FIGURE 5.1 • The HPA Axis Stress activates the hypothalamus, which releases corticotropin-releasing factor (CRF), which in turn stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH), which then leads the adrenal glands to release cortisol. According to the stress–diathesis model of depression, people who become depressed have high levels of cortisol, which leads to heightened reactivity to stress and increased serotonin levels.