Research appearing in the journal Psychosomatic Medicine (2005;67 (Supplement 1): S26-S28) helps to make the connection between the HPA (hypothalamus, pituitary, adrenal) axis and severe depression. The researchers tested the HPA axis by giving the subjects dexamethasone (a synthetic glucocorticoid) and measuring plasma cortisol levels at different times on the following day. Dexamethasone works to reduce the release of cortisol by the adrenal glands. Dexamethasone accomplishes this by suppressing ACTH (adrenocorticotrophic hormone) in the pituitary. If the suppression of cortisol does not occur with dexamethasone, the assumption is that the HPA axis is hyperactive.
Corticotropin releasing factor acts to increase ACTH secretion. In the corticotropin releasing factor stimulation test corticotropin releasing factor is given as an IV and ACTH and cortisol levels are measured every half-hour for two to three hours. In a normal, healthy individual, the test will increase ACTH production. Depressed individuals tend to have a lower ACTH level, but the cortisol level does not decrease. Depressed individuals tend to have high levels of corticotropin releasing factor, possibly as a response to stress. When clinical symptoms are resolved, HPA issues like adrenal hypertrophy and hypersecretion of corticotropin releasing factor also resolve.