Anti-TNFα therapy in IBD alters brain activity reflecting visceral sensory function and cognitive-affective biases

Background In inflammatory bowel disease (IBD), immune activation with increased circulating TNF-alpha is linked to the intensity of gastrointestinal symptoms and depression or anxiety. A central feature of depression is cognitive biases linked to negative attributions about self, the world and the future. We aimed to assess the effects of anti-TNF alpha therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn's disease. Methods We examined 9 patients with Crohn's disease (age 26.1 +/- 10.6. yrs, 5 female, 5 ileocolonic, 2 colonic and 2 ileal disease) during chronic anti-TNF alpha therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNF alpha administration. On each occasion patients underwent functional magnetic resonance imaging (fMRI) of the brain during a test of implicit attribution biases regarding sickness/health and undertook a standardized nutrient challenge. Results Following anti-TNFa treatment, ratings of 'fullness' following nutrient challenge reduced compared to pre-treatment ratings (p<0.05). Reaction times revealed improved processing of self-related and positive health words, consistent with improved implicit sense of wellbeing that correlated with improvements in sensory function after treatment (r = 0.67, p<0.05). Treatment-associated improvements in implicit processing were mirrored by alterations of prefrontal, amygdala, posterior cingulate and visual regions. Between patients, the degree of functional amygdala change was additionally explained by individual differences in attention regulation and body awareness rankings. Conclusion In patients with Crohn's disease, anti-TNF alpha administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.