Since the formulation of the neurotrophin hypothesis of depression by Duman and Nestler in 1997, neuropathological studies consistently report decreased BDNF production in limbic–cortical circuits, with the hippocampus, prefrontal cortex, and amygdala showing particularly pronounced deficits in both human depression and experimental models (Li et al., 2023). This evidence concerns the gene BDNF and major depressive disorder.