BDNF and major depressive disorder: BDNF can initiate multiple signaling pathways by activating distinct receptor types, primarily the TrkB and the p75 neurotrophic factor receptor (p75NTR) pathways, which can activate phosphatidylinositol 3-kinase (PI3K)-AKT and extracellular signal-regulated kinase (ERK) by binding to TrkB, etc (115), and chronic exposure to stress or inflammation leads to decreased BDNF levels (116), which can also be found in animal models of MDD.