Mental health: future challenges

The aim of the Foresight Project on Mental Capital and Wellbeing(www.foresight.gov.uk) is to advise the Government on how to achieve the best possible mental development and mental wellbeing for everyone in the UK in the future. The starting point of the Project was to generate an understanding of the science of mental capital and wellbeing (MCW) and to develop a vision for how the size and nature of the challenges exposed by the Project could evolve over the next 20 years. To make this analysis tractable, the work was divided into five broad areas: ● Mental capital through life ● Learning through life ● Mental health ● Wellbeing and work, and ● Learning difficulties. This report presents the findings for “Mental health” and draws upon a comprehensive assessment of the scientific state-of-the art: overall, around 80 reviews have been commissioned across the five areas. Mental health is a term which is used in a number of different ways and which has unfortunately acquired a substantial stigma in all layers of society. While the main focus of this report is on mental ill-health, positive mental health is also vitally important and is also discussed. However, a more comprehensive consideration of positive mental health has been performed in other parts of the Project (as commissioned reviews and in the context of the future of work. This report starts by looking at the situation today, examining the prevalence of important categories of mental disorder. It then considers the risk and protective factors which influence mental ill health, and determines how its prevalence and impact could change in the future, if existing policies and expenditure remain broadly unchanged. An assessment of strategic choices and interventions to meet the future challenges of mental health (and the challenges associated with the other four areas listed above) will be documented in the final Project report which is due for publication in the autumn of 2008

Primary group size, social support, gender and future mental health status in a prospective study of people living in private households throughout Great Britain

Background. Structural characteristics of social networks such as primary group size have received less attention than measures of perceived social support. Previous research suggests that associations between social network size and later common mental disorder status may differ according to sex and initial mental state. Method. Adults participating in the 2000 British National Household Survey of psychiatric morbidity were randomly selected for follow-up 18 months later. The revised Clinical Interview Schedule (CIS-R) and the Interview Measure of Social Relations (IMSR) were administered at baseline and follow-up. Primary group size was defined as the total number of close relatives and friends. A four-level scale of common mental disorder was modelled with ordinal logistic regression, based on weighted data (n=2413). Findings. After adjusting for confounders, a primary group size of three or less at time 1 predicted worse mental health at time 2. This effect was greatest in men who were initially non-cases at baseline (averaged odds 4.5) and in women who were initially cases at baseline (average odds 2.9). Primary group size at time 2 was significantly predicted by level of common mental disorder at time 1 in women but not in men. Thus, confounding by baseline disorder does not explain risk of developing poor mental health in socially isolated men. Conclusion. This study replicates the strong effects of primary group size on future mental health that emerge when men and women are studied separately and when subjects are categorized according to baseline mental health status

The population impact of common mental disorders and long-term physical conditions on disability and hospital admission

Background: Long-term physical conditions (LTCs) consume the largest share of healthcare budgets. Although common mental disorders (CMDs) and LTCs often co-occur, the potential impact of improved mental health treatment on severe disability and hospital admissions for physical health problems remains unknown. Method: A cross-sectional study of 7403 adults aged 16–95 years living in private households in England was performed. LTCs were ascertained by prompted self-report. CMDs were ascertained by structured clinical interview. Disability was assessed using questions about problems with activities of daily living. Population impact and potential preventive gain were estimated using population-attributable fraction (PAF), and conservative estimates were obtained using ‘treated non-cases’ as the reference group. Results: Of the respondents, 20.7% reported at least one LTC. The prevalence of CMDs increased with the number of LTCs, but over two-thirds (71.2%) of CMD cases in people with LTCs were untreated. Statistically significant PAFs were found for CMDs and recent hospital admission [13.5%, 95% confidence intervals (CI) 6.6–20.0] and severe disability (31.3%, 95% CI 27.1–35.2) after adjusting for LTCs and other confounders. Only the latter remained significant when using the most conservative estimate of PAF (21.8%, 95% CI 14.0–28.9), and this was reduced only slightly when considering only participants with LTCs (18.5%, 95% CI 7.9–27.9). Conclusions: Better treatments for CMDs in people with LTCs could achieve almost the same population health gain in terms of reducing severe disability as those targeted at the entire population. Interventions to reduce the prevalence of CMDs among people with LTCs should be part of routine medical care

Indentation and self-healing mechanisms of a self-assembled monolayer:a combined experimental and modeling study

A combination of in situ vibrational sum-frequency generation (SFG) spectroscopy and molecular-dynamics (MD) simulations has allowed us to study the effects of indentation of self-assembled octadecylphosphonic acid (ODPA) monolayers on α-Al2O3(0001). Stress-induced changes in the vibrational signatures of C–H stretching vibrations in SFG spectra and the results of MD simulations provide clear evidence for an increase in gauche-defect density in the monolayer as a response to indentation. A stress-dependent analysis indicates that the defect density reaches saturation at approximately 155 MPa. After stress is released, the MD simulations show an almost instantaneous healing of pressure-induced defects in good agreement with experimental results. The lateral extent of the contact areas was studied with colocalized SFG spectroscopy and compared to theoretical predictions for pressure gradients from Hertzian contact theory. SFG experiments reveal a gradual increase in gauche-defect density with pressure before saturation close to the contact center. Furthermore, our MD simulations show a spatial anisotropy of pressure-induced effects within ODPA domains: molecules tilted in the direction of the pressure gradient increase in tilt angle while those on the opposite side form gauche-defects

Debt income and mental disorder in the general population

Background The association between poor mental health and poverty is well known but its mechanism is not fully understood. This study tests the hypothesis that the association between low income and mental disorder is mediated by debt and its attendant financial hardship. Method The study is a cross-sectional nationally representative survey of private households in England, Scotland and Wales, which assessed 8580 participants aged 16–74 years living in general households. Psychosis, neurosis, alcohol abuse and drug abuse were identified by the Clinical Interview Schedule – Revised, the Schedule for Assessment in Neuropsychiatry (SCAN), the Alcohol Use Disorder Identification Test (AUDIT) and other measures. Detailed questions were asked about income, debt and financial hardship. Results Those with low income were more likely to have mental disorder [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.68–2.59] but this relationship was attenuated after adjustment for debt (OR 1.58, 95% CI 1.25–1.97) and vanished when other sociodemographic variables were also controlled (OR 1.07, 95% CI 0.77–1.48). Of those with mental disorder, 23% were in debt (compared with 8% of those without disorder), and 10% had had a utility disconnected (compared with 3%). The more debts people had, the more likely they were to have some form of mental disorder, even after adjustment for income and other sociodemographic variables. People with six or more separate debts had a six-fold increase in mental disorder after adjustment for income (OR 6.0, 95% CI 3.5–10.3). Conclusions Both low income and debt are associated with mental illness, but the effect of income appears to be mediated largely by debt

CBT for people with intellectual disabilities : emerging evidence, cognitive ability and IQ effects

Historically people with intellectual disabilities have not been offered or received cognitive behavioural interventions that have been shown to be effective for mental health and emotional problems experienced by those without such disabilities. This is despite many people with intellectual disabilities having life experiences that potentially result in them having an increased risk to such problems. This paper discusses whether such therapeutic disdain is justified based on the evidence that is available and emerging concerning the application of cognitive behavioural interventions for this population. Issues concerning access to services, the ability of people with intellectual disabilities to engage in and benefit from the cognitive components of CBT, and the effect of cognitive abilities and IQ level on treatment effectiveness are explored in relation to this question

A Molecular Function Map of Ewing's Sarcoma

EWS-FLI1 is a chimeric ETS transcription factor that is, due to a chromosomal rearrangement, specifically expressed in Ewing's sarcoma family tumors (ESFT) and is thought to initiate the development of the disease. Previous genomic profiling experiments have identified EWS-FLI1-regulated genes and genes that discriminate ESFT from other sarcomas, but so far a comprehensive analysis of EWS-FLI1-dependent molecular functions characterizing this aggressive cancer is lacking.In this study, a molecular function map of ESFT was constructed based on an integrative analysis of gene expression profiling experiments following EWS-FLI1 knockdown in a panel of five ESFT cell lines, and on gene expression data from the same platform of 59 primary ESFT. Out of 80 normal tissues tested, mesenchymal progenitor cells (MPC) were found to fit the hypothesis that EWS-FLI1 is the driving transcriptional force in ESFT best and were therefore used as the reference tissue for the construction of the molecular function map. The interrelations of molecular pathways were visualized by measuring the similarity among annotated gene functions by gene sharing. The molecular function map highlighted distinct clusters of activities for EWS-FLI1 regulated genes in ESFT and revealed a striking difference between EWS-FLI1 up- and down-regulated genes: EWS-FLI1 induced genes mainly belong to cell cycle regulation, proliferation, and response to DNA damage, while repressed genes were associated with differentiation and cell communication.This study revealed that EWS-FLI1 combines by distinct molecular mechanisms two important functions of cellular transformation in one protein, growth promotion and differentiation blockage. By taking MPC as a reference tissue, a significant EWS-FLI1 signature was discovered in ESFT that only partially overlapped with previously published EWS-FLI1-dependent gene expression patterns, identifying a series of novel targets for the chimeric protein in ESFT. Our results may guide target selection for future ESFT specific therapies

Micro-Environment Causes Reversible Changes in DNA Methylation and mRNA Expression Profiles in Patient-Derived Glioma Stem Cells

In vitro and in vivo models are widely used in cancer research. Characterizing the similarities and differences between a patient\u27s tumor and corresponding in vitro and in vivo models is important for understanding the potential clinical relevance of experimental data generated with these models. Towards this aim, we analyzed the genomic aberrations, DNA methylation and transcriptome profiles of five parental tumors and their matched in vitro isolated glioma stem cell (GSC) lines and xenografts generated from these same GSCs using high-resolution platforms. We observed that the methylation and transcriptome profiles of in vitro GSCs were significantly different from their corresponding xenografts, which were actually more similar to their original parental tumors. This points to the potentially critical role of the brain microenvironment in influencing methylation and transcriptional patterns of GSCs. Consistent with this possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to return to their initial in vitro states even after a short time in culture, supporting a rapid dynamic adaptation to the in vitro microenvironment. These results show that methylation and transcriptome profiles are highly dependent on the microenvironment and growth in orthotopic sites partially reverse the changes caused by in vitro culturing