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Platelet Serotonin Signaling in Patients With Cardiovascular Disease and Comorbid Depression

Williams, Marlene S., MD; Ziegelstein, Roy C., MD; McCann, Una D., MD; Gould, Neda F., PhD; Ashvetiya, Tamara, MD; Vaidya, Dhananjay, PhD

doi: 10.1097/PSY.0000000000000689

Objective Depression in patients with cardiovascular disease is associated with increased risk of adverse clinical outcomes. Investigators have searched for potential biobehavioral explanations for this increased risk. Platelet activation and response to serotonin is an attractive potential mechanism. The aim of the study was to examine platelet serotonin signaling in a group of patients with coronary artery disease (CAD) and comorbid depression to define the relationship between platelet serotonin signaling and cardiovascular complications.

Methods A total of 300 patients with CAD were enrolled (145 with acute coronary syndrome and 155 with stable CAD). Depression was assessed using the Structured Clinical Interview for DSM-IV as well as Beck Depression Inventory II in a dichotomous and continuous manner. Platelet serotonin response was measured by serotonin augmented aggregation, direct platelet serotonin activation, platelet serotonin receptor density, and platelet serotonin uptake. Cardiovascular outcomes were assessed at 12-month follow-up.

Results One third of enrolled participants had at least minimal depressive symptoms and 13.6% had major depressive disorder. Depressed cardiovascular patients had significantly higher incidence of major (odds ratio = 3.43, 95% confidence interval = 1.49–7.91, p = .004) and minor (odds ratio = 2.42, 95% confidence interval = 1.41–4.13, p = .001) adverse cardiac events. Platelet serotonin response was not significantly different in patients with depression. Participants with major depressive disorder had higher serotonin receptor density (997.5 ± 840.8 vs 619.3 ± 744.3 fmol/ug, p = .009) primarily found in ACS patients. Depressed patients with minor adverse cardiac events had increased platelet response to serotonin.

Conclusions Depressed cardiovascular patients had higher serotonin receptor density and significantly higher incidence of major and minor cardiac adverse events. Future studies with larger sample sizes including patients with more severe depression are needed to expand on the present hypothesis-generating findings.

From the Johns Hopkins University School of Medicine, Baltimore, MD.

Supplemental Content

Address correspondence to Marlene S. Williams, MD, Division of Cardiology, Johns Hopkins Bayview Medical Center, 4940 Eastern Ave, 301 Bldg Suite 2400, Baltimore, MD 21224. E-mail:

Received for publication April 27, 2018; revision received January 17, 2019.

Copyright © 2019 by American Psychosomatic Society
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