Concurrently, the lifestyle or behaviors of patients with depression may excessively activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to immune system dysregulation, stimulating the production of ROS as well as pro-inflammatory cytokines (such as IL-1β, TNF-α), which can cause endothelial dysfunction and induce the formation of atherosclerotic plaques [50,51]. This evidence concerns the gene TNF and major depressive disorder.