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

Fernandes BS, Molendijk ML, Köhler CA, Soares JC, Leite CM, Machado-Vieira R, Ribeiro TL, Silva JC, Sales PM, Quevedo J, Oertel-Knöchel V, Vieta E, González-Pinto A, Berk M, Carvalho AF - BMC Med (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Geelong, Australia. brisasf@gmail.com.

ABSTRACT

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.

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Forest plots of between-group meta-analyses measuring peripheral brain-derived neurotrophic factor (BDNF) levels in subjects with bipolar disorder compared to healthy controls, separated by mood state and medication status. (a) Mania, studies separated according use of medication. (b) Depression, studies separated according use of medication. The sizes of the circles are proportional to the sample size. Circles depict individual studies and diamonds depict the pooled effect sizes. Serum and plasma BDNF levels were decreased in subjects with bipolar disorder in mania and depression on and off psychiatric medication when compared to healthy controls
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Fig1: Forest plots of between-group meta-analyses measuring peripheral brain-derived neurotrophic factor (BDNF) levels in subjects with bipolar disorder compared to healthy controls, separated by mood state and medication status. (a) Mania, studies separated according use of medication. (b) Depression, studies separated according use of medication. The sizes of the circles are proportional to the sample size. Circles depict individual studies and diamonds depict the pooled effect sizes. Serum and plasma BDNF levels were decreased in subjects with bipolar disorder in mania and depression on and off psychiatric medication when compared to healthy controls

Mentions: Forty-four studies were included in the between-group meta-analyses of subjects with BD versus healthy controls in the different mood states [7–9, 42–50, 52, 53, 55, 57–64, 66, 68–77, 79–87, 90], providing data on 5,741 participants, of whom 2,599 were subjects with BD and 3,142 were healthy controls, which are summarized in Additional file 2: Table S2. Overall, random-effects between-group meta-analysis showed that peripheral BDNF levels were decreased in subjects with BD in mania with moderate effect sizes (g = −0.57, 95 % CI −0.99 to −0.14, P = 0.010, 19 between-group comparisons, n = 1,397) and decreased in depression with large effect sizes (g = −0.93, 95 % CI −1.37 to −0.50, P = 0.001, 15 between-group comparisons, n = 1,074) when compared to healthy controls. In contrast, there were no changes in peripheral BDNF levels in euthymia (g = 0.05, 95 % CI −0.13 to 0.24, P = 0.569, 24 between-group comparisons, n = 3,057; Table 1, Figs. 1 and 2).Table 1


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

Fernandes BS, Molendijk ML, Köhler CA, Soares JC, Leite CM, Machado-Vieira R, Ribeiro TL, Silva JC, Sales PM, Quevedo J, Oertel-Knöchel V, Vieta E, González-Pinto A, Berk M, Carvalho AF - BMC Med (2015)

Forest plots of between-group meta-analyses measuring peripheral brain-derived neurotrophic factor (BDNF) levels in subjects with bipolar disorder compared to healthy controls, separated by mood state and medication status. (a) Mania, studies separated according use of medication. (b) Depression, studies separated according use of medication. The sizes of the circles are proportional to the sample size. Circles depict individual studies and diamonds depict the pooled effect sizes. Serum and plasma BDNF levels were decreased in subjects with bipolar disorder in mania and depression on and off psychiatric medication when compared to healthy controls
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666054&req=5

Fig1: Forest plots of between-group meta-analyses measuring peripheral brain-derived neurotrophic factor (BDNF) levels in subjects with bipolar disorder compared to healthy controls, separated by mood state and medication status. (a) Mania, studies separated according use of medication. (b) Depression, studies separated according use of medication. The sizes of the circles are proportional to the sample size. Circles depict individual studies and diamonds depict the pooled effect sizes. Serum and plasma BDNF levels were decreased in subjects with bipolar disorder in mania and depression on and off psychiatric medication when compared to healthy controls
Mentions: Forty-four studies were included in the between-group meta-analyses of subjects with BD versus healthy controls in the different mood states [7–9, 42–50, 52, 53, 55, 57–64, 66, 68–77, 79–87, 90], providing data on 5,741 participants, of whom 2,599 were subjects with BD and 3,142 were healthy controls, which are summarized in Additional file 2: Table S2. Overall, random-effects between-group meta-analysis showed that peripheral BDNF levels were decreased in subjects with BD in mania with moderate effect sizes (g = −0.57, 95 % CI −0.99 to −0.14, P = 0.010, 19 between-group comparisons, n = 1,397) and decreased in depression with large effect sizes (g = −0.93, 95 % CI −1.37 to −0.50, P = 0.001, 15 between-group comparisons, n = 1,074) when compared to healthy controls. In contrast, there were no changes in peripheral BDNF levels in euthymia (g = 0.05, 95 % CI −0.13 to 0.24, P = 0.569, 24 between-group comparisons, n = 3,057; Table 1, Figs. 1 and 2).Table 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Geelong, Australia. brisasf@gmail.com.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus