Studies on leukocyte β-adrenergic receptors in depression: A critical appraisal

Alterations in beta-adrenergic receptors (BAR) of human mononuclear leukocytes (MNL) are considered to reflect changes in central noradrenergic function and have been studied in a number of diseases. This paper critically reviews the results of recent studies on MNL-BAR in depression, with particular emphasis on the biochemical and clinical methodologies used. Despite considerable differences in these methods, a number of laboratories report consistent decreases in MNL-BAR density and significantly reduced functional response in patients as compared to controls. These studies used MNL, isolated from patients who had a greater than 14 day drug washout, and BAR-densities were measured in membrane preparations, using full Scatchard analyses, and 125I-ICYP or 3H-DHA as the ligand. Functional response of MNL-BARs was assessed by the determination of isoproterenol-stimulated cyclic AMP accumulation. A comparison of methods used by these groups further indicates that additional biochemical parameters such as lymphocyte preparation and standardized experimental conditions for the binding assays are also important for obtaining consistent results. The clinical methods in rigorous study designs also include clearly stated inclusion/exclusion criteria for patients, and age-, and gender-matched patient-control populations. Whether the reduced MNL-BAR density and function is an inherited abnormality in depressed patients, or results from downregulation by elevated catecholamines is at present not known. Studies are needed to characterize further the changes in MNL-BARs in depression and to evaluate the effects of caetcholamines and hormones on this system. Based on critical assessment of the methods reviewed we propose specific biochemical and clinical guidelines, and recommend, that these be followed in future studies on MNL-BARs in this disease.