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Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies

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 pathophy...

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Autores principales: Fernandes, Brisa S., Molendijk, Marc L., Köhler, Cristiano A., Soares, Jair C., Leite, Cláudio Manuel G. S., Machado-Vieira, Rodrigo, Ribeiro, Thamara L., Silva, Jéssica C., Sales, Paulo M. G., Quevedo, João, Oertel-Knöchel, Viola, Vieta, Eduard, González-Pinto, Ana, Berk, Michael, Carvalho, André F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666054/
https://www.ncbi.nlm.nih.gov/pubmed/26621529
http://dx.doi.org/10.1186/s12916-015-0529-7
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author Fernandes, Brisa S.
Molendijk, Marc L.
Köhler, Cristiano A.
Soares, Jair C.
Leite, Cláudio Manuel G. S.
Machado-Vieira, Rodrigo
Ribeiro, Thamara L.
Silva, Jéssica C.
Sales, Paulo M. G.
Quevedo, João
Oertel-Knöchel, Viola
Vieta, Eduard
González-Pinto, Ana
Berk, Michael
Carvalho, André F.
author_facet Fernandes, Brisa S.
Molendijk, Marc L.
Köhler, Cristiano A.
Soares, Jair C.
Leite, Cláudio Manuel G. S.
Machado-Vieira, Rodrigo
Ribeiro, Thamara L.
Silva, Jéssica C.
Sales, Paulo M. G.
Quevedo, João
Oertel-Knöchel, Viola
Vieta, Eduard
González-Pinto, Ana
Berk, Michael
Carvalho, André F.
author_sort Fernandes, Brisa S.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0529-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-46660542015-12-02 Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies Fernandes, Brisa S. Molendijk, Marc L. Köhler, Cristiano A. Soares, Jair C. Leite, Cláudio Manuel G. S. Machado-Vieira, Rodrigo Ribeiro, Thamara L. Silva, Jéssica C. Sales, Paulo M. G. Quevedo, João Oertel-Knöchel, Viola Vieta, Eduard González-Pinto, Ana Berk, Michael Carvalho, André F. BMC Med Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0529-7) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-30 /pmc/articles/PMC4666054/ /pubmed/26621529 http://dx.doi.org/10.1186/s12916-015-0529-7 Text en © Fernandes et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fernandes, Brisa S.
Molendijk, Marc L.
Köhler, Cristiano A.
Soares, Jair C.
Leite, Cláudio Manuel G. S.
Machado-Vieira, Rodrigo
Ribeiro, Thamara L.
Silva, Jéssica C.
Sales, Paulo M. G.
Quevedo, João
Oertel-Knöchel, Viola
Vieta, Eduard
González-Pinto, Ana
Berk, Michael
Carvalho, André F.
Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
title Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
title_full Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
title_fullStr Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
title_full_unstemmed Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
title_short Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
title_sort peripheral brain-derived neurotrophic factor (bdnf) as a biomarker in bipolar disorder: a meta-analysis of 52 studies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666054/
https://www.ncbi.nlm.nih.gov/pubmed/26621529
http://dx.doi.org/10.1186/s12916-015-0529-7
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