Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder

Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d=0.54, p<0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d=0.47, p<0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d=0.40, p=0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d=-0.05, p=0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression

A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain

Higher levels of physical fitness or activity (PFA) have been shown to have beneficial effects on cognitive function and grey matter volumes in older adults. However, the relationship between PFA and the brain's white matter (WM) is not yet well established. Here, we aim to provide a comprehensive and systematic review of magnetic resonance imaging studies examining the effects of PFA on the WM of the ageing brain. Twenty-nine studies were included in the review: eleven examined WM volume, fourteen WM lesions, and nine WM microstructure. While many studies found that higher levels of PFA were associated with greater WM volumes, reduced volume or severity of WM lesions, or improved measures of WM microstructure, a number of negative findings have also been published. Meta-analyses of global measures of WM volume and WM lesion volume yielded significant, but small, effect sizes. Overall, we found evidence for cautious support of links between PFA and WM structure, and highlighted key areas for future research including the extent to which the relationship between PFA and WM structure is anatomically specific, the influence of possible confounding factors, and the relationship between PFA, WM and cognition

A systematic review and meta-analysis of cross-sectional studies examining the relationship between mobility and cognition in healthy older adults

Ageing is associated with declines in cognitive function and mobility. The extent to which this relationship encompasses the subdomains of cognition and mobility remains unclear, however. We searched MEDLINE and EMBASE databases for cross-sectional studies examining the association between objective mobility measures (gait, lower-extremity function, balance) and cognitive function (global, executive function, memory, processing speed) in healthy older adults. Of the 642 studies identified, 26 studies met the inclusion criteria, with a total of 26,355 participants. For each feature of physical mobility, the relation to each aspect of cognition was reviewed. In the context of each association, we summarised the results to date and performed random-effects meta-analyses of published data. Reviewed findings suggest that individuals with better mobility perform better on assessments of global cognition, executive function, memory and processing speed. Not all measures of mobility were equally associated with cognitive function, however. Although there was a larger number of gait and lower-extremity function studies, and this may have driven findings, most studies examining balance and cognition measures reported no significant results. Meta-analyses on reported associations supported results by revealing significant, albeit small, effect sizes in favour of a positive association between performance on mobility measures and cognitive assessments. Future research should aim to establish the mechanisms driving this relationship, as this may identify predictors of age-related impairments

The relation between school leadership from a distributed perspective and teachers' organizational commitment: examining the source of the leadership function

Purpose: In this study the relationship between school leadership and teachers’ organizational commitment is examined by taking into account a distributed leadership perspective. The relation between teachers’ organizational commitment and contextual variables of teachers’ perceptions of the quality and the source of the supportive and supervisory leadership function, participative decision making, and cooperation within the leadership team are examined. Research Design: A survey was set up involving 1,522 teachers from 46 large secondary schools in Flanders (Belgium). Because the data in the present study have an inherent hierarchical structure, that is, teachers are nested into schools, hierarchical linear modeling techniques are applied. Findings: The analyses reveal that 9% of the variance in teachers’ organizational commitment is attributable to differences between schools. Teachers’ organizational commitment is mainly related to quality of the supportive leadership, cooperation within the leadership team, and participative decision making. Who performed the supportive leadership function plays only a marginally significant positive role. The quality of the supervisory leadership function and the role of the leadership team members in this function were not significantly related to teachers’ organizational commitment. Conclusions: The implications of the findings are that to promote teachers’ organizational commitment teachers should feel supported by their leadership team and that this leadership team should be characterized by group cohesion, role clarity, and goal orientedness. Recommendations for further research are provided

Development and validation of a dementia risk score in the UK Biobank and Whitehall II cohorts

BACKGROUND: Current dementia risk scores have had limited success in consistently identifying at-risk individuals across different ages and geographical locations. OBJECTIVE: We aimed to develop and validate a novel dementia risk score for a midlife UK population, using two cohorts: the UK Biobank, and UK Whitehall II study. METHODS: We divided the UK Biobank cohort into a training (n=176 611, 80%) and test sample (n=44 151, 20%) and used the Whitehall II cohort (n=2934) for external validation. We used the Cox LASSO regression to select the strongest predictors of incident dementia from 28 candidate predictors and then developed the risk score using competing risk regression. FINDINGS: Our risk score, termed the UK Biobank Dementia Risk Score (UKBDRS), consisted of age, education, parental history of dementia, material deprivation, a history of diabetes, stroke, depression, hypertension, high cholesterol, household occupancy, and sex. The score had a strong discrimination accuracy in the UK Biobank test sample (area under the curve (AUC) 0.8, 95% CI 0.78 to 0.82) and in the Whitehall cohort (AUC 0.77, 95% CI 0.72 to 0.81). The UKBDRS also significantly outperformed three other widely used dementia risk scores originally developed in cohorts in Australia (the Australian National University Alzheimer's Disease Risk Index), Finland (the Cardiovascular Risk Factors, Ageing, and Dementia score), and the UK (Dementia Risk Score). CLINICAL IMPLICATIONS: Our risk score represents an easy-to-use tool to identify individuals at risk for dementia in the UK. Further research is required to determine the validity of this score in other populations

Mediator and cohesin connect gene expression and chromatin architecture

Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator–cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.National Institutes of Health (U.S.) (Fellowship)Canadian Institutes of Health Research (Research Fellowship)National Institutes of Health (U.S.) (Grant R01 HG002668

Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly

The authors perform a cryo-EM study of the 1.9 MDa human Mediator-RNA polymerase II-TFIIF assembly, which reveals the structural organization of the human transcription initiation apparatus

Strategies for improving the communication of satellite-derived InSAR data for geohazards through the analysis of Twitter and online data portals

Satellite-based earth observation sensors are increasingly able to monitor geophysical signals related to natural hazards, and many groups are working on rapid data acquisition, processing, and dissemination to data users with a wide range of expertise and goals. A particular challenge in the meaningful dissemination of Interferometric Synthetic Aperture Radar (InSAR) data to non-expert users is its unique differential data structure and sometimes low signal-to-noise ratio. In this study, we evaluate the online dissemination of ground deformation measurements from InSAR through Twitter, alongside the provision of open-access InSAR data from the Centre for Observation and Modelling of Earthquakes, Volcanoes and Tectonics (COMET) Looking Into Continents from Space with Synthetic Aperture Radar (LiCSAR) processing system. Our aim is to evaluate (1) who interacts with disseminated InSAR data, (2) how the data are used, and (3) to discuss strategies for meaningful communication and dissemination of open InSAR data. We found that the InSAR Twitter community was primarily composed of non-scientists (62 %), although this grouping included earth observation experts in applications such as commercial industries. Twitter activity was primarily associated with natural hazard response, specifically following earthquakes and volcanic activity, where users disseminated InSAR measurements of ground deformation, often using wrapped and unwrapped interferograms. For earthquake events, Sentinel-1 data were acquired, processed, and tweeted within 4.7±2.8 d (the shortest was 1 d). Open-access Sentinel-1 data dominated the InSAR tweets and were applied to volcanic and earthquake events in the most engaged-with (retweeted) content. Open-access InSAR data provided by LiCSAR were widely accessed, including automatically processed and tweeted interferograms and interactive event pages revealing ground deformation following earthquake events. The further work required to integrate dissemination of InSAR data into longer-term disaster risk-reduction strategies is highly specific, to both hazard type and international community of practice, as well as to local political setting and civil protection mandates. Notably, communication of uncertainties and processing methodologies are still lacking. We conclude by outlining the future direction of COMET LiCSAR products to maximize their useability.</p

Depression and Anxiety Change from Adolescence to Adulthood in Individuals with and without Language Impairment

This prospective longitudinal study aims to determine patterns and predictors of change in depression and anxiety from adolescence to adulthood in individuals with language impairment (LI). Individuals with LI originally recruited at age 7 years and a comparison group of age-matched peers (AMPs) were followed from adolescence (16 years) to adulthood (24 years). We determine patterns of change in depression and anxiety using the Child Manifest Anxiety Scale-Revised (CMAS-R) and Short Moods and Feelings Questionnaire (SMFQ). In addition to examining associations with gender, verbal and nonverbal skills, we use a time-varying variable to investigate relationships between depression and anxiety symptoms and transitions in educational/employment circumstances. The results show that anxiety was higher in participants with LI than age matched peers and remained so from adolescence to adulthood. Individuals with LI had higher levels of depression symptoms than did AMPs at 16 years. Levels in those with LI decreased post-compulsory schooling but rose again by 24 years of age. Those who left compulsory school provision (regardless of school type) for more choice-driven college but who were not in full-time employment or study by 24 years of age were more likely to show this depression pathway. Verbal and nonverbal skills were not predictive of this pattern of depression over time. The typical female vulnerability for depression and anxiety was observed for AMPs but not for individuals with LI. These findings have implications for service provision, career/employment advice and support for individuals with a history of LI during different transitions from adolescence to adulthood

Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland:Scottish Family Health Study (GS:SFHS)

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD