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March 1988

Blunted β-Adrenergic Responsivity of Peripheral Blood Mononuclear Cells in Endogenous DepressionIsoproterenol Dose—Response Studies

Author Affiliations

From the Laboratory of Psychopharmacology, Department of Psychiatry, Cornell University Medical College, New York.

Arch Gen Psychiatry. 1988;45(3):241-244. doi:10.1001/archpsyc.1988.01800270053006

• Previous studies of peripheral blood mononuclear cells isolated from drug-free, hospitalized patients with endogenous major depression have demonstrated a diminished adenosine 3',5'-monophosphate (cyclic AMP) response to single concentrations of isoproterenol as compared with that obtained from normal control subjects. We now report results of isoproterenol dose-response studies that indicate lower basal levels of cyclic AMP as well as diminished cyclic AMP levels in response to isoproterenol stimulation at concentrations ranging from 10 -10 to 10 -5 mol/L in drug-free, hospitalized patients with endogenous depression. The major factor responsible for the diminished cyclic AMP production in the depressed patients was a loss of receptor sites capable of cyclic AMP production. Taken together with our previously reported finding that β-adrenergic antagonist binding was normal in peripheral blood mononuclear cells obtained from depressed patients, the results of the dose-response studies suggest a loss of receptor function (desensitization) rather than a diminished number of receptor binding sites (down-regulation) as the underlying mechanism. Potential explanations for β-adrenergic desensitization and its implications for the catecholamine hypothesis of depressive disorders are discussed.