Taken together, both the recent work emphasizing the role of uncoupled eNOS-induced oxidative stress in the pathogenesis of vascular diseases [230,231] and the epidemiological studies establishing depression as an independent risk factor for vascular pathologies, such as stroke and heart disease [219,221], add further support to the clinical relevance of uncoupled eNOS-mediated endothelial oxidative damage in depression. The gene discussed is NOS3; the disease is major depressive disorder.