Psychosocial stress and inflammation driving tryptophan breakdown in children and adolescents: A cross-sectional analysis of two cohorts

Psychoneuroendocrinology. 2018 Aug:94:104-111. doi: 10.1016/j.psyneuen.2018.05.013. Epub 2018 May 21.


Background: Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group.

Methods: Two cross-sectional population-based samples of children/adolescents (8-18 y) were available: 315 from the European HELENA study and 164 from the Belgian ChiBS study. In fasting serum samples, tryptophan, kynurenine, kynurenic acid, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-ɣ, soluble vascular adhesion molecule 1 (sVCAM1) and soluble intercellular adhesion molecule 1 (sICAM1) were measured. Psychological stress was measured by stress reports (subjective) and cortisol (objective - awakening salivary cortisol or hair cortisol). Linear regressions with stress or inflammation as predictor were adjusted for age, sex, body mass index, puberty, socio-economic status and country.

Results: In both cohorts, inflammation as measured by higher levels of CRP, sVCAM1 and sICAM1 was associated with kynurenine/tryptophan ratio and thus enhanced tryptophan breakdown (beta: 0.145-0.429). Psychological stress was only associated with tryptophan breakdown in the presence of higher inflammatory levels (TNF-α in both populations).

Conclusions: Inflammatory levels were replicable key in enhancing tryptophan breakdown along the kynurenine pathway, even at young age and in a non-clinical sample. The stress-inflammation interaction indicated that only the stress exposures inducing higher inflammatory levels (or in an already existing inflammatory status) were associated with more tryptophan breakdown. This data further contributes to our understanding of pathways to disease development, and may help identifying those more likely to develop stress or inflammation-related illnesses.

Keywords: Cytokines; Early aging; Indoleamine 2,3-dioxygenase; Moderation; Psychophysiology; Tryptophan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • C-Reactive Protein / analysis
  • Child
  • Cohort Studies
  • Cross-Sectional Studies / methods
  • Cytokines / blood
  • Depression / metabolism
  • Depressive Disorder / metabolism
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism
  • Interferon-gamma / blood
  • Interleukin-6 / blood
  • Kynurenic Acid / blood
  • Kynurenine / blood
  • Male
  • Stress, Psychological / metabolism*
  • Tryptophan / metabolism*
  • Tumor Necrosis Factor-alpha / blood


  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Kynurenine
  • Interferon-gamma
  • Tryptophan
  • C-Reactive Protein
  • Kynurenic Acid