IARS1 and major depressive disorder: Moreover, products of the IRS and nitro-oxidative stress response during MDD/BD may activate indoleamine-2,3-dioxygenase (IDO), the rate limiting enzyme of the TRP catabolite (TRYCAT) pathway, which may cause increased TRYCATs production and lower TRP thereby diverting TRP from serotonin synthesis (Maes et al., 2011d) (Fig. 1).