Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action

Biol Psychiatry. 2021 Jul 15;90(2):128-136. doi: 10.1016/j.biopsych.2021.05.008. Epub 2021 May 14.


Neurotrophic factors, particularly BDNF (brain-derived neurotrophic factor), have been associated with depression and antidepressant drug action. A variety of preclinical and clinical studies have implicated impaired BDNF signaling through its receptor TrkB (neurotrophic receptor tyrosine kinase 2) in the pathophysiology of mood disorders, but many of the initial findings have not been fully supported by more recent meta-analyses, and more both basic and clinical research is needed. In contrast, increased expression and signaling of BDNF has been repeatedly implicated in the mechanisms of both typical and rapid-acting antidepressant drugs, and recent findings have started to elucidate the mechanisms through which antidepressants regulate BDNF signaling. BDNF is a critical regulator of various types of neuronal plasticities in the brain, and plasticity has increasingly been connected with antidepressant action. Although some equivocal data exist, the hypothesis of a connection between neurotrophic factors and neuronal plasticity with mood disorders and antidepressant action has recently been further strengthened by converging evidence from a variety of more recent data reviewed here.

Keywords: Antidepressants; BDNF; Ketamine; Mood disorders; Neurotrophins; TrkB.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Brain-Derived Neurotrophic Factor*
  • Depression* / drug therapy
  • Humans
  • Mood Disorders / drug therapy
  • Receptor, trkB / metabolism
  • Signal Transduction


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Receptor, trkB