Furthermore, the hippocampus is a key structure in the regulation of the hypothalamic-pituitary-adrenal axis observed in MDD [50], so that compromise of the hippocampus produces an alteration of neuroendocrine regulation which gives rise to high cortisol levels which can act as toxins in the body and these high levels of cortisol can also affect neuronal plasticity and survival through the modulation of a neuro- trophic factor, brain-derived neurotrophic factor (BDNF) [51] (Fig. 2. Here, BDNF is linked to major depressive disorder.