Neuroprotective roles of neurotrophic growth factors in mood disorders

Neurotrophic growth factors (neurotrophins), other growth factors, and their receptors and downstream signaling pathways have long been appreciated to play critical roles in the modulation of depressive behavior and the regulation of antidepressant efficacy. Mechanisms by which neurotrophin actions impact depression-like behavior and antidepressant responses in animal models include regulation in the CNS of neuroprotection, neurogenesis, synaptic plasticity and stability, and neuronal cytoarchitecture, including dendritic length and spine density, with correlative genetic association and big data studies in humans. Here, we review the role that neurotrophins in general and brain-derived neurotrophic factor (BDNF) in particular play in the modulation of mood disorders and antidepressant efficacy. We discuss the neurotrophin protein family and their receptors; review evidence that associates neurotrophin gene polymorphisms, transcript levels, and circulating protein levels with susceptibility or resilience to mood disorders; and finally focus on the specific mechanisms by which neurotrophins regulate depressive behavior and antidepressant actions.