Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action

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.

Automated summary

Neurotrophic factors, especially BDNF, are associated with depression and the action of antidepressant drugs, with impaired BDNF signaling linked to mood disorders. Increased BDNF expression and signaling have been linked to the mechanisms of antidepressant drugs, and BDNF regulates various types of neuronal plasticities in the brain, which are connected to antidepressant action. The hypothesis of a connection between neurotrophic factors and neuronal plasticity with mood disorders and antidepressant action has been further supported by recent evidence.