The antidepressant effect of whole-body hyperthermia is associated with the classical interleukin-6 signaling pathway.

There is urgent need for novel antidepressant treatments that confer therapeutic benefits via engagement with identified mechanistic targets. The objective of the study was to determine whether activation of the classical anti-inflammatory interleukin-6 signaling pathways is associated with the antidepressant effects of whole-body hyperthermia. A 6-week, randomized, double-blind study compared whole-body hyperthermia with a sham condition in a university-based medical center. Medically healthy participants aged 18-65 years who met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score ≥ 16 were randomized with 1-to-1 allocation in blocks of 6 to receive whole-body hyperthermia or sham. Of 338 individuals screened, 34 were randomized, 30 received interventions and 26 had ≥ 2 blood draws and depressive symptom assessments. Secondary data analysis examined change in the ratio of IL-6:soluble IL-6 receptor pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling tested whether increased IL-6:soluble IL-6 receptor ratio post-intervention was associated with decreased depressive symptom at weeks 1, 2, 4 and 6 for those randomized to whole-body hyperthermia. Twenty-six individuals were randomized to whole-body hyperthermia [n = 12; 75 % female; age = 37.9 years (SD = 15.3) or sham [n = 14; 57.1 % female; age = 41.1 years (SD = 12.5). When compared to the sham condition, active whole-body hyperthermia only increased the IL-6:soluble IL-6 receptor ratio post-treatment [F(3,72) = 11.73,p < .001], but not pre-intervention or at weeks 1 and 4. Using hierarchical linear modeling, increased IL-6:sIL-6R ratio following whole-body hyperthermia moderated depressive symptoms at weeks 1, 2, 4 and 6, such that increases in the IL-6:soluble IL-6 receptor ratio were associated with decreased depressive symptoms at weeks 1, 2, 4 and 6 for those receiving the active whole-body hyperthermia compared to sham treatment (B = -229.44, t = -3.82,p < .001). Acute activation of classical intereukin-6 signaling might emerge as a heretofore unrecognized novel mechanism that could be harnessed to expand the antidepressant armamentarium.

Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder.

Whole-body hyperthermia (WBH) shows promise for the treatment of major depressive disorder (MDD). Because MDD is associated with increased inflammation, and anti-inflammatory agents show some promise as antidepressants, the current study sought to identify the acute and longer-term immune effects of WBH in participants with MDD and to explore whether these effects associate with the procedure's antidepressant properties. Thirty participants who met DSM-IV-TR criteria for MDD were randomized to receive a single session of WBH (n = 16) or sham treatment (n = 14). Hamilton Depression Rating Scale (HDRS) scores were assessed at baseline and 1, 2, 4, and 6 weeks post-treatment (WBH vs. sham), and plasma cytokine concentrations were assessed at baseline, immediately post-treatment, and 1 and 4 weeks post-treatment. As previously reported, WBH produced a rapid and sustained antidepressant effect. When compared to sham, WBH increased plasma interleukin (IL)-6 immediately post-treatment (time by treatment: χ2(3, N=108) = 47.33, p < 0.001), while having no effect on other cytokines acutely and no impact on IL-6, or any other cytokine, at 1 or 4 weeks post treatment. In the study sample as a whole, increased IL-6 post-treatment was associated with reduced HDRS depression scores over the 6 weeks of follow-up (F(1, 102.3) = 6.74, p = 0.01). These results suggest a hitherto unrecognized relationship between hyperthermia, the immune system, and depression, and may point to WBH as a novel modality for exploring behavioral effects of IL-6 when the cytokine is activated in isolation from the inflammatory mediators with which it frequently travels.

The Language of Compassion: Hospital Chaplains' Compassion Capacity Reduces Patient Depression via Other-Oriented, Inclusive Language.

Objectives: Although hospital chaplains play a critical role in delivering emotional and spiritual care to a broad range of both religious and non-religious patients, there is remarkably little research on the best practices or "active ingredients" of chaplain spiritual consults. Here, we examined how chaplains' compassion capacity was associated with their linguistic behavior with hospitalized inpatients, and how their language in turn related to patient outcomes. Methods: Hospital chaplains (n = 16) completed self-report measures that together were operationalized as self-reported "compassion capacity." Next, chaplains conducted consultations with inpatients (n = 101) in five hospitals. Consultations were audio-recorded, transcribed, and analyzed using Linguistic Inquiry Word Count (LIWC). We used exploratory structural equation modeling to identify associations between chaplain-reported compassion capacity, chaplain linguistic behavior, and patient depression after the consultation. Results: We found that compassion capacity was significantly associated with chaplains' LIWC clout scores, a variable that reflects a confident leadership, inclusive, and other-oriented linguistic style. Clout scores, in turn, were negatively associated with patient depression levels controlling for pre-consult distress, indicating that patients seen by chaplains displaying high levels of clout had lower levels of depression after the consultation. Compassion capacity exerted a statistically significant indirect effect on patient depression via increased clout language. Conclusions: These findings inform our understanding of the linguistic patterns underlying compassionate and effective chaplain-patient consultations and contribute to a deeper understanding of the skillful means by which compassion may be manifest to reduce suffering and enhance well-being in individuals at their most vulnerable.

A 30-Day Adjunct Wellness Intervention for the Management of Extra-Articular Symptoms of Rheumatoid Arthritis: A Formative Study.

Individuals with rheumatoid arthritis (RA) continually fall short of treatment targets using standard drug therapies alone. There is growing evidence that emphasizing physical and mental wellness is equally crucial for improving functioning among people with RA. The purpose of this formative study is to examine the feasibility of offering the wellness-based intervention ("KickStart30") in patients with RA. Thirteen individuals with RA on targeted immune modulators (a biologic or JAK inhibitor) enrolled in the KickStart30 program. Participants completed self-report measures of RA-specific disability (eg, pain) and other functional areas (eg, mood) in a pre- versus post- intervention design. Paired samples t-tests (and Related-Samples Wilcoxon Signed Rank Tests for non-normal distributions) detected statistically significant results for 10 of 12 measures, including reductions in pain (M = 4.54 to M = 3.54; p = .025; BPI), functional disability (M = 0.94 to M = 0.73, p = .032; HAQ-II), cognitive and physical dysfunction (M = 25.46 to M = 13.54, p < .001; CPFQ), depressive symptoms (M = 9.31 to M = 5.54, p = .003; PHQ-9), anxiety (M = 5.69 to M = 3.23, p = .005; GAD-7), insomnia (M = 11.62 to M = 17.32, p = .007; Note: higher scores on the SCI indicate less insomnia), stress-related eating (M = 75.46 to M = 84.54, p = .021; Note: higher scores on the EADES indicate less stress-related eating), along with significant increases in mindfulness (M = 62.54 to M = 67.85, p = .040; MAAS), mental wellness (M = 4.46 to M = 5.69; HERO), and well-being (Md = 8.00 to Md = 5.00, p = .004; WHO-5). All significant measures had medium to large effect sizes (Cohen's d). The study gives preliminary support for the possibility that the adjunct intervention may have an effect.

Effects of Naturalistic Psychedelic Use on Depression, Anxiety, and Well-Being: Associations With Patterns of Use, Reported Harms, and Transformative Mental States.

Survey-based studies suggest naturalistic psychedelic use provides mental health benefits similar to those observed in clinical trials. The current study sought to confirm these findings in a large group of psychedelic users and to conduct a novel examination of associations between amount of psychedelic use and behavioral outcomes, as well as frequency of harms ascribed to psychedelic use. A cross-sectional, online survey was completed by 2,510 adults reporting at least one lifetime psychedelic experience. Participants retrospectively completed a battery of instruments assessing depression, anxiety, and emotional well-being prior to and following psychedelic exposure. Participants also reported preferred psychedelic agent, number of uses, and harms attributed to psychedelic use. Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being. These improvements increased in magnitude with increasing psychedelic exposure, with a ceiling effect. However, improvements were noted following a single lifetime use. Strong evidence for benefit of one preferred psychedelic agent over another was not observed, but enduring increases in factors related to mystical-experience and prosocial perspective taking associated with enhanced mental health. Thirteen percent of the survey sample (n = 330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit. Results from the current study add to a growing database indicating that psychedelic use-even outside the context of clinical trials-may provide a wide range of mental health benefits, while also posing some risk for harm in a minority of individuals.

Impact of Mirrors on Body Image of Beginning Modern and Ballet Students.

This mixed methods study compared the impact of studio mirrors on body image in beginning level female collegiate modern dance and ballet students utilizing the Cash 69-item Body Self-Relations Questionnaire and semi-structured interviews. For the overall Body-Areas Satisfaction there was a statistically significant mirror condition x time interaction (p = 0.029); regardless of dance genre, students' body satisfaction in mirrored classes decreased. Specifically at the mid torso, a statistically significant class type x time interaction (p = 0.012) occurred; ballet dancers decreased in satisfaction. Interviews reflected that: 1. students in the mirrored classes spent more time discussing specific body parts with objectifying language; and 2. students in the non-mirrored classes spent more time describing their participation in dance in terms of kinesthetic sensations. These findings suggest that satisfaction with one's body in beginner ballet and modern classes may be compromised by the use of mirrors.

HERO Wellness Scale: Examining a new mental wellness scale.

BACKGROUND: Mental wellness has traditionally not been tracked by mental health clinicians. The aim is to examine the reliability and validity of the HERO Wellness Scale. METHODS: Eighty-four college students (age ≥18) with and without psychiatric morbidity from a small, private college in the north-central United States enrolled in the WILD 5 Wellness Program-a longitudinal, quasi-experimental clinical trial that included 2 groups (intervention and waitlist). Mental wellness scores at the beginning of the WILD 5 intervention were assessed by the HERO Wellness Scale and the World Health Organization-Five (WHO-5) Well-Being Index. RESULTS: Internal consistency was calculated from baseline data (N = 84) using Cronbach's alpha for the 5-item HERO composite = .93. The corrected item-total correlations were adequate (>.50), ranging from .67 (resilience) to .86 (mental wellness). The HERO Wellness Scale covers a representative sample of the domain of wellness. It diverges from WHO-5 items by specifically assessing for well-established positive psychology traits such as happiness, enthusiasm, resilience, and optimism. CONCLUSIONS: The HERO Wellness Scale showed good validity and reliability, and should be considered for individual-level assessment of mental wellness. The HERO Wellness Scale adds to the body of knowledge in psychiatry, nursing, and psychology.

Wellness Interventions in Psychiatrically Ill Patients: Impact of WILD 5 Wellness, a Five-Domain Mental Health Wellness Intervention on Depression, Anxiety, and Wellness.

BACKGROUND: The efficacy of individual wellness interventions are well studied in relation to their respective impacts on psychiatric and mental wellness. To date, there is limited research on programs that incorporate multiple wellness domains and measure psychiatric and wellness markers. AIM: To assess the psychiatric and wellness impact of a nonpharmacologic wellness intervention on subjects receiving psychiatric treatment. METHOD: Forty-one adults with a psychiatric disorder completed the first 30 days of WILD 5 Wellness (Wellness Interventions for Life's Demands), a 90-day self-management mental wellness program that incorporated exercise, mindfulness, sleep, social connectedness, and nutrition. Subjects recorded participation in both workbooks and online surveys. Participants were recruited nationally via online and outpatient clinic advertisements. Wellness and mental health were measured on Days 1 and 30 of the intervention via five instruments: the Patient Health Questionnaire-9 for mood, the Generalized Anxiety Disorder 7-Item Scale for anxiety, the Sleep Condition Indicator for sleep quality, the Sheehan Disability Scale for functionality in psychiatric patients, and the HERO Wellness Scale, which measures happiness, enthusiasm, resilience, optimism, and overall mental wellness. RESULTS: Subjects reported statistically significant improvements across all measures on Day 30. CONCLUSION: The research suggests that this multidomain wellness program may be a valuable adjunct to traditional psychiatric treatment and an accessible tool for all health care providers.

Benefits of Sequentially Adding Cognitive-Behavioral Therapy or Antidepressant Medication for Adults With Nonremitting Depression.

OBJECTIVE: Adults with major depressive disorder frequently do not achieve remission with an initial treatment. Addition of psychotherapy for patients who do not achieve remission with antidepressant medication alone can target residual symptoms and protect against recurrence, but the utility of adding antidepressant medication after nonremission with cognitive-behavioral therapy (CBT) has received little study. The authors aimed to evaluate the acute and long-term outcomes resulting from both sequences of combination treatments. METHODS: Previously untreated adults with major depression who were randomly assigned to receive escitalopram, duloxetine, or CBT monotherapy and completed 12 weeks of treatment without achieving remission entered an additional 12 weeks of combination treatment. For patients who did not achieve remission with CBT, escitalopram was added (CBT plus medication group) to their treatment, and for those who did not achieve remission with an antidepressant, CBT was added (medication plus CBT group) to their treatment. Patients who responded to the combination treatment entered an 18-month follow-up phase to assess risk of recurrence. RESULTS: A total of 112 patients who did not achieve remission with a monotherapy entered combination treatment (41 who responded to monotherapy but did not achieve remission and 71 who did not respond to monotherapy). Overall, remission rates after subsequent combination therapy were significantly higher among patients who responded to monotherapy but did not achieve remission (61%) than among patients who did not respond to monotherapy (41%). Among patients who responded to monotherapy but did not achieve remission, the remission rate in the CBT plus medication group (89%) was higher than in the medication plus CBT group (53%). However, among patients whose depression did not respond to monotherapy, rates of response and remission were similar between the treatment arms. Higher levels of anxiety, both prior to monotherapy and prior to beginning combination treatment, predicted poorer outcomes for both treatment groups. CONCLUSIONS: The order in which CBT and antidepressant medication were sequentially combined did not appear to affect outcomes. Addition of an antidepressant is an effective approach to treating residual symptoms for patients who do not achieve remission with CBT, as is adding CBT after antidepressant monotherapy. Patients who do not respond to one treatment modality warrant consideration for addition of the alternative modality.

Differential change on depressive symptom factors with antidepressant medication and cognitive behavior therapy for major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a heterogeneous condition and individual patients are likely to be differentially responsive to specific treatments. In an exploratory factor analysis of three rating scales, the Genome-based Therapeutic Drugs for Depression (GENDEP) trial identified three factors that were differentially associated with outcome to nortriptyline and escitalopram. However, this factor analysis has neither been replicated or applied to a psychotherapy treatment. METHODS: We replicated the GENDEP analytic method in the Emory Predictors of Remission to Individual and Combined Treatments (PReDICT) study. The 17-item Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, and Beck Depression Inventory were administered to 306 MDD patients in the PReDICT study, which randomized previously untreated adults to 12 weeks of treatment with cognitive behavior therapy (CBT), escitalopram, or duloxetine. Utilizing Item Response Theory methodologies, factor scores were derived from the three scales and the efficacy of the three treatments was compared for the identified factor scores. RESULTS: Four factors were identified: "Despair," "Mood and Interest," "Sleep," and "Appetite." These factors closely aligned with the factors identified in GENDEP. Compared to CBT, escitalopram and duloxetine produced more rapid but ultimately similar improvement on the Despair and Mood and Interest factors; no significant differences between treatments emerged on the other factors. LIMITATIONS: The scales contained differing numbers of items pertaining to specific depressive symptoms. CONCLUSION: The heterogeneity of MDD can be parsed into a consistent factor structure, with the factors showing differential rapidity, but ultimately similar, improvement across treatments.

Comparison Study of Body Image Satisfaction Between Beginning- and Advanced-Level Female Ballet Students.

This mixed methods study compares the level of satisfaction with one's body image between beginning- and advanced-level female collegiate ballet students. Thirty-six beginning-level students were enrolled in two ballet classes, and a second group of 16 advanced-level students was enrolled in a third class. A mirror was used in the teaching of both groups. During the first and thirteenth week of a 14-week semester, students completed the Cash 69-item Body Self-Relations Questionnaire. In addition, five students from each group were randomly selected to participate in semi-structured interviews during the second and last week of the semester. Researchers asked students questions about their kinesthetic experience and the mirror's role in the studio. The quantitative results indicated that over the course of the semester the beginning dancers decreased in feeling physically fit, while the advanced dancers felt more in shape. For both beginning and advanced dancers there was a decrease in body image satisfaction. By semester's end, the advanced dancers were more preoccupied with weight and exercised more than the beginning dancers. The interviews revealed that four out of the five beginning ballet students discussed the use of the mirror in class and reported experiencing thoughts and sensations characteristic of the objective self-awareness state, such as heightened self-consciousness, comparison of self to others, or negative self-evaluation. The advanced dancers, on the other hand, focused on developing ways to avoid the mirror and preferred to "feel" movements muscularly before using the mirror for feedback. Even though the advanced dancers had more knowledge of how to use a mirror beneficially in class, their body image scores were equally as compromised as the beginning students'. These results suggest that both beginning- and advanced-level ballet students experience a decrease in body image satisfaction in a mirrored studio environment.

Informed Consent for Intravenous Tissue Plasminogen Activator in New York State Designated Stroke Centers.

OBJECTIVE: Our objective was to assess informed consent procedures for intravenous tissue plasminogen activator in acute stroke among New York State (NYS) Department of Health (DOH) designated stroke centers. METHODS: A 13-question survey stratified by 0- to 3-hour and 3.0- to 4.5-hour treatment windows was used to determine the type of consent or if no consent was required. RESULTS: Of the 117 hospitals, 111 responded (95%). All 111 hospitals provided treatment within the 3-hour window, whereas 97 (87%) provided treatment beyond the 3-hour window (P < .001). For hospitals that did provide treatment, there was a difference between the percentages of hospitals requiring consent (verbal or written) within 3 hours (82%) and beyond 3 hours (92%) (P = .04). Of the hospitals requiring consent, there was a difference in the type of consent: 31 of 91 (34%) required written consent within the 3-hour window, whereas 57 of 89 (64%) required written consent beyond the 3-hour window (P < .001). Within both treatment windows, 98% accepted a health-care proxy or surrogate in lieu of the patient. Of the hospitals with less than 500 beds, 11 of 81 (14%) did not require consent within the 3-hour treatment window, compared to hospitals with 500 or more beds where 9 of 30 (30%) did not require consent within the 3-hour treatment window (P < .05). Beyond the 3-hour treatment window, hospitals with more than 500 beds required written consent-2-fold increase "compared to less than 3 hour window" (P < .05). Fifty-five percent of the hospitals were academic, whereas 45% were nonacademic. Academic status was not related to the type of consent in either window. CONCLUSIONS: Significant variability exists in the types of informed consent based on hospital bed size and treatment windows across NYS DOH designated stroke centers.

Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial.

IMPORTANCE: Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention. OBJECTIVE: To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment. DESIGN, SETTING, AND PARTICIPANTS: A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater. INTERVENTIONS: A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat. MAIN OUTCOMES AND MEASURES: Between-group differences in postintervention Hamilton Depression Rating Scale scores. RESULTS: The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P < .001; week 2: -6.35, 95% CI, -9.95 to -2.74, P = .001; week 4: -4.50, 95% CI, -8.17 to -0.84, P = .02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild. CONCLUSIONS AND RELEVANCE: Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01625546.

Engagement with Cognitively-Based Compassion Training is associated with reduced salivary C-reactive protein from before to after training in foster care program adolescents.

BACKGROUND: Children exposed to early life adversity (ELA) have been shown to have elevated circulating concentrations of inflammatory markers that persist into adulthood. Increased inflammation in individuals with ELA is believed to drive the elevated risk for medical and psychiatric illness in the same individuals. This study sought to determine whether Cognitively Based Compassion Training (CBCT) reduced C-reactive protein (CRP) in adolescents in foster care with high rates of ELA, and to evaluate the relationship between CBCT engagement and changes in CRP given prior evidence from our group for an effect of practice on inflammatory markers. It was hypothesized that increasing engagement would be associated with reduced CRP from baseline to the 6-week assessment. METHODS: Seventy-one adolescents in the Georgia foster care system (31 females), aged 13-17, were randomized to either 6 weeks of CBCT or a wait-list condition. State records were used to obtain information about each participant's history of trauma and neglect, as well as reason for placement in foster care. Saliva was collected before and again after 6 weeks of CBCT or the wait-list condition. Participants in the CBCT group completed practice diaries as a means of assessing engagement with the CBCT. RESULTS: No difference between groups was observed in salivary CRP concentrations. Within the CBCT group, practice sessions during the study correlated with reduced CRP from baseline to the 6-week assessment. CONCLUSIONS: Engagement with CBCT may positively impact inflammatory measures relevant to health in adolescents at high risk for poor adult functioning as a result of significant ELA, including individuals placed in foster care. Longer term follow-up will be required to evaluate if these changes are maintained and translate into improved health outcomes.

The impact of mirrors on body image and performance in high and low performing female ballet students.

This study assesses the effect of mirrors on body image and performance in high and low performing female collegiate ballet students. Twenty-three females enrolled in a beginning ballet class were taught using mirrors, and a second group of 23 beginning females were taught without mirrors. All participants completed the Cash 69-item Body Self-Relations Questionnaire during the first and last class of a 14-week semester. They were videotaped performing in the studio during the fifth and fourteenth weeks. Two ballet teachers independently viewed the videotapes to evaluate the dancers' rhythmic accuracy, ease and flow of movement, and mastery of steps and alignment, and rated the students' skill level on a 1-5 scale. For analysis purposes, students whose scores averaged three or higher were categorized as "high performers," and those who averaged less than three were "low performers." Two (mirror, non-mirror) by two (high performance, low performance) by two (pre-test, post-test) repeated measures ANOVAs were used to test class differences over the course of the semester. There were significant 3-way interactions for overweight preoccupation (p < 0.01) and body-areas satisfaction (p < 0.05). Low performers increased in overweight preoccupation in the non-mirror class while decreasing in the mirror class. High performers significantly increased in satisfaction for most areas of their body in the non-mirror class, while there were smaller increases for both low and high performers in the mirror class. It is concluded that while use of the mirror has some benefits in training, higher performing dancers feel better about their body image when they do not use the mirror. Lower performers who use the mirror worry less about their weight; those who do not use the mirror worry more. The mirror may provide feedback that helps low performing dancers feel more comfortable with their weight.

Innate immune, neuroendocrine and behavioral responses to psychosocial stress do not predict subsequent compassion meditation practice time.

Increasing data suggest that meditation impacts stress-related physiological processes relevant to health and disease. For example, our group recently reported that the practice of compassion meditation was associated with reduced innate immune (plasma interleukin [IL]-6) and subjective distress responses to a standardized laboratory psychosocial stressor (Trier Social Stress Test [TSST]). However, because we administered a TSST after, but not prior to, meditation training in our initial study, it remained possible that associations between practice time and TSST outcomes reflected the fact that participants with reduced stress responses prior to training were more able to practice compassion meditation, rather than that meditation practice reduced stress responses. To help resolve this ambiguity, we conducted the current study to evaluate whether innate immune, neuroendocrine and behavioral responses to a TSST conducted prior to compassion meditation training in an independent sample of 32 medically health young adults would predict subsequent amount of meditation practice time during a compassion meditation training protocol identical to the one used in our first study. No associations were found between responses to a TSST administered prior to compassion meditation training and subsequent amount of meditation practice, whether practice time was considered as a continuous variable or whether meditators were divided into high and low practice time groups based on a median split of mean number of practice sessions per week. These findings contrast strikingly with our original study, in which high and low practice time meditators demonstrated marked differences in IL-6 and distress responses to a TSST administered after meditation training. In addition to providing the first published data regarding stress responsivity as a potential predictor of subsequent ability/willingness to practice meditation, the current study strengthens findings from our initial work by supporting the conclusion that in individuals who actively engage in practicing the technique, compassion meditation may represent a viable strategy for reducing potentially deleterious physiological and behavioral responses to psychosocial stress.

Pulsed electromagnetic fields to reduce diabetic neuropathic pain and stimulate neuronal repair: a randomized controlled trial.

OBJECTIVE: To determine whether repetitive and cumulative exposure to low-frequency pulsed electromagnetic fields (PEMF) targeting painful feet can reduce neuropathic pain (NP), influence sleep in symptomatic diabetic peripheral neuropathy (DPN), and influence nerve regeneration. DESIGN: Randomized, double-blind, placebo-controlled parallel study. SETTING: Sixteen academic and clinical sites in 13 states. PARTICIPANTS: Subjects (N=225) with DPN stage II or III were randomly assigned to use identical devices generating PEMF or sham (placebo) 2 h/d to feet for 3 months. INTERVENTIONS: Nerve conduction testing was performed serially. MAIN OUTCOME MEASURES: Pain reduction scores using a visual analog scale (VAS), the Neuropathy Pain Scale (NPS), and the Patient's Global Impression of Change (PGIC). A subset of subjects underwent serial 3-mm punch skin biopsies from 3 standard lower limb sites for epidermal nerve fiber density (ENFD) quantification. RESULTS: Subjects (N=225) were randomized with a dropout rate of 13.8%. There was a trend toward reductions in DPN symptoms on the PGIC, favoring the PEMF group (44% vs 31%; P=.04). There were no significant differences between PEMF and sham groups in the NP intensity on NPS or VAS. Twenty-seven subjects completed serial biopsies. Twenty-nine percent of PEMF subjects had an increase in distal leg ENFD of at least 0.5 SDs, while none did in the sham group (P=.04). Increases in distal thigh ENFD were significantly correlated with decreases in pain scores. CONCLUSIONS: PEMF at this dosimetry was noneffective in reducing NP. However neurobiological effects on ENFD, PGIC and reduced itching scores suggest future studies are indicated with higher dosimetry (3000-5000 G), longer duration of exposure, and larger biopsy cohort.

Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress.

Meditation practices may impact physiological pathways that are modulated by stress and relevant to disease. While much attention has been paid to meditation practices that emphasize calming the mind, improving focused attention, or developing mindfulness, less is known about meditation practices that foster compassion. Accordingly, the current study examined the effect of compassion meditation on innate immune, neuroendocrine and behavioral responses to psychosocial stress and evaluated the degree to which engagement in meditation practice influenced stress reactivity. Sixty-one healthy adults were randomized to 6 weeks of training in compassion meditation (n=33) or participation in a health discussion control group (n=28) followed by exposure to a standardized laboratory stressor (Trier social stress test [TSST]). Physiologic and behavioral responses to the TSST were determined by repeated assessments of plasma concentrations of interleukin (IL)-6 and cortisol as well as total distress scores on the Profile of Mood States (POMS). No main effect of group assignment on TSST responses was found for IL-6, cortisol or POMS scores. However, within the meditation group, increased meditation practice was correlated with decreased TSST-induced IL-6 (r(p)=-0.46, p=0.008) and POMS distress scores (r(p)=-0.43, p=0.014). Moreover, individuals with meditation practice times above the median exhibited lower TSST-induced IL-6 and POMS distress scores compared to individuals below the median, who did not differ from controls. These data suggest that engagement in compassion meditation may reduce stress-induced immune and behavioral responses, although future studies are required to determine whether individuals who engage in compassion meditation techniques are more likely to exhibit reduced stress reactivity.

A randomized controlled trial of the effects of a combination of static and dynamic magnetic fields on carpal tunnel syndrome.

OBJECTIVE: To determine if a physics-based combination of simultaneous static and time-varying dynamic magnetic field stimulation to the wrist 4 hours/day for 2 months can reduce subjective neuropathic pain and influence objective electrophysiologic parameters of patients with carpal tunnel syndrome (CTS). METHODS: Randomized, double-blinded, placebo-controlled trial of 36 symptomatic hands. Primary endpoints were visual analog scale (VAS) and neuropathic pain scale (NPS) scores at baseline and 2 months and a Patient's Global Impression of Change (PGIC) questionnaire at the end of 2 months. Secondary endpoints were neurologic examination, median nerve distal latencies (compound muscle action potential [CMAP]/sensory nerve action potential [SNAP]), dynamometry, pinch gauge readings, and current perception threshold (CPT) scores. An "active" device was provided gratis at the end of the study, with 15 subjects voluntarily remaining within the open protocol an additional 2-10 months and using the preselected primary and secondary parameters. RESULTS: (two months). Of the 31 hands, 25 (13 magnet, 12 sham) had moderate to severe pain (VAS > 4). The VAS and PGIC revealed a nonsignificant pain reduction. NPS analyses (anova) demonstrated a statistically significant reduction of "deep" pain (35% downward arrow vs 12% upward arrow, P = 0.018), NPS Total Composite (decreases of 42% vs 24%, P = 0.042), NPS Total Descriptor Score (NPS 8; 43% vs 24%), and NPS 4 (42% vs 11%). Motor strength, CMAP/SNAP, and CPT scores were not significantly changed. Of the 15 hands with up to 10 months of active PEMF (pulsed electromagnetic fields) exposure, there was objective improvement in nerve conduction (CMAP = 53%, SNAP = 40%, >1 SD), and subjective improvement on examination (40%), pain scores (50%), and PGIC (70%). No detectable changes in motor strength and CPT. CONCLUSIONS: PEMF exposure in refractory CTS provides statistically significant short- and longterm pain reduction and mild improvement in objective neuronal functions. Neuromodulation appears to influence nociceptive-C and large A-fiber functions, probably through ion/ligand binding.