1098 Central Serotonin Neurotransmission Disorders Correlate with Visceral Perception and Psychological Characteristics in Patients with Functional Dyspepsia

Abstract

Background& Aims: Visceral perception of functional dyspepsia (FD) is based on the braingut interaction via various neurotransmission pathways. Peripheral or central serotonergic abnormalities are associated with the pathophysiology of functional gastrointestinal disorders or psychiatric depression and anxiety. To examine the roles of the cerebral serotonin (5HT) neurotransmission systems in visceral perception of FD patients, we examined both 5HT transporter (5-HTT) binding potential in the brain and the correlation between differences between patients and controls in 5-HTT binding potential and abdominal symptoms. Methods: Patients with FD diagnosed according to the Rome III criteria (N=9, female: 6, age range 25-61 yrs) were recruited for this study. There were 9 healthy controls (female: 3, age range 36-76 yrs). To measure 5-HTT binding potential with region-of-interest data in areas of the thalamus, putamen, caudate, amygdala, midbrain, and cerebellum (as a reference region), positron emission tomography (PET) with [11C]N,N-dimethyl-2-(2-amino4-cyanophenylthio) benzylamine ([11C]DASB), which binds specifically to 5-HTT, was performed. We used the Multi-linear Reference Tissue Mode method within the standard software package of PMOD Technologies for analysis of [11C]DASB with reference to the co-registered MRI images. Clinical symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale (GSRS) including subscales for abdominal pain and indigestion. Depression and anxiety were evaluated on the Self-Rating Depression Scale and the State-Trait Anxiety Inventory. Results: All scores for abdominal pain, indigestion, depression, and anxiety were higher for FD patients than for controls (p<0.01). In FD patients, the binding potential of [11C]DASB in the midbrain (p=0.001) and amygdala (p=0.065) was higher than in the corresponding areas in controls, while there were no differences between the groups in the thalamus, putamen, or caudate. Binding potential of [11C]DASB in the midbrain was correlated with total GSRS (p=0.018, r=0.572), indigestion (p=0.021, r=0.565), and abdominal pain (p=0.091, r=0.420) scores, while in the amygdala it was correlated with total GSRS (p=0.080, r=0.426), indigestion (p=0.057, r=0.469), depression (p=0.091, r=0.413), and anxiety (p=0.096, r=0.406) scores. Conclusion: These findings suggest that in FD patients there are disorders of central 5-HT neurotransmission, especially in the midbrain and amygdala, which are correlated with their visceral symptoms and psychological characteristics.