Corticotropin-releasing hormone (CRH) is released by the hypothalamus in response to stress, leading to activation of the HPA axis and the release of cortisol. Early life stress has been linked to chronically high levels of CRH in human and animal studies20 (BOX 2). Although the short-term actions of cortisol are protective and promote adaptation, sustained exposure to abnormally high levels of cortisol can be harmful, leading to hypertension, immunosuppression, cardiovascular disease and other health problems21. In the brain, excessive cortisol is associated with complex structural effects in the hippocampus and amygdala in humans and animals, including atrophic effects in certain types of neurons22,23. Thus, reduced CRH release and adaptive changes in CRH receptor activity might promote resilience.
