THE ROLE OF CORTICOTROPIN-RELEASING FACTOR IN DEPRESSIVE-ILLNESS - A CRITICAL-REVIEW

Corticotropin-releasing factor (CRF) is the principal neuropeptide inv olved in regulating the stress response. When centrally administered t o animals it produces somatic changes analogous to those seen in both depression and anxiety. In humans, it is capable of reproducing the ho rmonal changes which are characteristically seen in depressed patients . A literature search using Medline, Embase Psychiatry, PsycLIT and BI DS from 1966-1997 revealed 25 studies that have examined CRF concentra tions in patients with affective disorder. The methodology of these st udies varies and they can be criticised, in particular, for failing to consider the stress response of the lumbar puncture. Recently, post-m ortem immunocytochemical techniques have been employed to help clarify the nature of these abnormalities in depression. On balance, evidence from CSF sampling, post-mortem findings and dynamic endocrine studies suggests that both hypothalamic and extra-hypothalamic concentrations of CRF are moderately elevated in a proportion of currently depressed patients. Which, if either, of these anatomical areas has more clinic al significance is unknown, although after effective antidepressant tr eatment, high CRF concentrations tend to normalise. The causes of incr eased CRF output in depression are also unknown but may involve an int egration of remote vulnerability factors and recent stressors perhaps mediated through impaired function of glucocorticoid receptors. Ultima tely, the careful manipulation of CRF may hold therapeutic promise for sufferers of mood disorders. (C) 1998 Elsevier Science Ltd. All right s reserved.