The Expression of VGF is Reduced in Leukocytes of Depressed Patients and it is Restored by Effective Antidepressant Treatment

Background: Major Depression is a disease characterized by an inability of neuronal systems to exhibit appropriate adaptive plasticity especially under challenging conditions, such as stress. Conversely, pharmacological intervention may normalize such defects through the modulation of factors that might act in concert for the functional recovery of depressed patients, like the neuropeptide VGF since it has previously shown to have an antidepressant like effect. Methods: We analyzed VGF mRNA levels in the brain of rodents exposed to stress or treated with antidepressant drugs. In addition, we assessed VGF expression in leukocytes obtained from 25 drug free depressed patients prior to and during antidepressant treatment. Results: We found a persistent reduction of VGF expression after exposure to prenatal stress and an up-regulation of its levels following chronic treatment with different antidepressant drugs. Moreover, VGF mRNA levels were significantly reduced in drug free depressed patients, as compared to controls (PT0=0.67±0.71, C=1.24±0.77, F=9.02, p=0.004). In addition we found that antidepressant therapy increased VGF levels, even though only in in patients whose symptoms ameliorated during the course of treatment (PT12=1.76 ±1.12), but not in non responders (PT12=0.82±0.72, p=0.040 vs. treatment responders). Conclusions: Our data provide further support to the role of VGF in mood disorders and suggest that VGF could be a more specific biomarker for treatment responsiveness.