Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

Introduction: Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods: Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results: Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions: In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding. Trial Registration ClinicalTrials.Gov NCT0213674

Enhancing exposure therapy with acute exercise : an initial test

Exposure-based therapies are one of the most effective strategies for treating a large range of anxiety disorders; yet there remains a substantial (20-50%) non-response rate. Since exposure therapies are based on fear extinction principles, strategies that can enhance the acquisition and retention of fear extinction memories should, theoretically, facilitate the outcome of exposure therapy. Pharmacological agents acting as cognitive enhancers have shown some effectiveness in augmenting exposure therapy. Aerobic exercise may similarly act as a cognitive enhancer as it has been shown to affect learning and memory processes broadly. The current study builds upon the extant literature by conducting an initial test of the efficacy of acute aerobic exercise for enhancing exposure therapy outcomes. Adults with a marked fear of heights were randomized to either 30-minutes of vigorous aerobic exercise or rest immediately prior to 30-minutes of virtual reality exposure therapy (VRET). Participants’ fear of heights was assessed 1- and 2-weeks later by clinician ratings and self-report questionnaires. On average, participants showed significant decreases in fear of heights from baseline to 1- and 2-weeks post-VRET, but these changes did not significantly differ by treatment condition. This remained true even after including potential moderators of treatment condition. These findings do not support acute exercise as an augmentation strategy for exposure therapy. Clinical and research implications are discussed.Psycholog

Exercise for mental health

With its far reaching physical and mental health benefits, exercise has the potential of being a strong transdiagnostic treatment tool in the arsenal of a clinician. This dissertation addresses how exercise may facilitate treatment goals by intervening on key mechanisms underlying the maintenance and amelioration of anxiety and depressed mood. This dissertation details three studies designed to introduce and generate further lines of inquiry related to the specific application of exercise in a clinical setting: 1) What are the mechanisms underlying the mental health benefits of exercise? 2) Can specific mental health benefits of exercise be harnessed to broadly facilitate the process of psychotherapy? And 3) What dose of exercise is required to obtain specific treatment outcomes? Specifically, the first study investigated whether exercise can serve as a method to learn arousal reappraisal techniques, thereby improving an individual’s ability to manage stressful events. The results from the first study provided initial evidence that exercise can facilitate learning arousal reappraisal techniques and this learning may help reduce stress reactivity. The second study examined the efficacy of acute aerobic exercise to augment exposure therapy for acrophobia. The results from the second study provided no evidence that exercise immediately prior to an exposure therapy session facilitates exposure therapy outcomes. The final study examined how attendance relates to the efficacy of an exercise-aided smoking cessation intervention for individuals with high anxiety sensitivity. The results from the third study suggested early treatment discontinuation did not impact the efficacy of an exercise-aided smoking cessation intervention. The studies reported on in this dissertation add to an ever-growing area of research regarding the application of exercise for improving mental health. By continuing to pursue and expand these lines of research, exercise intervention parameters may be optimized to achieve specific mental health benefits. Equipped with such knowledge, exercise can become a widely available, easily accessible treatment method many clinicians could offer their patients. Having accessible a range of strategies that engage therapeutic targets allows clinicians to attend to patient preferences and needs when seeking to ameliorate mental health disorders.Psycholog

Correction: Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease.

[This corrects the article DOI: 10.1371/journal.pone.0123861.]

Outcome measures after intervention and at 3-week follow-up for irritable bowel syndrome (IBS) (N = 19) and inflammatory bowel disease (IBD) (N = 29).

<p>*P<0.05</p><p>**P<0.01</p><p>***P<0.001</p><p>Indicate mixed model analysis estimating change from baseline scores</p><p>Outcome measures after intervention and at 3-week follow-up for irritable bowel syndrome (IBS) (N = 19) and inflammatory bowel disease (IBD) (N = 29).</p

Network representation of the biological functions significantly altered by 8-weeks of RR-MBI in IBD patients.

<p>Networks shown: A) Cellular morphology and tissue development related genes with UBC, MAPK8, NF-κB and ERK1/2 as primary regulatory nodes; B) Genes involved in cell death, apoptosis and inflammation with UBC, APP and IRF7 as a critical regulatory node. We used the Ingenuity Pathways Analysis tool (IPA 8.0) to generate the networks of genes altered by RR-MBI in <b>IBD</b> patients and merged the major networks with obvious related functions. Each node represents a gene and each edge represent a molecular interaction. The intensity of the node color indicates the degree of upregulation (red) and downregulation (green), while white nodes indicate non-modified genes that may be affected in a non-transcriptional manner.</p

State-Trait Anxiety Inventory (STAI)—Trait scores at each of the four time points.

<p>STAI—Trait scores at each of the four time points in Irritable Bowel Syndrome (<b>IBS</b>, light bars, top) and Inflammatory Bowel Disease (<b>IBD</b>, dark bars, bottom). (*p<0.05, **p<0.01).</p

CONSORT Enrollment diagram.

<p>CONSORT Enrollment diagram.</p

Disease-specific quality of life and symptom measures at each of the four time points.

<p>A) Irritable Bowel Syndrome Quality of Life (<b>IBS</b>-QOL) scores; lower scores indicate improvement. B) Irritable Bowel Syndrome Symptom Severity Index (<b>IBS</b>-SSI) scores; lower scores indicate improvement. C) Inflammatory Bowel Disease Questionnaire (<b>IBD</b>-Q) scores; higher scores indicate improvement. *p<0.05, **p<0.01, ***p<0.001.</p

The syllabus for the relaxation response-based group mind body intervention (RR-MBI) for irritable bowel syndrome or inflammatory bowel disease.

<p>Session content varied by week but always included an activity that elicited the relaxation response (RR) and a discussion of the homework from the previous week. Homework for the sessions included eliciting the RR daily, daily mini-relaxation exercises, filling out a diary sheet, making an entry in an appreciation journal, and practicing cognitive restructuring exercises and other skills previously learned.</p><p>The syllabus for the relaxation response-based group mind body intervention (RR-MBI) for irritable bowel syndrome or inflammatory bowel disease.</p