Modified dexamethasone suppression-corticotropin-releasing hormone stimulation test: A pilot study of young healthy volunteers and implications for alcoholism research in adolescents and young adults.

The key neuroendocrine component of a response to stress is the hypothalamic-pituitary-adrenocortical (HPA) system. Abnormalities in the HPA system have been implicated in the pathophysiology of psychiatric disorders such as depression, post-traumatic stress disorder, alcoholism and suicide. The dexamethasone suppression test (DST) is the most frequently used test to assess HPA-system function in psychiatric disorders. This neuroendocrine test consists of the administration of a low dose of dexamethasone at 11 pm and the measurement of cortisol levels at one or more time points on the following day. After corticotropin-releasing hormone (CRH) became available for clinical studies, the DST was combined with CRH administration. In this test, patients are pretreated with a single dose of dexamethasone at 11 pm and receive human CRH intravenously at 3 pm the following day. The resulting DST-CRH test proved to be much more sensitive in detecting HPA system alterations than the DST. We have modified the DST-CRH test and used ovine CRH instead of human CRH in a pilot study of a group of young healthy volunteers. Results indicated that it produces results similar to the results obtained with human CRH. This suggests that ovine CRH can be used in psychiatric research. Alcoholism is associated with abnormalities in HPA function. Nonalcoholic subjects with a family history of alcoholism exhibit lower plasma ACTH and beta-endorphin as well as lower ACTH, cortisol, and beta-endorphin responses to psychological stress and CRH stimulation. This suggests that in children of alcoholics, alterations in the mechanisms that regulate HPA axis activity predate the development of alcohol dependence and may be considered inherited traits. Therefore, studies of the HPA system in persons at risk for alcoholism may help understand the neurobiological mechanisms of predisposition to alcoholism.