In a VNS treatment study, O'Keane et al. [38] found that the CRF/ACTH (adrenocorticotropic hormone) responses in the depressed group before VNS implantation were significantly higher than in the healthy group and were reduced to normal values after 3 months of VNS treatment; in addition, they also found significant improvement in depression symptoms. This evidence concerns the gene POMC and major depressive disorder.