Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a comprehensive systematic review and meta-analysis

Munkholm, K; Vinberg, M; Kessing, L V

doi:10.1038/mp.2015.54

Cited by 157Bipolar Disorder and TreatmentSchizophrenia research and treatmentTreatment of Major Depression

Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a comprehensive systematic review and meta-analysis

Munkholm, K, Vinberg, M, Kessing, L V·2016·Molecular Psychiatry

DOI 10.1038/mp.2015.54

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Abstract

Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control subjects and between affective states in bipolar disorder patients, including assessment of the effect of treatment of acute episodes on BDNF levels. A systematic review of English language studies without considering publication status was conducted in PubMed (January 1950-November 2014), Embase (1974-November 2014) and PsycINFO (1806-November 2014), and 35 studies comprising a total of 3798 participants were included in the meta-analysis. The results indicated that crude peripheral blood BDNF levels may be lower in bipolar disorder patients overall (Hedges' g=-0.28, 95% CI: -0.51 to -0.04, P=0.02) and in serum of manic (g=-0.77, 95% CI: -1.36 to -0.18, P=0.01) and depressed (g=-0.87, 95% CI: -1.42 to -0.32, P=0.002) bipolar disorder patients compared with healthy control subjects. No differences in peripheral BDNF levels were observed between affective states overall. Longer illness duration was associated with higher BDNF levels in bipolar disorder patients. Relatively low study quality, substantial unexplained between-study heterogeneity, potential bias in individual studies and indications of publication bias, was observed and studies were overall underpowered. It could thus not be excluded that identified differences between groups were due to factors not related to bipolar disorder. In conclusion, limitations in the evidence base prompt tempered conclusions regarding the role of peripheral BDNF as a biomarker in bipolar disorder and substantially improving the quality of further research is warranted.

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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 [89]

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Dr. Woodside Replies
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Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation
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Association among obesity, overweight and autism spectrum disorder: a systematic review and meta-analysis
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Unfolding the Role of BDNF as a Biomarker for Treatment of Depression
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Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders
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Novel metabolic role for BDNF in pancreatic β-cell insulin secretion
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Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder
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Na+, K+-ATPase Signaling and Bipolar Disorder
Lichtstein, D., Ilani, A., Rosen, H., Horesh, N., Singh, S. V., Buzaglo, N., & Hodes, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082314 · Cited by 68 · see citing works
Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder
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Associations of BDNF/BDNF-AS SNPs with Depression, Schizophrenia, and Bipolar Disorder
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Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment: a Comprehensive Systematic Review and Meta-analysis
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Brain-Derived Neurotrophic Factor: A Novel Dynamically Regulated Therapeutic Modulator in Neurological Disorders
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Combined serum levels of multiple proteins in tPA-BDNF pathway may aid the diagnosis of five mental disorders
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Seeking an Objective Diagnosis of Depression
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Risk of miscarriage in women with psychiatric disorders
Magnus, M. C., Havdahl, A., Morken, N., Wensaas, K., Wilcox, A. J., & Håberg, S. E. (2021) · The British Journal of Psychiatry · doi:10.1192/bjp.2020.259 · Cited by 49 · see citing works
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Adipokines, metabolic dysfunction and illness course in bipolar disorder
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Significantly Higher Peripheral Insulin-Like Growth Factor-1 Levels in Patients With Major Depressive Disorder or Bipolar Disorder Than in Healthy Controls
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Update on bipolar disorder biomarker candidates
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Antidepressant-like effects of standardized gypenosides: involvement of brain-derived neurotrophic factor signaling in hippocampus
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The evolutionary old forebrain as site of action to develop new psychotropic drugs
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Biomarkers of neuroprogression and late staging in bipolar disorder: A systematic review
Grewal, S. K., McKinlay, S., Kapczinski, F. P., Pfaffenseller, B., & Wollenhaupt-Aguiar, B. (2022) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/00048674221091731 · Cited by 39 · see citing works
The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder
Valvassori, S. S., Mariot, E., Varela, R. B., Bavaresco, D. V., Dal-Pont, G. C., Ferreira, C. L., Andersen, M. L., Tye, S. J., & Quevedo, J. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.10.370 · Cited by 37 · see citing works
Analysis of blood mature BDNF and proBDNF in mood disorders with specific ELISA assays
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Association of Lipid Peroxidation and Brain-Derived Neurotrophic Factor with Executive Function in Adolescent Bipolar Disorder
Newton, D. F., Naiberg, M. R., Andreazza, A. C., Scola, G., Dickstein, D. P., & Goldstein, B. I. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4500-x · Cited by 35 · see citing works
Peripheral brain-derived neurotrophic factor in attention-deficit/hyperactivity disorder: A comprehensive systematic review and meta-analysis
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Blood homocysteine levels in children with autism spectrum disorder: An updated systematic review and meta-analysis
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Peripheral blood nerve growth factor levels in major psychiatric disorders
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Blood biomarker levels of methylation capacity in autism spectrum disorder: a systematic review and meta‐analysis
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Circulating Brain-Derived Neurotrophic Factor, Antioxidant Enzymes Activities, and Mitochondrial DNA in Bipolar Disorder: An Exploratory Report
Wang, D., Li, H., Du, X., Zhou, J., Liu, Y., Ren, H., Yang, X., Zhang, G., & Chen, X. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.514658 · Cited by 30 · see citing works
Molecular mechanism linking BDNF/TrkB signaling with the NMDA receptor in memory: the role of Girdin in the CNS
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Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis
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Brain-Derived Neurotrophic Factor (Bdnf) and Gray Matter Volume in Bipolar Disorder
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Val66Met functional polymorphism and serum protein level of brain-derived neurotrophic factor (BDNF) in acute episode of schizophrenia and depression
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EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar Disorder
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Neurotrophic and inflammatory markers in bipolar disorder: A prospective study
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Brain‐derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course
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BDNF in antipsychotic naive first episode psychosis: Effects of risperidone and the immune-inflammatory response system
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Decreased S100B serum levels after treatment in bipolar patients in a manic phase
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New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data
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Brain Derived Neurotrophic Factor and Cognitive Dysfunction in the Schizophrenia-Bipolar Spectrum: A Systematic Review and Meta-Analysis
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Association of serum BDNF levels and the BDNF Val66Met polymorphism with the sleep pattern in healthy young adults
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BDNF and BMI effects on brain structures of bipolar offspring: results from the global mood and brain science initiative
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Brain-derived neurotrophic factor levels in newly diagnosed patients with bipolar disorder, their unaffected first-degree relatives and healthy controls
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CaMKK2 as an emerging treatment target for bipolar disorder
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Inter‐relation between brain‐derived neurotrophic factor and antioxidant enzymes in bipolar disorder
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Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation
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RESEARCH ARTICLE Open Access Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
Fern, 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., et al. (2016)
Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
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Additional file 2: of Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
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Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: A systematic review and meta-regression analysis
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Authors: Munkholm, K., Vinberg, M., & Kessing, L. V.
Affiliations: University of Copenhagen (DK)
Corresponding author: Munkholm, K
ORCID: Munkholm, K
Vinberg, M
Kessing, L V
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2015-07-21
Volume: 21
Issue: 2
Pages: 216-228
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/mp.2015.54
OpenAlex: W1553642515
Cited by: 157
References: 156
Citations by year: 2026: 12 · 2025: 10 · 2024: 16 · 2023: 8 · 2022: 16 · 2021: 18 · 2020: 16 · 2019: 12 · 2018: 11 · 2017: 17 · 2016: 18 · 2015: 3
FWCI: 2.25
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: Sundhed og Sygdom, Det Frie Forskningsråd
Lundbeckfonden (R34-2009-3696)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords: bipolar disorder, brain-derived neurotrophic factor, peripheral blood biomarkers, serum BDNF, manic state, depressive state, disease duration, neuroprogression, disease activity
MeSH terms: Affective Symptoms, Bipolar Disorder, Female, Humans, Male, Biomarkers, Case-Control Studies, Brain-Derived Neurotrophic Factor

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Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a comprehensive systematic review and meta-analysis

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