Abstract: There are different theories and hypotheses related to the etiology of depression. Among them, cytokine hypothesis, hypothalamic-pituitary-adrenal axis hypothesis, monoamine hypothesis and neuroplasticity hypothesis are much more widely accepted. These hypotheses may discuss depression from different points, but they are all related to indoleamine 2, 3-dioxygenase (IDO). IDO is a kind of enzyme which can convert tryptophan (TRP), the precursor of serotonin to kynurenine (KYN). It can be activated by some proinflammatory cytokines. Once activated, more TRP would be siphoned from the formation of serotonin to KYN, which may cause a reduction in serotonin production. IDO can also be activated by stress hormones through tryptophan 2, 3-dioxygenase (TDO) or immune system. In addition, some downstream metabolites of KYN, such as kynurenic acid (KYNA), quinolinic acid (QUIN) and 3-hydroxykynurenine (3HKYN), may contribute to neuroplasticity, as they are neurotoxic or neuroprotective. IDO, the mutual regulation factor among these theories, may play an important role in the onset of depression.

Key words: depression, IDO, cytokine, serotonin, neuroplasticity