Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium

Alexandre A. Loch, Marcus V. Zanetti, Rafael T. de Sousa, Tiffany M. Chaim, Mauricio H. Serpa, Wagner F. Gattaz, Antonio L. Teixeira, Rodrigo Machado-Vieira

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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 6weeks 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)243-246
Number of pages4
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
StatePublished - Jan 2 2015
Externally publishedYes


  • Biomarkers
  • Bipolar disorder
  • Lithium
  • Neurotrophic
  • Treatment

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry


Dive into the research topics of 'Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium'. Together they form a unique fingerprint.

Cite this