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Objective: In a platelet/endothelial biomarker substudy of the Sertraline Anti-Depressant Heart Attack Randomized Trial (SADHART), the authors sought to determine whether plasma levels of sertraline and its primary metabolite N-desmethylsertraline affect the release of platelet/endothelial biomarkers. Method: Fifty-five acute coronary syndrome patients with depression were randomly assigned to receive sertraline (N = 23) or placebo (N = 32). Twenty-six serial plasma samples collected at week 6 (N = 12) and week 16 (N = 14) were analyzed. Platelet factor 4 (PF4), [beta]-thromboglobulin ([beta]-TG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane [B.sub.2] (Tx[B.sub.2]), prostacyclin (6-keto-PGF1[alpha]), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured by enzyme-linked immunosorbent assay. Concentrations of sertraline and N-desmethylsertraline were determined by liquid chromatography with fluorescence detection in autologous samples. Results: Strong, mostly time-dependent negative correlations were found for the plasma levels of sertraline and N-desmethylsertraline with PF4 (week 6:r=-0.69 and -0.33, respectively; week 16:r = -0.63 for both), [beta]-TG (week 6: r = -0.43 and -0.29; week 16: r = -0.66 and -0.57), PECAM-1 (week 6: r = -0.82 and -0.49; week 16: r = -0.60 for both), P-selectin (week 6: r = -0.82 and -0.49; week 16: r = -0.73 and -0.43), and Tx[B.sub.2] (week 6: r = -0.66 and -0.59; and week 16: r = -0.64 and -0.41). Regression analysis revealed some borderline correlations for endothelial markers such as 6-keto- PGF1[alpha] and E-selectin and a positive correlation for VCAM-1. Conclusions: This is the first documented evidence that plasma release of platelet/endothelial biomarkers is directly related to the levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. The clinical significance of these findings should be assessed in the setting of a randomized clinical trial.

Objective: The authors investigated the links between depression, cardiac disease, and microcirculatory cerebral blood flow (CBF). Method: A magnetic resonance imaging technique based on arterial spin tagging was used to estimate microcirculatory CBF in depressed (N=5) and comparison (N=14) elderly subjects with coronary artery disease. Signal intensity ratios corresponding to relative microcirculatory CBF were calculated for four regions on two axial images through the upper and lower halves of the lateral ventricles. Results: On the superior image, estimates of microcirculatory CBF were statistically significantly lower on the left side in the depressed subjects than in the nondepressed group. When the ratios in the superior and inferior images were averaged, the depressed subjects had lower values for both left periventricular regions of interest and the parietal region. Conclusions: Despite the small study group and indirect estimates of blood flow, these preliminary findings suggest that a relative cerebral hypoperfusion may underlie depression in elderly cardiac patients.

Objective: There is an impressive literature implicating abnormalities in serotonergic neural systems in depression. Many investigators, but not all, have reported low numbers of platelet and brain serotonin (5-HT) transporter sites in drug-free depressed patients. In the present study the authors sought to determine whether the low platelet 5-HT transporter binding in depressed patients is due to previous antidepressant drug exposure. In addition, the binding of both [3H]imipramine and the more specific ligand [3H]paroxetine to the platelet 5-HT transporter was compared in drug-free depressed patients and age- and sex-matched normal comparison subjects. Method: In the first experiment blood samples were obtained from 12 depressed patients who had never received antidepressant drugs and 12 normal comparison subjects, and platelet 5-HT transporter binding was measured by using [3H]imipramine. In the second experiment blood samples were obtained from 28 drug-free depressed patients and 28 age- and sex-matched comparison subjects, and platelet 5-HT transporter binding was assessed by using both [3H]imipramine and [3H]paroxetine. Results: In the first experiment the never-medicated depressed patients exhibited fewer platelet [3H]imipramine binding sites than did the comparison subjects. In the second experiment the drug-free depressed patients had fewer platelet binding sites for both [3H]imipramine and [3H]paroxetine than did the comparison subjects. Conclusions: The low number of platelet [3H]imipramine binding sites does not appear to be due to prior antidepressant drug exposure. The [B.sub.max] of platelet binding sites for both [3H]imipramine and [3H]paroxetine, ligands used to measure 5-HT transporter binding, is abnormally low in depressed patients.