Hormonal imbalances also may play a role in depression. A possible mechanism is a default in the hypothalamic-pituitary-adrenal (HPA) axisthe system that manages the body's response to stress. When a person perceives a frightening situation, the hypothalamus amplifies the production of substances such as corticotropin-releasing factor (CRF). These substances then stimulate the pituitary gland to release various hormones that prepare the body for a "fight or flight" response.
Chronic activation of the HPA axis may contribute to depression. Indeed, depressed patients often exhibit higher blood levels of stress hormones than those who are not depressed.
One theory suggests that abuse or neglect early in life may contribute to permanent changes in the brain that result in, for example, a persistent overproduction of CRF. Studies have shown that antidepressant drugs can lower CRF levels and improve symptoms, although it is unclear whether the beneficial effect is from lower levels of stress hormones.
Currently, researchers are developing therapies that directly target the HPA axis.