Changes in grey matter volume (GMV) and cortical thickness (CT) have been previously documented in adult Crohn’s Disease (CD) patients in remission, however data is inconsistent and not explored in patients with active CD. Here, we investigate alterations in GMV and CT in patients with active CD, and their correlation with disease activity biomarkers such as faecal calprotectin (FCP), C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and TNFαMethods
25 active ileal/colonic CD patients and 25 healthy controls (HC) age-, BMI- and gender-matched were scanned. Active CD was defined as Harvey Bradshaw index >5 and CRP >5 mg/dl, or FCP >250 µg/g or assessed through ileocolonoscopy or magnetic resonance enterography. Cytokine levels were measured from serum samples using colorimetric ELISA. FCP were acquired at inclusion. Anatomical T1-weighted brain images were acquired on a 3T Philips Achieva scanner using a 32-channel receive coil. GMV was measured using voxel based morphometry and cortical thickness was determined using computational anatomy toolbox (CAT12) in Statistical Parametric Mapping (SPM) software.Results
In CD patients, significant cortical thinning in the right rostral middle-frontal area (involved in attention and working memory) was found compared with HCs. A significant decrease in GMV was found in CD compared with HC in pre-central gyrus (motor cortex) and post-central gyrus (somatosensory cortex). Correlating IL-6 with CT in CD showed cortical thinning in the right superior-frontal area (involved in self-awareness) and right lingual regions (involved in vision processing) with increasing IL-6 levels. IL-6 was negatively correlated with the GMV in bilateral insula (involved in pain processing) and pre- and post-central gyrus. FCP was negatively correlated with the right insula. Further cytokine assays of TNFα and IL-1β are presently underway in this study.Conclusions
A significant reduction in CT and GMV in cortical areas has been shown in patients with active CD compared with HCs. This observation may be associated with a chronic inflammatory response, attributed to high levels of circulating neurotoxic cytokines. Serum TNFα and IL-1β levels will also be correlated to CT and GMV in this study to validate the aforementioned observation. Investigating structural brain changes in active CD will aid our understanding of the cross-linking between chronic inflammation, brain morphology and changes in behaviour, cognitive function and unexplained symptoms such as fatigue in CD. This will inform new medical and psychological therapies.