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Evidence for a Possible Alteration in Noradrenergic-Neuroendocrine Relationships

Larry J. Siever, MD; Thomas W. Uhde, MD; David C. Jimerson, MD; Robert M. Post, MD; C. Raymond Lake, MD; Dennis L. Murphy, MD

Arch Gen Psychiatry. 1984;41(1):63-68.

Abstract
• Plasma cortisol responses to the intravenous administration of clonidine hydrochloride and placebo were evaluated in depressed patients and controls. Depressed patients had higher mean baseline cortisol levels than controls. Cortisol levels decreased during the morning study period following both placebo and 2 µg/kg of clonidine hydrochloride in the depressed patients, but the cortisol decrease was sixfold greater on the day of clonidine administration; these placeboclonidine differences were statistically significant, whether calculated on an absolute decrement basis or as a percent change. In contrast, controls responded to clonidine with only a 1.5-fold greater cortisol reduction than that found after placebo, a nonsignificant difference from the day of placebo administration. Reductions in the concentration of plasma 3-methoxy-4-hydroxyphenylglycol following clonidine administration were significantly negatively correlated with baseline plasma cortisol levels, raising the possibility that abnormalities in the responsiveness of the ₂-norad renerg ic system may be associated with the hypothalamo-pituitary-adrenal (HPA) axis dysfunction found in depressed patients.

Author Affiliations
From the Clinical Neuropharmacology Branch (Drs Siever and Murphy), the Section on Psychobiology, Biologic Psychiatry Branch (Dr Uhde), the Laboratory of Clinical Science (Dr Jimerson), and the Biologic Psychiatry Branch (Dr Post), National Institute of Mental Health; and the Department of Psychiatry and Pharmacology (Dr Lake), University of the Health Sciences Medical School; Bethesda, Md. Dr Siever is now with the Bronx Veterans Administration Medical Center and the Mount Sinai Medical School, New York.

Footnotes
Accepted for publication May 10, 1983.

Reprint requests to Department of Psychiatry, Room 3B50, Bronx Veterans Administration Medical Center, 130 W Kingsbridge Rd, Bronx, NY 10468 (Dr Siever).

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