title: Executive dysfunction in euthymic bipolar disorder patients and its association with plasma biomarkers.
abstract: BACKGROUND
  Despite the old Kraepelinean concept that bipolar disorder (BD) does not evolve with cognitive decline, the presence of cognitive impairment, especially executive dysfunction has been recognized in BD patients. Brain-derived neurotrophic factor (BDNF) and pro-inflammatory molecules are important contributors to the pathophysiology of BD, and imbalance in peripheral levels of these molecules may be implicated in the cognitive decline observed in BD patients. We aimed to investigate the executive performance of BD type I euthymic patients and its relation with the plasma levels of BDNF, TNF-α and its related soluble receptors (sTNFR1 and sTNFR2).
  
  
  METHODS
  We evaluated executive functioning through the Frontal Assessment Battery (FAB). Plasma levels of BDNF, TNF-α, sTNFR1 and sTNFR2 were measured using enzyme-linked immunosorbent assay (ELISA) in 25 euthymic type I BD patients and 25 age and gender matched healthy controls.
  
  
  RESULTS
  BD patients had an impairment in executive functioning (p<0.006), particularly sensitivity of interference (p=0.02), inhibitory control (p=0.02), and increased BDNF plasma levels (p=0.001) in comparison with controls. Plasma levels of TNF-α were correlated with inhibitory control in BD patients (ρ=0.50, p=0.02) while motor programming was negatively correlated with sTNFR2 plasma levels (ρ=-0.47, p=0.02) in controls. Executive function correlated with age and MMSE, but not with BDNF, neither was influenced by psychiatric and clinical comorbidities nor medications in use.
  
  
  CONCLUSIONS
  BDNF is altered in BD but do not correlate with executive functioning.
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. izabela.barbosa@kcl.ac.uk
authors.forename: Izabela Guimarães
authors.initials: IG
authors.lastname: Barbosa
authors.forename: Natalia Pessoa
authors.initials: NP
authors.lastname: Rocha
authors.forename: Rodrigo Barreto
authors.initials: RB
authors.lastname: Huguet
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Ferreira
authors.forename: João Vinícius
authors.initials: JV
authors.lastname: Salgado
authors.forename: Livia A
authors.initials: LA
authors.lastname: Carvalho
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000523:psychology*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D056344:Executive Function; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha