Reduced peripheral availability of tryptophan and increased activation of the kynurenine pathway and cortisol correlate with major depression and suicide. (21st October 2019)

• Record Type: Journal Article
• Authors: Messaoud, Amel; Mensi, Rym; Douki, Wahiba; Neffati, Fadoua; Najjar, Mohamed Fadhel; Gobbi, Gabriella; Valtorta, Flavia; Gaha, Lotfi; Comai, Stefano
• Is Part Of: World journal of biological psychiatry. Volume 20:Number 9(2019)
• Page Start: 703
• Page End: 711
• Publication Date: 2019-10-21
• Subjects: Major depression -- suicide -- serotonin -- kynurenine -- tryptophan; Biological psychiatry -- Periodicals; Biological Psychiatry -- Periodicals; 616.89
• DOI: 10.1080/15622975.2018.1468031
• Languages: English
• ISSNs: 1562-2975

Abstract

Abstract: Objectives: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of tryptophan and indoleamino 2, 3-dioxygenase (TDO, IDO) enzymes has not been yet clarified in MDD with or without suicidal behaviours. Methods: We analysed peripheral markers of Trp via 5-HT and Kyn pathways, Kyn/Trp ratio as a measure of TDO/IDO activities, cortisol, and psychopathology in 73 non-suicidal and 56 suicidal MDD patients, and in 40 healthy controls. Results: Plasma Trp levels were lower and the ratio Kyn/Trp higher in suicidal MDD than in non-suicidal MDD patients and controls. Trp levels and the ratio Kyn/Trp correlated with suicidal ideation, and cortisol with the Kyn/Trp ratio. Finally, Trp levels discriminated controls from non-suicidal and suicidal MDD patients, and also non-suicidal from suicidal MDD patients. Conclusions: Reduced availability of Trp for 5-HT synthesis and increased activation of the Kyn pathway and cortisol correlate with depression and suicide. Low plasma Trp levels may be a biomarker of MDD and suicide in MDD.