Proposal summaries
B3033 - Antibodies to Infectious Agents and Psychiatric Disorders - 11/01/2018
The goal of the study is to determine the relationship between exposure to common infectious agents and measurements of cognitive and psychiatric functioning in children and adults
B3043 - Applied epidemiology and the human gut microbiome evidence for causal effects versus confounded companionship - 30/01/2018
The human gut microbiome is a large community of bacterial microbes, which interact to aid digestion, protect against pathogens and create essential metabolites. Whilst the gut microbiome has been implicated in adverse health outcomes, robust applied epidemiological evidence able to discern causation from correlation does not exist. With my expertise, data resources built in my current position, preliminary results, established collaborations and desire to work within this clinically relevant field, I am setting out to apply robust epidemiological and causal inference methods to human gut microbiome research. The proposed fellowship sits in a specific area for intended future research, in which I wish to establish myself as an academic leader, with the additional aims of further characterising the causal and functional role of the gut microbiome at scale (combining both metagenomics and metabolomics), understanding the range of modifiable causal risk factors that lead to gut microbiomic variation (using MR, randomized controlled trials and genotype-directed recall studies) and identifying therapeutic targets to migrate within an industry or pharmaceutical setting.
B3042 - The Workplace Maternal Depression Prevention Network - 18/01/2018
The distal and proximal causes of depression and common mental health problems are poorly understood. There is limited success in preventing the onset of depression with individual, or group structured psychological support, such as cognitive behaviour and counselling approaches, offered to adults with subthreshold (fewer than 4) symptoms of depression (Van Zoonen, 2014).
Many studies (Leka & Jain, 2017) suggest that employees who report high levels of work stress are at a greater risk of developing a range of mental and physical health conditions such as depression (ILO, 2016). Well-being at work is defined as individualsâ ability to work productively and creatively, to engage in strong and positive relationships, fulfilment of personal and social goals, contribution to community, and a sense of purpose.
Addressing mental health in its totality recognises the complex interrelationships among risks to mental health, including? sub-threshold conditions of poor psychological health that may not have yet resulted in diagnosed mental ill health problems.
Policies and practices that tackle a wider range of risk factors could improve mental health through appropriate interventions in the work environment. They could promote positive and supportive organisational cultures and organisational justice, increase employee control and participation, introduce teamwork (where appropriate) in combination with interventions at the individual level (selected and targeted prevention, for example, coaching, cognitive-behavioural therapy, physical activity and problem- focused return-to-work programmes). There is a notable dearth of knowledge on the effects of the structural environment (sound, light, air quality) on mental health at work.
Women make up 45% of the labour force. Pregnancy, childbirth and the transition to motherhood are profoundly transformative experiences for women in physical, psychological, social and even organisational terms (Millward, 20065; Smith, 1999). Such transition points broadly relate to the personal experiences and organisational procedures surrounding maternity leave: pre-leave, maternity leave, and (for many) return to work.
Each one of these stages can yield important opportunities for psychological growth and emotional fulfilment; but, conversely, can pose mental and physical challenges and strains for mothers, also an equality issue.
Most adults avoid or fail to access free depression prevention services [Cuijpers Ref] and under use treatment services globally [WHO]. The public tell us they do not feel able to be open about mental health with occupational health or counselling services provided through their employer. Presenteeism (being mentally ill at work: cost to UK employers £16.8bnâ£26.4bn) costs more than absenteeism (£7.9bn) (Deloitte, 2017).
The Workplace Maternal Depression Prevention Network (WMDPN) will join together expertise in discovering social, psychological and physical determinants of depression, in interventional practice skills, and in complex population and intervention outcome designs. It will create fundable proposals for research on maternal mental health (selected prevention) and subsequently on universal workplace prevention. Proposals will address the fundamental problem that access to such interventions is difficult, most adults avoid or fail to access services that can prevent depression or treat it early and employers also resist change in their management practices.
A UK based network is needed with expertise in the psychological and structural environment, public health and epidemiology, mathematical modelling (of complex systems and outcomes), intervention development and complex evaluation designs (see 4.3).
Surprisingly little attention has been devoted to mental health prevention research in the UK. We lack interdisciplinary work bringing together researchers interested in the determinants of poor mental health and in intervention and behaviour change. Our network would create new relationships and commitments to developing research proposals, co-designed by such researchers, together with the public and with employers, for whom the economic returns on investment are substantial. We also bring to the table achievements and expertise from outside the UK, demonstrating those successes necessary encourage change in the UK research and employment cultures.
We propose to site research in the employment sector to address three important change targets: the psychological and organisational work environment; the perceptions and behaviour of managers and of employees; and incentives and barriers to behaviour change.
The wellbeing and mental health of women in work is crucial to maintaining the future adult workforce and raises key gender and equality issues. Our initial proposed membership includes expertise in changing group and management practice and individual psychological change. An 'early win' could grow out of previous work by two of us (TB, PS). We have identified potentially promising approaches to prevention of maternal depression, developed by altering routine NHS maternity professional training and care (Psychol Med. 2011;41:739-748). This could be adapted to the work place by redesigning employee support practices by adapting mentoring and coaching to address psychological needs. Successful adaptions like this could eventually be scaled up as (universal) mental health prevention practices across the wider workforce.
B3037 - Behavioural PheWAS Alcohol tobacco and caffeine use in ALSPAC subpopulations - 11/01/2018
Through genome wide association studies (GWAS), common genetic variants have been identified that are associated with alcohol, tobacco and caffeine use in the general population, allowing the generation of polygenic risk scores (PRS) for these substances. However, uncertainty remains as to whether these variants also predict use in pregnancy or at other time points in life.
Further investigation is required to confirm if these previously found genetic variants are predictive of alcohol, tobacco or caffeine use in specific subpopulations in ALSPAC; in adults (as a positive control), pregnancy, and adolescence. These variants may also have considerable pleiotropic effects, affecting the outcome through pathways other than the exposure of interest. As consumption of alcohol, tobacco and caffeine is highly comorbid with mental health problems, it is possible that common genetic variants are predisposing individuals for both an increased consumption of these substances, and development of mental health problems. A PheWAS tests the association of a single or set of genetic risk variants with a finite group of human traits, termed âthe phenomeâ. The strength of the ALSPAC data is its longitudinal design, that enables to track health behaviour over a long period of time.
B3040 - Examining cumulative effects of general and central adiposity on cardiometabolic traits through Mendelian randomisation - 11/01/2018
Higher total adiposity (body fatness) is known to harm health. Studies tend to observe that adiposity stored centrally in the abdominal region is most strongly linked with factors which trigger type 2 diabetes and heart disease, but this has been little examined within a causal framework and so the relative importance of central vs total adiposity for disease risk is still uncertain. This study aims to harness the unique strengths of ALSPAC to examine whether higher central adiposity (indicated through higher waist-to-hip ratio) is likely to cause cardiometabolic trait levels in childhood and young adulthood. Of particular interest is whether effects of higher central adiposity get stronger with the amount of time exposed, and whether they are stronger than effects of total adiposity (indicated through body mass index). Causal methods of Mendelian randomisation will be used at both life stages (childhood and young adulthood), and outcomes will include an extensive set of blood-based cardiometabolic traits through novel targeted metabolomics. Altogether, this study aims to provide deeper insight into the causal impact of central adiposity on cardiometabolic health than ever before.
B3039 - Physical activity in early adulthood Analysis of the ALSPAC cohort to identify influences on physical activity that can inform - 18/01/2018
Physical activity is associated with reduced risk of depression, heart disease, stroke, type 2 diabetes and many forms of cancer. Physical inactivity has been estimated to cost the NHS £1.06 billion per year in direct costs, with a further £6.5 billion in lost work productivity. Thus, inactivity is a major drain on the physical, mental and economic health of the UK and understanding the key factors that influence physical activity is the critical first phase of developing strategies to change behaviour at the population level. This application focusses on assessing the physical activity patterns of young adults (age 28-30) in the ALSPAC cohort and the aspects of their current life and their development that help to explain why they adopt their current pattern of physical activity behaviour. This is potentially a very important time for the establishment of future disease risk but for which there is a lack of information on physical activity or how to transition to adulthood well
B3036 - Expansion of Andhra Pradesh Children Parents Study APCAPS to esablish an Urbanizing Population Laboratory - 18/01/2018
Andhra Pradesh Children and Parents Study (www.apcaps.lshtm.ac.uk) is a cohort of households which took part in a mother-child nutritional supplementation trial (1987-90). Located in vicinity of Hyderabad city, an emerging technology hub in south India, the study district is undergoing rapid uneven urbanisation, providing a unique window of opportunity (analogous to a stepped-wedge design) to investigate of health effects of urbanisation. So far, we have collected data on built environment and air quality of study villages, and serial longitudinal data for chronic disease risk factors on cohort participants (n=7000). We now propose to expand clinical data collection, on a wide range of health outcomes (e.g. chronic diseases, mental health, ageing, injuries, infectious diseases), making extensive use of wearable sensors and other digital technologies, to all remaining residents (N=100,000) of the 29 study villages. The resulting Urbanising Population Laboratory â a complete eco-system of health data, including bio-repository, on all individuals, their inter-relationships/networks, and their environment (natural, physical, social) â set within a backdrop of rapid uneven urbanisation, will offer the global research community unparalleled opportunities to investigate how environment shapes human health. We will establish a linked electronic health surveillance system to enable ongoing data collection. Collaboration with an established LPS (ALSPAC) will add further value to both cohorts.
B3041 - Methods Measures of Context Consistency in Longitudinal Neighborhood Analysis - 05/02/2018
This would involve support to develop statistical methods to both characterize spatial-social volatility in neighbourhoods, as well as identify its potential impact on longitudinal models that incorporate contextual effects. This support also encompasses developing an open source implementation of these statistical methods to serve as the reference-in-praxis, made freely available to all scholars. Further, example data sets constructed to both illustrate the potential for instability and geographies to correct for these problems will be generated. In addition, travel support to discuss, develop, and collect professional feedback on these methods & questions is requested, as well as a postgraduate research assistant to conduct a significant portion of the work in collaboration with the requesting committee.
B3032 - Child neurodevelopmental problems and parent functioning - 10/01/2018
Neurodevelopmental disorders (NDDs) are a group of highly heritable childhood-onset conditions characterized by impairments in developmental domains such as communication, social interaction, motor skills, cognition, activity and emotion (1). Common NDDs are attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). While schizophrenia is a psychiatric disorder typically diagnosed after puberty, the onset is commonly preceded by childhood neurodevelopmental impairment (2,3). Although ASD, ADHD and schizophrenia are categorically defined for clinical purposes, they can also be viewed as the extremes of continuous trait dimensions found in the general population (4,5).
A large body of observational studies suggest that having a child with an NDD is associated with poorer parent functioning, including depression, inter-parental discord and maladaptive parenting behavior (6-10). While such parental traits have been proposed to increase risk or exacerbate child NDD problems, important alternative explanations are shared familial factors (e.g., shared genetic risk for NDD) and reverse causation (e.g., child NDD problems evoking inter-parental discord) (8). Previous studies attempting to disentangle these alternative explanations have primarily relied on twin and adoption study designs (8,11), with findings suggesting that child NDD traits evoke maternal negative parenting behaviors and inter-parental discord. However, twin and adoption studies are generally limited by small samples and potential non-representativeness of twin and adoption families. Better understanding of the potential effects of NDDs on parent functioning is needed in order to improve interventions for children with NDDs and their families.
Genetic advances now allow for direct measurement of the genetic risk burden for NDDs in individuals from the general population. If raising a child with an NDD, such as ASD, affects parent functioning, then childrenâs genetic risk burden for ASD should contribute to explaining variance in parent functioning over and above the parentsâ genetic risk burden for ASD.
In the present study, we will examine whether child genetic risk burden for ASD, ADHD and schizophrenia predicts parent functioning (mental health, relationship harmony, parenting) when adjusting for parental genetic risk burden. We will use family trio data from two population based pregnancy cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the Norwegian Mother and Child Cohort (MoBa). Data from the two cohorts will be analysed separately, and the results may be meta-analysed.
References
1 American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). (APA, 2013).
2 Pine, D. S. & Fox, N. A. Childhood antecedents and risk for adult mental disorders. Annu Rev Psychol 66, 459-485 (2015).
3 Rutter, M., Kim-Cohen, J. & Maughan, B. Continuities and discontinuities in psychopathology between childhood and adult life. J Child Psychol Psychiatry 47, 276-295 (2006).
4 Rossler, W. What is Normal? The Impact of Psychiatric Classification on Mental Health Practice and Research. Front Public Health 1, 68 (2013).
5 Thapar, A., Cooper, M. & Rutter, M. Neurodevelopmental disorders. The Lancet Psychiatry 4, 339-346 (2017).
6 Kessler, R. C. et al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. The British journal of psychiatry : the journal of mental science 197, 378-385 (2010).
7 Harold, G. T., Leve, L. D. & Sellers, R. How Can Genetically Informed Research Help Inform the Next Generation of Interparental and Parenting Interventions? Child Development 88, 446-458 (2017).
8 Harold, G. T. et al. Biological and rearing mother influences on child ADHD symptoms: revisiting the developmental interface between nature and nurture. Journal of Child Psychology and Psychiatry 54, 1038-1046 (2013).
9 Wüsten, C. & Lincoln, T. M. The association of family functioning and psychosis proneness in five countries that differ in cultural values and family structures. Psychiatry Research 253, 158-164 (2017).
10 Benson, P. R. & Kersh, J. Marital quality and psychological adjustment among mothers of children with ASD: Cross-sectional and longitudinal relationships. Journal of autism and developmental disorders 41, 1675-1685 (2011).
11 Schermerhorn, A. C. et al. Offspring ADHD as a risk factor for parental marital problems: Controls for genetic and environmental confounds. Twin Research and Human Genetics 15, 700-713 (2012).
B3028 - Puberty timing and physical activity in adolescents and adults findings from the ALSPAC and UK Biobank cohorts - 10/01/2018
Studies suggest that the timing of puberty may be associated with physical activity (PA) in adolescence and with a range of health outcomes in adulthood. The aim of our study is examine associations between markers of puberty timing and accelerometer-measured PA in adolescents from ALSPAC and adults from the large UK Biobank cohort. In ALSPAC, we will make use of repeated measures of PA at ages 11, 13 and 15 to examine how puberty timing associates with PA across adolescence, and in both cohorts we will examine how genetic markers of puberty timing might relate to accelerometer-measured PA.
B3029 - Progression of mood and psychotic symptoms from adolescence to young adulthood validation of a cross-syndromal staging model - 11/01/2018
Symptoms of mental disorders commonly begin in the early adolescent years. However, whether they are indicative of the risk of young people developing serious mental disorders remains unclear. Such symptoms assessed in young people in clinical or high-risk settings have provided support for âstagingâ models for serious mental disorders. In these models, sub-threshold symptoms are hypothesized to progress to later stages of psychosis and mood disorders. In order to understand whether such staging models are valid for young people in the community, it is necessary to study cohorts of young people recruited from the community who are prospectively followed over time. Such cohorts also help avoid biases associated with selecting participants or their recall of symptoms. We propose to examine the ALSPAC cohort to determine whether subthreshold mood and psychotic symptoms in early adolescence progress to later stages (threshold stages) of these disorders, or predict difficulties in functioning in young adulthood. Specifically, we will examine the symptoms of mania, depression and psychosis in young adulthood. We propose to compare those with and without progressive symptoms of these mental disorders with respect to their birth, early life and parental characteristics in order to identify predictors of later difficulties. We also propose to examine the role of intermediate or late adolescent life events or substance use in the progression of mental health symptoms. This project could help young teenagers and their families understand the risk factors that predict better or worse outcomes in the following decade. This could help plan further interventions for at least a sub-proportion of these youth.
B3030 - Capacity of the genome and methylome to predict BMI - 07/02/2018
Our genes influence our height, BMI and many other characteristics including susceptibility to disease. Environmental factors such as diet and stress also play a role, possibly mediated by changes in DNA methylation patterns. By analysing DNA sequence together with DNA methylation, we hope to better understand how each relates to characteristics like BMI and blood metabolite levels both separately and together.
B3034 - Associations between disordered eating and socioeconomic status in the ALSPAC cohort - 09/01/2018
Like obesity and type 2 diabetes, eating disorders (anorexia nervosa, bulimia nervosa, binge eating disorder, and other specified feeding and eating disorders) are associated with adverse prenatal and perinatal conditions. However, unlike obesity and type 2 diabetes, the prenatal and perinatal risk factors associated with eating disorders have not been analysed through the lens of health inequalities. This is an important gap. While eating disorders are commonly depicted as conditions that afflict middle-class women, recent studies have found that adults who experience economic precarity are more likely to endorse disordered eating attitudes and practices, suggesting that low socioeconomic status may be associated with the development of eating disorders. The proposed project will develop the first prospective analysis of the influence of parental socioeconomic status on children's disordered eating in adolescence. The project will use data collected as part of ALSPAC (Avon Longitudinal Study of Parents and Children). The ALSPAC cohort includes 14,000 children born between 1991 and 1993, who have been followed intensively since the early 1990s until the present day, with clinical assessments and self administered questionnaires charting the children's development into adulthood from physiological, emotional, cognitive, behavioural, and social angles. Notably, ALSPAC collects detailed longitudinal data on parental socioeconomic status, maternal eating disorders, and children's disordered eating, allowing for an analysis of the influence of parental socioeconomic status on children's disordered eating. The proposed project is therefore uniquely positioned to examine an important gap in the literature which, if confirmed, will reposition eating disorders within the health inequalities field.
B3035 - ALSPAC MRI-II - 06/02/2018
The Avon Longitudinal Study of Parents and Children (ALSPAC) has shown that over 9% of 18 year olds have psychotic experiences (PEs) such as hallucinations and delusions, verified by trained psychologists and using strict criteria. When persistent, PEs increase the likelihood of a person developing psychotic disorders such as schizophrenia, other psychiatric conditions (eg depression) and poor psychosocial outcomes such as unemployment. PEs can sometimes recede as people pass from adolescence to adulthood but we don't know how changes in the brain, which continues to develop and mature through these years, underlie and affect PEs. Thanks to grants from the MRC, we have recently shown, using magnetic resonance imaging (MRI) brain scans, that at age 20+, individuals from ALSPAC with PEs have small changes in regional brain volumes, and global and local connectivity which cannot be ascribed to the consequences of having a psychiatric diagnosis or treatment with medication. We have also shown that individuals from ALSPAC who may be at a slightly increased risk of psychosis due to their genetic makeup (using a ârisk scoreâ made out of the contribution of the many genes which when added together, are associated with a small but significantly increased risk of schizophrenia) also have subtle changes in brain thickness and volume.
Our objective is to re-scan these same individuals, numbering about 450 in total, at age 26 using the full range of MRI scanning techniques. This will enable us to test the hypothesis that persistent PEs are underpinned by anomalous pathways or trajectories of brain development and abnormalities in function, as compared with those without PEs and against their original baseline scans. Additional objectives are to plot changes in cognition (using IQ tests) which we expect might show some decline in those with persistent PEs. We will make use of the latest genetic risk for schizophrenia scores from genome-wide association studies available in ALSPAC to examine the potential of our brain measures to be used as intermediate links between genes and clinical outcomes. Finally we will see if blood markers of inflammation which can act on the brain, measured in the same individuals when they were children and again when adults, might explain the brain changes we see on MRI.
We will use a powerful 3 Tesla MRI brain scanner located in Cardiff to obtain detailed structural images and measures of grey and white matter volumes and a particular variant of scanning called diffusion tensor imaging which picks up the integrity of white matter tracts - nature's wires - that connect together groups of brain cells. Functional MRI, which picks up those parts of the brain that are active during a task, will be carried out while participants are trying to remember a sequence of letters and also while they are at rest (although their brains will still be working). This will help us to determine the degree of physiological compromise/compensation evident in the brain in those with PEs and structural changes. This will also help us look at how the different specialised parts of the brain are working together as a coherent unit.
This project will enable us to map the change in brain development in young people with and without potentially important psychotic experiences (PEs) taken from ALSPAC, one of the most well-studied epidemiological samples available to medical science. Because there is such a wealth of information available, it means that when we analyse the brain scans we can take into account lots of other factors which might otherwise obscure or falsely exaggerate the effects of PEs such as cannabis and alcohol misuse. The project as a whole has the potential to advance in our understanding of the biological basis of psychotic and related disorders and to help guide the development of primary prevention and early intervention strategies in mental health care.
B3038 - Big Data in the Social Sciences Statistical methods for multi-source high-dimensional data - 10/01/2018
Social science research has entered the era of big data: Many detailed measurements are taken and multiple sources of information are used to unravel complex multivariate relations. For example, in studying obesity as the outcome of environmental and genetic influences, researchers increasingly collect survey, dietary, biomarker and genetic data from the same individuals. Such novel integrated research can inform us on health strategies to prevent obesity.
Although linked more-variables-than-samples (called high-dimensional) multi-source data form an extremely rich resource for research, extracting meaningful and integrated information is challenging and not appropriately addressed by current statistical methods: A first problem is that relevant information is hidden in a bulk of irrelevant variables. Second, the sources are often very heterogeneous, which may obscure apparent links between the shared mechanisms. A statistical framework is needed to select the relevant groups of variables within each source and link them throughout data sources. In this project we develop a new framework by extending principal component analysis to common components defined by relevant clusters of variables. We use it both for exploration and outcome modelling of linked high-dimensional social sciences and (epi)genetic data.
The advanced component analysis method will be a widely applicable and novel method for knowledge extraction also allowing for more accurate predictions in many social science contexts with big data. In addition, the proposed empirical study will generate important insights on the gene-environment interaction in socially relevant outcomes like obesity.
B3031 - Predictors and patterns of GP contacts for young people who have self-harmed - 10/01/2018
Self-harm in young people is a major problem. As many as 1-in-6 teenagers have self-harmed at some point in their lives, and self-harm is particularly common between the ages of 10 and 16 years. Young people who self-harm seem to be more likely to do poorly in a number of ways in early adulthood, including being more likely to have a mental health problem, and to use substances like alcohol and drugs. It is also the strongest known risk factor for suicide. Although self-harm is very common in young people, most do not seek help. In this project we plan to investigate whether individuals who self-harm are visiting their GP and, if so, what they are visiting the GP for and how often. We would also like to identify what proportion of teenagers who have self-harmed are picked up by their GP and whether there are important differences between those who are picked up by their GP and those who are not.
B3026 - Cellular phenotyping of Placentas and Prediction of outcomes - 08/01/2018
This project aims to use state of the art analysis technology to look at placenta with the aim to characterize the cells that make up the placenta and see if any features of them are related to pregnancy outcomes for mom and child.
B3025 - Using genetics to understand interactions between CHD risk factors and physical activity / sleep - 27/03/2018
We would like to apply for funding to obtain objective measures of physical activity and sleep in the ALSPAC CO90s cohort. A large proportion of CO90s underwent studies of their activity when they agreed to wear a waist accelerometer at the age of 11 and several time points throughout their teenage years. We believe it would be a unique and extremely powerful resource to have objective measures of activity in the same individuals in early adulthood in addition to their earlier measures. We would propose to use a more sophisticated accelerometer device - a wrist worn device that does not need to be removed when washing or sleeping and that has been worn for 2 consecutive weeks with high compliance. We intend to apply for full funding to support the collection of activity data from the C090s, including admin support, devices and data curation. If funded, this would need to occur during late 2018 - 2020. The data would be owned by ALSPAC and made available to all. Our specific interest is around the effects of genes and activity on obesity. The specific research question is to provide an advance in the understanding of whether or not genes and activity measures interact to predispose some people to modifiable CHD risk factors including obesity.
B3027 - Placental pathology linking the health of two generations - 08/01/2018
Problems with the placenta can cause preeclampsia, preterm delivery and small babies.
These problems with how the placenta develops to support a pregnancy may be linked with heart disease in both mothers and their children.
We plan to characterise existing placentas in order to gain a better understanding of what a healthy and a non-healthy placenta looks like and how these characteristics relate to pregnancy outcomes but also to long tern health of mothers and offspring.
B3022 - Genetic variations associated with exacerbations in children despite treatment with inhaled corticosteroids GWAS meta-analysis - 18/12/2017
This project aims to identify genetic markers associated with increased risk of exarcerbations in children with asthma despite the use of inhalers.