TNF is involved in depression through several mechanisms, including activation of 5-hydroxytryptamine transporter proteins to mediate the depletion of the active fraction of 5-HT, disruption of the negative feedback loop of the HPA axis by stimulating the excessive release of corticotrophin-releasing hormone, contribution to increased nitric oxide (NO) redox signaling, and participation in hippocampal neurogenesis [48–50]. Here, TNF is linked to major depressive disorder.