Contrasting to the TrkB-mediated effects of mBDNF, the activation of sortilin and p75NTR, which is localized in dendritic spines and axon terminals by proBDNF, promotes cell death and attenuation of synaptic transmission through long-term depression (LTD), in addition to increasing anxiety and depression-like behaviors [28,29,30,31]. This evidence concerns the gene NTRK2 and major depressive disorder.