Figure 2.

Pathophysiology of inflammation-induced depression linked to folate deficiency. The figure illustrates the cascade of events involved in inflammation-induced depression associated with folate deficiency. Inflammatory stimuli trigger the production of proinflammatory cytokines, which activate various enzymatic processes. One such process is the conversion of tryptophan to kynurenine catalyzed by indoleamine 2,3 dioxygenase (IDO). Cytokine signaling to the brain stimulates microglia activation, resulting in the production of inflammatory mediators. Simultaneously, kynurenine is transported into the brain where it is further metabolized into neurotoxic compounds, including quinolinic acid. Activated microglia also release glutamate, a key excitatory neurotransmitter. Both glutamate and quinolinic acid contribute to the enhancement of glutamatergic neurotransmission, ultimately leading to the development of depressive symptoms.