Neurotrophic factors and antidepressant action: Recent advances

It is now commonly accepted that neuronal plasticity plays a central role in depression and antidepressant drug action. Accumulating evidence from studies in both humans and animals suggests that depression is associated with alterations in the cellular architecture of specific brain regions that are important for the regulation of mood. Moreover, many of these changes are attenuated or reversed by chronic antidepressant treatment. Since neurotrophic factors regulate many features of neuronal plasticity including the proliferation and structure of neurons, there is a rapidly growing interest in determining whether growth factor signalling might contribute to the pathophysiology and treatment of depression. Several families of neurotrophic factors are found in the adult brain including the neurotrophins, fibroblast growth factors, insulin-like growth factors, transforming growth factors, neuropoietic cytokines as well as various other growth factors such as vascular endothelial growth factor. Of all the neurotrophic factors, brain-derived neurotrophic factor (BDNF) has been the most intensively investigated in the depression and antidepressant research field, and there is convincing supporting evidence of a role for BDNF in the pathophysiology and treatment of depression. Additional evidence suggests that other neurotrophic factors, such as fibroblast growth factor, vascular endothelial growth factor and insulin-like growth factor 1, might also contribute to the mechanism of antidepressant drug action, although more exhaustive investigations are required. The present chapter reviews both human and animal studies investigating the roles of neurotrophic factors in the pathophysiology and treatment of depression.