Akt (a target of PI3K) acts as a pivot position in the treatment of depression through connecting with downstream targets, including glycogen synthase kinase-3 beta (GSK3β), mammalian target of rapamycin, IκB kinaseα, γ-aminobutyric acid A receptor, and forkhead box O, which are involved in the regulation of glucose and lipid metabolism, synaptic plasticity, angiogenesis, proliferation and apoptosis, synaptic signaling, and mitochondrial function. Here, MTOR is linked to major depressive disorder.