Pro-inflammatory cytokines can directly or indirectly stimulate the hypothalamic-pituitary-adrenal(HPA) axis and sympathetic nervous system(SNS) axis to overactivate indoleamine 2,3-dioxygenase(IDO), breaking down tryptophan into neurotoxic metabolites such as canine uric acid instead of 5-hydroxytryptamine(5-HT), leading to depression (19, 20). Here, IDO2 is linked to major depressive disorder.