title: Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis.
abstract: Brain-derived neurotrophic factor (BDNF) plays a central role in synaptic plasticity and neurogenesis. Bipolar disorder (BD) is among the most disabling of all psychiatric disorders and is associated with poor outcomes. Some studies suggest that BDNF levels decrease during mood states and remain normal during euthymia, but other studies have contradicted this paradigm. Therefore, the aim of this study was to perform a meta-analysis of all studies that measured peripheral BDNF levels in adults with BD. We conducted a systematic review using electronic databases. Inclusion criteria were studies that measured BDNF in plasma or serum in vivo in adult patients with BD. The resulting studies were compiled to measure the effect sizes (ESs) of the differences in BDNF levels between BD patients in different mood states and controls. Thirteen studies were included with a total of 1113 subjects. The BDNF levels were decreased in both mania and depression when compared to controls (ES -0.81, 95% CI -1.11 to -0.52, p < 0.0001 and ES -0.97, 95% CI -1.79 to -0.51, p = 0.02, respectively). The BDNF levels were not different in euthymia when compared to controls (ES -0.20, 95% CI -0.61 to 0.21, p = 0.33). Meta-regression analyses in euthymia showed that age (p < 0.0001) and length of illness (p = 0.04) influenced the variation in ES. There was also an increase in BDNF levels following the treatment for acute mania (ES -0.63, 95% CI -1.11 to -0.15, p = 0.01). In conclusion, BDNF levels are consistently reduced during manic and depressive episodes and recover after treatment for acute mania. In euthymia, BDNF decreases with age and length of illness. These data suggest that peripheral BDNF could be used as a biomarker of mood states and disease progression for BD.
authors.affiliation: Bipolar Disorder Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. brisasf@gmail.com
authors.forename: Brisa Simões
authors.initials: BS
authors.lastname: Fernandes
authors.forename: Clarissa Severino
authors.initials: CS
authors.lastname: Gama
authors.forename: Keila Maria
authors.initials: KM
authors.lastname: Ceresér
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
authors.forename: Gabriel Rodrigo
authors.initials: GR
authors.lastname: Fries
authors.forename: Gabriela
authors.initials: G
authors.lastname: Colpo
authors.forename: David
authors.initials: D
authors.lastname: de Lucena
authors.forename: Mauricio
authors.initials: M
authors.lastname: Kunz
authors.forename: Fabiano Alves
authors.initials: FA
authors.lastname: Gomes
authors.forename: Flavio
authors.initials: F
authors.lastname: Kapczinski
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood* / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D016208:Databases, Factual / Q000706:statistics & numerical data; D006801:Humans; D012044:Regression Analysis
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor