TDO2 and depressive disorder: In depression, elevated glucocorticoids activate TDO, increasing kynurenine levels and its downstream neurotoxic metabolite, quinolinic acid, which damages hippocampal neurons, overactivates NMDA receptors, and leads to hippocampal atrophy, a hallmark of AD (Allison and Ditor, 2014; Rubin, 1967; Wolkowitz et al., 2009).