title: Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis.
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.
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.|INSERM U1163 and CNRS ERL 8254 and Laboratory of Physiopathology and Treatment of Hematological Disorders, Hôpital Necker-Enfants malades, Paris, France.|Service de médecine Interne, Hôpital Tenon, Université Pierre et Marie Curie, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Georgin-Lavialle
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.|INSERM U1163 and CNRS ERL 8254 and Laboratory of Physiopathology and Treatment of Hematological Disorders, Hôpital Necker-Enfants malades, Paris, France.|Laboratoire de Psychopathologie et Processus de Santé, EA 4057, IUPDP, Institut de Psychologie, Université Paris Descartes, Paris, France.
authors.forename: D S
authors.initials: DS
authors.lastname: Moura
authors.affiliation: Laboratoire de "Physiopathologie des maladies Psychiatriques", Centre de Psychiatrie et Neurosciences U894, INSERM, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Service de Psychiatrie, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Salvador
authors.affiliation: Service de Psychiatrie, Département de Neurosciences, Dijon, France.|Laboratoire de Psychologie et Psychopathologie Médicale (IFR 100), Université de Bourgogne, Dijon, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Chauvet-Gelinier
authors.affiliation: Laboratoire de biochimie et biologie moléculaire, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: J-M
authors.initials: JM
authors.lastname: Launay
authors.affiliation: Service des Maladies du Sang, Centre Hospitalier Universitaire, Hôpital Sud, Amiens, France.
authors.forename: G
authors.initials: G
authors.lastname: Damaj
authors.affiliation: INSERM U1163 and CNRS ERL 8254 and Laboratory of Physiopathology and Treatment of Hematological Disorders, Hôpital Necker-Enfants malades, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Côté
authors.affiliation: INSERM UMR 891, Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Hématopoïèse Moléculaire et Fonctionnelle, Marseille, France.
authors.forename: E
authors.initials: E
authors.lastname: Soucié
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.
authors.forename: M-O
authors.initials: MO
authors.lastname: Chandesris
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.|INSERM U1163 and CNRS ERL 8254 and Laboratory of Physiopathology and Treatment of Hematological Disorders, Hôpital Necker-Enfants malades, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Barète
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Grandpeix-Guyodo
authors.affiliation: Service de médecine Interne, Hôpital Tenon, Université Pierre et Marie Curie, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Bachmeyer
authors.affiliation: Laboratoire d'immunologie, Hôpital Necker, Paris, France.
authors.forename: M-A
authors.initials: MA
authors.lastname: Alyanakian
authors.affiliation: Service d'Hématologie Adulte, Université Paris Descartes, Sorbonne, Paris Cité, Assistance Publique-Hôpitaux de Paris, Institut Imagine, Hôpital Necker-Enfants malades, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Aouba
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.|Service des infectieuses et tropicales, Université Paris Descartes, Sorbonne, Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants malades, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.|INSERM UMR 891, Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Hématopoïèse Moléculaire et Fonctionnelle, Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Dubreuil
authors.affiliation: Laboratoire de génétique, CHU, PTB, 2 rue Angélique Ducoudray, Dijon, France.
authors.forename: J-R
authors.initials: JR
authors.lastname: Teyssier
authors.affiliation: Service de Psychiatrie, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, Paris, France.|Service de Psychiatrie, Département de Neurosciences, Dijon, France.
authors.forename: B
authors.initials: B
authors.lastname: Trojak
authors.affiliation: Laboratoire de génétique, CHU, PTB, 2 rue Angélique Ducoudray, Dijon, France.|Service de Psychiatrie, CHU de Besançon, Besançon, France.|Laboratoire de Neurosciences EA 481, IFR 133, Université of Franche-Comté, Besançon, France.
authors.forename: E
authors.initials: E
authors.lastname: Haffen
authors.affiliation: Laboratoire de Neurosciences EA 481, IFR 133, Université of Franche-Comté, Besançon, France.|Centre d'Investigation Clinique CIC-IT 808 INSERM, CHU de Besaçon, Besançon, France.
authors.forename: P
authors.initials: P
authors.lastname: Vandel
authors.affiliation: Service de Psychiatrie, Département de Neurosciences, Dijon, France.|Laboratoire de Psychologie et Psychopathologie Médicale (IFR 100), Université de Bourgogne, Dijon, France.
authors.forename: B
authors.initials: B
authors.lastname: Bonin
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.|INSERM U1163 and CNRS ERL 8254 and Laboratory of Physiopathology and Treatment of Hematological Disorders, Hôpital Necker-Enfants malades, Paris, France.|Service d'Hématologie Adulte, Université Paris Descartes, Sorbonne, Paris Cité, Assistance Publique-Hôpitaux de Paris, Institut Imagine, Hôpital Necker-Enfants malades, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Centre de référence des mastocytoses, Université Paris Descartes, Sorbonne, Paris Cité, Hôpital Necker Enfants malades, Fondation Imagine, Paris, France.|Laboratoire de "Physiopathologie des maladies Psychiatriques", Centre de Psychiatrie et Neurosciences U894, INSERM, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Service de Psychiatrie, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, Paris, France.|Human Histopathology and Animal Models, Infection and Epidemiology Department, Institut Pasteur, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Gaillard
mesh_terms: D003863:Depression / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000378:metabolism; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007249:Inflammation / Q000378:metabolism; D007736:Kynurenic Acid; D007737:Kynurenine; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology; D008415:Mastocytosis / Q000378:metabolism; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012701:Serotonin; D013315:Stress, Psychological; D014364:Tryptophan / Q000378:metabolism* / Q000502:physiology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012701:Serotonin; D007737:Kynurenine; D014364:Tryptophan; D007736:Kynurenic Acid
references.citation: Brain Behav Immun. 2009 Feb;23(2):149-58
references.pmid: 18793712
references.citation: Mol Psychiatry. 2014 Jun;19(6):699-709
references.pmid: 24342992
references.citation: J Clin Psychiatry. 2005 Jan;66(1):41-8
references.pmid: 15669887
references.citation: Immunol Allergy Clin North Am. 2014 May;34(2):207-18
references.pmid: 24745670
references.citation: J Health Soc Behav. 1983 Dec;24(4):385-96
references.pmid: 6668417
references.citation: Pharmacol Ther. 2011 May;130(2):226-38
references.pmid: 21334376
references.citation: Brain Behav Immun. 1998 Jun;12(2):123-33
references.pmid: 9646937
references.citation: Clin Chim Acta. 1993 Nov 30;221(1-2):143-58
references.pmid: 7512001
references.citation: Encephale. 2014 Feb;40(1):15-23
references.pmid: 24434008
references.citation: J Neuroimmunol. 2004 Jan;146(1-2):1-12
references.pmid: 14698841
references.citation: Nat Rev Neurosci. 2014 May;15(5):300-12
references.pmid: 24713688
references.citation: Nat Rev Immunol. 2009 Jun;9(6):418-28
references.pmid: 19461672
references.citation: JAMA Psychiatry. 2013 Jan;70(1):31-41
references.pmid: 22945416
references.citation: CNS Neurol Disord Drug Targets. 2014;13(10):1654-66
references.pmid: 25470401
references.citation: Shock. 2011 Jul;36(1):5-11
references.pmid: 21368716
references.citation: Brain Res. 2001 Jan 5;888(1):117-127
references.pmid: 11146058
references.citation: J Clin Oncol. 2006 Apr 20;24(12):1852-9
references.pmid: 16622259
references.citation: Psychosom Med. 1986 Jul-Aug;48(6):437-47
references.pmid: 3749421
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2015 Jan;388(1):79-86
references.pmid: 25344204
references.citation: J Affect Disord. 2009 Dec;119(1-3):181-5
references.pmid: 19269036
references.citation: PLoS One. 2012;7(6):e39468
references.pmid: 22745762
references.citation: Blood. 2013 Apr 18;121(16):3195-204
references.pmid: 23462117
references.citation: J Neural Transm (Vienna). 2012 Feb;119(2):245-51
references.pmid: 22139324
references.citation: Eur J Clin Invest. 2008 Dec;38(12):953-8
references.pmid: 19021721
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):664-75
references.pmid: 20599581
references.citation: Neurosci Biobehav Rev. 2010 Jan;34(1):130-43
references.pmid: 19666048
references.citation: Neurology. 1977 Sep;27(9):878-83
references.pmid: 408735
references.citation: Joint Bone Spine. 2013 Mar;80(2):141-5
references.pmid: 23116710
references.citation: Science. 1983 Jan 21;219(4582):316-8
references.pmid: 6849138
references.citation: Immunol Allergy Clin North Am. 2014 Feb;34(1):181-96
references.pmid: 24262698
references.citation: Brain Res. 2007 Sep 26;1171:18-29
references.pmid: 17764664
references.citation: Neuropsychopharmacology. 2012 Jan;37(1):137-62
references.pmid: 21918508
references.citation: Lancet. 2006 Jan 7;367(9504):29-35
references.pmid: 16399150
references.citation: J Neuroinflammation. 2011 Aug 10;8:94
references.pmid: 21831269
references.citation: Psychosomatics. 2002 Sep-Oct;43(5):386-93
references.pmid: 12297607
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):702-21
references.pmid: 21185346
references.citation: Br J Dermatol. 2007 Dec;157(6):1275-7
references.pmid: 17916204
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):18053-7
references.pmid: 19004805
references.citation: Nature. 1966 May 14;210(5037):756-7
references.pmid: 5961212
references.citation: Brain Behav Immun. 2005 Sep;19(5):453-60
references.pmid: 15963684
references.citation: J Neurosci. 2009 Apr 1;29(13):4200-9
references.pmid: 19339614
references.citation: Expert Opin Ther Targets. 2012 Nov;16(11):1097-112
references.pmid: 22925041
references.citation: Nat Rev Neurosci. 2008 Jan;9(1):46-56
references.pmid: 18073775
references.citation: N Engl J Med. 2001 Mar 29;344(13):961-6
references.pmid: 11274622
references.citation: Mol Psychiatry. 2010 Apr;15(4):393-403
references.pmid: 19918244
references.citation: Nat Rev Neurosci. 2012 Jul;13(7):465-77
references.pmid: 22678511
references.citation: Anal Biochem. 1988 Oct;174(1):349-59
references.pmid: 2975477
references.citation: Trends Neurosci. 2013 Sep;36(9):513-21
references.pmid: 23845731
references.citation: Acta Neuropathol. 2013 May;125(5):637-50
references.pmid: 23404369
references.citation: Expert Opin Ther Targets. 2014 May;18(5):495-512
references.pmid: 24548241
references.citation: Neuropsychopharmacology. 2013 Apr;38(5):743-52
references.pmid: 23299933
references.citation: J Interferon Cytokine Res. 2015 Jul;35(7):554-62
references.pmid: 25756191
references.citation: Arch Gen Psychiatry. 2001 May;58(5):445-52
references.pmid: 11343523
references.citation: CNS Drugs. 2005;19(2):105-23
references.pmid: 15697325
references.citation: Transl Psychiatry. 2014 Nov 11;4:e479
references.pmid: 25386956
references.citation: Arch Biochem Biophys. 1998 Oct 15;358(2):329-35
references.pmid: 9784247
references.citation: BMC Med. 2012 Jun 29;10:66
references.pmid: 22747645
references.citation: Biol Psychiatry. 2009 Sep 1;66(5):415-22
references.pmid: 19409533
references.citation: J Immunol. 2012 Jul 1;189(1):120-7
references.pmid: 22649193
references.citation: Allergy. 2014 Apr;69(4):445-52
references.pmid: 24397465
references.citation: Immunology. 2014 Mar;141(3):314-27
references.pmid: 24032675
references.citation: Immunol Allergy Clin North Am. 2014 May;34(2):407-22
references.pmid: 24745683
references.citation: Trends Neurosci. 2014 Jan;37(1):39-46
references.pmid: 24239063
references.citation: PLoS One. 2011;6(10):e26375
references.pmid: 22031830
references.citation: Mol Psychiatry. 2005 Jun;10(6):538-44
references.pmid: 15494706
references.citation: J Clin Psychopharmacol. 2002 Apr;22(2):103-8
references.pmid: 11910253
references.citation: Neuropsychopharmacology. 2013 Aug;38(9):1609-16
references.pmid: 23511700
references.citation: Biol Psychiatry. 2012 Oct 1;72(7):537-47
references.pmid: 22705040
references.citation: Brain Behav Immun. 2014 Nov;42:222-31
references.pmid: 25066466
references.citation: J Neurosci. 1990 Sep;10(9):2965-73
references.pmid: 2168940
references.citation: PLoS One. 2008 May 28;3(5):e2266
references.pmid: 18509466
references.citation: Biomarkers. 2015 Feb;20(1):35-46
references.pmid: 25495125
references.citation: Neuropsychopharmacology. 2015 Jan;40(2):463-71
references.pmid: 25074636
references.citation: Trends Immunol. 2006 Jan;27(1):32-9
references.pmid: 16269267
references.citation: J Affect Disord. 2002 Dec;72(3):237-41
references.pmid: 12450640
references.citation: Blood. 2011 Nov 10;118(19):5246-9
references.pmid: 21878676
references.citation: Immunol Rev. 2008 Apr;222:206-21
references.pmid: 18364004
references.citation: Brain Behav Immun. 2011 Feb;25(2):256-9
references.pmid: 20955776