Effects of stress associated with academic examination on the kynurenine pathway profile in healthy students

PLoS One. 2021 Jun 3;16(6):e0252668. doi: 10.1371/journal.pone.0252668. eCollection 2021.

Abstract

The effects of stress on the neuroendocrine, central nervous and immune systems are extremely complex. The kynurenine pathway (KP) of the tryptophan metabolism is recognised as a cross-link between the neuroendocrine- and immune systems. However, the effects of acute stress from everyday life on KP activation have not yet been studied. This study aims to investigate changes in the levels of the KP neuroactive metabolites and cytokines in response to stress triggered by academic examinations. Ninety-two healthy first year medical students benevolently participated in the study. Parameters were measured pre- examination, which is considered to be a high-stress period, and post-examination, as a low-stress period. Stress induced by academic examinations significantly increases the perceived stress scores (p<0.001), serum cortisol levels (p<0.001) and brain-derived neurotrophic factor (BDNF) levels (p<0.01). It decreased IL-10 levels (p<0.05) but had no effect on IL-6 and TNF-alpha levels. Only the KP neuroactive metabolite, 3-hydroxykynurenine (3-HK) significantly increased (p<0.01) in the post-examination period. In addition, the stress scores positively correlated with the levels of cortisol (r2 = 0.297, p<0.01) at post examination. Acute stress triggered by academic examinations increases cortisol and BDNF production and suppresses the anti-inflammatory cytokine, IL-10, but did not increase significantly the levels of other pro-inflammatory cytokines, tryptophan, kynurenine and downstream KP metabolites. The concomitant increased levels of BDNF under the duress of acute examination stress appear to limit the levels pro-inflammatory markers, which may attenuate the action of cortisol and the neuroinflammatory branch of the KP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor / blood
  • Female
  • Healthy Volunteers
  • Humans
  • Hydrocortisone / blood
  • Interleukin-10 / blood
  • Kynurenine / analogs & derivatives
  • Kynurenine / blood
  • Kynurenine / metabolism*
  • Male
  • Stress, Psychological*
  • Students, Medical / psychology*
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor
  • Interleukin-10
  • 3-hydroxykynurenine
  • Kynurenine
  • BDNF protein, human
  • Hydrocortisone

Grants and funding

This study was funded by grants (RG266/10HTM) from the University of Malaya Research Grant Health and Translational Medicine Cluster to KM. GJG was supported by the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC) and Macquarie University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.