Title:Investigation of the Relationship among Cortisol, Pro-inflammatory
Cytokines, and the Degradation of Tryptophan into Kynurenine in
Patients with Major Depression and Suicidal Behavior
Volume: 22
Issue: 25
Author(s): Amel Messaoud, Mensi Rym, Douki Wahiba, Fadoua Neffati, Mohamed Fadhel Najjar, Gabriella Gobbi, Mirko Manchia, Flavia Valtorta, Gaha Lotfi*Stefano Comai*
Affiliation:
- Neuropsychopharmacology Unit, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy
- Neuropsychopharmacology Unit, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy
- Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
- Department of Biomedical Sciences, University of Padua, Padua, Italy
Keywords:
Suicide, Major depression, Inflammatory cytokines, Cortisol, Kynurenine/tryptophan ratio, Hypothalamicpituitary- adrenal (HPA) axis.
Abstract:
Background: The increased degradation of tryptophan (Trp) along the kynurenine (Kyn)
pathway due to inflammation and/or activation of the hypothalamic-pituitary–adrenal (HPA) axis
has been reported among the biological factors involved in the pathophysiology of major depressive
disorder (MDD) and suicide. However, the interaction among these multiple factors is not yet completely
clarified.
Methods: We studied plasma levels of Trp, Kyn, cortisol and proinflammatory cytokines (IL-1, IL-
6, IL-12, IL-20) and calculated the ratio Kyn/Trp as an index of the breakdown of Trp into Kyn in
31 suicidal MDD patients and 67 non-suicidal MDD patients.
Result: We confirmed that suicidal MDD patients have reduced plasma Trp, higher Kyn and
Kyn/Trp ratio, and no difference in cortisol levels than non-suicidal MDD patients. IL-1 and IL-12
levels were significantly higher in suicidal MDD than in non-suicidal MDD (p=0.034 and p=0.023,
respectively), whereas Il-6 and IL-20 levels were equal in the two groups. The Kyn/Trp ratio was
positively correlated with a pro-inflammatory cytokines index (r=0.309, p=0.002) and cortisol
(r=0.368, p=0.001). Notably, the variance in the Kyn/Trp ratio explained by the model including
both cortisol and inflammatory parameters as dependent variables, substantially improved compared
with the models in which the two parameters were considered separately.
Conclusion: These findings show that both cortisol and proinflammatory cytokines are involved in
the enhanced breakdown of Trp into Kyn occurring in suicidal MDD patients, thus adding new
knowledge on the biological mechanisms leading to the activation of the Kyn pathway in MDD and
suicide.
