Proposal summaries
B4363 - Longitudinal mental health outcomes for people with childhood eye disease - 28/06/2023
Children with squint may be more likely to have depression in their teenage years. We do not know why this happens but think it could be:-
-because children with squint are treated differently by others, or
-because children with squint are different to others in some way (for example, they may be more likely to have autism).
A sample of 7,825 children taking part in the ALSPAC study had their eyes tested for squint when they were 7 years old. In addition, the participants have completed a variety of tests for depression throughout their adolescent, and young-adult lives.
Our study is going to use these data to:
a) Find out if childhood squint is associated with adolescent mental health conditions.
b) Explore other associations with squint and identify possible causes of the association.
We will do this by looking at all the children who had their eyes tested at age 7 years and compare the adolescent depression scores of those that had squint to those that did not.
B4360 - Co-occurrence of homelessness and autism in a population based cohort - 28/06/2023
There is emerging evidence of high levels of (often undiagnosed) autism within homeless populations, with current estimates of around 12-18% of people receiving support for homelessness meeting criteria for an autism diagnosis. However there is a lack of population-wide studies exploring the co-occurrence of homelessness or insecure housing and autism diagnosis or traits.
B4341 - Lifelong understanding of cerebrovascular health - 26/07/2023
Currently, vascular ill-health appears to be the most preventable component of cognitive decline in older age. There is however very limited understanding about the time at which signs of damage are already present in diseases that take decades to result in symptoms. In this project we will work to identify through imaging the markers that can help us quantify the health status of vessels and associated tissues in the brain. We will also work to better understand their relationship to known risk factors for cardiovascular disease.
B4362 - Metabolomic associations with liver enzymes and fatty liver disease - 28/06/2023
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains poorly understood. Investigation of circulating metabolites may help in elucidating underlying mechanisms and identify new biomarkers for NAFLD. In this meta-analysis we will examine the association between plasma metabolites and NAFLD as well as liver enzymes using data from four CHARGE cohorts (Rotterdam Study – RS, Avon Longitudinal Study of Parents and Children – ALSPAC, Study of Latinos – SOL, Insulin Resistance Atherosclerosis Family Study – IRASFS).
B4292 - The Impact of Environmental Adversity on the Brain Identifying Biomarkers and Modifiers of Environmental Risk in Psychosis - 31/07/2023
Experiencing environmental adversity is associated with a greater likelihood of developing a mental health disorder. There is a need to identify biomarkers that predict the emergence of poor mental health outcomes following environmental adversity, as the targeted removal of these risk factors could reduce the rates of mental illness by up to a third. Understanding which environmental risk factors impact brain structure and function, and the identification of protective factors, could be the key to preventive medicine approaches. This current proposal would acquire magnetic resonance imaging (MRI) scans in the Avon Longitudinal Study of Parents and Children Generation 2 study (ALSPAC-G2). We are applying for funding from the Wellcome and MRC Career Development Awards.
As ALSPAC-G1 participants are now entering child-bearing age, this presents a unique opportunity to study their offspring (currently n=1875 and growing) to examine inter-generational determinants of mental health. The proposed project uses an accelerated longitudinal design, and would obtain MRI scans in 200 children aged between 5 and 15, who would be followed up and rescanned after 2 years. This project would examine trajectories of brain structure and function during critical periods of neurodevelopment, at a time when most mental disorders first occur.
B4367 - ALSPAC longitudinal metabolomic data collection - 14/07/2023
Whilst other studies exist elsewhere charting the metabolome of disease or of adult or mid-to-late age participants, there are few examples of longitudinal metabolomic data. ALSPAC does have proton nuclear magnetic resonance spectroscopy data on an extended lipidome and select protein panel (Nightingale), however data do not exist for longitudinal liquid chromatography/mass-spectroscopy derived metabolites. This approach has the potential to substantially expand the metabolite collection in ALSPAC, to allow new association analyses and also to provide a benchmark or longitudinal standard for circulating metabolites across ages. This work proposes to collect new data (from existing samples) under a sampling framework aiming to maximise capture of longitudinal changes in metabolic profile.
B4357 - Longitudinal trajectories between sports participation and mental health in ADHD - 27/06/2023
Attention deficit hyperactivity disorder is a major neurodevelopmental disorder during childhood, affecting 5% of children across the UK. Mental health difficulties, such as anxiety, stress, and depression, often cooccur with ADHD and can persist from childhood, through adolescence, to adulthood. Separately, ADHD has also been linked to increased levels of obesity and a more sedentary lifestyle. This issue is concerning given that research has shown that participation in exercise and sports provides a range of health-related benefits, including better mental health. Hence, we aim to 1) explore the biological, social, and psychological factors that predict higher sports participation in individuals with ADHD, 2) evaluate whether higher sports participation predicts better mental health in the long-term in individuals with ADHD, and 3) explore whether the longitudinal relationship between sports participation and mental health to be different between individuals with higher and lower symptoms of ADHD.
B4366 - Child poverty early life adversities and adolescent health and education outcomes - 03/07/2023
4.2 million (29%) children in the UK lived in relative poverty in 2021-22. Similarly, adverse childhood experiences (ACEs), such as child maltreatment and parental mental health problems, are common in the UK. Child poverty and ACEs can have lifelong consequences for children. However, the extensive research undertaken to date on the effects of ACEs on lifelong health has largely ignored the role that child poverty plays, and vice versa. Consequently, the ways in which child poverty and ACEs are related to one another and, subsequently, to adolescent mental health and education outcomes, are not well understood. Partly, this is due to:
i) a lack of longitudinal studies which track the same people over time. Longitudinal studies enable us to investigate how child poverty and adversities relate to one another over time, how quickly a move into poverty affects different ACEs, and the importance of the timing and duration of early life experiences;
ii) a focus only on income-based poverty, when poverty is experienced by families as more than a lack of income;
iii) investigating a limited set of adversities (e.g. only child maltreatment), rather than taking a broader view of adversities to include parental mental health and domestic abuse, for example;
iv) assuming that all families experience child poverty and adversities similarly when we know that some families, e.g. those with more children or from ethnically minoritised groups, have higher risks of being driven into and remaining in poverty.
B4365 - Desistance from violent and non-violent crime - exploring pathways across space and time - 04/07/2023
Criminal behaviour peaks in mid- to late-adolescence,
and then declines throughout early adulthood. However, there are
individual differences in the course of criminal behaviour across this time period,
with a small proportion of young people continuing to commit crimes beyond the
peak age for criminal offending. Desistance is defined as “the process by which
criminality, or the individual risk for antisocial conduct, declines over the life course,
generally after adolescence”. Life-course theories of desistance, based on
high-income countries, suggest that ‘turning points’ (e.g., employment) may
encourage desistance from crime, whereas ‘snares’ (e.g., substance use) may
prohibit desistance. Given that nearly 90% of the world’s population live in low and
middle-income countries, and these countries (particularly in Latin America,
and Sub-Saharan Africa) have much higher rates of serious crime than high-income
countries, it is essential to establish whether the process and theories of
desistance are universal and replicable.
B4355 - The association between maternal and infant omega-3 fatty acid iron and vitamin D status and childhood obesity An ALSPAC study - 22/06/2023
This project aims to explore the direct and programming effect of maternal and infant consumption of three key nutrients (omega-3 fatty acids, iron, vitamin D) on subsequent indicators of childhood obesity. Dietary records and anthropometric/body composition data and genetic profiles from ALSPAC will be analysed to determine if there are any associations between maternal/infant omega-3 fatty acid, iron and/or vitamin D status and body composition measures, including weight, length/height, levels of adiposity and muscle mass. To investigate if these nutrients have an obesity programming effect, the dietary intake of pregnant women (in week 32 of pregnancy) will be analysed, along with the serum samples for the same nutrients to explore if the nutritional status has an effect on infant levels of obesity. To see if these nutrients influence levels of infant and childhood body composition, both short-term and longer term effects will be investigated (infant at age 4 months and child at age 36 months).
B4347 - Smoking behaviours and transitions to vaping in early adulthood - additional data collection - 22/06/2023
We will use data from ALSPAC to investigate predictors of trajectories of smoking behaviours, and transitions from smoking to vaping in early adulthood. Smoking remains the leading cause of preventable cancer; understanding factors associated with smoking and vaping, particularly during early adulthood (a critical period when transitions out of smoking are likely to begin), will inform future cancer prevention programmes and public health policy. This includes identifying predictors that can be used to tailor these programmes more effectively, as well as establishing causal risk factors where interventions could be targeted.
We are proposing to collect measures of smoking and vaping in the next questionnaire. This would enable us to extend existing work being carried out as part of B3499.
B4356 - Eating Disorders Delineating illness and recovery trajectories to inform personalised prevention and early intervention - 20/06/2023
Eating disorders are serious psychiatric conditions that often start in adolescence. Prevalence and burden of eating disorders are rising, they are developing at earlier ages and hospital admissions rising sharply. Currently, there is a lack in our understanding of how sociocultural factors (e.g., food insecurity, racial discrimination) interact with psychobiological factors (e.g., gender) and comorbidities (e.g., depression). This information is vital for informing prevention and early intervention methods for eating disorders in adolescents.
B4336 - Developmental origins of thyroid function regulation and its neurocognitive and reproductive consequences - 20/06/2023
Thyroid dysfunction due to hypo- or hyperthyroidism affects 200 million people worldwide and is a major health burden, particularly in women who are 4-10 times more likely to suffer from hypothyroidism as a result of autoimmune disease. Thyroid hormones are vital for healthy metabolism, tissue differentiation, neurodevelopment, growth, immune function, reproduction, and ageing, yet the relative contribution of environmental exposures (e.g. nutrition, psycho-socio-economic adversity, etc.) in shaping thyroid function regulation remains unknown. The thyroid axis is especially important for the health of women and their children, but currently there is a lack of intergenerational data that can help understand the complex interplay between iodine, environmental factors in early life and thyroid function regulation in the offspring. We aim to fill that gap by investigating (1) critical environmental exposures that impact thyroid function regulation, and their subsequent influence on (2) reproductive health and (3) neurocognitive outcomes. Within these analyses we will look at both natural variation in thyroid function parameters as well as pathological variation due to thyroid dysfunction. At the centre of this exploration is the complex interplay between mother and offspring around limited iodine resources and thyroid function regulation during pregnancy and its long-term consequences. Identifying critical periods of thyroid function plasticity may have significant implications for the optimal timing of comprehensive public health interventions that can decrease the burden of thyroid dysfunction and its health costs over the life course. This proposal has been adjusted from proposal B3905 submitted in 2021.
B4354 - Pre-Clinical Atherosclerosis in Children with Polygenic Hypercholesterolaemia - 19/06/2023
There are different causes for high cholesterol in the blood. Sometimes, it is because of faulty genes that people inherit from their parents. ‘Polygenic hypercholesterolaemia’ is a condition where the cholesterol is raised because of the combined effect of several faulty genes together. ‘Familial hypercholesterolaemia’ is caused by a severe problem with one gene, rather than many. We know that having high cholesterol could cause heart attack or stroke. In this study we will find out to what extent cholesterol deposits in the neck artery of children with polygenic hypercholesterolaemia and how does it compare to children who have familial hypercholesterolaemia and those who don’t have and cholesterol problems. There are currently no data supporting a treatment of children with polygenic high cholesterol.
B4352 - Land Use and Respiratory Health over the life course in ASLPAC - 19/06/2023
Urbanisation has a profound effect on respiratory health in children, partly through some of the adverse environmental exposures such as air pollution and loss of biodiversity. However, relatively little is known about how different land use types within a given neighbourhood affect respiratory health in children over the life course. Evidence is scarce regarding the so-called grey space (industrial, transport hub etc) on children respiratory health in the UK. Recent studies have reported health impacts of certain land use types in children respiratory health, such as green and blue spaces, although the evidence is not always consistent. Parts of the reasons were due to the less accurate assessment of multidimensional nature of green space (amount, types, quality, usages) and the use of a crude indicator in statistical models without strong statistical justifications. This project therefore aims to investigate the effects of land use mix (LUM) around the residential environment on children respiratory health, using both conventional and novel statistical techniques.
B4353 - Associations between prenatal urban environment and cardiometabolic health from childhood to adolescence - 19/06/2023
Living in an urbanized environment undeniably leads to more exposure to urban environmental exposures. Previous studies conducted on urban health were mostly focused on air pollution, while the urban environment is also characterized by its built environment and access to natural spaces. Recently, there is a surging interest to better understand the interplay of different environmental factors that define the urban environment and its effect on children health. Living in a more urbanized environment has been associated with greater adiposity and higher blood pressure in children. Importantly, child cardiometabolic health parameters were mostly investigated individually, while they are intercorrelated. Two approaches have been used to study child cardiometabolic health, a clustering method and a risk score.
B4351 - Executive Function as transdiagnostic cognitive marker of ADHD and eating disorders in early adulthood - 12/06/2023
ADHD and eating disorders have been indicated to be highly comorbid disorders, however research is still unclear of mediators in the comorbidity. Research has shown executive functions to have associations with both disorders, despite this, there is currently limited literature aiming to determine executive function as a potential transdiagnostic cognitive marker in the comorbidity. Biological, social and cognitive factors have been proposed to explain the comorbidity, yet research is still limited in its investigation of the role of executive function in the comorbidity. To address this gap in the literature, I plan to examine whether executive function mediates ADHD and eating disorder relationship at 24/25 years of age.
B4349 - Investigating associations between social connectedness mental health stress and inflammation across childhood development - 13/06/2023
How children develop both emotionally and physically may be shaped by their social experiences. Studies investigating adverse experiences in early life suggest that such experiences may have long-term negative effects on mental wellbeing and stress that continue into adulthood. Furthermore, experiencing chronic stress can have physical effects on the body – for example, increased levels of the stress hormone cortisol can elevate inflammation. Over the long term, these effects may increase the risk of diseases such as heart disease and diabetes. This evidence establishes the role of a “psychosocial pathway” linking our social experiences to mental and physical health.
In contrast, social relationships research suggests that positive, supportive social connections confer a psychological benefit, that promotes wellbeing in children and adults and may improve resilience in face of stressful events. This may be achieved by providing a sense of belonging and attachment to others – in other words, social connectedness. Children may experience social connectedness to a range of people across different social contexts, for example within their family; their school; their peers; and their community.
Unpinning the functional aspects of social connections that foster this may therefore identify opportunities to promote mental and physical health and development. However, to date, there has been limited research exploring the physiological effects of social connectedness, and how these may be mediated via stress and its downstream effects, such as inflammation. Epigenetic modification of stress-response genes may underpin long-term effects, however there has been limited research investigating these pathways using birth cohort data. Furthermore, few studies exploring these associations in childhood have included or compared multiple social contexts. Lastly, there is limited research utilising longitudinal data to explore how associations between social connectedness, mental health, stress and inflammation may change over time.
This project aims to address these research gaps by investigating the associations between early life social connectedness, mental health and biological indicators of stress and inflammation across different social contexts – namely, family, school, friends, and community. This project will investigate how these social experiences may establish longitudinal trends in mental health and stress across childhood and into early adulthood. To investigate one potential mechanism that may underpin long-term physical effects, this project will assess the relationship between social connectedness and epigenetic modification of stress-response genes.
B4350 - Parenting Practices and Depression in adolescents the mediating - 08/06/2023
Studies have documented close relationship between parenting behaviour (e.g., harsh parenting, abuse, and neglect) and depression (Cole et al., 2016). It is however not entirely clear what’s the mechanism underlying such association. How individual process rewards has been found to be closely associated with depression (Beck, 1967; Disner et al., 2011),and can potentially be a mediator exaplaining the link between parenting and depression. Specifically, research has shown that an individual suffering from depression differs from people without depression in terms of how they value rewards according to time (Pulcu et al., 2014). In this study, we aim to investigate the mediating effect of reward valuation in the association between parenting in adolescence and depression in early adulthood, a period characterised by heightened risk for depression, as well as time poses parenting challenges. We will also explore the association with financial difficulties, gambling problems, employment status, and romantic relationship quality in early adulthood as a proxy of individual functioning.
B4348 - The role of DNA methylation in pubertal development and timing of sexual reproduction - 12/06/2023
According to life-history theory, any organism will strategically divide resources toward growth, maintenance and reproduction (Ellis, 2004). In a harsh environment, humans might mature earlier to enable earlier reproduction – to secure the transmission of one’s own genes in the next generations (Belsky et al., 1991). Previous research has indeed indicated that harsh family environments, such as chaotic life environments or rejecting, inconsistent parental behavior, and severe stressors can lead to earlier pubertal maturation (in girls) (Belsky et al., 2010; Belsky, Steinberg, et al., 2007; Ellis et al., 1999; Holdsworth & Appleton, 2020; Sheppard et al., 2016). Recently, a two-hit model of accelerated aging has been proposed (Belsky & Shalev 2016), specifying that early adversity does not necessarily lead to earlier sexual reproduction even though it has been found to predict pubertal maturation. Belsky and Shalev hypothesized that a supportive environment during puberty can act as a buffer against early sexual reproduction. Moreover, they hypothesized a potential biological mechanism, wherein early childhood adversity may result in epigenetic changes (i.e. advanced biological age compared to chronological age measured via epigenetic clocks) which might result in earlier pubertal maturation and (in case of a non-supportive environment) in earlier sexual reproduction.
Some previous proposals have looked at parts of this model (e.g. B878, B897, B2760, B2883, B3077, B3690), but we will be the first to combine these parts, such as relation between father absence and puberty or the relation between pubertal development and sexual risky behaviors into one overarching model of the life history theory.