Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis

Sophie Georgin-Lavialle (1, 2, 3) , Daniela Silva Moura (4, 2, 3) , Alexandre Salvador (5, 6) , Jean-Christophe Chauvet-Gélinier (7, 8) , Jean-Marie Launay (9) , Ghandi Damaj (10) , F. Côté (2) , Erinn Soucié (11) , Marie-Olivia Chandesris (3) , Stéphane Barète (2, 3) , Catherine Grandpeix-Guyodo (3) , Claude Bachmeyer (1) , Marie-Alexandra Alyanakian (12) , Achille Aouba (12) , Olivier Lortholary (13, 3) , Patrice Dubreuil (11, 3) , Jean-Raymond Teyssier (14) , Benoit Trojak (6, 7) , Emmanuel Haffen (15, 14, 16) , Pierre Vandel (17, 16) , Bernard Bonin (8, 7) , Olivier Hermine (2, 3, 12) , Raphaël Gaillard (18, 3, 5, 6) , Odile Beyne-Rauzy , Christian de Gennes , Isabelle Durieu , O Fain , Bernard Grosbois , Isabelle Guichard , Mohamed Hamidou , David Launay , Christian Lavigne , Christina Livideanu , Franck Nicolini , R Retornaz , Michel Arock , Jean-Benoit Arlet

1 CHU Tenon [AP-HP]
2 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
3 CEREMAST - Centre de référence des mastocytoses
4 LPPS - EA 4057 - Laboratoire de Psychopathologie et Processus de Santé
5 Physiopathologie des Maladies Psychiatriques, Développement et Vulnérabilité
6 CMME - Service de psychiatrie - Clinique des maladies mentales et de l'encéphale
7 Service de psychiatrie générale et addictologie [CHU de Dijon]
8 LPPM - Laboratoire de psychopathologie et psychologie médicale
9 Service de biochimie INSERM UMR-S942
10 Laboratoire d'Hématologie [CHU Amiens]
11 CRCM - Centre de Recherche en Cancérologie de Marseille
12 Service d'immuno-hématologie pédiatrique [CHU Necker]
13 Centre d'infectiologie Necker-Pasteur [CHU Necker]
14 Laboratoire de génétique moléculaire (hôpital général, CHU Dijon)
15 Département de psychiatrie [CHRU de Besançon]
16 NEURO - Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481)
17 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
18 Histopathologie humaine et Modèles animaux

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.

Mots clés: Acute stress; Aryl-hydrocarbon receptor; Central-nervous-system; Immune-system; Indoleamine 2?3-dioxygenase; Interferon-alpha; Mammalian brain; Quinolinic acid; Rat-brain

Domaines: Biochimie, Biologie Moléculaire; Neurosciences; Psychologie

Sophie Georgin-Lavialle, Daniela Silva Moura, Alexandre Salvador, Jean-Christophe Chauvet-Gélinier, Jean-Marie Launay, et al.. Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis. Molecular Psychiatry, 2016, 21 (11), pp.1511 - 1516. ⟨10.1038/mp.2015.216⟩. ⟨hal-01548862⟩