In patients with major depression, serum tryptophan, serotonin, dopamine, norepinephrine, and brain derived neurotrophic factor (BDNF) levels are reduced, and SAMe supplementation along with physical exercises is reported to help replenish them, increase cerebrovascular perfusion, and afford relief at levels comparable to tricyclic antidepressants [98,99]. Here, BDNF is linked to major depressive disorder.