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Cognitive function and serum levels of brain-derived neurotrophic factor in patients with bipolar disorder


  • VVD has served as a consultant for Angelini Pharmaceuticals. SB has served as a consultant for Janssen-Cilag Pharmaceuticals. BNF has received research support from the Canadian Institutes of Health Research, Stanley Research Center and Wyeth Pharmaceuticals, as well as speaker/advisory honoraria from Wyeth Pharmaceuticals and AstraZeneca. FK is a NARSAD independent investigator and is supported by the Stanley Research Center and CNPq. ACA and CC have no conflicts of interest to report.

Corresponding author:
Flávio Kapczinski, M.D., Ph.D.
Bipolar Disorder Program
and Molecular Psychiatry Unit
Hospital de Clínicas de Porto Alegre
Federal University
Av. Ramiro Barcelos 2350
90035-903, Porto Alegre RS, Brazil
Fax: +55 512 1018846


Objectives:  Brain-derived neurotrophic factor (BDNF) is an important contributor to the pathophysiology of bipolar disorder (BD), and abnormalities in the BDNF-signaling system may be implicated in the cognitive decline observed in BD patients. We aimed to investigate serum BDNF levels in BD patients and its relation to neurocognitive function.

Methods:  We measured serum BDNF levels using an enzyme-linked immunosorbent assay method in 65 euthymic type I BD patients and 50 healthy controls, and administered a neuropsychological test battery to assess attention and mental control, perceptual-motor skills, executive functions, verbal fluency and abstraction, visuospatial attention, and memory.

Results:  We found no significant differences regarding serum BDNF levels in BD patients and healthy controls. We found significant positive associations between serum BDNF levels and illness duration, and manic and depressive episodes in female BD patients only. Serum BDNF levels were lower in patients medicated with antipsychotics and/or lithium, whereas patients on valproate and/or antidepressants showed higher serum BDNF levels. Patients performed significantly worse on 11 out of 16 neurocognitive tests as compared to controls. We found a significant positive association between serum BDNF levels and a test of verbal fluency in both BD patients and controls.

Conclusions:  Present results support the hypothesis that BDNF normalizes with mood stabilization and pharmacological treatment. Our findings in young and physically healthy patients with short illness duration and few mood episodes may explain the lack of association between serum BDNF levels and neurocognitive performance, even though cognitive performance in patients was overall significantly worse as compared to healthy controls.