title: Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.
abstract: Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.
authors.affiliation: Grenoble Institut des Neurosciences (GIN), Centre de Recherche INSERM 836 Equipe : Stress et Interactions Neuro-Digestives (EA3744), Université Joseph Fourier, Grenoble, France; Département de Psychologie, Université de Savoie, Chambéry, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pellissier
authors.affiliation: Laboratoire Interuniversitaire de Psychologie: Personnalité, Cognition, Changement social (LIP/PC2S), Université de Savoie, Chambéry, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Dantzer
authors.affiliation: Laboratoire de Psychologie Sociale et Cognitive (LAPSCO, CNRS UMR6024), Université Blaise Pascal, Clermont-Ferrand, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Mondillon
authors.affiliation: Institut de Biologie, Centre Hospitalo-Universitaire de Grenoble, Grenoble, France.
authors.forename: Candice
authors.initials: C
authors.lastname: Trocme
authors.affiliation: Institut de Biologie, Centre Hospitalo-Universitaire de Grenoble, Grenoble, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gauchez
authors.affiliation: Institut de Biologie, Centre Hospitalo-Universitaire de Grenoble, Grenoble, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Ducros
authors.affiliation: Clinique Universitaire d'Hépato-Gastroentérologie, Centre Hospitalo-Universitaire de Grenoble, Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mathieu
authors.affiliation: Institut de Biologie, Centre Hospitalo-Universitaire de Grenoble, Grenoble, France; Laboratoire TIMC/TheREx UMR 5525, Université Joseph Fourier, Grenoble, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toussaint
authors.affiliation: Laboratoire de Psychologie Sociale et Cognitive (LAPSCO, CNRS UMR6024), Université Blaise Pascal, Clermont-Ferrand, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Unité de Neurophysiologie du Stress, Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France; Ecole du Val de Grâce, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Canini
authors.affiliation: Grenoble Institut des Neurosciences (GIN), Centre de Recherche INSERM 836 Equipe : Stress et Interactions Neuro-Digestives (EA3744), Université Joseph Fourier, Grenoble, France; Clinique Universitaire d'Hépato-Gastroentérologie, Centre Hospitalo-Universitaire de Grenoble, Grenoble, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonaz
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016000:Cluster Analysis; D003424:Crohn Disease / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood*; D005260:Female; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D043183:Irritable Bowel Syndrome / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D012463:Saliva / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014630:Vagus Nerve / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine