TNF and major depressive disorder: Compared to healthy individuals or periodontitis patients without depression, those with both chronic periodontitis and depression exhibit significantly elevated levels of LPS in the root canal (34), which can trigger the production of various pro-inflammatory cytokines—such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).