Depression and anxiety are comorbidities of inflammatory bowel disease (IBD). Though previous studies have proposed a relationship between anxiety, depression, and IBD, causality and directionality are largely unknown. Current and future research in these areas is aimed at exploring the biological underpinnings of this relationship, specifically pertaining to small molecule metabolism, such as tryptophan. Tryptophan is acquired through the diet and is the precursor to several vital bioactive metabolites including the hormone melatonin, the neurotransmitter serotonin, and vitamin B3. In this review, we discuss previous findings relating mental health comorbidities with IBD and underline ongoing research of tryptophan catabolite analysis.
Background Depression and anxiety are comorbidities of inflammatory bowel disease (IBD). Though previous studies have proposed a relationship between anxiety, depression and IBD, causality and directionality are unknown. We used a novel computerised adaptive testing technology to screen IBD patients for depression and anxiety and compared the screening results to recent measures of C-reactive protein (CRP). Methods Consecutive patients at our tertiary IBD clinic were asked to complete the validated CAT-MH™ survey from Adaptive Testing Technologies (Chicago, IL); we then reviewed disease and patient characteristics. CRP measures from within 6 months of survey administration were used and levels ≥5 mg/l were considered positive. Patients who are CRP non-reactive were excluded. Pearson Chi-Square test was used to assess correlation. Results 134 patients (75 women, 112 Caucasian, 84 Crohn’s disease) participated in the study, 85 of whom had no prior history of psychiatric disorders. We identified 51 patients with depression (46 mild, 3 moderate, 2 severe) and 36 subjects with anxiety (24 mild, 10 moderate, 2 severe). Of the 134 patients recruited for this study, 57 had CRP reported. Median time between CRP measurement and CAT-MH™ administration was 2 days (IQR = 70). Categorical analysis stratified patients with positive and negative CRP who are also positive for depression and/or anxiety. Compared with patients with negative CRP values, patients with positive CRP were more likely to also test positive for depression and anxiety. These results were statistically significant for depression (p = 0.008) and nearly significant for anxiety (p = 0.058) (Figure 1). Quartile analysis of the 21 patients with elevated CRP levels revealed an increasing trend of average depression and anxiety severity scores. However, this correlation was lost when CRP >21 mg/l (Figure 2). Conclusion We illustrate the significant association between CRP and depression and anxiety severity scores on the CAT-MH™ survey. These findings suggest a positive relationship between inflammation and depression and anxiety in IBD patients. Physicians should consider patients with elevated CRP levels at risk for these mental health conditions.
BACKGROUND: Updated goals of management of IBD patients include monitoring disease activity, yet compliance with such strategies is poorly studied. We are performing a multi-year study of patients with active and quiescent IBD to assess the utility of a wearable, continuously active biosensor and validating disease activity with scheduled stool (calprotectin) and serum (CRP) testing. This study assessed compliance with these passive and active monitoring strategies. METHODS: Patients with diagnosed IBD were recruited for a prospective study using a biosensor (Fitbit Alta HR, San Francisco, CA) and mobile application (Litmus Health, Austin, TX). Each patient was instructed to wear a biosensor for a one-year period with stool sample drop-offs and blood draws for the first 6 months. The biosensor collected step count, sleep time, and heart rate during the study. Compliance was calculated as the number of days of heart rate, step count, and sleep data received over the duration of the study measured in days. Compliance was defined as ≥80% data collection in the time studied. A t-test was performed to determine the significant difference (P < 0.05) in compliance based on age, sex, disease activity, and body mass index (BMI); and between day time and night time wear. RESULTS: A total of 40 patients were analyzed; 23 men (57.5%), 24 with ulcerative colitis (60%), and 20 in remission (50%). 28 patients were <50 years of age (70%). The average BMI was 26.5 kg/m2. Overall, there was a 78% biosensor compliance rate among IBD patients. 45% of patients in clinical remission were compliant in stool drop-offs, while 60% of patients with clinically active disease were compliant in stool drop-offs (P > 0.05; 95% CI: -14.8 to 41.39). There were significant differences between biosensor compliance at night (57%) and day (98%) (P < 0.01; 95% CI: 0.31 to 0.5) and active disease (P < 0.01; 95% CI: -1.13 to -0.80). There was no significant difference in compliance and sex (P > 0.05; 95% CI: -0.53 to 0.11), age (P > 0.05; 95% CI: -11.14 to 7.84), and BMI (P > 0.05; 95% CI: -3.62 to 5.57). There were insufficient data to analyze compliance in answering questionnaires. CONCLUSION(S): In this study, patients were more compliant wearing the biosensor during the day than during the night and were more compliant if they had clinically active disease. In future studies, it will be important to provide an incentive and intervention to promote compliance in both active and passive monitoring strategies.
Background Tofacitinib is an oral Janus kinase (JAK) inhibitor used to treat ulcerative colitis (UC). It is generally well tolerated and safe with mild to no side effects. Tofacitinib is FDA-approved for use in multiple inflammatory conditions such as rheumatoid arthritis, psoriasis and polyarticular course juvenile idiopathic arthritis as well as for ulcerative colitis (UC). Patients with UC often have extra-intestinal manifestations (EIMs) with up to 20% of patients having arthropathy. There are limited data describing the effect of tofacitinib therapy on EIMs in UC. The aim of this study is to determine whether tofacitinib therapy improves arthralgia in this patient population. Methods This retrospective study includes consecutive patients with active UC who initiated tofacitinib at our center since 2014 and remained on the therapy for at least 8 weeks. We reviewed electronic medical records to collect demographic and clinical data. Patients diagnosed with any EIM by the treating physician were included. Improvement in EIM symptoms was determined through patient reports or physician assessment. In the UC patients, a decrease in Simple Clinical Colitis Activity Index (SCCAI) of ≥ 3 was considered response and remission as a score of ≤ 2. In the CD patients, a 3-point reduction in Harvey Bradshaw index (HBI) was considered clinical response and a score of <5 remission. Results 112 patients were included in this cohort, with 36 (31 UC; 5 CD) having confirmed EIMs (32.1% of total). Basic demographic and clinical data are detailed in Table 1. 35 patients had peripheral arthralgia, 2 patients had primary sclerosing cholangitis (PSC) and 1 had pyoderma gangrenosum. 5 (13.9%) patients discontinued treatment during the induction phase due to lack of response. By 24 weeks, 26 (74.2%) out of 35 patients reported improvement in arthralgias, and 14 (40%) patients reporting resolution of joint symptoms. In terms of gastrointestinal disease activity, at week 24, 17/35 (48.6%) patients achieved clinical response and 11/35(31.4%) patients achieved clinical remission. There was no treatment effect noted on the other EIMs. Conclusion In our real world experience, treatment refractory IBD patients with peripheral arthralgia on tofacitinib showed significant improvement in joint symptoms, and this often paralleled improvement in gastrointestinal symptoms. This supports that tofacitinib is a suitable treatment for patients with IBD and concomitant peripheral arthralgia.
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