Scientists believe that PTSD may occur because of complex occurrences in the brain. One section of the brain, the hypothalamus, releases the corticotropin-releasing factor (CRF), which triggers the pituitary gland to release adrenocorticotropic hormone. These processes stimulate the adrenal glands to release glucocorticoid (cortisol). Cortisol affects the pituitary gland as well as the hypothalamus and another region of the brain, the hippocampus.

CRF is responsible for mediating fear-based behaviors and triggers other neurochemical responses to stress, such as the noradrenergic system. When this system activates, it could produce the hyper alert and vigilant behaviors often seen in PTSD.