BACKGROUND & AIMS: 5-Hydroxytryptamine (5-HT)3 receptor (5-HT3R) antagonists are effective in treating patients with irritable bowel syndrome (IBS) and have anxiolytic effects. Their therapeutic effects are related, in part, to reducing amygdala engagement during expected visceral pain. A single nucleotide polymorphism in HTR3A, c.-42C>T;(C178T; rs1062613), is associated with altered reactivity of the amygdala during emotional face processing in healthy subjects (controls). We evaluated the influence of this single nucleotide polymorphism on amygdala reactivity to emotional faces and nonemotional stimuli in female patients with IBS and controls. METHODS: We measured brain responses during an affect-matching paradigm in 54 women (26 with IBS, 29 controls) using functional magnetic resonance imaging. We examined associations between HTR3A c.-42C>T genotype (C/C vs T carrier) and responses in amygdala and other regions of brain that expressed high levels of 5-HT3R. RESULTS: The C/C genotype was associated with greater anxiety symptoms in patients with IBS and controls and increased activation of the amygdala under emotional and nonemotional conditions. Among patients with IBS, C/C genotype was associated with greater symptom ratings. A subset of IBS patients with the C/C genotype had increased amygdala responses to nonemotional stimuli, compared with other subjects with C/C genotype. CONCLUSIONS: Regardless of diagnosis, the C/C genotype of the c.-42C>T polymorphism in HTR3A, compared with T carrier status, is associated with increased anxiety and amygdala responsiveness during emotional and nonemotional tasks. This polymorphism was associated with severity of IBS symptoms. Although this genotype is not sufficient for diagnosis of IBS, it is associated with severity of symptoms.
BACKGROUND & AIMS:5-Hydroxytryptamine (5-HT)3 receptor (5-HT3R) antagonists are effective in treating patients with irritable bowel syndrome (IBS) and have anxiolytic effects. Their therapeutic effects are related, in part, to reducing amygdala engagement during expected visceral pain. A single nucleotide polymorphism in HTR3A, c.-42C>T;(C178T; rs1062613), is associated with altered reactivity of the amygdala during emotional face processing in healthy subjects (controls). We evaluated the influence of this single nucleotide polymorphism on amygdala reactivity to emotional faces and nonemotional stimuli in female patients with IBS and controls. METHODS: We measured brain responses during an affect-matching paradigm in 54 women (26 with IBS, 29 controls) using functional magnetic resonance imaging. We examined associations between HTR3A c.-42C>T genotype (C/C vs T carrier) and responses in amygdala and other regions of brain that expressed high levels of 5-HT3R. RESULTS: The C/C genotype was associated with greater anxiety symptoms in patients with IBS and controls and increased activation of the amygdala under emotional and nonemotional conditions. Among patients with IBS, C/C genotype was associated with greater symptom ratings. A subset of IBSpatients with the C/C genotype had increased amygdala responses to nonemotional stimuli, compared with other subjects with C/C genotype. CONCLUSIONS: Regardless of diagnosis, the C/C genotype of the c.-42C>T polymorphism in HTR3A, compared with T carrier status, is associated with increased anxiety and amygdala responsiveness during emotional and nonemotional tasks. This polymorphism was associated with severity of IBS symptoms. Although this genotype is not sufficient for diagnosis of IBS, it is associated with severity of symptoms.
Authors: Johannes Kapeller; Lesley A Houghton; Hubert Mönnikes; Jutta Walstab; Dorothee Möller; Heinz Bönisch; Barbara Burwinkel; Frank Autschbach; Benjamin Funke; Felix Lasitschka; Nikolaus Gassler; Christine Fischer; Peter J Whorwell; Wendy Atkinson; Catherine Fell; Karl J Büchner; Marco Schmidtmann; Ivo van der Voort; Anna-Sophia Wisser; Thomas Berg; Gudrun Rappold; Beate Niesler Journal: Hum Mol Genet Date: 2008-07-09 Impact factor: 6.150
Authors: A P Rajkumar; B Poonkuzhali; A Kuruvilla; A Srivastava; M Jacob; K S Jacob Journal: Psychopharmacology (Berl) Date: 2012-06-15 Impact factor: 4.530
Authors: Kristen R Weaver; LeeAnne B Sherwin; Brian Walitt; Gail D'Eramo Melkus; Wendy A Henderson Journal: World J Gastrointest Pharmacol Ther Date: 2016-05-06
Authors: Paul Enck; Qasim Aziz; Giovanni Barbara; Adam D Farmer; Shin Fukudo; Emeran A Mayer; Beate Niesler; Eamonn M M Quigley; Mirjana Rajilić-Stojanović; Michael Schemann; Juliane Schwille-Kiuntke; Magnus Simren; Stephan Zipfel; Robin C Spiller Journal: Nat Rev Dis Primers Date: 2016-03-24 Impact factor: 52.329
Authors: Steven Berman; Brandall Suyenobu; Bruce D Naliboff; Joshua Bueller; Jean Stains; Heng Wong; Mark Mandelkern; Leah Fitzgerald; Gordon Ohning; Arpana Gupta; Jennifer S Labus; Kirsten Tillisch; Emeran A Mayer Journal: Neuroimage Date: 2012-08-21 Impact factor: 6.556