The Cannabinoid 1 Receptor (CNR1) 1359 G/A Polymorphism Modulates Susceptibility to Ulcerative Colitis and the Phenotype in Crohn's Disease

Recent evidence suggests a crucial role of the endocannabinoid system, including the cannabinoid 1 receptor (CNR1), in intestinal inflammation. We therefore investigated the influence of the CNR1 1359 G/A (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) on disease susceptibility and phenotype in patients with ulcerative colitis (UC) and Crohn's disease (CD). Genomic DNA from 579 phenotypically well-characterized individuals was analyzed for the CNR1 1359 G/A SNP. Amongst these were 166 patients with UC, 216 patients with CD, and 197 healthy controls. Compared to healthy controls, subjects A/A homozygous for the CNR1 1359 G/A SNP had a reduced risk to develop UC (p = 0.01, OR 0.30, 95% CI 0.12-0.78). The polymorphism did not modulate CD susceptibility, but carriers of the minor A allele had a lower body mass index than G/G wildtype carriers (p = 0.0005). In addition, homozygous carriers of the G allele were more likely to develop CD before 40 years of age (p = 5.9x10(-7)) than carriers of the A allele. The CNR1 p.Thr453Thr polymorphism appears to modulate UC susceptibility and the CD phenotype. The endocannabinoid system may influence the manifestation of inflammatory bowel diseases, suggesting endocannabinoids as potential target for future therapies

Association between <i>CNR1</i> 1359 G/A (p.Thr453Thr) genotype and UC disease characteristics.

1<p>Immunosuppressive agents included azathioprine, 6-mercaptopurine, and/or infliximab.</p>2<p>Only UC-related surgery (e.g., colectomy) was included.</p>3<p>Extraintestinal manifestations were defined as one or more of the following IBD-related diseases: non-medication-induced arthropathies (e.g., ankylosing spondylitis, sacroileitis, peripheral arthritis), eye involvement (e.g., episcleritis and iritis/uveitis), skin involvement (e.g., erythema nodosum and pyoderma gangrenosum), non-medication-induced biliary disease (e.g., sclerosing cholangitis).</p

Genotype frequencies of <i>CNR1</i> 1359 G/A (p.Thr453Thr) polymorphism in patients with Crohn's disease (CD) and ulcerative colitis (UC) as well as in controls.

<p>Genotype frequencies of <i>CNR1</i> 1359 G/A (p.Thr453Thr) polymorphism in patients with Crohn's disease (CD) and ulcerative colitis (UC) as well as in controls.</p

The German research consortium for the study of bipolar disorder (BipoLife): a magnetic resonance imaging study protocol

Bipolar disorder is one of the most severe mental disorders. Its chronic course is associated with high rates of morbidity and mortality, a high risk of suicide and poor social and occupational outcomes. Despite the great advances over the last decades in understanding mental disorders, the mechanisms underlying bipolar disorder at the neural network level still remain elusive. This has severe consequences for clinical practice, for instance by inadequate diagnoses or delayed treatments. The German research consortium BipoLife aims to shed light on the mechanisms underlying bipolar disorders. It was established in 2015 and incorporates ten university hospitals across Germany. Its research projects focus in particular on individuals at high risk of bipolar disorder, young patients in the early stages of the disease and patients with an unstable highly relapsing course and/or with acute suicidal ideation. Functional and structural magnetic resonance imaging (MRI) data was acquired across nine sites within three different studies. Obtaining neuroimaging data in a multicenter setting requires among others the harmonization of the acquisition protocol, the standardization of paradigms and the implementation of regular quality control procedures. The present article outlines the MRI imaging protocols, the acquisition parameters, the imaging paradigms, the neuroimaging quality assessment procedures and the number of recruited subjects. The careful implementation of a MRI study protocol as well as the adherence to well-defined quality assessment procedures is one key benchmark in the evaluation of the overall quality of large-scale multicenter imaging studies. This article contributes to the BipoLife project by outlining the rationale and the design of the MRI study protocol. It helps to set the necessary standards for follow-up analyses and provides the technical details for an in-depth understanding of follow-up publications