Figure 4
From: The common inflammatory etiology of depression and cognitive impairment: a therapeutic target
Inflammatory mechanisms of depression. Proinflammatory cytokines may contribute to depressive symptoms by means of various mechanisms. (1) Proinflammatory cytokines act on serotonin transporter (SERT) proteins within the brain causing a re-uptake of serotonin (5-HT) and corresponding reduced extracellular concentrations. (2) Proinflammatory cytokines up-regulate enzymes such as indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulting in reduced tryptophan (TRP) availability, ultimately contributing to reduced 5-HT synthesis. (3) Both 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) may contribute to elevated levels of reactive oxygen species (ROS) and oxidative stress within the brain. (4) QUIN may induce N-methyl-D-aspartate (NMDA) over-activity thereby contributing to hippocampal atrophy and a loss of glucocorticoid receptors, ultimately leading to a loss of negative feedback and hypothalamic-pituitary-adrenal (HPA) axis over-activity.