POMC and major depressive disorder: On the other hand, neuroendocrine disturbances along the hypothalamic-pituitary-adrenal axis (e.g., increased secretion of ACTH) also occur as sequelae of experienced stress due to helplessness, depression, social isolation, and can lead to cell death in hippocampus, amygdala, cerebellum and medial prefrontal cortex [17].