Marked Reduction in the Number of Platelet\p=m-\TritiatedImipramine Binding Sites in Geriatric Depression Charles B. Nemeroff, MD, PhD; David L. Knight; K. Ranga R. Krishnan, MD; Theodore A. Slotkin, PhD; Garth Bissette, PhD; Mary Lou Melville, MD; Dan G. Blazer, MD, PhD \s=b\The number (Bmax) and affinity (Kd) of platelet\p=m-\tritiated imipramine binding sites was determined in young and middle- aged controls 50 years of age and younger (n = 25), elderly normal controls over 60 years of age (n=18), patients who fulfilled DSM-III criteria for major depression who were under 50 years of age (n=29), patients who fulfilled DSM-III criteria for major depression who were 60 years of age and older (n=19), and patients who fulfilled both DSM-III criteria for primary degenerative dementia and National Institute of Neu- rological and Communicative Disorders and Stroke\p=m-\Alzhei- mer's Disease and Related Disorders Association criteria for probable Alzheimer's disease (n =13). Both groups of de- pressed patients (under 50 and over 60 years of age) exhibited significant reductions (\ar=d\42%) in the number of platelet\p=m-\ tritiated imipramine binding sites with no change in affinity, when compared with their age-matched controls. There was little overlap in Bmax values between the elderly depressed patients and their controls. The patients with probable Alz- heimer's disease showed no alteration in platelet\p=m-\tritiated imipramine binding. There was no statistically significant relationship between postdexamethasone plasma cortisol concentrations and tritiated imipramine binding. These results indicate that platelet\p=m-\tritiatedimipramine binding may have potential utility as a diagnostic adjunct in geriatric depression, and moreover that the reduction in the number of platelet\p=m-\ tritiated imipramine binding sites is not due to hypercortiso- lemia. (Arch Gen Psychiatry 1988;45:919-923) The search for biochemical correlates of psychiatric disorders has received considerable attention in the past 20 years and much of this work has focused on depressive disorders. Although neuroendocrine measures such as the dexamethasone suppression test (DST) have been intensively studied1·2 and have engendered consider¬ able controversy,3·4 some other putative biochemical in¬ dexes of affective disorder also have been studied. The involvement of disordered serotonergic neurotransmission in depressive disorder has been postulated by several workers, based largely on measurement of decreased concentrations of the serotonin metabolite 5-hydroxyin- doleacetic acid (5-HIAA) in cerebrospinal fluid in de¬ pressed patients,5 as well as the ability of many tricyclic antidepressants to block serotonin-reuptake into presyn- aptic terminals.6 Langer and colleagues7·8 have studied alterations in platelet-tritiated imipramine binding in patients with ma¬ jor depression. Because several experiments in laboratory animals have demonstrated that tritiated imipramine binds to presynaptic serotonergic nerve terminals in the central nervous system (CNS) with kinetic characteristics that are nearly identical to those found in platelets,9·10 it was interesting to examine the binding of tritiated imipramine to platelets of depressed patients. The tritiated imipramine binding site is closely linked to, but distinct from, the serotonin uptake site in platelets.11 The vast majority of investigators1216 have reported significant reductions in the number (Bmax) of tritiated imipramine binding sites on platelets of depressed patients, without any change in the affinity (Kj). A few discordant reports have also ap¬ peared.16·17 It is important to recognize the common embryological origins of platelets and their relation to neurons of the CNS. Platelets are formed in megakaryocytes that, like primordial CNS tissue, are derived from tissue embryolog- ically similar to (if not identical to) neural crest. Platelets, like brain tissue, are part of the amine-precursor-uptake- decarboxylation system described by Pearse.18 The purpose of the present study was first to determine Accepted for publication Dec 14, 1987. From the Departments of Psychiatry (Drs Nemeroff, Krishnan, Slotkin, Bissette, Melville, and Blazer and Mr Knight) and Pharmacology (Drs Nemeroff and Slotkin), Center for Aging and Human Development (Drs Nemeroff, Slotkin, and Blazer), Duke University Medical Center, Durham, NC. Reprint requests to Department of Psychiatry, Duke University Medical Center, Box 3859, Durham, NC 27710 (Dr Nemeroff). at University of Miami School of Medicine, on March 8, 2011 www.archgenpsychiatry.com Downloaded from