Abstract
Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5-HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression.
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Acknowledgements
Sophie Georgin-Lavialle is a recipient of a grant from SNFMI-Genzyme-maladies rares and Centre National de la Recherche Scientifique (CNRS) and Assistance Publique Hôpitaux de Paris (AP-HP). Daniela S Moura is a recipient of a grant from the Cancéropôle Ile-de-France (Appel d’Offre SHS 2009). Jean-Christophe Chauvet-Gélinier is supported by a Program Hospitalier de Recherche Clinique Interrégional grant (PHRC-IR 2009), GIRCI Est, France.
Author contributions
DSM, RG, J-ML, OH, SG-L, AS: study concept and design. SG-L, DSM, J-ML, J-CC-G, OH, AS: acquisition of data, analysis and interpretation of data. SG-L, RG and AS: drafting of the manuscript. DSM, J-ML, J-CC-G, FC, GD, ES, RG, SB, CG-G, CB, M-AA, AA, OL, BT, EH, PV, J-RT, PD, BB, OH and SG-L: acquisition of data and edition of the manuscript.
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RG has received compensation as a member of the scientific advisory board of Janssen, Lundbeck, Roche, Takeda. He has served as consultant and/or speaker for Astra Zeneca, Pierre Fabre, Lilly, Otsuka, SANOFI, Servier and received compensation, and he has received research support from Servier. AS has consulted for Servier and received compensation. SGL has served as consultant and/or speaker for SOBI and Novartis and received financial help from SOBI and Bayer for travelling to congress. OH received research funding and honorarium from AB Science. The remaining authors declare no conflict of interest.
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French Mast Cell Study Group Odile Beyne-Rauzy, Christian de Gennes, Isabelle Durieu, Olivier Fain, Bernard Grosbois, Isabelle Guichard, Mohamed Hamidou, David Launay, Christian Lavigne, Christina Livideanu, Franck Nicolini, Frederique Retornaz, Michel Arock and Jean-Benoit Arlet.
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Georgin-Lavialle, S., Moura, D., Salvador, A. et al. Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis. Mol Psychiatry 21, 1511–1516 (2016). https://doi.org/10.1038/mp.2015.216
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DOI: https://doi.org/10.1038/mp.2015.216
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