Sex Differences of Brain Serotonin Synthesis in Patients with Irritable Bowel Syndrome Using α-[<sup>11</sup>C]methyl-L-tryptophan, Positron Emission Tomography and Statistical Parametric Mapping

  • Akio Nakai
    Montreal Neurological Institute, McGill University, Montreal, Canada
  • Yoshikata Kumakura
    Montreal Neurological Institute, McGill University, Montreal, Canada
  • Michel Boivin
    Centre Hospitalier de l’Universite de Montreal, Montreal, Quebec, Canada
  • Pedro Rosa
    Montreal Neurological Institute, McGill University, Montreal, Canada
  • Mirko Diksic
    Montreal Neurological Institute, McGill University, Montreal, Canada
  • Doreen D’Souza
    Glaxo Wellcome Inc, Mississauga, Ontario, Canada
  • Kathryn Kersey
    Glaxo Wellcome Inc, Mississauga, Ontario, Canada

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<jats:p>BACKGROUND: Irritable bowel syndrome (IBS) is the most common functional bowel disorder and has a strong predominance in women. Recent data suggest that the brain may play an important role in the pathophysiology of IBS in the brain-gut axis. It is strongly suspected that serotonin (5-HT), a neurotransmitter found in the brain and gut, may be related to the pathophysiology of IBS. It is reported that a 5-HT<jats:sub>3</jats:sub>antagonist is effective only in female patients with diarrhea-predominant IBS.</jats:p><jats:p>OBJECTIVE: In the present study, 5-HT synthesis was measured using positron emission tomography, with α-[<jats:sup>11</jats:sup>C]methyl-l-tryptophan as the tracer, in patients with IBS. The aim of the present study was to compare 5-HT synthesis in the IBS patients with that in the controls, and to compare 5-HT synthesis between male and female IBS patients.</jats:p><jats:p>METHODS: Six male and six female nonconstipated IBS patients were scanned. Age-matched healthy volunteers were scanned as controls. Eighty minute dynamic scans were performed. Functional 5-HT synthesis images were analyzed using statistical parametric mapping.</jats:p><jats:p>RESULTS: 5-HT synthesis was greater only in the female IBS patients in the right medial temporal gyrus (multimodal sensory association cortex) compared with the female controls (P<0.001).</jats:p><jats:p>CONCLUSIONS: The greater brain 5-HT synthesis in the female IBS patients than in the controls may be related to the pathological visceral pain processing of the IBS patients, a larger female predominance of the disorder, and the sex difference of the efficacy of the 5-HT<jats:sub>3</jats:sub>antagonist in treatment.</jats:p>

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