Matthew T. Bernstein

The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease.

OBJECTIVES:Previous studies have demonstrated that stress is associated with increased disease activity in individuals with inflammatory bowel disease (IBD). The association between perceived stress and gastrointestinal inflammation is not well described.METHODS:Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn’s disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen’s Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 μg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity.RESULTS:Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03–1.10 and 1.03–1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65–9.43), but not in CD (OR 0.98, 95% CI 0.51–1.88).CONCLUSIONS:Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.

Gastrointestinal symptoms before and during menses in women with IBD.

It is believed that women with inflammatory bowel disease (IBD) have heightened symptoms around their menses. However, there is little information regarding normative changes and which symptoms emerge in relation to menses.

Evidence of Bidirectional Associations Between Perceived Stress and Symptom Activity: A Prospective Longitudinal Investigation in Inflammatory Bowel Disease

Background: Our aim was to explore the relationships among perceived stress, intestinal inflammation, and inflammatory bowel disease (IBD) symptoms over time. Methods: Participants were recruited from a population-based registry of persons with IBD and assessed at months 0, 3, and 6. Key dependent measures were the Manitoba IBD Index (symptom activity), Cohens Perceived Stress Scale, and fecal calprotectin in stool (intestinal inflammation). Results: Complete data were available for 417 participants at months 0; 369 provided follow-up data. Active symptoms were reported by 54% of those with Crohns disease (CD) and 40% of those with ulcerative colitis (UC) and approximately one-third consistently had fecal calprotectin measures ≥250 &mgr;g/g, suggestive of active inflammation. A significant proportion of participants had indications of inflammation but no active symptoms over the 6 months. Correlations of month 0 perceived stress and disease activity measures with values at months 3 and 6 for both CD and UC indicated strong temporal stability. In hierarchical multiple regression analyses, month 0 symptom activity was thus a strong predictor of later symptom activity for CD and UC. Perceived stress predicted change in symptom activity from 0 to 3 months for CD, as did use of prednisone for UC. Comparably, month 0 perceived stress was a strong predictor of later perceived stress for CD and UC, while month 0 symptom activity predicted change in perceived stress from 0 to 3 months for both CD and UC. Conclusions: The analysis revealed prospective bidirectional relationships between perceived stress and IBD symptoms but no relationship between perceived stress and change in intestinal inflammation as assessed by fecal calprotectin.

Gastrointestinal symptoms before and during menses in healthy women

BackgroundLittle is known as to the extent gastrointestinal (GI) complaints are reported by women around menses. We aimed to describe GI symptoms that occurred premenstrually and during menses in healthy women, and to specifically assess the relationship of emotional symptoms to GI symptoms around menses.MethodsWe recruited healthy, premenopausal adult women with no indication of GI, gynecologic, or psychiatric disease who were attending an outpatient gynecology clinic for well-woman care. They completed a survey that queried menstrual histories and the presence of GI and emotional symptoms. We compared the prevalence of primary GI symptoms (abdominal pain, diarrhea, constipation, nausea, vomiting), as well as pelvic pain and bloating, in the 5 days preceding menses and during menses, and assessed whether emotional symptoms or other factors were associated with the occurrence of GI symptoms.ResultsOf 156 respondents, 73% experienced at least one of the primary GI symptoms either pre- or during menses, with abdominal pain (58% pre; 55% during) and diarrhea (24% pre; 28% during) being the most common. Those experiencing any emotional symptoms versus those without were more likely to report multiple (2 or more) primary GI symptoms, both premenstrually (depressed p = 0.006; anxiety p = 0.014) and during menses (depressed p < 0.001; anxiety p = 0.008). Fatigue was also very common (53% pre; 49% during), and was significantly associated with multiple GI symptoms in both menstrual cycle phases (pre p < 0.001; during p = 0.01).ConclusionsEmotional symptoms occurring in conjunction with GI symptoms are common perimenstrually, and as such may reflect shared underlying processes that intersect brain, gut, and hormonal pathways.

Assessing the Relationship between Sources of Stress and Symptom Changes among Persons with IBD over Time: A Prospective Study

Objective. To describe the sources of stress for persons with IBD and changes with changes in symptoms. Methods. 487 participants were recruited from a population-based IBD registry. Stress was measured at study entry and three months later, using a general stress measure and the Sources of Stress Scale. Four symptom pattern groups were identified: persistently inactive, persistently active, inactive to active, and active to inactive. Results. General stress levels were stable within each symptom pattern group over the three-month period, even for those with changing symptom activity. The persistently active group had higher general stress at month 0 and month 3 than the persistently inactive group and higher mean ratings of most sources of stress. IBD was rated as a highly frequent source of stress by 20–30% of the persistently active group compared to 1-2% of the inactive group. Finances, work, and family were rated as high frequency stresses in the persistently active group at a similar level to IBD stress. In the groups with fluctuating symptoms, there was little change in stress ratings with changes in symptom activity. Conclusion. Stress was experienced across several domains in addition to stress related to IBD. Persons with active symptoms may benefit from targeted stress interventions.

Reply: To PMID 26077178.

Reply. We thank Drs Gracie and Ford for their summation and insightful commentary on our recent publication, which aimed to delineate the complex relationship between perceived stress, symptom reporting, and intestinal inflammation. They have effectively highlighted the main conclusions of our study: that the correlation between inflammatory bowel disease (IBD) symptom scores and markers of intestinal inflammation is poor, and that perceived stress may be playing an important role in increasing symptom burden and vice versa.

963 Sources of Concern Over Time in IBD: A Prospective Study of the Complex Relationship Between Symptomatic Disease Activity and Perceived Stress

Background: The incidence of Crohns disease (CD) and ulcerative colitis (UC) in the elderly population is reported to be increasing. Comorbid diseases, which are more prevalent with advanced age, may impact the natural history of inflammatory bowel disease (IBD) and treatments. We sought to characterize the population-based burden and outcomes of elderlyonset CD and UC in comparison to IBD of younger onset. Methods: We identified incident cases of IBD in Ontario, Canada between 1999 and 2008 from health administrative databases at the Institute for Clinical Evaluative Sciences using algorithms that were validated specifically in Ontario. The primary outcomes were hospitalizations and first IBD-related surgery. We compared groups defined by age at diagnosis: young adult (18-44y); middle-adult (45-64y); and elderly (≥65y) in univariate and regression analysis. Comorbidity was assessed using the validated Johns Hopkins Adjusted Clinical Group (ACG) case-mix system. Results: There were 8,985 incident cases of CD and 12,233 incident cases of UC during the study period. Of these, 725 new cases of CD and 1,749 new cases of UC occurred in the elderly. There was a slightly greater female predominance among the elderly group. More than a quarter of elderly IBD patients (29% of CD; 26% of UC) were in the top quartile for ACG comorbidity score, which was about twice as frequent as the middle-adult group. The incidence of IBDrelated hospitalization adjusted for sex, ACG comorbidity, and geographic region was lower for elderly IBD subjects when compared with young adults in both CD (incidence rate ratio [IRR], 0.76; 95% CI: 0.69 0.83) and UC (IRR, 0.88; 95% CI: 0.82 0.96). The KaplanMeier survival curves for bowel surgery for UC and CD stratified by age at diagnosis are shown in Figure 1. The cumulative risk of CD-related bowel resection at 2, 5, and 10 years were 18%, 24%, and 31%, respectively for elderly CD patients which were similar to the 15%, 23%, and 30% cumulative risks observed in young adults with CD. In contrast, the cumulative risk of colectomy among elderly UC patients at 2, 5, and 10 years (9%, 14%, and 18%, respectively) was higher than that of middle-age adults (8%, 11%, and 15%, respectively) and young adults (7%, 10%, and 13%, respectively). The adjusted hazard ratio for colectomy among elderly UC patients compared with their young adult counterparts was 1.36 (95% CI: 1.18 1.57). Conclusion: In this population-based study, UC patients who were diagnosed after age 65 years incurred increased risk of colectomy compared to those diagnosed as young, or middle-age adults. It is unclear whether this was due to more a more aggressive disease course or a lower threshold for colectomy due to the potential adverse effects of immunosuppressive medical therapy.