Specific Transcriptome Changes Associated with Blood Pressure Reduction in Hypertensive Patients After Relaxation Response Training.

OBJECTIVE: Mind-body practices that elicit the relaxation response (RR) have been demonstrated to reduce blood pressure (BP) in essential hypertension (HTN) and may be an adjunct to antihypertensive drug therapy. However, the molecular mechanisms by which the RR reduces BP remain undefined. DESIGN: Genomic determinants associated with responsiveness to an 8-week RR-based mind-body intervention for lowering HTN in 13 stage 1 hypertensive patients classified as BP responders and 11 as nonresponders were identified. RESULTS: Transcriptome analysis in peripheral blood mononuclear cells identified 1771 genes regulated by the RR in responders. Biological process- and pathway-based analysis of transcriptome data demonstrated enrichment in the following gene categories: immune regulatory pathways and metabolism (among downregulated genes); glucose metabolism, cardiovascular system development, and circadian rhythm (among upregulated genes). Further in silico estimation of cell abundance from the microarray data showed enrichment of the anti-inflammatory M2 subtype of macrophages in BP responders. Nuclear factor-κB, vascular endothelial growth factor, and insulin were critical molecules emerging from interactive network analysis. CONCLUSIONS: These findings provide the first insights into the molecular mechanisms that are associated with the beneficial effects of the RR on HTN.

Advanced Metrics for Assessing Holistic Care: The "Epidaurus 2" Project.

In response to the challenge of military traumatic brain injury and posttraumatic stress disorder, the US military developed a wide range of holistic care modalities at the new Walter Reed National Military Medical Center, Bethesda, MD, from 2001 to 2017, guided by civilian expert consultation via the Epidaurus Project. These projects spanned a range from healing buildings to wellness initiatives and healing through nature, spirituality, and the arts. The next challenge was to develop whole-body metrics to guide the use of these therapies in clinical care. Under the "Epidaurus 2" Project, a national search produced 5 advanced metrics for measuring whole-body therapeutic effects: genomics, integrated stress biomarkers, language analysis, machine learning, and "Star Glyphs." This article describes the metrics, their current use in guiding holistic care at Walter Reed, and their potential for operationalizing personalized care, patient self-management, and the improvement of public health. Development of these metrics allows the scientific integration of holistic therapies with organ-system-based care, expanding the powers of medicine.

A Pilot, Randomized Controlled Study of Tai Chi With Passive and Active Controls in the Treatment of Depressed Chinese Americans.

OBJECTIVE: This pilot, randomized clinical trial investigates the effectiveness of tai chi as the primary treatment for Chinese Americans with major depressive disorder (MDD). METHODS: 67 Chinese Americans with DSM-IV MDD and no treatment for depression were recruited between March 2012 and April 2013 and randomized (1:1:1) into a tai chi intervention, an education program, or a waitlisted group for 12 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17); positive response for this outcome was defined as a decrease in total score of 50% or more, and remission was defined as HDRS17 ≤ 7. RESULTS: Participants (N = 67) were 72% female with a mean age of 54 ± 13 years. No serious adverse events were reported. After the end of the 12-week intervention, response rates were 25%, 21%, and 56%, and remission rates were 10%, 21%, and 50% for the waitlisted, education, and tai chi intervention groups, respectively. The tai chi group showed improved treatment response when compared to both the waitlisted group (odds ratio [OR] = 2.11; 95% CI, 1.01-4.46) and to the education group (OR = 8.90; 95% CI, 1.17-67.70). Tai chi intervention showed significantly improved remission rate over the waitlisted group (OR = 3.01; 95% CI, 1.25-7.10), and a trend of improved remission compared to the education group (OR = 4.40; 95% CI, 0.78-24.17). CONCLUSIONS: As the primary treatment, tai chi improved treatment outcomes for Chinese Americans with MDD over both passive and active control groups. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01619631.

Correction: Genomic Counter-Stress Changes Induced by the Relaxation Response.

[This corrects the article DOI: 10.1371/journal.pone.0002576.].

Correction: The Feasibility and Impact of Delivering a Mind-Body Intervention in a Virtual World.

[This corrects the article DOI: 10.1371/journal.pone.0033843.].

Correction: Relaxation Response and Resiliency Training and Its Effect on Healthcare Resource Utilization.

[This corrects the article DOI: 10.1371/journal.pone.0140212.].

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.].

Correction: Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways.

[This corrects the article DOI: 10.1371/journal.pone.0062817.].

The effect of meditative movement on sleep quality: A systematic review.

The purpose of this systematic review was to identify and assess evidence related to the efficacy of meditative movement (MM) on sleep quality. We conducted a comprehensive review of relevant studies drawn from English and Chinese databases. Only randomized controlled trials (RCTs) reporting outcomes of the effects of MM (tai chi, qi gong, and yoga) on sleep quality were taken into consideration. Twenty-seven RCTs fulfilled our inclusion criteria and formed the basis for this review. Due to clinical heterogeneity, no meta-analysis was performed. Seventeen studies received a Jadad score of ≥3 and were considered high-quality studies. Findings of the 17 studies showed that MM has beneficial effects for various populations on a range of sleep measures. Improvement in sleep quality was reported in the majority of studies and was often accompanied by improvements in quality of life, physical performance, and depression. However, studies to date generally have significant methodological limitations. Additional RCTs with rigorous research designs focusing on sleep quality or insomnia and testing specific hypotheses are needed to clearly establish the efficacy of MM in improving sleep quality and its potential use as an intervention for various populations.

Relaxation Response and Resiliency Training and Its Effect on Healthcare Resource Utilization.

BACKGROUND: Poor psychological and physical resilience in response to stress drives a great deal of health care utilization. Mind-body interventions can reduce stress and build resiliency. The rationale for this study is therefore to estimate the effect of mind-body interventions on healthcare utilization. OBJECTIVE: Estimate the effect of mind body training, specifically, the Relaxation Response Resiliency Program (3RP) on healthcare utilization. DESIGN: Retrospective controlled cohort observational study. SETTING: Major US Academic Health Network. SAMPLE: All patients receiving 3RP at the MGH Benson-Henry Institute from 1/12/2006 to 7/1/2014 (n = 4452), controls (n = 13149) followed for a median of 4.2 years (.85-8.4 yrs). MEASUREMENTS: Utilization as measured by billable encounters/year (be/yr) stratified by encounter type: clinical, imaging, laboratory and procedural, by class of chief complaint: e.g., Cardiovascular, and by site of care delivery, e.g., Emergency Department. Subgroup analysis by propensity score matched pre-intervention utilization rate. RESULTS: At one year, total utilization for the intervention group decreased by 43% [53.5 to 30.5 be/yr] (p <0.0001). Clinical encounters decreased by 41.9% [40 to 23.2 be/yr], imaging by 50.3% [11.5 to 5.7 be/yr], lab encounters by 43.5% [9.8 to 5.6], and procedures by 21.4% [2.2 to 1.7 be/yr], all p < 0.01. The intervention group's Emergency department (ED) visits decreased from 3.6 to 1.7/year (p<0.0001) and Hospital and Urgent care visits converged with the controls. Subgroup analysis (identically matched initial utilization rates-Intervention group: high utilizing controls) showed the intervention group significantly reduced utilization relative to the control group by: 18.3% across all functional categories, 24.7% across all site categories and 25.3% across all clinical categories. CONCLUSION: Mind body interventions such as 3RP have the potential to substantially reduce healthcare utilization at relatively low cost and thus can serve as key components in any population health and health care delivery system.

The effectiveness of a brief mind-body intervention for treating depression in community health center patients.

OBJECTIVE: The objective of this pilot study was to examine the effects of a brief, 6-week, 1.5-hour mind-body intervention for depression (MBID) in patients being treated for depression in 2 community health centers. DESIGN: The MBID taught techniques such as meditation that elicit the relaxation response (RR) in combination with additional resiliency-enhancing components. Clinical outcomes of 24 depressed patients were measured pre-MBID, at completion of MBID, and 3 months post-MBID, using the Center for Epidemiological Studies Depression Scale (CES-D 10), Quality of Life Scale (QoL5), SF-12 Health Survey (SF-12), and Health-Promoting Lifestyle Profile-II (HPLP-II). RESULTS: Significant post-treatment improvements were shown in depressive symptoms, spiritual growth, mental health, and quality of life, with a median CES-D 10 change from 17.5 (interquartile ratio [IQR] 13.3-22) to 12 (IQR 10-17.5; P<.001); a median HPLP-II Spiritual Growth subscale change from 2.0 (IQR 1.8-2.3) to 2.3 (IQR 2.0-3.0; P=.002) and a median HPLP-II Stress Management subscale change from 2.0 (IQR 1.8-2.4) to 2.4 (IQR 2.0-2.9; P=.027); significant improvement in median score on the QoL-5 from 53.3 (IQR 47.5-62.5) at baseline to 63.3 at endpoint (IQR 50-70; P=.008). Three-month follow-up data suggest that the improvement in outcomes were sustained 3 months after the intervention. CONCLUSIONS: Participation in a 6-week RR-based MBID is associated with an improvement in depression, spiritual growth, and mental health among depressed community health center patients.

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 NCT02136745.

Teacher-led relaxation response curriculum in an urban high school: impact on student behavioral health and classroom environment.

CONTEXT: Recent data suggest that severe stress during the adolescent period is becoming a problem of epidemic proportions. Elicitation of the relaxation response (RR) has been shown to be effective in treating anxiety, reducing stress, and increasing positive health behaviors. OBJECTIVE: The research team's objective was to assess the impact of an RR-based curriculum, led by teachers, on the psychological status and health management behaviors of high-school students and to determine whether a train-the-trainer model would be feasible in a high-school setting. DESIGN: The research team designed a pilot study. SETTING: The setting was a Horace Mann charter school within Boston's public school system. PARTICIPANTS: Participants were teachers and students at the charter school. INTERVENTION: The team taught teachers a curriculum that included (1) relaxation strategies, such as breathing and imagery; (2) psychoeducation regarding mind-body pathways; and (3) positive psychology. Teachers implemented this curriculum with students. OUTCOME MEASURES: The research team assessed changes in student outcomes (eg, stress, anxiety, and stress management behaviors) using preintervention/postintervention surveys, including the Perceived Stress Scale (PSS), the State-Trait Anxiety Inventory-Form Y (STAI-Y), the stress management subscale of the Health-promoting Lifestyle Profile II (HPLP-II), the Rosenberg Self-Esteem Scale (RSES), the Locus of Control (LOC) questionnaire, and the Life Orientation Test-Revised (LOTR). Classroom observations using the Classroom Assessment Scoring System (CLASS)-Secondary were also completed to assess changes in classroom environment. RESULTS: Using a Bonferroni correction (P < .007), the study found that students experienced a significant reduction (P < .001) in measures of state-level anxiety on the STAI from pre- to postintervention. The study also found an increase in the use of stress management behaviors at that point. Using a Bonferroni correction (P < .007), the study found that students had significantly less perceived stress (P < .001), less state anxiety (P < .001) and trait anxiety (P < . 001), and increased use of positive stress management behaviors (P < .004) at the follow-up assessment in the fall of the following year. Using a Bonferroni correction (P < .002), the study found a significant increase in overall classroom productivity (eg, increased time spent on activities and instruction from pre- to postintervention). CONCLUSIONS: This study showed that teachers can lead an RR curriculum with fidelity and suggests that such a curriculum has positive benefits on student emotional and behavioral health and on classroom functioning.

Standardised mindfulness-based interventions in healthcare: an overview of systematic reviews and meta-analyses of RCTs.

BACKGROUND: Mindfulness-based therapies are being used in a wide range of common chronic conditions in both treatment and prevention despite lack of consensus about their effectiveness in different patient categories. OBJECTIVE: To systematically review the evidence of effectiveness MBSR and MBCT in different patient categories. METHODS: A systematic review and meta-analysis of systematic reviews of RCTs, using the standardized MBSR or MBCT programs. We used PRISMA guidelines to assess the quality of the included reviews and performed a random effects meta-analysis with main outcome measure Cohen's d. All types of participants were considered. RESULTS: The search produced 187 reviews: 23 were included, covering 115 unique RCTs and 8,683 unique individuals with various conditions. Compared to wait list control and compared to treatment as usual, MBSR and MBCT significantly improved depressive symptoms (d=0.37; 95%CI 0.28 to 0.45, based on 5 reviews, N=2814), anxiety (d=0.49; 95%CI 0.37 to 0.61, based on 4 reviews, N=2525), stress (d=0.51; 95%CI 0.36 to 0.67, based on 2 reviews, N=1570), quality of life (d=0.39; 95%CI 0.08 to 0.70, based on 2 reviews, N=511) and physical functioning (d=0.27; 95%CI 0.12 to 0.42, based on 3 reviews, N=1015). Limitations include heterogeneity within patient categories, risk of publication bias and limited long-term follow-up in several studies. CONCLUSION: The evidence supports the use of MBSR and MBCT to alleviate symptoms, both mental and physical, in the adjunct treatment of cancer, cardiovascular disease, chronic pain, depression, anxiety disorders and in prevention in healthy adults and children.

Effectiveness of the relaxation response-based group intervention for treating depressed chinese american immigrants: a pilot study.

BACKGROUND: This study examined the feasibility, safety and efficacy of an 8-week Relaxation Response (RR)-based group. METHODS: Twenty-two depressed Chinese American immigrants were recruited. Outcomes measures were response and remission rates, the Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and the Multidimensional Scale of Perceived Social Support Scale. RESULTS: Participants (N = 22) were 82% female, mean age was 53 (± 12). After intervention, completers (N = 15) showed a 40% response rate and a 27% remission rate, and statistically significant improvement in most outcome measures. DISCUSSION: The RR-based group is feasible and safe in treating Chinese American immigrants with depression.

The effectiveness of a community-based, mind-body group for symptoms of depression and anxiety.

CONTEXT: The prevalence of depression and other mental health conditions is on the rise, with an estimated 350 million people affected. Populations with lower socioeconomic status are at higher risk for mental health problems, including depression and anxiety. Community health centers (CHCs) often have wait lists for individual counseling. Group mind-body interventions (MBIs) that are based on the relaxation response (RR) are plausible options for treating mental health conditions at CHCs. OBJECTIVE: The study examined the feasibility and effectiveness of an 8-wk MBI developed at the Benson-Henry Institute for Mind Body Medicine (BHI) for treatment of symptoms of depression and anxiety in a community-based population. DESIGN: The research team designed a retrospective, open-label study of 124 patients with symptoms of depression or anxiety enrolled in an MBI as a group. SETTING: The setting for the study was 2 CHCs at Massachusetts General Hospital (MGH) in Boston, MA, USA. PARTICIPANTS: Participants were adult patients at MGH with symptoms of depression and/or anxiety. The program was billed as treatment related to behavioral health and accessible to people with all levels of education. INTERVENTION: The MBI for depression and/or anxiety in the current study teaches techniques that elicit a relaxation response (RR), in combination with additional resiliencyenhancing components. OUTCOME MEASURES: To examine effects of the program, self-report clinical measures were administered pre- and postintervention: (1) for depression, the Center for Epidemiologic Studies Depression Scale (CES-D10); (2) for anxiety, the State-Trait Anxiety Inventory-State Subscale (STAI-State); and (3) for perceived stress, the Perceived Stress Scale (PSS-10). RESULTS: The intervention was associated with a significant decrease in depressive symptoms: 95% CI, -6.0 to -2.6 (P < .001); anxiety--95% CI -12.6 to -2.2 (P = .007); and perceived stress--95% CI -7.6 to -2.0 (P = .001). Approximately 52.4% of the participants completed at least 75% of the 8 sessions, with 5 sessions attended on average. CONCLUSIONS: Participation in this MBI was associated with an improvement in symptoms of depression and anxiety as well as decreases in perceived stress among CHC patients.

The effects of tai chi on depression, anxiety, and psychological well-being: a systematic review and meta-analysis.

BACKGROUND: Tai chi, also called taiji or tai chi chuan, is a form of mind-body exercise that originated from China. It combines Chinese martial arts and meditative movements that promote balance and healing of the mind and body, involving a series of slowly performed, dance-like postures that flow into one another. As it comprises mental concentration, physical balance, muscle relaxation, and relaxed breathing, tai chi shows great potential for becoming widely integrated into the prevention and rehabilitation of a number of medical and psychological conditions. PURPOSE: A growing body of clinical research has begun to evaluate the efficacy of tai chi as a therapy for a variety of health issues. A systematic review and meta-analysis were carried out on randomized controlled trials (RCTs) and quasi-experimental (Q-E) trials that studied the effects of tai chi on psychological well-being. METHOD: Drawn from English and Chinese databases, 37 RCTs and 5 Q-E studies published up to May 31, 2013 were included in the systematic review. The methodological quality of the RCTs was evaluated based on the following criteria: adequate sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting, and other potential biases. Statistical analyses were performed using Review Manager version 5.0. RESULTS: The studies in this review demonstrated that tai chi interventions have beneficial effects for various populations on a range of psychological well-being measures, including depression, anxiety, general stress management, and exercise self-efficacy. Meta-analysis was performed on three RCTs that used depression as an outcome measure (ES=-5.97; 95% CI -7.06 to -4.87), with I2=0%. CONCLUSION: In spite of the positive outcomes, the studies to date generally had significant methodological limitations. More RCTs with rigorous research design are needed to establish the efficacy of tai chi in improving psychological well-being and its potential to be used in interventions for populations with various clinical conditions.

The effectiveness of a comprehensive mind body weight loss intervention for overweight and obese adults: a pilot study.

OBJECTIVES: This pilot study evaluated the effectiveness of a comprehensive mind body intervention for weight loss in overweight and obesity and the maintenance of weight loss at 6-month follow-up. DESIGN: Thirty-one overweight and obese employees (Body Mass Index (BMI) 28.6-47.9 kg/m²) from a large corporation participated in a 20-week comprehensive mind body intervention targeting weight loss. MAIN OUTCOME MEASURES: Weight, BMI, waist and hip circumference, rate pressure product (RPP), blood pressure, fasting blood glucose, cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and psychological variables were collected at baseline, post-intervention, and 6-month follow-up. RESULTS: Using linear mixed model analyses, the intervention resulted in significant mean weight loss (-4.3 kg, 95% CI -5.8 to -2.8), decreases in BMI (-1.51, 95% CI -2.1 to -1.0), hip circumference measurement (-4.3 cm, 95% CI -6.9 to -1.5), and triglyceride levels (95% CI -33.1 to -4.8). In 6-month follow-up after intervention, statistically significant improvements in weight, BMI and waist measurement were sustained. Participants also showed positive changes in self-reported psychological indices: food-related disinhibition, and hunger both decreased significantly (p<0.01); general self-efficacy increased (p<0.05); positive affect increased (p<0.001); physical function and self-esteem increased (p<0.01); and measures of health-promoting behaviors on 4 subscales (health responsibility, physical activity, nutrition, and stress management) also showed statistically significant improvements (p<0.001) at post-intervention and 6-month follow-up. CONCLUSIONS: This comprehensive mind body intervention showed modest effects on physical, laboratory, and psychological outcomes, both immediately following treatment and at 6-month follow-up, in overweight and obese individuals.

The treatment of depressed chinese americans using qigong in a health care setting: a pilot study.

Background. This pilot study examined the feasibility and efficacy of providing Qigong treatment in a health center to Chinese Americans with major depressive disorder (MDD). Methods. Fourteen Chinese Americans with MDD were enrolled, and they received a 12-week Qigong intervention. The key outcome measurement was the 17-item Hamilton Rating Scale for Depression (HAM-D17); the Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), and the Multidimensional Scale of Perceived Social Support (MSPSS) were also administered. Positive response was defined as a decrease of 50% or more on the HAM-D17, and remission was defined as HAM-D17 ≤ 7. Patients' outcome measurements were compared before and after the Qigong intervention. Results. Participants (N = 14) were 64% female, with a mean age of 53 (±14). A 71% of participants completed the intervention. The Qigong intervention resulted in a positive treatment-response rate of 60% and a remission rate of 40% and statistically significant improvement, as measured by the HAM-D17, CGI-S, CGI-I, Q-LES-Q-SF, and the family support subscale of the MSPSS. Conclusions. The Qigong intervention provided at a health care setting for the treatment of primary care patients with MDD is feasible. Further studies with larger sample sizes are warranted.