Elevated p-selectin on platelets in depression: response to bupropion

increased platelet activation has been suggested as a possible reason for t he increased vulnerability of depressed patients to ischemic heart disease (IHD). Translocation of p-selectin, an integral alpha -granule membrane pro tein, to the platelet surface is a measure of platelet activation. Herein, western blots of platelet plasma membranes containing p-selectin were quant ified in patients with major depression (it = 19: mean age = 39 +/- 2 years ) and healthy comparison subjects (n = 17; mean age = 36 +/- 2 years). None evidenced clinical signs of IHD, and only two patients had a lifestyle IHD risk factor (smoking), Blood was obtained from all 19 depressed patients b efore treatment, and 15 returned after 6-8 weeks of open-label bupropion tr eatment. Bupropion was chosen as the antidepressant because it did not elev ate plasma norepinephrine or serotonin, endogenous agonists that can induce platelet degranulation. Western blotting revealed more p-selectin immunore activity (75 kD band) in depressed patients compared to healthy controls (P = 0.003). After bupropion treatment, p-selectin remained high in depressed patients. beta3-Integrin; a reference plasma membrane protein that does no t translocate during activation, was of equivalent density in depressed pat ients and healthy control subjects, and was unchanged after treatment with bupropion. p-Selectin failed to correlate with severity of illness based on the Hamilton Depression scale, or with the post-treatment plasma concentra tion of bupropion. The results suggest an elevation in p-selectin on platel et plasma membranes might be a trait marker for depression. (C) 2001 Elsevi er Science Ltd. All rights reserved.