Su2085 The Impact of Fear of GI Symptoms on Quality of Life Impairment Due to Irritable Bowel Syndrome

Abstract

G A A b st ra ct s (Kennedy et al, 2013), which may be mediated by changes in downstream neuroactive metabolites of the kynurenine pathway. Therefore, in this study we investigated if modulating tryptophan availability using acute tryptophan depletion (ATD) altered peripheral levels of kynurenine and tryptophan in patients with IBS, and if modulating these parameters impacted on measures of cognition, mood, arousal, and self-reported GI symptoms. Design: Doubleblind, placebo-controlled, crossover design. Methods: Female patients with IBS who met Rome III criteria (N = 9; mean age = 22.8 +/1.2) and age and IQ matched female healthy controls (HC; N = 14; mean age = 21.5 +/0.5) each attended two study visits, receiving the tryptophan depleting (ATD) or control (TRP+) amino acid drink on each visit. Plasma samples were collected pre and post drink, and participants completed a range of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), including the paired associates learning (PAL) test, and self report measures of GI symptoms, mood and arousal. Results: As expected, ATD reduced total plasma tryptophan, by 74.02% in healthy controls and by 85.86% in IBS patients, p < .001. In addition, ATD reduced total plasma kynurenine, by 63.12% in healthy controls and by 69.63% in IBS patients, p < .001. Following TRP+, kynurenine concentrations were significantly elevated in both IBS patients and healthy control participants, p < .001. Moreover, patients with IBS exhibited impaired visuospatial memory performance following TRP+, PAL mean errors: HC = 2.4 +/0.9, IBS = 7.8 +/1.9, p < 0.05. However, ATD eliminated this deficit. ATD had no effect on GI symptoms in patients with IBS. Conclusions: Although the peripheral changes in kynurenine following ATD are similar in patients with IBS and healthy control participants, it appears patients with IBS process tryptophan or kynurenine differentially in the central nervous system. Our results have significant implications for our understanding of the underlying pathophysiology of IBS, and suggest that targeting the kynurenine pathwaymay be a novel strategy to normalise central dysfunction in IBS. References Fitzgerald, P., et al. (2008). Neurogastroenterology & Motility, 20, 1291-1297. Kennedy, P. J., et al. (2013). Psychological Medicine, doi:10.1017/ S0033291713002171