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Increased Coronary Events in Depressed Cardiovascular Patients: 5-HT_2A Receptor as Missing Link?

From the Department of Psychiatry, Academic Hospital Maastricht, Maastricht, The Netherlands.

Address reprint requests to: Dr. Adriaan Honig, Academic Hospital Maastricht, Department of Psychiatry, P. Debyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Email: adriaan.honig{at}spsy.azm.nl

OBJECTIVE: Major depressive disorder and depressive symptoms have been identified as independent risk factors for cardiac mobidity and mortality in patients with ischemic heart disease. Increased susceptibility to platelet activation has been proposed as one of the mechanisms by which depression acts as a significant risk factor for thrombotic events. In this review, data on platelet activation and platelet aggregation measures in depressed patients with or without concomitant cardiovascular disease are given. Data on the influence of antidepressants on parameters of platelet activation are summarized.

METHODS: A literature search was done by checking MEDLINE Advanced and PsycInfo from 1990 to 2003 and through checking the bibliographies of these sources. The following key words were used for this search: platelet activation, platelet aggregation, depression, depressive disorder, ischemic heart disease, calcium, and serotonin.

RESULTS: There is an indication of enhanced platelet activation and aggregation in depressed patients. Next, patients with a depressive disorder show signs of a hyperactive platelet 5-HT_2A receptor signal transduction system as measured by increased platelet calcium mobilization after stimulation of platelets with serotonin.

CONCLUSIONS: Depression appears to be associated with an increased susceptibility for serotonin-mediated platelet activation. Upregulation and/or increased sensitivity of 5-HT_2A/1B receptors and downregulated 5-HT transporter receptors in the periphery may contribute to increased risk of thromboembolic events in patients with depression and cardiovascular disease. Increased platelet reactivity based on a hyperreactive 5-HT_2A receptor signaling system might be influenced by antidepressive medication that antagonizes platelet 5-HT_2A receptors.

Key Words: platelet activation, • myocardial infarction, • 5-HT_2A receptor, • depression, • PF4, serotonin.

Abbreviations: post-MI = post myocardial infarction;; IHD = ischemic heart disease;; 5-HT = serotonin;; SSRI = selective serotonin reuptake inhibitor;; PF4 = platelet factor 4;; ßTG = ß-thromboglobulin;; ADP = adenosine diphosphate;; GPCR = G-protein-coupled receptor.

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