A Mind-Body Approach to Study Irritable Bowel Syndrome: Role of Psychological Distress, Effectiveness and Mechanisms of Mindfulness Training(2/3)

Aims: (1) To determine whether patients with depression have an increased risk of developing IBS compared with age- and urbanization-matched controls; to explore the gender difference in the relationship between depression and the risk of developing subsequent IBS. (2) To determine whether patients with anxiety have an increased risk of developing IBS compared with age- and urbanization-matched controls; to determine the gender difference in the relationship between depression/anxiety and the risk of developing subsequent IBS. (3) To examine the effectiveness of mindfulness training in comparison to an attention-control condition on symptom severity, depression, anxiety, and QOL in patients with IBS. (4) To determine the differences in resting-state functional magnetic resonance imaging (rsfMRI) between the mindfulness and the support groups; to determine the association between brain imaging data with symptom severity. Methods: For Aims 1 and 2, we will conduct two matched cohort studies and analyze data from the claims of the National Health Insurance program will be analyzed. Between January 1, 2000 and December 31, 2012, patients who were diagnosed with depression and those who were diagnosed with anxiety on at least two occasions will be identified from ambulatory and inpatient claims data by using ICD-9-CM codes. The study end point is a new diagnosis of IBS. Comorbidities frequently associated with IBS will also be identified. To identify IBS, the depression/anxiety and matched non-depression/non-anxiety cohorts will be tracked from the index date until the end of 2013 or loss to follow-up. A logistic regression method, in which depression/anxiety is regressed on baseline covariates, will be performed to estimate the propensity score. The propensity score-adjusted multivariate Cox proportional-hazards regression models will be performed to estimate the risk of new onset IBS for individuals with depression and individuals with anxiety. For Aims 3 and 4, we will conduct an assessor-blind, parallel-group, randomized controlled trial and enroll 80 participants with IBS. Participants will be randomized to an eight-week Mindfulness Group (MG) and an eight-week IBS Support Group (SG). Both the MG and the SG will undergo a one-week run-in period during which the participants record a daily symptom diary. The primary outcome is IBS severity score and the secondary outcomes include IBS-QOL, depression, and anxiety, which will be examined at baseline, post-training, and the 6th month follow-up. Data will be analyzed according to the intention-to-treat principle. To determine the effectiveness of mindfulness training on primary and secondary outcomes, differences in outcome variables will be analyzed with mixed-effects linear regression models with the covariance structure unstructured. The between-group differences at the two post-tests examined using a mixed-model will include group x time interaction. We will adjust for the baseline score on the outcome variable and for demographics and comorbidities that differ significantly between the intervention and control groups at baseline. The first 15 participants from each group will be tested for rsfMRI before and after the eight-week intervention period. We will use fractional amplitude of low-frequency fluctuation (fALFF) to identify region-specific abnormalities in resting-state brain function. Group differences in fALFF in the different frequency bands will be tested using linear contrast analyses. Associations between symptom severity and frequency oscillation shifts will be conducted by correlating IBS-SS with the frequency shifts.