title: Regional brain disorders of serotonin neurotransmission are associated with functional dyspepsia.
abstract: OBJECTIVE
  To elucidate the role of cerebral serotonin neurotransmission in visceral perception in functional dyspepsia (FD), we observationally examined the regional expression level of the serotonin transporter (SERT) and its correlation with clinical symptoms.
  
  
  METHODS
  FD patients (Rome III criteria; N=9, age range: 36-76years) and healthy controls (N=8, age range: 25-61years) participated in this study. Positron emission tomography scanning with [(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([(11)C]DASB), which binds specifically to SERT, was used to quantify the binding potential (BPND) of [(11)C]DASB in the midbrain, thalamus, caudate, putamen, amygdala, and hippocampus with reference to co-registered magnetic resonance images. Clinical symptoms were assessed using the Gastrointestinal Symptoms Rating Scale (GSRS). Self-Rating Depression Scale (SDS), and State-Trait Anxiety Inventory (STAI).
  
  
  RESULTS
  BPND of the midbrain (P=0.041) and thalamus (P=0.031) was higher in FD patients than in controls. The BPND values in the midbrain correlated with total GSRS (r=0.663, P=0.004) and abdominal pain (r=0.419, P=0.047) scores. Its values in the thalamus correlated with total GSRS (r=0.423, P=0.044), abdominal pain (r=0.502, P=0.022), and indigestion (r=0.476, P=0.028) scores. Its value in the hippocampus correlated with abdominal pain and state-STAI scores (r=0.528, P=0.017; r=0.428, P=0.043).
  
  
  CONCLUSIONS
  Up-regulation of the SERT level in the midbrain and thalamus may underlie the pathogenesis of FD such as abdominal and psychological symptoms via a brain-gut interaction.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan. Electronic address: tomy@med.osaka-cu.ac.jp.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Tsumoto
authors.affiliation: Department of Geriatric Medicine, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Suzuka
authors.initials: S
authors.lastname: Ataka
authors.affiliation: Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, Japan; Department of Medical Science on Fatigue, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.affiliation: Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kawabe
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Shiomi
authors.affiliation: Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, Japan; Department of Physiology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000328:Adult; D001596:Benzylamines; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D004415:Dyspepsia / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000378:metabolism*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis; D063189:Symptom Assessment; D009435:Synaptic Transmission; D013788:Thalamus / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin
keywords: Brain–gut axis; Dyspepsia; Neurotransmission; Serotonin transporter; Visceral symptoms