title: Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium.
abstract: BACKGROUND
  Bipolar disorder (BD) has been associated with diverse abnormalities in neural plasticity and cellular resilience. Neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) support synaptic neuronal survival and differentiation. NT-3 and NT-4/5 levels were found to be altered in BD, potentially representing a physiological response against cellular stress. However, the use of psychopharmacological agents and heterogeneous mood states may constitute important biases in such studies. Thus, we aimed to assess NT-3 and NT-4/5 levels in medication-free BD type I or II individuals in a current depressive episode, before and after 6 weeks of lithium monotherapy and matched with healthy controls.
  
  
  METHODS
  Twenty-three patients with BD type I or II during a depressive episode and 28 healthy controls were studied. Patients were required to have a 21-item Hamilton Depression Rating Scale score ≥18 and had not undergone any psychopharmacological treatment for at least 6 weeks prior to study entry. Patients were treated with lithium for 6 weeks and plasma NT-3 and NT-4/5 levels were determined at baseline and endpoint using ELISA method.
  
  
  RESULTS
  Baseline plasma levels of both NT-3 and NT-4/5 were significantly increased in acutely depressed BD subjects in comparison to healthy controls (p=0.040 and 0.039, respectively). The NT-3 and NT-4/5 levels did not significantly change after lithium treatment. NT-3 and NT-4/5 levels were positively correlated to illness duration in BD (p=0.032 and 0.034, respectively).
  
  
  CONCLUSIONS
  Our findings suggest that NT-3 and NT-4/5 levels are increased in the depressive phase of BD, which seems directly associated with illness duration. The increased levels of NT-3 and NT-4/5 may underlie a biological response to cellular stress associated with the course of BD.
authors.affiliation: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Loch
authors.affiliation: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Zanetti
authors.affiliation: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors.forename: Rafael T
authors.initials: RT
authors.lastname: de Sousa
authors.affiliation: Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Chaim
authors.affiliation: Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
authors.forename: Mauricio H
authors.initials: MH
authors.lastname: Serpa
authors.affiliation: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil.
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.affiliation: Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA. Electronic address: machadovieirar@gmail.com.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D018021:Lithium Chloride / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D020933:Neurotrophin 3; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; C000595808:NTF3 protein, human; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; C071951:neurotrophin 5; D018021:Lithium Chloride; C073922:neurotrophin 4
keywords: Biomarkers; Bipolar disorder; Lithium; Neurotrophic; Treatment