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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Detalles Bibliográficos
Autores: 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 Arrillaga, Ana María, Berk, Michael, Carvalho, André F.
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/32392
Acceso en línea:http://hdl.handle.net/10810/32392
Access Level:acceso abierto
Palabra clave:biomarker
bipolar disorder
brain-derived neurotrophic factor
meta-analysis
factor serum-levels
open-label trial
VS. late-stage
Val66Met polymorphism
decreased levels
plasma BDNF
acute mania
I disorder
International Society
serotonin transporter
Descripción
Sumario: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.