Amel Messaoud1,2,3, Rym Mensi2,3, Wahiba Douki2,3, Fadoua Neffati3, Mohamed Fadhel Najjar3, Gabriella Gobbi4, Flavia Valtorta1, Lotfi Gaha2, Stefano Comai1,4. 1. Neuropsychopharmacology Unit, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. 2. Department of Psychiatry, Monastir University Hospital, University of Monastir, Monastir, Tunisia. 3. Biochemistry Department, CHU Fattouma Bourguiba, Monastir, Tunisia. 4. Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada.
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.
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 MDDpatients, and in 40 healthy controls. Results: Plasma Trp levels were lower and the ratio Kyn/Trp higher in suicidal MDD than in non-suicidal MDDpatients 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 MDDpatients, and also non-suicidal from suicidal MDDpatients.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.
Entities:
Keywords:
Major depression; kynurenine; serotonin; suicide; tryptophan
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