For example, positive ELS/CT history has been repeatedly associated with HPA axis hyperactivity in adults patients with depression and anxiety, but also in healthy individuals [e.g., higher circulating cortisol levels, enhanced cortisol awakening response (CAR), increased adrenocorticotropic hormone (ACTH) and cortisol responses to psychosocial stress or endocrine challenges] (67–75). Here, POMC is linked to major depressive disorder.