Although there is some evidence to suggest that BDNF signaling might be compromised in depression (Castrén and Monteggia, 2021), this model does not suggest that antidepressants act simply by restoring reduced BDNF signaling, but it emphasizes the role of BDNF-mediated plasticity that allows reorganization of networks through coherent activity provided by external and internal environment (Castrén, 2005; Branchi and Giuliani, 2021; Figures 1B,C). Here, BDNF is linked to major depressive disorder.