Clinical tests of this hypothesis are needed to assess its validity. If the immune activation that accompanies MS supports a potential role for inflammation in the pathogenesis of mood disorders,

then anti-inflammatory medications might be expected to ameliorate depression. Statins, a family of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are used primarily to reduce atherogenesis and cardiovascular morbidity. Recently they have also been shown to have immunomodulatory properties that might be of benefit Inhibitors,research,lifescience,medical for the treatment of autoimmune disorders, and are currently being investigated in clinical trials for their potential use in treating MS.121 Inhibitors,research,lifescience,medical Previous studies have also found that statins may be of benefit in the treatment of depression. Young-Xu and colleagues studied patients from an outpatient cardiology clinic, and found that long-term use of statins appeared to be associated with a reduced incidence of anxiety,

depression, and hostility.122 Analysis from the United Kingdom General Practice Research Database found that individuals currently on statins have a lower Inhibitors,research,lifescience,medical risk of developing depression.123 In a double-blind pilot study, subjects who took statins for 1 year were found to improve in ratings of depressive symptoms.124 A potential role of inflammation mediated by prostaglandin E2 (PGE2) in depression has recently been explored. As cyclo-oxygenase-2 (COX-2) inhibitors inhibit PGE2 production and the production of proinflammatory cytokines, there

are a growing number of investigations into a potential role for these medications for treating depression. Aspirin has been shown to dramatically Inhibitors,research,lifescience,medical accelerate the onset of action of a selective serotonin reuptake inhibitor (SSRI) in an animal model of depression.125 More persuasively, a double-blind placebo TGF-beta inhibitor controlled trial in 40 patients with MDD demonstrated that addition of celecoxib had significant therapeutic Inhibitors,research,lifescience,medical effects on the action of the antidepressant reboxetine compared with treatment with reboxetine and a placebo.126 The potential interrelatedness of treatments for depression and their impact on inflammation is Edoxaban suggested by vagus nerve stimulation (VNS). VNS therapy is an effective adjunctive treatment for chronic or recurrent treatment-resistant depression in adults. The mechanism of action of VNS and how it ameliorates depression is not known. A series of elegant studies by Tracey and colleagues have identified the cholinergic anti-inflammatory pathway as a neural, efferent vagus nerve-based mechanism that controls inflammation.127 Vagus nerve cholinergic signaling interacts with α-7nAchR on immune cells and inhibits the production of TNF and other proinflammatory cytokines and excessive inflammatory responses.