• 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.
Halper JP, Brown RP, Sweeney JA, Kocsis JH, Peters A, Mann JJ. Blunted β-Adrenergic Responsivity of Peripheral Blood Mononuclear Cells in Endogenous DepressionIsoproterenol Dose—Response Studies. Arch Gen Psychiatry. 1988;45(3):241-244. doi:10.1001/archpsyc.1988.01800270053006