Reduced Sensitivity of Lymphocyte Beta-Adrenergic Receptors in Patients with Endogenous Depression and Psychomotor Agitation

Abstract

It has been suggested that there are altered levels of norepinephrine or other neurotransmitters at functionally important receptors in patients with depressive disorders. This hypothesis is difficult to study in the human central nervous system. However, noradrenergic function can be assessed indirectly with peripheral-blood lymphocytes used as a model of the beta-adrenergic receptor complex. We found that drug-free inpatients with endogenous depression had lower isoproterenol-stimulated cyclic AMP levels in intact lymphocytes than did healthy control subjects (3.9±0.5 vs. 7.4±1.0 pmol per 10⁶ cells, P6 cells; binding affinity, 106±7.6 vs. 99.2±11.4 pM, respectively). When the depressed patients were subdivided by psychomotor manifestations, binding characteristics were indistinguishable among the subgroups. However, a significant reduction in beta-adrenergic responsiveness was observed in patients with psychomotor agitation, as compared with controls (2.6±0.5 vs. 7.4±1.0 pmol per 10⁶ cells, P6 cells, P<0.05). Thus, the desensitization of beta-adrenergic receptors was correlated more closely with the severity of psychomotor agitation than with the overall severity of depression. (N Engl J Med 1985; 313: 715–20.)