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September 1976

Neuroendocrine Regulation in DepressionI. Limbic System-Adrenocortical Dysfunction

Author Affiliations

From the Department of Psychiatry (Drs Carroll and Curtis), University of Michigan, Ann Arbor, and the Department of Psychiatry (Dr Mendels), University of Pennsylvania and Veterans Administration Hospital, Philadelphia.

Arch Gen Psychiatry. 1976;33(9):1039-1044. doi:10.1001/archpsyc.1976.01770090029002

• The regulation of hypothalamopituitary-adrenal (HPA) function in depressed patients was studied by a midnight dexamethasone suppression test. By using an observation period of 24 hours postadministration of dexamethasone, a graded series of abnormal test responses was identified. Depressed patients show abnormal early escape from suppression rather than absolute resistance to HPA suppression by dexamethasone. With increasing severity of depression, this escape occurs progressively more early on the day after administration of dexamethasone. These abnormalities were strongly related to the presence of HPA hyperactivity before dexamethasone was given. The essential disturbance of neuroendocrine regulation in depression is a failure of the normal brain inhibitory influence on the HPA system. This disinhibition of HPA activity suggests that there is an abnormal limbic system drive on the HPA axis in primary depressive illness.