ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Early environmental quality and life-course mental health effects : The Equal-Life project

Background: There is increasing evidence that a complex interplay of factors within environments in which children grows up, contributes to children's suboptimal mental health and cognitive development. The concept of the life-course exposome helps to study the impact of the physical and social environment, including social inequities, on cognitive development and mental health over time. Methods: Equal-Life develops and tests combined exposures and their effects on children's mental health and cognitive development. Data from eight birth-cohorts and three school studies (N = 240.000) linked to exposure data, will provide insights and policy guidance into aspects of physical and social exposures hitherto untapped, at different scale levels and timeframes, while accounting for social inequities. Reasoning from the outcome point of view, relevant stakeholders participate in the formulation and validation of research questions, and in the formulation of environmental hazards. Exposure assessment combines GIS-based environmental indicators with omics approaches and new data sources, forming the early-life exposome. Statistical tools integrate data at different spatial and temporal granularity and combine exploratory machine learning models with hypothesis-driven causal modeling. Conclusions: Equal-Life contributes to the development and utilization of the exposome concept by (1) integrating the internal, physical and social exposomes, (2) studying a distinct set of life-course effects on a child's development and mental health (3) characterizing the child's environment at different developmental stages and in different activity spaces, (4) looking at supportive environments for child development, rather than merely pollutants, and (5) combining physical, social indicators with novel effect markers and using new data sources describing child activity patterns and environments.Peer reviewe

Investigating the impact of distinct contemplative mental trainings on daily life stress, thoughts and affect: Evidence from a nine-month longitudinal ecological momentary assessment study

Mindfulness-based mental training interventions have become a popular means to alleviate stress and stress-associated health risks. Previous scientific investigations emphasize the importance of exploring the effects of such interventions in naturalistic settings to evaluate their implementation into daily life. Therefore, the current study examined the effects of three distinct mental training modules on a range of measures of daily life experience in the scope of the ReSource Project, a 9-month longitudinal mental training study comparing modules targeting attention and interoception (Presence), socio-affective (Affect) or socio-cognitive abilities (Perspective). We used ecological momentary assessment (EMA) to repeatedly probe levels of stress and stress-coping efficacy combined with stress-reactive cortisol levels, and further explored arousal, affective states, and thought patterns in the daily lives of 289 healthy adults (172 women; 20–55 years). We found increased presence-focused thought and heightened arousal after a training duration of 3–6 months, independent of the type of prior training. Increased coping efficacy emerged specifically after socio-cognitive Perspective training, following 6–9 months of training duration. No training effects were found for subjective stress, stress-reactive cortisol levels, or daily life affect. Our findings corroborate and add ecological validity to previous ReSource findings by showing that they replicate in participants’ everyday environment. Regarding endocrine and subjective stress markers, our results suggest caution in generalizing acute laboratory findings to individuals’ everyday routines. Overall, the current study provides substantiated insights into how cultivating one’s mind through contemplative mental training translates to daily life experience, enhances stress-coping, and may ultimately aide in maintaining health

Riktad metabolomik med 'Ultra Performans' Vätskekormatografi Mass Spekrometri (UPLC-MS) visar metaboliska skillnader i hälsosamma samt atopiska Staffordshire bullterrier efter två olika dieter : en pilotstudie

While anecdotal evidence has long claimed that a raw meat–based diet (RMBD) improves the metabolic health of canines, no rigorous scientific study has clarified this issue. Canine atopic dermatitis (CAD) has also been linked to metabolic health, but its relation to diet remains poorly understood. This study investigates whether dietary choice is linked to metabolic health in healthy and CAD-diagnosed canines via targeted serum and urine metabolomic analysis of polar, non-ionic metabolites, as well as whether the underlying CAD condition modulates the response to nutritional intake. Serum metabolites of client-owned Staffordshire Bull Terriers, divided into CAD-diagnosed (n=14) and healthy (n=6) cohorts, were studied. Urine metabolites of a subset of the CAD-diagnosed canines (n=8) were also studied. The canines were split into two cohorts based on diet. The first cohort were fed a commercially available high-fat, moderate-protein, low-carbohydrate RMBD (n=11, CAD diagnosed n=8, healthy n=3). The second cohort were fed a commercially available moderate-fat, moderate-protein, high-carbohydrate kibble diet (KD) (n=9, CAD diagnosed n=6, healthy n=3). The diet intervention period lasted approximately 4.5 months (median 135d). Statistical analysis of the serum profiles across all dogs (n=20) and the urine profiles of the CAD-diagnosed subset (n=8) were performed. The KD cohort was found to have higher concentrations of methionine than the RMBD cohort, both in serum (all dogs, p<0.0001) and in urine (CAD-only cohort, p<0.0002), as well as cystathionine and 4-pyridoxic acid. Methionine plays important roles in homocysteine metabolism, and elevated levels have been implicated in various pathologies. The CAD (n=14) cohort dogs showed starker metabolic changes in response to diet regarding these pathways compared to the healthy (n=6) cohort. However, there was no significant change in CAD severity as a result of either diet. Likely due to the higher meat content of the RMBD, higher concentrations of several carnitines and creatine were found in the RMBD cohort. Citrulline was found in higher concentrations in the KD cohort. While the findings from this experiment provide insight into the relationship between diet and the serum and urine metabolite profiles of canines, they also suggest that neither diet significantly affected CAD severity.Anekdotiskt bevis har länge påstått att en rå köttbaserad diet (RKBD) förbättrar hundens metaboliska hälsa. Dock har ingen noggrann vetenskaplig studie klargjort denna fråga. Hund atopisk dermatit (HAD) har också kopplats till metabolisk hälsa, men dess förhållande till diet har ej studerats via studien av hundens metabolism tidigare. Denna studie undersöker om diet val är kopplade till metabolisk hälsa hos friska och HAD-diagnostiserade hundar genom att köra riktad blodserum- och urinmetabolomik analys av polära, icke-joniska metaboliter, samt för att svara huruvida det underliggande HAD-sjukdomen modulerar hur hunden reagerar till dess diet. Serum metaboliter från Staffordshire bullterrierrar som indelades till antingen HAD-diagnoserade (n=14) eller friska (n=6) studerades. Urinmetaboliter från en portion av de HAD-diagnoserade hundarna (n=8) studerades också. Hundarna indelades vidare till två dietgrupper. Förstå gruppen åt en kommersiell RKBD som hade låg kolhydrathat och högt protein samt fetthalt (n=11, HAD diagnoserade n=8, friska n=3). Andra gruppen (n=9, HAD diagnoserade n=6, friska n=3) åt ett kommersiellt torrfoder (TF) som hade hög kolhydrathalt, måttlig proteinhalt samt låg fetthalt. Dietinterventionen räckte cirka 4.5 månader (median=135d). Statistisk analys of hundarnas serum metabolitprofiler (n=20) samt urin metabolitprofiler från en del av HAD-diagnoserade hundarna (n=8) kördes och resultaten studerades. Efter dietinterventionen hade gruppen som åt TF dieten betydligt högre koncentrationer av metionin än RKBD gruppen, både i blodserum (alla hundar, n=9, p<0.0001) och i deras urin (HAD-gruppen, n=6, p<0.0002). I urinet fanns det också betydligt högre koncentrationer cystationin samt 4-pyridoxalsyra. Dess metaboliter spelar viktiga roller inom metaboliska rutten som bryter ner homocystein, där speciellt förhöjda metioninkoncentrationer har visats sig korrelera med diverse kroniska sjukdomar. Större ändringar i metabolitkoncentrationerna som påföljd av diet observerades i HAD-gruppen (n=14) jämfört med friska gruppen (n=6). Dock fanns det ingen betydlig ändring på deras HAD-symtom som påföljd av diet efter dietinterventionen avslutades. Högre hater av karnitiner samt kreatin hittades i RKBD-gruppens blodserum, antagligen på grund av höga kötthaltet i deras diet. Betydligt högre citrullinhalter hittades också i blodserumet från TF-gruppen. Resultaten från detta experiment ger insikt till hur diet och hundens blodserum samt urin metabolitprofiler påverkar varandra. Vidare visar resultatet att varken TF eller RKBD dieten betydligt ändrar på HAD-symtom

Addendum to Informatics for Health 2017: Advancing both science and practice

This article presents presentation and poster abstracts that were mistakenly omitted from the original publication

The Empowering Role of Mobile Apps in Behavior Change Interventions: The Gray Matters Randomized Controlled Trial

BACKGROUND: Health education and behavior change programs targeting specific risk factors have demonstrated their effectiveness in reducing the development of future diseases. Alzheimer disease (AD) shares many of the same risk factors, most of which can be addressed via behavior change. It is therefore theorized that a behavior change intervention targeting these risk factors would likely result in favorable rates of AD prevention. OBJECTIVE: The objective of this study was to reduce the future risk of developing AD, while in the short term promoting vascular health, through behavior change. METHODS: The study was an interventional randomized controlled trial consisting of subjects who were randomly assigned into either treatment (n=102) or control group (n=42). Outcome measures included various blood-based biomarkers, anthropometric measures, and behaviors related to AD risk. The treatment group was provided with a bespoke “Gray Matters” mobile phone app designed to encourage and facilitate behavior change. The app presented evidence-based educational material relating to AD risk and prevention strategies, facilitated self-reporting of behaviors across 6 behavioral domains, and presented feedback on the user’s performance, calculated from reported behaviors against recommended guidelines. RESULTS: This paper explores the rationale for a mobile phone–led intervention and details the app’s effect on behavior change and subsequent clinical outcomes. Via the app, the average participant submitted 7.3 (SD 3.2) behavioral logs/day (n=122,719). Analysis of these logs against primary outcome measures revealed that participants who improved their high-density lipoprotein cholesterol levels during the study duration answered a statistically significant higher number of questions per day (mean 8.30, SD 2.29) than those with no improvement (mean 6.52, SD 3.612), t(97.74)=−3.051, P=.003. Participants who decreased their body mass index (BMI) performed significantly better in attaining their recommended daily goals (mean 56.21 SD 30.4%) than those who increased their BMI (mean 40.12 SD 29.1%), t(80) = −2.449, P=.017. In total, 69.2% (n=18) of those who achieved a mean performance percentage of 60% or higher, across all domains, reduced their BMI during the study, whereas 60.7% (n=34) who did not, increased their BMI. One-way analysis of variance of systolic blood pressure category changes showed a significant correlation between reported efforts to reduce stress and category change as a whole, P=.035. An exit survey highlighted that respondents (n=83) reported that the app motivated them to perform physical activity (85.4%) and make healthier food choices (87.5%). CONCLUSIONS: In this study, the ubiquitous nature of the mobile phone excelled as a delivery platform for the intervention, enabling the dissemination of educational intervention material while simultaneously monitoring and encouraging positive behavior change, resulting in desirable clinical effects. Sustained effort to maintain the achieved behaviors is expected to mitigate future AD risk. TRIAL REGISTRATION: ClinicalTrails.gov NCT02290912; https://clinicaltrials.gov/ct2/show/NCT02290912 (Archived by WebCite at http://www.webcitation.org/6ictUEwnm

Is markerless, smart phone recorded two-dimensional video a clinically useful measure of relevant lower limb kinematics in runners with patellofemoral pain? A validity and reliability study.

OBJECTIVES: Investigate the validity and reliability of markerless, smart phone collected, two-dimensional (2D) video, analysed using the 'Hudl technique' application, compared to three-dimensional (3D) kinematics during running, in participants with patellofemoral pain (PFP). DESIGN: Validity/reliability study. SETTING: Biomechanics laboratory. PARTICIPANTS: Males/females with PFP (n = 21, 10 males, 11 females, age 32.1 months [±12.9]). MAIN OUTCOME MEASURES: Manually synchronised 2D and 3D measurement of peak hip adduction (HADD) and peak knee flexion (KFLEX) during running. RESULTS: 2D and 3D measures of peak KFLEX (p = 0.02, d = 1.13), but not peak HADD (p = 0.25, d = -0.27), differed significantly. Poor validity was identified for 2D measurement of peak HADD (ICC 0.06, 95% CI -0.35, 0.47) and peak KFLEX ICC 0.42, 95% CI (-0.10, 0.75). Moderate intra-rater reliability was identified for both variables (ICC 0.61-65), alongside moderate inter-rater reliability for peak KFLEX (ICC 0.71) and poor inter-rater reliability for peak HADD (ICC 0.31). CONCLUSIONS: Measurement of peak HADD and KFLEX in runners with PFP using markerless, smart phone collected 2D video, analysed using the Hudl technique Application is invalid, with poor to moderate reliability. Investigation of alternate 2D video approaches to increase precision is warranted. At present, 2D video analysis of running using Hudl Technique cannot be advocated

The discovery and validation of metabolites as candidate biomarkers for the diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) constitutes a major disease burden worldwide. Much of its high mortality-to-incidence ratio can be attributed to late diagnosis, resulting in poor survival. Motivated by the need to develop a novel non-invasive diagnostic test to improve the chances of early diagnosis, this thesis makes use of metabonomic technologies to discover and validate metabolites as potential novel diagnostic markers for HCC. First, a systematic review of the literature on the topic was conducted to collate all published evidence of metabolites that were reported to be discriminatory for HCC. A bespoke risk of bias assessment tool was developed for metabonomic studies and a weighted score system was implemented to rank metabolites based on the strength of evidence. This resulted in a ranked list of metabolites with the greatest potential to be followed up for validation for each of the sample types (tissue, blood and urine). Then, validation of urinary metabolites with the greatest potential concluded from the systematic review was performed using data acquired from a UK cohort. None of the previously reported difference between HCC and cirrhosis groups could be reproduced, indicating the current lack of candidate markers specific for HCC detectable in urine. Finally, an exploratory analysis of serum 1H-NMR data from a UK and a Nigerian cohort was performed. Common and different alterations in metabolite levels between the two cohorts were compared. Glutamine-to-glutamate ratio was identified as a potential marker with the best discriminatory power between HCC and cirrhosis patients and this was validated using an independent cohort from the Gambia. This work adds to the ongoing effort to elucidate metabolites with the best potential to be further validated with the goal of developing a novel diagnostic test for HCC.Open Acces