Plasma Nitrate Levels and Flow-Mediated Vasodilation in Untreated Major Depression

Objective: Findings from several studies have revealed that major depression is associated with an increased cardiovascular risk. The physiopathologic mechanisms of this association remain unclear, although recently, it has been hypothesized that a decreased production of nitric oxide could be a potential contributor to vascular dysfunction in depressive patients. The objective of this study was to evaluate nitric oxide production and vascular endothelial function in treatment-naive young healthy adults with a first episode of major depression. Methods: A case-control study in 50 treatment-naive young adults with a first episode of major depression and 50 healthy control subjects was conducted. Plasma levels of nitric oxide metabolites (nitrates/nitrites) were determined using a colorimetric assay based on Griess reaction. Endothelial function was assessed by flow-mediated vasodilation measurements after reactive hyperemia. Results: The mean age of the depressed patients was 22.6 (standard deviation [SD], 4.6) years, whereas the controls were 23.4 (SD, 4.8) years. Sixteen men (32%) and 34 women (68%) were included in each group. The plasma nitrite/nitrate concentrations were significantly lower in depressive subjects compared with healthy controls (17.5 [SD, 4.9] mu mol/L versus 21.6 [SD, 7.0] mu mol/L, p < .001); however, flow-mediated vasodilation values were similar in both groups (13.1% [SD, 4.3%] versus 12.1% [SD, 5.0%], p = .10). Conclusions: Decreased plasma concentrations of nitric oxide metabolites are not associated with vascular endothelial dysfunction in young subjects with a first episode of major depression. Reduced nitrate/nitrite levels could reflect a decreased nitric oxide production in the central nervous system of depressed subjects. Further studies are needed to confirm this hypothesis.