Journal Article

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

Gray, Marcus A., Chao, Che-yung, Talley, Nicholas J., Kolosky, Natasha A., Staudacher, Heidi M., Holtmann, Gerald

2018

Overview

In inflammatory bowel disease (IBD), immune activation with increased circulating TNF-α 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-TNFα therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn's disease. 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-TNFα therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNFα 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. Following anti-TNFα 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. In patients with Crohn's disease, anti-TNFα administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adalimumab - therapeutic use / Adolescent / Adult / Affect - drug effects / Affect - physiology / Amygdala / Anti-Inflammatory Agents - therapeutic use / Anxiety / Behavioral sciences / Biology and Life Sciences / Brain / Brain - drug effects / Brain - physiopathology / Brain Mapping / Brain research / Cognition - drug effects / Cognition - physiology / Cognitive ability / Crohn Disease - drug therapy / Crohn Disease - physiopathology / Crohn Disease - psychology / Crohn's disease / Diagnostic Self Evaluation / Female / Functional magnetic resonance imaging / Gastroenterology / Gastrointestinal Agents - therapeutic use / Gastrointestinal symptoms / Hepatology / Hospitals / Humans / Immune response / Inflammation / Inflammatory bowel disease / Inflammatory bowel diseases / Infliximab / Infliximab - therapeutic use / Intestine / Irritable bowel syndrome / Magnetic resonance / Magnetic Resonance Imaging / Male / Medicine and Health Sciences / Mental depression / Monoclonal antibodies / Neuroimaging / Neuropsychological Tests / NMR / Nuclear magnetic resonance / Nutrients / Pain / Patients / Psychiatry / Random Allocation / Ratings / Research and Analysis Methods / Satiation - drug effects / Satiation - physiology / Sensory neurons / Social Sciences / Therapy / Tumor Necrosis Factor-alpha - immunology / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Visceral Afferents - drug effects / Visceral Afferents - physiopathology / Young Adult