Behavioral tests in the murine MRL/MpJ-Faslpr (MRL/lpr or LPR) model of neuropsychiatric lupus (NP-SLE) confirmed cognitive deficits and depression-like behavior, concomitant with increased levels of specific cytokines and altered brain metabolites of the indoleamine-2,3-dioxygenase (IDO) pathway, although these were not associated with decreased brain levels of tryptophan or serotonin. Here, IDO2 is linked to major depressive disorder.