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

J. J. Mann, R. P. Brown, J. P. Halper, J. A. Sweeney, J. H. Kocsis, P. E. Stokes, J. P. Bilezikian

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124 Scopus citations


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, P<0.01). The density and affinity of beta-adrenergic receptors were similar in controls and depressed subjects (beta-receptor number, 5.4±0.7 and 5.3±0.8 fmol per 106 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, P<0.01), but not in patients with psychomotor retardation (5.8±1.1 pmol per 106 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). THE classic“amine hypothesis” suggests that at least a subgroup of depressive disorders is associated with a deficiency of norepinephrine or serotonin or both at functionally important synapses and that antidepressant agents elevate intrasynaptic concentrations of either or both of these transmitters.1 Recent studies indicate that depressive disorders may indeed be biochemically heterogeneous and include at least three different subgroups: (1) a hyperadrenergic hypercortisolemic depressive disorder characterized by increased urinary levels of cortisol and 3-methoxy-4-hydroxyphenylglycol (MHPG, an end product of norepinephrine catabolism),2 3 4 increased plasma levels of norepinephrine, cortisol, and possibly epinephrine,5 6 7 8 and elevated cerebrospinal fluid levels of norepinephrine and MHPG.

Original languageEnglish (US)
Pages (from-to)715-720
Number of pages6
JournalNew England Journal of Medicine
Issue number12
StatePublished - Sep 19 1985

ASJC Scopus subject areas

  • Medicine(all)


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