Formononetin can up-regulate the PI3K-Akt pathway by activating the downstream regulator of the phosphatase and tensin homolog (PTEN) to improve neuronal atrophy [63,64] and depressive behavior in the mouse model of depression by inhibiting the activity of PI3K-Akt-GSK-3β and the downstream Notch1 signaling pathway [65]. This evidence concerns the gene AKT1 and major depressive disorder.