Abstract: As a major cause of disability, depression is expected to become the second highest burden of disease worldwide by
the year 2020. The shift of research in depression from monoamine hypothesis to the realm of neurotrophic hypothesis, neural
plasticity hypothesis, and enhancing neurogenesis as an antidepressant-like agent brings about crucial insights to find novel
mediator of antidepressant activity. Studies have shown that the neuropeptide VGF participates in the regulation of
hippocampal neurogenesis and neuroplasticity and also plays an important role in the regulation of neuronal proliferation and
survival, suggesting that the neuropeptide VGF may be a novel regulator in antidepressant treatment. The authors review the
latest progress in the regulatory mechanisms of neurpeptide VGF on neurogenesis, neurotrophic and synaptic activity in
depression. Further understanding of the role of neuropeptide VGF in depression can identify novel targets for
pharmacological interventions.