Abstract
BackgroundThe 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.MethodsWe conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder.ResultsThrough 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.ConclusionsIn 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 materialThe online version of this article (doi:10.1186/s12916-015-0529-7) contains supplementary material, which is available to authorized users.
Highlights
The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF)
We performed four between-group meta-analyses of peripheral levels of BDNF in subjects with BD according to mood state: (1) in subjects with BD in mania compared to healthy controls; (2) in subjects with BD in depression compared to healthy controls; (3) in subjects with BD in a mixed episode compared to healthy controls; and (4) in subjects with BD in euthymia compared to healthy controls
One study for the between-group meta-analysis was excluded because it assessed BDNF levels in different mood states in rapid cycling subjects in a longitudinal manner; the BDNF assessed was subject to the risk of being influenced by the last episode [41]
Summary
The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). BD followed, with Laske et al [7], in 2005, first showing decreased serum BDNF levels in mania, and Palomino et al [8], in 2006, showing that peripheral BDNF increased after treatment of acute mania. Research on peripheral BDNF was originally driven by the aim of better understanding the pathophysiology of mood disorders; in the last few years, BDNF has been attracting attention as a potential biomarker capable of advancing the elusive field of personalised medicine in psychiatry [9,10,11]. In BD, several studies have been conducted with discrepant results Most of these studies have suggested peripheral BDNF as a state-marker in BD, with decreased levels in mania and depression returning to normal in euthymia, and being correlated with severity of mania and depression [14, 15]. It has been suggested that BDNF levels may reflect neuroprogressive changes in BD, and may hold promise as a stage biomarker [11, 14, 20]
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