Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
Open accessAbstract
BACKGROUND: The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). However, its role in peripheral blood as a biomarker of disease activity and of stage for BD, transcending pathophysiology, is still disputed. In the last few years an increasing number of clinical studies assessing BDNF in serum and plasma have been published. Therefore, it is now possible to analyse the association between BDNF levels and the severity of affective symptoms in BD as well as the effects of acute drug treatment of mood episodes on BDNF levels. METHODS: We conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder. RESULTS: Through a series of meta-analyses including a total of 52 studies with 6,481 participants, we show that, compared to healthy controls, peripheral BDNF levels are reduced to the same extent in manic (Hedges' g = -0.57, P = 0.010) and depressive (Hedges' g = -0.93, P = 0.001) episodes, while BDNF levels are not significantly altered in euthymia. In meta-regression analyses, BDNF levels additionally negatively correlate with the severity of both manic and depressive symptoms. We found no evidence for a significant impact of illness duration on BDNF levels. In addition, in plasma, but not serum, peripheral BDNF levels increase after the successful treatment of an acute mania episode, but not of a depressive one. CONCLUSIONS: In summary, our data suggest that peripheral BDNF levels, more clearly in plasma than in serum, is a potential biomarker of disease activity in BD, but not a biomarker of stage. We suggest that peripheral BDNF may, in future, be used as a part of a blood protein composite measure to assess disease activity in BD.
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Two recent meta-analyses have shown that serum and plasma levels of BDNF in BD patients during depressive and manic episodes are decreased, but no difference in BDNF levels between BD patients in an euthymic episode and healthy controls was found.
“Two recent meta-analyses have shown that serum and plasma levels of BDNF in BD patients during depressive and manic episodes are decreased, but no difference in BDNF levels between BD patients in an euthymic episode and healthy controls was found [88, 89].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [88]
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- Authors
- Fernandes, B. S., Molendijk, M. L., Köhler, C. A., Soares, J. C., Leite, C. M. G. S., Machado-Vieira, R., Ribeiro, T. L., Silva, J. C., Sales, P. M. G., Quevedo, J., Oertel-Knöchel, V., Vieta, E., González-Pinto, A., Berk, M., & Carvalho, A. F.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Leiden University (NL)
- Universidade Federal do Ceará (BR)
- Texas Health and Science University (US)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- University of the Basque Country (ES)
- Deakin University (AU)
- Corresponding author
- Fernandes, Brisa S.
- ORCID
- Venue
- BMC Medicine
- Published
- 2015-11-30
- Volume
- 13
- Issue
- 1
- Pages
- 289-289
- ISSN
- 1741-7015 (ISSN-L)
- PMC
- PMC4666054
- OpenAlex
- W2184290988
- Cited by
- 291
- References
- 111
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 26 · 2023: 22 · 2022: 23 · 2021: 48 · 2020: 34 · 2019: 24 · 2018: 24 · 2017: 33 · 2016: 22 · 2015: 1
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, cc-by)
- Communities in ADDI (Universidad del Pais Vasco) (submittedVersion, cc-by)
- Leiden Repository (Leiden University) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Hispana (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by)
- Funders
- John S. Dunn Foundation
- University of Texas Health Science Center at Houston
- Universiteit Leiden
- Deakin University (1059660)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (MCTI/CNPQ/Universal 14/2014461833/2014-0)
- Euskal Herriko Unibertsitatea
- Ministério da Ciência, Tecnologia e Inovação
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (2014‐0)
- Universidade Federal do Rio Grande do Sul
- Leids Universitair Medisch Centrum
- Universidade de São Paulo
- Universitat de Barcelona
- Centro de Investigación Biomédica en Red de Salud Mental
- National Institutes of Health
- U.S. Public Health Service (R01085667)
- National Health and Medical Research Council (1059660)
- National Institute of Mental Health (R01 085667, 1059660)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- brain-derived neurotrophic factor, bipolar disorder, peripheral biomarkers, serum BDNF, plasma BDNF, manic episodes, depressive episodes, disease activity, disease stage, acute mania treatment, mood stabilizers
- MeSH terms
- Bipolar Disorder, Depression, Female, Humans, Male, Middle Aged, Biomarkers, Brain-Derived Neurotrophic Factor
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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