The association of depression with platelet activation: evidence for a treatment effect

Background: Depression is associated with an increased risk of cardiovascular disease (CVD). Although the mechanism is uncertain, prothrombotic and inflammatory factors may play a role. Objectives: As platelets play a key role in CVD, we determined first, whether depressed individuals had more activated platelets than non-depressed individuals and second, whether treatment of depression reduced platelet activation levels. Patients/methods: We recruited 108 depressed outpatients and 45 control subjects all without a history of CVD. After psychological assessment, the depressed patients were offered treatment with medication and/or psychotherapy. Flow cytometric markers of platelet activation and level of depression were assessed at baseline and at 4 weeks and 6 months after treatment. Results: Depression was associated with increased platelet activation with a higher number of circulating CD62p (0.76 x 10(9) L-1 vs. 0.46, P = 0.019) and CD63 (P = 0.05) positive platelets compared with controls. Patients with depression also had more circulating platelet-leukocyte aggregates than controls (P < 0.001). There was a positive correlation between the severity of depression and the level of platelet activation. Platelets from depressed patients were also hyperreactive to adenosine 5-diphosphate (ADP) stimulation with increased CD62p and CD63 exposure (P = 0.003 and 0.019, respectively). Six months of treatment resulted in a reduced number of circulating CD62p and CD63 positive platelets (29.84% and 53.38% decrease) and a 20.9% reduction in CD63 exposure after ADP activation. Conclusions: Depression is associated with increased in vivo platelet activation and resolution of depression using psychotherapy and/or medication reduces platelet activation. These findings provide insights into the link between depression and cardiovascular risk.