In summary, evidence reviewed herein support the importance of the new neurotrophic factor, NFα1/CPE, in ameliorating depression and neurodegeneration; hence future treatment strategies should explore stimulating NFα1/CPE expression, either by drugs or gene therapy, as well as finding agonists for the HTR1E, a receptor for NFα1/CPE. This evidence concerns the gene HTR1E and major depressive disorder.