Because of the documented effects of normal aging upon catecholamine levels and beta receptor function; because of the potential role of catecholamines and beta receptors in Major Depressive Disorders and the action of chronic somatic antidepressant treatment in downregulating beta receptors; and since the incidence of Major Depression increases with aging, studies of the relationship of central and peripheral beta receptor function to normal aging and depression are of considerable interest. Since it is not feasible to directly study central beta receptor function in man, we have developed convenient assays for measuring both beta receptor binding parameters and isoproterenol-induced cAMP production in intact human lymphocytes under similar assay conditions. We propose to study the relationship of 125I-cyanopindolol binding parameters and isoproterenol-induced cAMP production to: aging; sex; Major Depressive Disorder with melancholia; and the effect of antidepressant treatment. Since receptors on lymphocytes may be modulated by circulating hormones, plasma and 24 hour urinary catecholamine and cortisol levels (which are potentially altered by aging or depression) will be assayed. Patients will be studied during a drug-free baseline period for comparison with age and sex-matched control subjects. Measures will be repeated weekly throughout treatment by ECT or imipramine in two groups of inpatients to study the effects upon lymphocyte beta receptor function or recovery plus or minus chronic tricyclic treatment. Our preliminary data suggest: a state-dependent reduction in beta receptor sensitivity in lymphocytes in drug-free patients with melancholia: an age effect upon beta receptor-linked adenylate cyclase sensitivity but not 125I-CYP binding parameters; and a sex effect upon both binding and cAMP response. This study will test and extend these preliminary findings and test their applicability as a biochemical means of diagnosis of depression and monitering antidepressant treatment effect and predicting outcome in major depression with melancholia, as well as increase our understanding of normal aging effects upon beta receptors. In addition, the sensitivity of beta receptors to modulation by plasma humoral factors (catecholamines and crotisol) will be contrasted in: young and old controls; males and females; and in patients while depressed and euthymic.
