Relation between lymphocyte beta-adrenergic responsivity and the severity of depressive disorders

Basal level and isoproterenol-induced response of cyclic adenosine monophosphate (cAMP) were determined in mononuclear leucocytes from 17 drug-free patients with major depressive (n = 9) or dysthymic disorders (n = 8) and 20 normal controls. No significant difference was observed between basal cAMP levels from depressed and control subjects. The cAMP production in response to maximal stimulation by isoproterenol (ISO), a beta-agonist, was significantly lower (-34.7%) in depressed patients than in controls, and was significantly negatively correlated to the severity of the depression as assessed by the Hamilton depression rating scale score (r = -0.62; p < 0.003). When the depressed group was subdivided on the basis of the DSM-III-R (APA 1987) diagnosis criteria into major depressive and dysthymic disorders, the ISO-stimulated cAMP levels in the two groups were indistinguishable. When evaluated at the same time than the density of beta-adrenoreceptors in eight depressed patients, the ISO-stimulated cAMP levels were highly significantly correlated with the Bmax values (r = 0.89; p < 0.003). The results indicate that the decrease in beta-adrenergic responsiveness of mononuclear leukocytes can be present in depressed patients whatever the nosographical subtype of the depressive disorder and is quantitatively related to the depression severity. Based on these data, it seems that the blunted beta-adrenergic sensitivity observed in mononuclear leukocytes (MNL) cells of depressed patients is closely associated with a loss of beta-adrenoceptors.