Our discussion of the association between KP activation and depression will explore these consequences related to the limited biosynthesis of serotonin (5HT) and melatonin in MS (Fig. 1A) and the impact of KP inducing disease-modifying-drugs on both disease exacerbation and mood to demonstrate how these mechanisms work together to produce the neurological and neuropsychiatric MS symptoms in tandem. Here, NPPA is linked to major depressive disorder.