Clinical—Alimentary TractThe HTR3A Polymorphism c. -42C>T Is Associated With Amygdala Responsiveness in Patients With Irritable Bowel Syndrome
Section snippets
Subjects
A sample of 26 female IBS patients and 29 female healthy controls (demographics are presented in Table 1) participated in functional magnetic resonance image (fMRI) studies of emotional reactivity and provided saliva samples for DNA analyses. Subjects were recruited through the University of California Los Angeles Digestive Disease Clinic and from community advertisements. The diagnosis of IBS was confirmed using Rome II criteria during a clinical examination by a gastroenterologist or nurse
HTR3A polymorphism
Fifteen of 29 HCs and 16 of 26 IBS patients were homozygous for the C allele, 9 HCs and 7 patients carried the heterozygous C/T genotype, and 5 HCs and 3 patients carried the homozygous T/T genotype. The c.-42C>T SNP had been found previously to be associated with IBS-D in a UK sample applying a minor allele dominant model.24 Thus, subjects carrying a T allele (C/T or T/T) were combined into a single group (T carriers) for analyses.
A HTR3A genotype (C/C, T carrier) × diagnosis (HC, IBS)
Discussion
We used a validated emotional reactivity paradigm to identify differences between IBS patients and HCs in emotional arousal–related brain responses. When contrasting the brain's response to the negative emotional faces with the response to neutral geometric forms (ME-MF), consistent activations in amygdala, thalamus, and lateral prefrontal and parietal cortices, and deactivations in medial PFC, insula, and posterior cingulate cortex were seen. C/C genotype, regardless of diagnosis, was
Summary and Future Directions
By using a validated emotional reactivity paradigm, unrelated to the gastrointestinal system, we found significant correlations of the HTR3A c.-42C>T polymorphism with amygdala responsiveness, anxiety, and IBS symptom severity in a relatively small sample. The study supports the important role of 5-HT3Rs in the modulation of emotional arousal circuits that previously have been shown to be related to 5-HT3R antagonist-mediated (alosetron) IBS symptom improvement.13 These findings suggest that
Acknowledgments
B.N. and E.A.M. shared senior authorship of the article.
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Conflicts of interest The authors disclose no conflicts.