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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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(a) Direct comparison of the effect sizes of the different studies in mania, depression, and euthymia. Peripheral brain-derived neurotrophic factor (BDNF) levels were equally decreased in mania and depression (P = 0.340), and both manic and depressive states presented BDNF levels decreased when compared to euthymic state (P = 0.002). (b) Meta-regression of the effect sizes of peripheral BDNF levels against severity of mania as assessed by the Young Mania Rating Scale (YMRS) scores, showing more accentuated decreases in BDNF levels with increase in YMRS scores (P = 0.004). (c) Meta-regression of the effect sizes of peripheral BDNF levels against severity of depression as assessed by the Hamilton Depression Rating Scale (HDRS) scores, showing more accentuated decreases in BDNF levels with increase in HDRS scores (P = 0.018). (d) Meta-regression of the effect sizes of peripheral BDNF levels against duration of illness in years in euthymic subjects, showing no association between BDNF levels and duration of bipolar illness in years during euthymia (P = 0.577)
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Fig3: (a) Direct comparison of the effect sizes of the different studies in mania, depression, and euthymia. Peripheral brain-derived neurotrophic factor (BDNF) levels were equally decreased in mania and depression (P = 0.340), and both manic and depressive states presented BDNF levels decreased when compared to euthymic state (P = 0.002). (b) Meta-regression of the effect sizes of peripheral BDNF levels against severity of mania as assessed by the Young Mania Rating Scale (YMRS) scores, showing more accentuated decreases in BDNF levels with increase in YMRS scores (P = 0.004). (c) Meta-regression of the effect sizes of peripheral BDNF levels against severity of depression as assessed by the Hamilton Depression Rating Scale (HDRS) scores, showing more accentuated decreases in BDNF levels with increase in HDRS scores (P = 0.018). (d) Meta-regression of the effect sizes of peripheral BDNF levels against duration of illness in years in euthymic subjects, showing no association between BDNF levels and duration of bipolar illness in years during euthymia (P = 0.577)

Mentions: We set to verify if there were differences in the extent of the decrease of peripheral BDNF levels according to mood states in order to assess the properties of peripheral BDNF levels as a possible state biomarker of disease activity in BD. For this, we performed a direct comparison of the ESs of the different studies in mania, depression, and euthymia. In general, the median and interquartile range of the ESs were different across the mood spectrum (−0.67, −1.09 to 0.06 in mania; −0.86, −1.91 to −0.13 in depression; −0.03, −0.24 to 0.31 in euthymia; P = 0.002, 58 comparisons, n = 5,528). Peripheral BDNF levels were equally decreased in mania and depression (P = 0.340, 34 comparisons, n = 2,471), and both manic and depressive states presented BDNF levels to be decreased when compared to the euthymic state (P = 0.014, 43 comparisons, n = 4,454 for mania vs. euthymia; P = 0.001, 39 comparisons, n = 4,131 for depression vs. euthymia; Bonferroni correction for multiple comparisons applied). Although the difference between those in acute manic and depressive episodes was statistically significant when compared to those in euthymia, the variability was large, and there was considerable overlap between the values of BDNF levels found in mania and depression with those in euthymia (Fig. 3a).Fig. 3


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)

(a) Direct comparison of the effect sizes of the different studies in mania, depression, and euthymia. Peripheral brain-derived neurotrophic factor (BDNF) levels were equally decreased in mania and depression (P = 0.340), and both manic and depressive states presented BDNF levels decreased when compared to euthymic state (P = 0.002). (b) Meta-regression of the effect sizes of peripheral BDNF levels against severity of mania as assessed by the Young Mania Rating Scale (YMRS) scores, showing more accentuated decreases in BDNF levels with increase in YMRS scores (P = 0.004). (c) Meta-regression of the effect sizes of peripheral BDNF levels against severity of depression as assessed by the Hamilton Depression Rating Scale (HDRS) scores, showing more accentuated decreases in BDNF levels with increase in HDRS scores (P = 0.018). (d) Meta-regression of the effect sizes of peripheral BDNF levels against duration of illness in years in euthymic subjects, showing no association between BDNF levels and duration of bipolar illness in years during euthymia (P = 0.577)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: (a) Direct comparison of the effect sizes of the different studies in mania, depression, and euthymia. Peripheral brain-derived neurotrophic factor (BDNF) levels were equally decreased in mania and depression (P = 0.340), and both manic and depressive states presented BDNF levels decreased when compared to euthymic state (P = 0.002). (b) Meta-regression of the effect sizes of peripheral BDNF levels against severity of mania as assessed by the Young Mania Rating Scale (YMRS) scores, showing more accentuated decreases in BDNF levels with increase in YMRS scores (P = 0.004). (c) Meta-regression of the effect sizes of peripheral BDNF levels against severity of depression as assessed by the Hamilton Depression Rating Scale (HDRS) scores, showing more accentuated decreases in BDNF levels with increase in HDRS scores (P = 0.018). (d) Meta-regression of the effect sizes of peripheral BDNF levels against duration of illness in years in euthymic subjects, showing no association between BDNF levels and duration of bipolar illness in years during euthymia (P = 0.577)
Mentions: We set to verify if there were differences in the extent of the decrease of peripheral BDNF levels according to mood states in order to assess the properties of peripheral BDNF levels as a possible state biomarker of disease activity in BD. For this, we performed a direct comparison of the ESs of the different studies in mania, depression, and euthymia. In general, the median and interquartile range of the ESs were different across the mood spectrum (−0.67, −1.09 to 0.06 in mania; −0.86, −1.91 to −0.13 in depression; −0.03, −0.24 to 0.31 in euthymia; P = 0.002, 58 comparisons, n = 5,528). Peripheral BDNF levels were equally decreased in mania and depression (P = 0.340, 34 comparisons, n = 2,471), and both manic and depressive states presented BDNF levels to be decreased when compared to the euthymic state (P = 0.014, 43 comparisons, n = 4,454 for mania vs. euthymia; P = 0.001, 39 comparisons, n = 4,131 for depression vs. euthymia; Bonferroni correction for multiple comparisons applied). Although the difference between those in acute manic and depressive episodes was statistically significant when compared to those in euthymia, the variability was large, and there was considerable overlap between the values of BDNF levels found in mania and depression with those in euthymia (Fig. 3a).Fig. 3

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