Fig. 2: Stress-induced activation of the HPA axis stress response.

The hypothalamus secretes AVP and CRH, which travel via the hypophyseal portal system to stimulate secretion of ACTH from the anterior pituitary. ACTH enters circulation and stimulates the release of cortisol from the adrenal medulla, resulting in metabolic effects such as gluconeogenesis. Cortisol inhibits the hypothalamus and anterior pituitary from secreting CRH and ACTH, respectively, working as a negative feedback mechanism. In PTSD, this negative feedback mechanism is impaired, resulting in increased CRH and ACTH as well as inflammation. Figure was created with BioRender.com.