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

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.

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“…Finally, cascades associated with the activation of the aforementioned pathways appear to lead to excitotoxic neural damage, a reduced expression of brain derived neurotrophic factor (BDNF) and consequently to a disruption of mechanisms subserving neural plasticity 53,54 . In addition, oxidative stress may reduce the activity of 5,6,7,8-tetrahydrobiopterin (BH4), which is a co-factor for several aromatic amino acid monooxygenases and is rate-limiting for the biosynthesis of the neurotransmitter serotonin and the catecholamines dopamine, epinephrine and norepinephrine 55 .…”

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“…Plasma and partially serum, BDNF levels were modified in several diseases and conditions such as: fibromyalgia [increased (196)], hemodialysis [increased, especially in diabetic patients (197)], metabolic syndrome and T2DM [increased (198)], bipolar disorder [decreased (199)], as well as with mood, cognition and motor function (200), alcohol consumption [decreased (201)], antidepressant treatments [increased (202)]. …”

Associations between Serum Brain-Derived Neurotrophic Factors and Bipolar Disorder

“…Several studies have adopted the BDNF as a molecular candidate for developing bipolar disorder [6,10]. Recent studies had demonstrated that BDNF levels are lower in patients during active phases than BDNF levels in healthy controls [10][11][12][13][14]. Changes in serum BDNF levels in different phases and in following pharmacological interventions for acute affective phase in patients with bipolar disorders were addressed in several studies, but the results are still inconclusive [8,13,[15][16][17].…”

“…Changes in serum BDNF levels in different phases and in following pharmacological interventions for acute affective phase in patients with bipolar disorders were addressed in several studies, but the results are still inconclusive [8,13,[15][16][17]. The serum BDNF protein level is reported to be a useful adjunctive tool for accurately diagnosing depressive bipolar disorder [18] and a marker for treatment response in bipolar disorder [11,14,19]. Bipolar disorder confers the higher risk of suicide and violence among major psychiatric disorders [20,21].…”