How acute physical and psychological stress differentially influence the kynurenine pathway: A randomized cross-over trial.

Psychological stress is associated with the pathogenesis of several neuropsychiatric disorders. In contrast, physical stress, as provoked by exercise, counteracts symptoms and potentially also disease progression. The kynurenine pathway, which is imbalanced in neuropsychiatric disorders, responds to both psychological and physical stress. Here, we compared the acute effects of psychological versus physical stress on the kynurenine pathway and inflammatory mediators. Thirty-five healthy males (mean age: 24.09±3.39 years) underwent both the Trier Social Stress Test (psychological stressor) and the Wingate-Test (physical stressor). The kinetics of tryptophan and its metabolites as well as cytokines IL-6, IFN-γ, TNF-α, and IL-10 were measured before and after the two stress conditions. After both stressors, there was a significant change over time for the kinetics of tryptophan metabolites and for cytokines. Furthermore, the reactivity of kynurenine pathway metabolite ratios and cytokines was statistically greater after physical stress than after psychological stress. The increased metabolic flux towards kynurenic acid following acute physical stress suggests an exercise-induced neuroprotective mechanism. Despite the paradoxical influence of both stressors on neuropsychiatric diseases, the acute kynurenine pathway reactivity appears to be similar, although effects were more pronounced in response to physical stress.

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