Getting nervous about IBD

Abstract

A paper published in The Journal of Clinical Investigation suggests that antidepressants used to treat psychological disorders often associated with gastrointestinal diseases may have the added therapeutic effect of reducing bowel inflammation. Harnessing this double effect to treat conditions such as ulcerative colitis and Crohn's disease will require determining which drugs are most efficient at achieving both therapeutic endpoints and whether such candidates would be used in place of, or on top of, existing treatments.Common strategies for treating inflammatory bowel disease (IBD) involve suppressing the immune response with small molecules or antibodies that target proinflammatory cytokines. 1 The major forms of IBD-ulcerative colitis (UC) and Crohn's disease-are characterized by inflammation of the large and small intestine. UC is usually restricted to the colon and rectum, and Crohn's disease can affect any part of the GI tract. 2 IBD patients often suffer from psychological disorders such as stress and depression that may have a negative impact on their response to IBD therapy. 3 However, it isn't known whether IBD patients suffer from depression prior to getting IBD or as a result of having IBD. Some researchers contacted by SciBX believe there is probably a bidirectional relationship between psychiatric disorders and inflammation.Stephen Collins, a professor of medicine at McMaster University, and his coauthors on the JCI study believe their data suggest strategies for treating inflammation by modulation of the nervous system. This includes antidepressants that act on the brain or nicotinic receptor agonists that act on the vagus nerve. Both types of compounds, according to the team's data, could potentially alleviate psychiatric symptoms while also reducing inflammation in regions of the gut.The researchers found that treating chemically induced colitis in mouse models of depression with a tricyclic antidepressant not only alleviated depressed behavior but also significantly reduced inflammation compared with what was seen in control mice (p<0.05). 4 Previous mouse data from Collins' lab had linked antidepressant therapy to reduced susceptibility to colitis 5 and implicated the vagus nerve in protecting the colon from the disease. 6 In the current paper, the researchers tested the hypothesis that antidepressants reduce colitis in depressed mice by restoring proper function of the vagus nerve in the gut. The vagus is a cranial nerve that innervates the pharynx, larynx, esophagus, heart and most GI organs.The researchers found that the generic tricyclic antidepressant desmethylimipramine (also known as desipramine) reduced multiple parameters of colon inflammation in depressed mice without directly acting on the colon. Furthermore, vagotomy-severing the vagus nerve-abolished the anti-inflammatory activity of the compound in the same mice. Thus, the antidepressant effect of desipramine "is due to restoration of vagal parasympathetic function," the authors concluded. Targeting IBD in the brainResearchers c...