abnormality that is evident during depression and normalizes during remission. Increases in serum levels of BDNF during antidepressant treatment appear to be confined to some antidepressants and do not parallel clinical characteristics, such as the severity of depressive symptoms.
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Lowered serum concentrations of BDNF are associated with MDD.
“Nevertheless, lowered serum concentrations of BDNF have often been associated with MDD (Karege et al. 2002, 2005; Sen et al. 2008, Molendijk et al. 2011).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Molendijk et al. 2011
Successful antidepressant treatment is usually associated with an increase in BDNF levels in serum and plasma, whereas treatment failure is associated with a lack of response of plasma BDNF levels.
“Successful antidepressant treatment is usually associated with an increase in BDNF levels in serum and plasma [65, 66], whereas treatment failure is associated with a lack of response of plasma BDNF levels.”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [66]
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Neurodevelopment and ages of onset in depressive disorders
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- Authors
- Molendijk, M. L., Bus, B. A. A., Spinhoven, P., Penninx, B. W. J. H., Kenis, G., Prickaerts, J., Voshaar, R. O., & Elzinga, B. M.
- Affiliations
- Leiden University (NL)
- Radboud University Nijmegen (NL)
- University Medical Center Groningen (NL)
- Maastricht University (NL)
- Corresponding author
- Molendijk, M L
- Venue
- Molecular Psychiatry
- Published
- 2010-09-21
- Volume
- 16
- Issue
- 11
- Pages
- 1088-1095
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3220395
- OpenAlex
- W2096699969
- Cited by
- 437
- References
- 55
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 26 · 2023: 19 · 2022: 16 · 2021: 40 · 2020: 31 · 2019: 32 · 2018: 28 · 2017: 21 · 2016: 28 · 2015: 30 · 2014: 38 · 2013: 44 · 2012: 29
- FWCI
- 23.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by-nc-nd)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Universiteit Leiden
- ZonMw
- Vrije Universiteit Amsterdam
- Universiteit Maastricht
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.085.353)
- Rivierduinen
- GGZ Friesland
- GGZ Drenthe
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- 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
- brain-derived neurotrophic factor, major depressive disorder, serum BDNF, selective serotonin reuptake inhibitors, Hypericum perforatum, trait versus state, clinical features of depression, depression severity
- MeSH terms
- Adult, Antidepressive Agents, Tricyclic, Anxiety Disorders, Convalescence, Major Depressive Disorder, Female, Humans, Male, Phytotherapy, Middle Aged, Models, Neurological, Models, Psychological, Plant Extracts, Recurrence, Severity of Illness Index, Biomarkers, Drug Monitoring, Selective Serotonin Reuptake Inhibitors, Brain-Derived Neurotrophic Factor, Hypericum
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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