Corticotropin-releasing factor, stress, and depression

Corticotropin-releasing factor (CRF), a 41 amino acid-containing neuropeptide, acts both as a hypothalamic releasing factor, controlling ACTH and corticosteroid secretion, and at extrahypothalamic CNS sites to modulate mammalian organisms' responses to stress. In this article, the evidence that CRF-containing neurons within the CNS are hyperactive in patients with depression is reviewed. The evidence, taken together, suggests that during depressive episodes, CRF is hypersecreted, resulting in both pituitary-adrenal axis hyperactivity and certain of the signs and symptoms of depression, including decreased appetite, decreased libido and disturbed sleep. There is also evidence that treatments for depression, including antidepressant medications and electroconvulsive therapy, reduce CRF hypersecretion within the CNS. Finally, evidence suggests that alterations in CRF-containing neurons and receptors are responsible for the widely held observation that early untoward life events increase an individual's vulnerability for affective disorders. These findings have a number of implications for treatment of the mood disorders, including the suggestion that the pharmacological manipulation of CRF receptors may provide a novel avenue for the treatment of depression.