The findings presented here show that the decrease in NRG1 correlates with an increase in Nedd4l in the mPFC, and promotes synaptic impairments and stress susceptibility in individuals subjected to CSDS, which, when correlated with the severity of MDD symptom, may provide the theoretical grounds for the development of treatment strategies for stress-related neuropsychologic disorders, including PTSD, anxiety and depressive disorders. Here, NEDD4L is linked to major depressive disorder.