Comprehensive Lifestyle Modification Influences Medium-Term and Artificially Induced Stress in Ulcerative Colitis-A Sub-Study within a Randomized Controlled Trial Using the Trier Social Stress Test.

OBJECTIVE: The present study presents long-term results of stress-related outcomes of a prospective RCT that evaluated effects of a ten-week comprehensive lifestyle-modification program (LSM) in patients with inactive ulcerative colitis (UC). In addition, exploratory results of a sub-study applying a laboratory stress protocol (Trier Social Stress Test; TSST) conducted within the RCT are reported. METHODS: Ninety-seven patients with inactive UC were randomized to LSM (n = 47; 50.28 ± 11.90 years; 72.3% female) or self-care (n = 50; 45.54 ± 12.49 years; 70% female). Patients' perceived stress, anxiety, flourishing and depression were assessed at week 0, 12, 24 and 48. After the respective intervention, 16 female patients (LSM: n = 8; 44.6 ± 14.3 years; Self-care: n = 8; 49.25 ± 4.30 years) additionally underwent the TSST. State anxiety, blood pressure, pulse, complete blood counts, adrenocorticotropic hormone (ACTH), cortisol, adrenalin and noradrenalin were measured at baseline (-15 min), stress (+10 min), recovery1 (+20 min) and recovery2 (+55 min). Statistical significance was set at p < 0.05; for the exploratory sub-study using the TSST, p-values < 0.10 were considered significant. RESULTS: Patients' perceived stress declined significantly after the LSM (p < 0.001) compared with control. This lasted until week 24 (p = 0.023) but did not persist until week 48 (p = 0.060). After 48 weeks, patients' flourishing was significantly increased compared with control (p = 0.006). In response to the TSST, significant group differences were evident for pulse (p = 0.015), adrenaline (p = 0.037) and anxiety (p = 0.066). After 55 min, group differences were found for ACTH (p = 0.067) and systolic blood pressure (p = 0.050). CONCLUSIONS: LSM has a medium-term positive effect on perceived stress. First indications show that it is promising to investigate these effects further under laboratory conditions. It is also desirable to find out how the effects of LSM can be maintained in the long term.

Comprehensive Lifestyle-Modification in Patients with Ulcerative Colitis-A Randomized Controlled Trial.

Patients with ulcerative colitis suffer from impaired health-related quality of life (HrQoL). Comprehensive lifestyle-modification might increase HrQoL and decrease disease activity. Ninety-seven patients in clinical remission with impaired HrQoL were randomly assigned to a 10 week comprehensive lifestyle-modification program (LSM; n = 47; 50.28 ± 11.90 years) or control (n = 50; 45.54 ± 12.49 years) that received a single workshop of intense training in naturopathic self-help strategies. Primary outcome was HrQoL (Inflammatory Bowel Disease Questionnaire; IBDQ) at week 12. Secondary outcomes included IBDQ subscales; generic HrQoL; disease activity and microbiome. Both groups showed improvement in HrQoL from baseline to post-treatment at week 12. The IBDQ sum score showed no significant group difference (p = 0.251). If patients attended more than 50% of the training sessions, a significant group effect (p = 0.034) was evident in favor of LSM. In addition, the SF-36 mental component summary (p = 0.002) was significantly different between the groups in favor of LSM. Disease activity microbiome and adverse events did not differ. Both a single workshop and a 10-week comprehensive lifestyle-modification program can improve HrQoL in patients with ulcerative colitis in remission with no apparent effects on clinical disease activity. A treatment difference was observed when examining a subsample of patients who attended ≥ 50% of sessions.

Perceived stress mediates the effect of yoga on quality of life and disease activity in ulcerative colitis. Secondary analysis of a randomized controlled trial.

OBJECTIVE: Yoga positively affects health-related quality of life and disease activity in ulcerative colitis. The underlying modes of action remain unclear. Within the present study we hypothesized that patients´ perceived stress mediates the effects of yoga on health-related quality of life and disease activity. METHODS: This is a secondary analysis of a randomized controlled trial comparing the effects of yoga to written self-care advice in patients with inactive ulcerative colitis and impaired quality of life. Perceived stress was assessed using the Perceived Stress Questionnaire, health-related quality of life using the Inflammatory Bowel Disease Questionnaire and disease activity using the Clinical Activity Index. Outcomes were assessed at weeks 0, 12 and 24. RESULTS: Seventy-seven patients participated. Thirty-nine patients attended the 12 supervised weekly yoga sessions (71.8% women; 45.0 ± 13.3 years) and 38 patients written self-care advice (78.9% women; 46.1 ± 10.4 years). Perceived stress correlated significantly with health-related quality of life and disease activity at week 24. Perceived stress at week 12 fully mediated the effects of yoga on health-related quality of life (B = 16.23; 95% Confidence interval [6.73; 28.40]) and disease activity (B = -0.28; 95% Confidence interval [-0.56; -0.06]) at week 24. CONCLUSION: Our findings confirm the importance of perceived stress in reducing disease activity and increasing health-related quality of life in patients with ulcerative colitis and impaired quality of life. Practitioners should keep psychosocial risk in mind as a risk factor for disease exacerbation, and consider yoga as an adjunct intervention for highly stressed patients with ulcerative colitis. CLINICALTRIALS. GOV REGISTRATION NUMBER: The trial was registered at clinicaltrials.gov prior to patient recruitment (registration number NCT02043600).

Stress burden and neuroendocrine regulation of cytokine production in patients with ulcerative colitis in remission.

Stress demonstrably contributes to disease course in patients with inflammatory bowel diseases but the underlying mechanisms remain elusive. Here, we investigated if neuroendocrine regulation of pro- and anti-inflammatory cytokine production by peripheral blood immune cells is altered in patients with ulcerative colitis in remission (UCR). Using a whole blood stimulation assay, we measured the sensitivity of lipopolysaccharide (LPS)-induced TNF-α and IL-10 production to the glucocorticoid receptor agonist dexamethasone (DEX), the ß2-adrenergic receptor agonist terbutaline (TERB), and the α7-nicotinic acetylcholine receptor agonist 3-[2,4-dimethoxy-benzylidene]-anabaseine (GTS-21) in UCR patients (N = 26) and in healthy controls (HC, N = 25). Additionally, we assessed anxiety and depression symptoms as well as chronic perceived stress and disease-specific quality of life. Results showed that UCR patients exhibited greater anxiety, depression and chronic stress levels than HC, and reduced disease-specific quality of life. Plasma concentrations of TNF-α, IL-8, C-reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were significantly higher, while LPS-induced IL-10 production was substantially lower in UCR compared to HC. Independent of group, DEX and GTS-21 dose-dependently inhibited TNF-α and IL-10 production, whereas TERB inhibited TNF-α and upregulated IL-10 production. However, at higher TERB doses (i.e., stress levels), upregulation of IL-10 production was significantly diminished in UCR compared to HC. Together, these findings demonstrate that downregulation of pro-inflammatory cytokine production in peripheral blood immune cells through glucocorticoid, adrenergic, and cholinergic mechanisms is essentially normal in UC in clinical remission and as efficient as in healthy individuals. However, UCR patients exhibited signs of systemic low-grade inflammation and dysregulation of anti-inflammatory IL-10 production. Impaired adrenergic upregulation of IL-10 production during remission could be one mechanism how stress facilitates relapse and conversion to symptomatic disease in these patients.

Effects of acute psychological stress on placebo and nocebo responses in a clinically relevant model of visceroception.

There is evidence to suggest a role of emotions in placebo and nocebo effects, but whether acute psychological stress changes the magnitude of placebo or nocebo responses has not been tested. In a clinically relevant model of visceroception, we assessed effects of acute psychological stress on changes in urgency and pain in response to positive or negative treatment suggestions. In 120 healthy volunteers, perceived urge-to-defecate and pain in response to individually calibrated rectal distensions were measured with visual analogue scales during a BASELINE. Participants then underwent the Trier Social Stress Test (N = 60) or a simple cognitive task (control, N = 60) and were randomized to positive (placebo), negative (nocebo), or neutral treatment information regarding intravenous administration of saline. The series of distensions was repeated, and changes in visual analogue scales from BASELINE to TEST were compared between groups using analysis of covariance and planned post hoc tests. Treatment information emerged as a main factor (P <0.001), supporting treatment information effects for both urgency and pain. Effects for urgency were modulated by stress (interaction effect: P <0.05): Positive information reduced urgency (P = 0.025), while negative information increased urgency (P = 0.026) only in stressed groups. For pain, effects of stress emerged for nocebo responses, which were only evident in stressed groups (P = 0.009). This is the first experimental study supporting effects of acute psychological stress on placebo and nocebo responses in visceroception. Results call for mechanistic as well as patient studies to assess how psychological stress shapes patients' treatment expectations and thereby affects health outcomes.