BDNF and major depressive disorder: This is especially fuelled by the significant number of treatment-resistant patients (only some of whom respond to combination therapy with extant treatments), as well as the recent surge in experimental and clinical studies demonstrating that, besides monoaminergic and hormonal alterations, reductions in trophic factors (particularly BDNF) together with fundamental disturbances in various elements of neuroplasticity might contribute to the development and evolution of depression.