Neurotrophins in depression and antidepressant effects.

Neurotrophins are important regulators of neuronal plasticity in the developing and adult brain. In particular, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are implicated in these functions. The synthesis and release of BDNF is regulated by neuronal activity, and synaptic reorganization mediated by BDNF is thought to be a critical process which shapes neuronal networks to code optimally for environmentally relevant information. Recent evidence links neuronal plasticity and neurotrophin signalling in mood disorders. A polymorphism in the BDNF gene has been associated with depression and bipolar disorder. BDNF levels are reduced in postmortem brain samples and in the blood of depressed patients, and these reductions are reversible by successful antidepressant treatment. Furthermore, BDNF signalling plays a critical role in the mechanism of antidepressant drug action; at least in rodents, BDNF signalling appears to be both necessary and sufficient for the behavioural effects produced by antidepressant drugs. These data suggest that neurotrophin-mediated neuronal plasticity is a critical factor in mood disorders and in their therapy. Antidepressant treatments may, through enhanced BDNF signalling, improve the ability of critical brain circuits to respond optimally to environmental demands, a process that may be critical in the recovery from depression.