POMC and major depressive disorder: Prolonged exposure to unpredictable physical stress in mice can lead to dysregulation of the endocrine system, such as hyperactivation of the HPA axis, which increases the secretion of cortisol (CORT), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH) and which can trigger harmful systemic biological responses and depression (Aas et al., 2019).