Changes in kynurenine pathway metabolites after acute psychosocial stress in healthy males: a single-arm pilot study

Abstract

Chronic stress is associated with an increased conversion of tryptophan (TRP) into kynurenine (KYN). However, only a few studies investigated KYN pathway metabolite concentrations following acute stress in healthy subjects. We hypothesized that TRP/KYN metabolism changes following acute stress, and that KYN pathway metabolites are associated with cortisol and subjective stress responses. In a single-arm pilot study, we explored whether KYN pathway metabolites concentrations were altered after acute stress induced by the Maastricht Acute Stress Test in healthy males (n = 56, mean age: 27 (SD = 4.5) years, BMI: 23 (SD = 1.8) kg/m2). In particular, we examined whether concentrations of TRP decreased, and KYN, kynurenic acid (KYNA), and the ratio of KYN to TRP (KYN:TRP) increased after acute stress. Furthermore, we assessed whether cortisol and subjective stress responses correlated with KYN pathway metabolite measures after stress induction, based on both the area under the curve with respect to the ground (AUCg) as well as the incremental area under the curve (AUCi). Concentrations of TRP, KYN, KYNA, and KYN:TRP were significantly lower after stress induction compared to pre-stress induction (all p < 0.01). AUCi and AUCg reflecting cortisol and subjective stress responses did not correlate with AUCi and AUCg reflecting KYN pathway metabolite responses. These preliminary results indicate that KYN pathway metabolites are lower after acute psychosocial stress induction. Moreover, although chronic stress and subsequent prolonged elevated cortisol concentrations and subjective stress stimulate the conversion of TRP into KYN, acute stress is not associated with such conversion up to 35 minutes after stress induction.