TDO2 and major depressive disorder: Since KYN can cross the blood brain barrier (Fukui et al., 1991) elevated plasma levels of KYN may also influence brain concentrations and indeed blocking the peripheral production of KYN, via inhibition of liver tryptophan-2,3-dioxygenase, produces anti-depressant effects in a repeated restraint stress model of depression (Gibney et al., 2014).