Su1966 An Assessment of Cognitive Function in Irritable Bowel Syndrome (IBS): Are Deficits in Visuo-Spatial Memory Stress-Related and Mediated by Tryptophan Metabolism Along the Kynurenine Pathway?

Background: Irritable bowel syndrome (IBS), a functional gastrointestinal disorder (FGID), is a poorly understood stress-related disorder of the brain-gut-microbiome axis. Recently, a cognitive neurobiological model of IBS has been proposed (Kennedy et al., 2011) based on some of the key pathophysiological features of IBS, including relevant stress-related changes in hypothalamic pituitary adrenal (HPA)-axis functioning, and the immune-mediated degradation of tryptophan along the kynurenine pathway. However, a detailed assessment of cognitive performance across the domains of memory, executive function and attention is lacking. Furthermore, the relationship between mechanistically relevant biological indices and cognitive function in IBS is unknown. AIM: This study sought to redress these deficits by assessing whether IBS patients exhibited altered cognitive functioning in comparison to healthy controls (HC) across a number of domains. Moreover, we investigated whether any deficits which were found could be related to cortisol, the main HPA-axis hormone in man, and the kynurenine:tryptophan ratio, a well validated index of the immune-mediated degradation of trytophan along the kynurenine pathway. Methods: 38 IBS patients (6M/ 32F; mean age 28 yrs; IQ:105.9; BMI: 23.9), and 38 matched HC (11M/27F; mean age 29 yrs; IQ:108.6; BMI: 23.6) were assessed using a selection of cogntive tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and Stroop test. A venous blood sample was acquired for tryptophan analysis by HPLC and saliva was collected for cortisol determination by ELISA. Results: No significant differences in performance were found between IBS patients and HC on the Intra-Extra Dimensional Set Shift (IED; executive functioning); total errors (25.2 & plusmn;3.3 vs 25.3 & plusmn;3.4, p >0.05), Spatial working memory (SWM); total errors (22.8 & plusmn;2.6 vs 19 & plusmn;3.1, p >0.05), or Stroop response time (219.9 & plusmn;35.7 vs 192.7 & plusmn;39.1, p >0.05). IBS patients made significantly more errors than HC on the Paired associated learning (PAL; visuo-spatial memory) 6 pattern stage (3.3 & plusmn;0.7 vs 1.5 & plusmn;0.4, p < 0.05). There was a trend towards an inverse correllation between cortisol concentrations and errors on the PAL 6 pattern stage in IBS patients (r= -0.32, p=0.06). Moreover, there was a positive correlation between PAL 6 errors and the kynurenine:tryptophan ratio in IBS patients (r = 0.37, p