Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific community.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors.

Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1) approaches. Behaviorally, genetic deletion of MIF resulted in increased anxiety- and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Together, our studies provide evidence supporting a pivotal function for MIF in both basal and antidepressant-stimulated adult hippocampal cell proliferation. Moreover, loss of MIF results in a behavioral phenotype that, to a large extent, corresponds with alterations predicted to arise from reduced hippocampal neurogenesis. These findings underscore MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition.

Moving beyond health to flourishing: the effects of yoga teacher training.

Research in the medical and psychological fields has primarily followed a "disease-focused" approach to health. Although there is growing research on the components and outcomes of well-being, very few studies have focused on traditional practices that can be used as interventions to encourage human flourishing. The current study was developed to address this research gap. We suggest one effective method of increasing psychological well-being, the practice of yoga, an age-old practice that has been said to produce physical and psychological health. In this observational study, we examined associations with participation in a 4-week yoga teacher training resident program. Measurement instruments were chosen to capture changes in psychosocial health and human flourishing. Measurements were taken before the start of the program, immediately after the program, and 3 months postprogram. As expected, in this healthy population, the human flourishing scales showed more change than the psychosocial health scales. For example, in this healthy sample, there were no significant changes in perceived social support, quality of life, or self-efficacy from baseline to the 3-month follow-up. However, optimism, a positive psychology research measure, improved from baseline to follow-up. The mindfulness subscales of observation, awareness, and nonreactivity all improved following the training, suggesting that one benefit of yoga practice is a more refined ability to attend to one's inner experience. This study adds to the growing literature focusing on interventions that move beyond relieving pathology to those that produce optimal functioning and human thriving.

Meta-analysis: the effects of placebo treatment on gastro-oesophageal reflux disease.

BACKGROUND: There appears to be a significant placebo response rate in clinical trials for gastro-oesophageal reflux disease. Little is known about the determinants and the circumstances associated with placebo response in the treatment of gastro-oesophageal reflux disease (GERD). AIMS: To estimate the magnitude of the placebo response rate in randomized controlled trials for GERD and to identify factors that influence this response. METHODS: A meta-analysis of randomized, double-blind, placebo-controlled trials, published in English language, which included >20 patients with GERD, treated with either a proton pump inhibitor or H(2)-receptor antagonist for at least 2 weeks. Medline, Cochrane and EMBASE databases were searched, considering only studies that reported a global response for 'heartburn'. RESULTS: A total of 24 studies included 9989 patients with GERD. The pooled odds ratio (OR) for response to active treatment vs. placebo was 3.71 (95% CI: 2.78-4.96). The pooled estimate of the overall placebo response was 18.85% (range 2.94%-47.06%). Patients with erosive oesophagitis had a non-significantly lower placebo response rate than patients without it (11.87% and 18.31%, respectively; P = 0.246). Placebo response was significantly lower in studies of PPI therapy vs. studies of H(2) RAs (14.51% vs. 24.69%, respectively; P = 0.05). CONCLUSIONS: The placebo response rate in randomized controlled trials for GERD is substantial. A lower placebo response was associated with the testing of PPIs, but not the presence of erosive oesophagitis.

Serum correlates of the placebo effect in irritable bowel syndrome.

BACKGROUND In diseases defined primarily by the subjective nature of patient self-report, placebo effects can overwhelm the capacity of randomized controlled trials to detect medication-placebo differences. Moreover, it is unclear whether such placebo effects represent genuine psychobiological phenomena or just shifts in selective attention. Knowledge of predictors of the placebo response could improve the design of clinical trials and the delivery of personalized medical care. METHODS In patients with irritable bowel syndrome (IBS), a subset of our previous study that were randomized to placebo treatment (sham acupuncture) or no-treatment group (waitlist), we tested an enriched panel of 10 serum biomarkers at the enrolment and the 3rd week of intervention, using a multiplex electrochemiluminescent immunoassay. KEY RESULTS More pronounced changes overtime in serum levels of osteoprotegerin (OPG) have been found in patients who received placebo treatment compared with the waitlist group (P = 0.039). Moreover, serum levels of OPG at baseline were found to be higher (P = 0.0167) in patients who subsequently achieved adequate relief (AR) of their IBS symptoms, independently of their treatment group. Besides, serum levels of TNF-related weak inducer of apoptosis (TWEAK) at baseline were also higher (P = 0.0144) in patients who reported AR and in particular in those who received the placebo treatment. CONCLUSIONS & INFERENCES These two measurable biological parameters associated with placebo, namely serum OPG and TWEAK, provide a proof of principle for discovering putative molecular signatures of placebo response in IBS and perhaps in other illnesses with patient self-reported outcomes.

A meta-analysis of the placebo response in complementary and alternative medicine trials of irritable bowel syndrome.

Among patients with irritable bowel syndrome (IBS) enrolled in clinical trials of conventional medical therapy, the placebo response rate is high. IBS patients also frequently use complementary and alternative medicine (CAM), which may act through an 'enhanced placebo effect'. The purpose of this study was to estimate the magnitude of the placebo response rate in CAM trials for IBS and to identify factors that influence this response. We performed a systematic review and meta-analysis of randomized, placebo-controlled clinical trials of CAM therapies for IBS identified from MEDLINE/EMBASE/PsychLIT databases from 1970 to 2006. Placebo and active treatment response rates for global symptom improvement were assessed. Nineteen studies met the inclusion criteria. The pooled estimate of the placebo response rate was 42.6% (95% confidence interval, 38.0-46.5%). Significant heterogeneity existed across trials (range 15.0-72.2%, P < 0.00001). Higher placebo response rates correlated with a longer duration of treatment (r = 0.455, P = 0.05) and a greater number of office visits (r = 0.633, P = 0.03). Among IBS patients in CAM trials, the placebo response rate is high. That this rate is similar in magnitude to that seen in conventional medicine trials suggests that the placebo response is independent of the type of therapy used and that it is not particularly 'enhanced' in CAM trials.

The placebo effect in irritable bowel syndrome trials: a meta-analysis.

BACKGROUND: Despite the apparent high placebo response rate in randomized placebo-controlled trials (RCT) of patients with irritable bowel syndrome (IBS), little is known about the variability and predictors of this response. OBJECTIVES: To describe the magnitude of response in placebo arms of IBS clinical trials and to identify which factors predict the variability of the placebo response. METHODS: We performed a meta-analysis of published, English language, RCT with 20 or more IBS patients who were treated for at least 2 weeks. This analysis is limited to studies that assessed global response (improvement in overall symptoms). The variables considered as potential placebo modifiers were study design, study duration, use of a run-in phase, Jadad score, entry criteria, number of office visits, number of office visits/study duration, use of diagnostic testing, gender, age and type of medication studied. FINDINGS: Forty-five placebo-controlled RCTs met the inclusion criteria. The placebo response ranged from 16.0 to 71.4% with a population-weighted average of 40.2%, 95% CI (35.9-44.4). Significant associations with lower placebo response rates were fulfillment of the Rome criteria for study entry (P=0.049) and an increased number of office visits (P=0.026). CONCLUSIONS: Placebo effects in IBS clinical trials measuring a global outcome are highly variable. Entry criteria and number of office visits are significant predictors of the placebo response. More stringent entry criteria and an increased number of office visits appear to independently decrease the placebo response.

Women at mid-life: symptoms, attitudes, and choices, an internet based survey.

OBJECTIVES: This Internet-based survey questioned middle-aged women (age 35-69) regarding their current attitudes, beliefs, symptoms, and treatment choices surrounding the climacteric. METHODS: 448 respondents completed the 189 item, WEB-based survey that included measures of quality of life, lifestyle habits, anxiety symptoms, and questions regarding attitude toward and sources of information about menopause. RESULTS: Three relationships were hypothesized and supported: frequency of self-reported menopause symptoms would be: (1) negatively associated with healthy behaviors; (2) positively associated with anxiety; (3) positively associated with stress. All measures were self-report. Fatigue, muscle and joint aches, and impatience were the most commonly reported symptoms. No particular symptom was strongly correlated (r > 0.4) to lifestyle behaviors. Questions regarding information exchange reveal that many women are not consulting with their healthcare providers about HRT or frequently discussing alternatives. Many receive health information from lay sources. CONCLUSIONS: There is a need for improved information exchange on this subject. Our results are similar to those found using large randomized telephone survey methods, which supports the use of the Internet as a reliable and convenient venue for gathering data regarding health issues. It is important to consider healthy lifestyle behaviors toward the regulation of the climacteric syndrome.

A qualitative evaluation of the Harvard Cancer Risk Index.

There is an extensive amount of information in the popular press about cancer risk factors. The volume and sometimes contradictory nature of this information makes it difficult for individuals to understand their own level of risk or how one risk factor compares with another. The Harvard Cancer Risk Index (HCRI) was developed by an interdisciplinary working group of epidemiologists and behavioral scientists to educate the public about the major risk factors associated with the 11 most common forms of cancer in the United States. Following the development and validation of the HCRI, we initiated a qualitative research study to obtain initial feedback on the wording and presentation of the index and to elicit information regarding the meaning of risks, perception of cancer, and interpretation of the HCRI results. The results indicated that the HCRI was well received by participants and that they highly regarded the inclusion of information related to the latest risks for cancer and the description of the mechanisms by which these factors impact on risk. Personalization of the risk score helped participants to focus on behaviors that they could change. However, dissatisfaction with the HCRI was noted by some participants because exposures they believed to be important were not included (e.g., poverty, toxic waste, air pollution). Evaluation of the impact of the index on intention to change provided preliminary evidence that this may be an effective toll for helping mobilize individuals toward change across a number of risk factors. Further quantitative evaluation of the HCRI is planned.