Neuroinflammation is thought to contribute to MDD pathogenesis through multiple mechanisms (Figure 1): compromising effects on the structural and functional integrity of the blood–brain barrier (BBB), dysregulation of mitogen‐activated protein kinases (MAPKs), and nuclear factor kappa‐B (NF‐κB) signaling pathways, inhibition of serotonin synthesis and dopamine release, disruption of HPA axis homeostasis, and alteration of microglial polarization states. This evidence concerns the gene NFKB1 and major depressive disorder.