On the other hand, glucocorticoids can activate TDO [90, 91], and there is a growing body of evidence suggesting that a hyperactive HPA axis often co-occurs with depression due to increased levels of glucocorticoid hormones, systemic inflammation and increased production of pro-inflammatory cytokines [90] all of which are released due to exercise-induced stress and increased intestinal permeability. Here, TDO2 is linked to depressive disorder.