Proposal summaries
B4413 - Building blocks of cognition The co-development of brain function and cognition across the first 5 years of life - 13/02/2024
The first 5 years of life is a key period of development – not only do children grow at the fastest rate in their lifetime, they also develop a vast range of new skills and abilities. In this study, we are interested in some of the most important skills that children develop during this period, including language skills, the ability to quickly understand and react to new information, and the ability to concentrate and adjust behaviour in everyday life. Alongside this, we are interested in how the brain develops and allows children to learn all these new things, and, in turn, how new experiences may lead to changes in the brain. To do this, we will see the same children in the lab for assessments at multiple time points between 6 months and 5 years. Participating families will be recruited from the ALSPAC sample, meaning that the study children’s parents (i.e., the ‘Children of the 90s’) will already have participated in many assessments themselves (since their own childhood). This gives us useful information about the parents and their background, which will help us understand more about how their children develop. At the final time point (when children are 5 years old), we will look at how development of the brain and the key cognitive skills prepare children to start school, with the ultimate aim of understanding more about why some children struggle in school, either academically and/or socially.
B4406 - Factors that Predict Immune Function Resilience of Adult Survivors of Childhood Sexual Abuse - 11/09/2023
Not long ago, we learned the extent to which adverse childhood experiences (ACE) lead to long-term physical and psychological health problems (Felitti et al., 1998). In the last two-and-a-half decades, there have been continuing developments in the research of why and how adverse childhood experiences lead to death and illness in adulthood. Now, thanks to current research, we have a better understanding of why and how adverse childhood experiences increase morbidity. Inflammation is increased in those with adverse childhood experiences (Rasmussen et al., 2020). Chronic inflammation increases the risk of developing cardiovascular disease, cancer, diabetes mellitus, autoimmune, and many other health concerns (Furman et al., 2019). Although researchers have investigated this issue, the topic has not been explored in this way: Despite knowing that ACE increases health concerns through inflammation, there is very little research regarding variables that promote resiliency of immune health. Additionally, there is minimal research that confronts the specific trauma experienced by those with childhood sexual abuse (CSA). The specific research problem that will be addressed through this study is that we do not know whether and to what extent environmental factors are associated with healthier immune function among survivors of CSA.
From a psychoneuroimmunological foundation, a collection of variables among survivors will be analyzed as potential protective factors. These variables include ease to talk about problems with parents, feelings of closeness to parents, religiosity, involvement in sports or other after-school activities, religiosity, and feeling close to someone. Then, various inflammatory biomarkers will be analyzed and a relationship between factors and biomarkers will be explored.
B4407 - Prospective relationship between emotional risk factors and development of overweight/obesity in adolescents and young adults - 11/09/2023
Overweight and obesity are common and can have debilitating physical and mental health consequences. Overweight and obesity can start in early childhood and track throughout adolescence and adulthood. While effective treatment and prevention is still lacking, increasing our understanding of contributing factors is invaluable in designing better interventions.
Connections between mental states and obesity are well known. However, a large number of studies have focused on the role of depression in weight development while other factors that reflect vulnerabilities based on emotional symptoms have less frequently been examined. Additionally, few studies have longitudinal data that tracks participants throughout different developmental stages, including childhood, adolescence, and young adulthood.
Adolescents who are overweight are more likely to resort to unhealthy disordered eating behaviors such as skipping meals, extreme dieting, and purging through vomiting. Other disordered eating symptoms include concerns about shape and weight, weight control methods and binge eating. Disordered eating attitudes and behaviors can have detrimental effects on dietary quality, weight gain, development of obesity over an extended period, increased risk of depression, and also a higher likelihood of developing eating disorders such as anorexia nervosa, bulimia nervosa, or binge eating disorder. While there likely is a bidirectional relationship between weight development and disordered eating, the progression to development of obesity and eating disorders throughout childhood, adolescence and young adulthood is currently unknown.
This study aims to identify developmental trajectories of emotional risk factors, disordered eating, as well as body weight and examine which pathways of emotional risk factors and disordered eating are associated with later development of overweight or obesity.
Besides the focus on children’s emotional risk factors, this study also aims to examine the role of maternal psychological factors in relation to disordered eating and body weight throughout the first 3 decades of life.
This study will be fundamental in starting to understand new risk mechanisms for adolescent and
young adult overweight/obesity that can be further investigated in intervention studies following this project.
B4409 - Cooperative childrearing in middle childhood and biosocial pathways to adolescent wellbeing - 11/09/2023
Are non-parental caregivers important for children and young people’s wellbeing, even in societies with strong nuclear family and intensive parenting norms? This mixed-method project uses the “Children of the 90s” cohort study to investigate the role of alloparents (non-parental caregivers) in England, examining the biosocial pathways between different forms of local childrearing systems and adolescent outcomes.
CONTEXT: Western family structures are often described as nuclear, and in the UK, this is coupled with intensive parenting norms. Childrearing is seen as a private matter, and parents (particularly mothers) are predominantly viewed as being responsible for raising children. From an evolutionary anthropological perspective, this way of raising children is highly unusual: anthropological studies from across populations show that non-parental caregivers (alloparents) are ubiquitous and crucial contributors to childcare, although who helps and how they help vary. Humans have therefore been hypothesised to have evolved a unique system of “cooperative childrearing,” co-evolving with an extended period of dependence through childhood and adolescence. In essence, it takes a village to raise a child.
CURRENT CHALLENGE: Despite intensive parenting norms, families in the UK exist within varied and complex systems of support. However, while evolutionary theory points to the importance of non-parental caregivers, much of our knowledge around raising children centre on parenting with particular focus on early years. There is limited focus on alloparenting, and few studies investigate the impact of alloparental care in middle childhood despite the reliance on continued after-school/weekend childcare for many families. It is therefore unclear how families exist within local systems of childrearing, and how these systems impact children and young people’s health and wellbeing. A comprehensive understanding of the wider childrearing system is crucial to design effective policy and practice impacting parents, children, and young people.
PROJECT AIMS: This project extends the focus of childrearing from parenting to incorporate alloparenting, building a comprehensive understanding of childrearing systems in middle childhood and their pathways to adolescent wellbeing in England (UK).
Specifically, this project aims to (1) identify and classify the different typologies of childrearing systems beyond parenting within England, and (2) investigate the biosocial pathways between alloparenting, markers of stress, and adolescent outcomes including affect (anxiety/depression), socio-emotional development, and health-related risky behaviours. We use data from Avon Longitudinal Study of Parents and Children (“Children of the 90s”) which uniquely holds detailed data on alloparenting during middle childhood (age 6-12), together with biomarkers of stress/inflammation (cortisol, c-reactive protein, interleukin-6). We apply an innovative combination of quantitative and qualitative methods by quantitatively identifying typologies of caregiving (latent class analysis), deepening our understanding of these typologies by using the longitudinal data to constructing life history case studies, then test the hypothesised causal pathways through structural equation modelling.
PROJECT BENEFITS: By extending the focus of caregiving to incorporate alloparents and taking an innovative mixed-method approach, this project contributes to an in-depth understanding of middle-childhood caregiving systems and their impact on young people within a parent-focused culture; and, in doing so, we improve our understanding of human childrearing systems more broadly. Overall, this project will: improve cross-disciplinary knowledge around optimal childrearing practices in middle childhood; contribute to methodological development by applying a novel combination of mixed methods to longitudinal cohort data; and contribute knowledge towards effective policy and practice development for children and families in England and beyond.
B4404 - Desistance from violent and non-violent crime - exploring the snaring role of substance use - 19/09/2023
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 suggest that certain ‘snares’ (such as substance use) may prohibit desistance.
B4401 - Making sense of the varying methylome and varying disease patterns - 11/09/2023
DNA methylation (DNAm) plays a central role in gene regulation. However, it is unknown how DNAm patterns change. For example, through genetic factors or physiological states.
Longitudinal birth cohort studies such as ALSPAC provide an unique opportunity to study DNAm patterns over time and to link it to varying physiological states. Quantitative traits comprising your physiological state (such as BMI, glucose and inflammation levels) have varying patterns over time. Similarly eczema and asthma have varying disease patterns over time. Identifying changes in DNAm preceding a change in physiological state or a disease status may lead to identification of a marker that predicts disease outcome.(1)
Multiple studies have identified genetic variants associated with DNAm (mQTL: methylation quantitative trait locus) by combining genome wide genotype information with DNAm levels.(2) The Genetics of DNA methylation Consortium brought together a large number of cohorts to identify mQTLs in blood and investigated whether the mQTLs play a role in disease etiology.(3) Modelling DNAm trajectories with genetic variation could improve our understanding of biological mechanisms.
1. Chen R, Xia L, Tu K, Duan M, Kukurba K, Li-Pook-Than J, et al. Longitudinal personal DNA methylome dynamics in a human with a chronic condition. Nat Med. 2018;24(12):1930-9.
2. Gaunt TR, Shihab HA, Hemani G, Min JL, Woodward G, Lyttleton O, et al. Systematic identification of genetic influences on methylation across the human life course. Genome Biol. 2016;17:61.
3. Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R, et al. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. Nat Genet. 2021;53(9):1311-21.
B4402 - Health Economic Model for Evaluating Interventions for Children of Parents with Mental Illness - 18/09/2023
Children of parents with mental illness (COPMI) face a heightened risk of developing mental disorders themselves. While the literature underscores the importance of early interventions, there is a scarcity of studies investigating the economic implications of such interventions. This project seeks to bridge this gap by constructing a health economic model that synthesizes both clinical and economic data, enabling a comprehensive analysis of the potential benefits and costs associated with different intervention approaches.
Hence, in this project, we will develop a health economic simulation model to examine the cost-effectiveness of interventions targeting these children/families. The ultimate goal is to demonstrate the added value of these interventions for children, their parents, and society as a whole.
Upon completion, the health economic model will provide a quantifiable assessment of the economic value of various interventions for children of parents with mental illness. It will enable decision-makers to compare the costs and benefits of different strategies, facilitating resource allocation based on a comprehensive understanding of both short-term and long-term outcomes. Sensitivity analyses will be conducted to assess the robustness of the model to variations in input parameters, and scenario analyses will explore the impact of different assumptions and policies.
B4391 - Resilience development and child health outcomes - 24/08/2023
Resilience is known to be the process and outcome of successfully adapting to difficult or challenging life experiences. Promoting resilience is helpful to minimizing the detrimental impact of life stressors which may be unavoidable at times. While interventions aiming to enhance resilience are increasing among different age groups, there remains gaps in our understanding of how and when resilience manifest, as well as the role of negative and positive emotions in this process. This project aims to use intergenerational data from ALSPAC to investigate predictors of the trajectories of resilient behavior, and connections between maternal resilience and offspring resilience from the prenatal stages through childhood years. This includes identifying time and environmental predictors that can be useful in designing future interventions to assist individuals who are at risk in coping with stress and difficult situations.
B4398 - Impact of paternal obesity on cognitive function of offspring - 24/08/2023
Parental health during pregnancy is a key driver of long-term brain health of offspring. Evidence suggests that children born to obese mothers have lower IQ and poorer memory compared to children of lean mothers. However, much less is known about the impact of paternal obesity on the brain function and mental health of their children. This project will analyse the cognitive function, memory performance and mental health of infants, children and adolescents born to obese and overweight vs lean fathers. We will also investigate the impact of paternal BMI on the brain structure of their children. In addition, we will evaluate the potential additive effect of maternal and paternal obesity on these outcomes. Where possible, we will include relevant genetic information in the analyses to ensure that conclusions about parent-child outcomes are not simply due to gene inheritance. Results from this project will generate important information about whether parental obesity influences the long-term brain health of offspring and the risk of developing neurodevelopmental disorders. The impact on long-term brain health up to young adulthood, as characterised in this study, may also have consequences for the future risk developing neurodegenerative disorders given the primary role of cognitive reserve in protecting against these age-related disorders. This study will play a key role in providing novel insight and new targets for interventional strategies to ensure brain health across the lifespan in the context of an increasing, global at-risk population.
B4400 - Dysanapsis genetic risk and lung function across the lifespan - 24/08/2023
There is a lot of variability in lung structure among healthy adults. This variability in lung structure is thought to arise during growth - a concept that is referred to as “dysanapsis” (from the Greek, dys=unequal and anaptixy = growth). Dysanapsis is strongly associated with lung disease and death later in life, but the origins of dysanapsis are poorly understood. A recent genetic investigation identified several variants associated with dysanapsis, but when dysanapsis genetic risk manifests in childhood and whether it interacts with environmental or social factors to impair lung function is unknown. This study has two objectives: i) describe the relationship between dysanapsis genetic risk and lung function at various timepoints during lung growth; ii) test whether environmental exposures (environmental tobacco smoke) or social deprivation modify these relationships. No new measurements or samples are required for this study.
B4394 - SLEEP AND YOUNG PEOPLES MENTAL HEALTH THE ROLE OF SOCIAL DETERMINANTS AND COGNITION - 22/08/2023
Sleep is vital for maintaining good mental health. Further, sleep and mental health problems are both public health concerns in their own right, with each having a substantive impact on both individuals and society. Adolescence and young adulthood are key periods in which to investigate mental health, as more than half of mental disorders start here. Similarly, sleep problems are often observed in young people. Further, it is crucial to understand under what circumstances and why sleep problems might lead to mental health problems, as this would shed some light on who are the young people most vulnerable for mental health problems. The proposed project will provide ground-breaking research on the prospective associations between sleep and mental health problems in young people using large longitudinal cohort studies, with a special emphasis on specific contributing and mediating factors of these associations. Among these, we will focus on social determinants (SD) (e.g., ethnicity, socio-economic status, housing conditions, food poverty) and cognitive factors as key aspects to consider in these associations in young people. To do this, we will use three population-based longitudinal cohort studies, which are the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Millennium Cohort Study (MCS), both from the UK, and the Adolescent Brain Cognitive Development (ABCD), from the US. We will obtain detailed information on sleep (e.g., sleep duration, sleep fragmentation, sleep efficiency) using subjective (e.g., questionnaires) and objective (e.g., actigraphy) measures, mental health (e.g., anxiety, depression, psychosis, self-harm), cognitive factors (e.g., working memory, inhibition), and SD (e.g., ethnicity, living condition, early life adversities) in large sample sizes (e.g., >10,000 potential participants in each cohort).
B4396 - Heavy and painful menstrual periods and their impact on depressive symptoms across the lifecourse - 23/08/2023
Heavy menstrual bleeding (HMB) and menstrual pain (MP) can have a significant negative impact on financial, social, physical and mental wellbeing. Yet people often present late and their symptoms are dismissed. This study will reveal who is at risk of these problematic menstrual symptoms, when they are experienced throughout the lifecourse, and how they might affect depressive symptoms. The findings will inform the prediction of HMB and MP to ensure appropriate management, as well as new ways to predict, prevent, and treat adverse effects of these problematic menstrual symptoms on mental health.
B4399 - Social determinants of health and psychotic experiences - 18/09/2023
This study aims to investigate longitudinal associations between social determinants of health with psychosis spectrum symptoms (e.g., hallucinations, delusions), as well as whether associations between psychosis spectrum symptoms with later diagnosable conditions can be modified through social determinants of health.
B4395 - Co-occurring socio-emotional difficulties combining development genetics and psychosocial risks - 22/08/2023
Approximately 10-20% of children and adolescents experience socio-emotional difficulties severe enough to merit a diagnosis of a mental health disorder. More than 40% of these youth develop at least one other mental illness throughout their life. A developmental perspective that investigates the interrelations between different domains of socio-emotional development from early life to adulthood can offer important insights into why socio-emotional difficulties commonly co-occur. Using state-of-the-art longitudinal statistical techniques, this project aims to significantly advance our understanding of the mechanisms underlying co-occurring socio-emotional difficulties. It will illuminate the roles of both genetics and psychosocial factors in linking different socio-emotional difficulties together using robust study designs that consider a range of confounders and providing the best available evidence yet on the causal mechanisms underlying the co-occurrence of socio-emotional difficulties. As well as informing preventions and interventions, this will contribute to better, more comprehensive theories of the developmental roots of mental health.
B4387 - Sweet child o mine a cohort-based study on adolescents body mass index and the introduction of duties on soft drinks - 21/08/2023
Our project aims to analyse the health consequences of the soda duty introduced in Finland in 1994. In particular, we aim to analyse whether the duty caused a change in kids’ height, weight, BMI and probability of being overweight or obese. We study the effect on the health outcomes of Finnish kids using the 1986 Northern Finland Birth Cohort (NFBC1986 hereafter) and would like to use data of the ALSPAC participants for comparison, given that they were born in a similar period but were not subject to the tax.
B4393 - Examining causal bidirectional relationships between mental health and urinary incontinence in women - 21/08/2023
Urinary incontinence (UI), defined as the complaint of any involuntary leakage of urine is a highly prevalent condition that can have adverse consequences for emotional well-being and quality of life in addition to being of economic importance to health services.
The cause of UI is not completely understood and includes psychological and physiological factors outside the lower urinary tract. The hypersensitivity of the bladder in urinary incontinence has guided researchers to consider psychological factors including anxiety and depression that may be of importance.
The comorbidity between UI and affective disorders including anxiety and depression is well established, but the precise nature of this relationship is unknown. Much of the existing research examining the relationship between UI and anxiety/depression is cross-sectional and is therefore unable to disentangle the temporal relationship between whether poor mental health is a cause or a consequence of UI.
The use of bidirectional MR can help to differentiate causality from correlation by testing the causal effects independently in each direction using single nucleotide polymorphisms (SNPs) found to be robustly associated with each trait in different genome-wide association studies (GWAS). We will use GWAS summary statistics in a two-sample MR analysis to examine bidirectional causal relationships between anxiety/depression/neuroticism and UI in females. Two subtypes of UI will be explored. Stress urinary incontinence (SUI) is defined as a loss of urine associated with physical exertion, coughing or sneezing whilst urgency urinary incontinence (UUI) is loss of urine associated with a sudden compelling need (an urgency) to void.
B4389 - Consortium Against Pain inEquality CAPE The impact of adverse childhood experiences on chronic pain responses to treatment - 21/08/2023
Having a traumatic experience as a child – for example, abuse or deprivation – can have a lifelong impact. People who report having several adverse childhood experiences, or ACEs, are more likely to have health problems later in life.
The Consortium Against Pain InEquality (CAPE) aims to further understand how ACEs might lead to chronic pain in adulthood. We want to consider how other factors (such as mental health or support from friends or family) contribute to pain vulnerability. Our main question is: Do ACEs cause an increased risk of chronic pain in later life, and, if so, what roles do other factors play?
Using existing data from several cohorts, of which the Avon Longitudinal Study of Parents and Children is one, we will run analyses to better understand the factors that may contribute to, or protect against, developing chronic pain, trying to describe the different ways ACEs (of different types, number and characteristics) may be linked to chronic pain (‘causal pathways’).
B4390 - Explore genetic epigenetic and metabolomic associations with longitudinal muscle strength physical fitness and mental health - 17/04/2024
Muscle strength and cognitive function are partially driven by genes inherited from parents. Reduction in muscle strength and cognitive function is associated with multiple adverse health outcomes including disability and mortality. Previous studies identified genes commonly associated with muscle strength and cognitive performance. However, impacts of genetic determinants of muscle strength and cognitive function on physical fitness and mental health longitudinally have not been fully studied mainly due to data unavailability. ALSPAC (Avon Longitudinal Study of Parents and Children) has collected physical fitness (hand grip strength, body DXA scan) and mental health (depression, anxiety, life events, etc.) data from mothers and children longitudinally, along with genetic data. Our aim is to leverage this dataset to better understand how genetic predispositions to muscle strength and cognitive performance contribute to physical fitness and mental health over time.
Reduction in physical fitness and motor function is associated with accelerated aging reflected by changes in DNA methylation, another heritable mark that can be modified by behavioral and environmental factors. Associations of DNA methylation with longitudinal physical fitness and mental health have not been fully understood. Using data from the ALSPAC, we plan to study the longitudinal association of physical fitness and mental health with DNA methylation throughout the genome. Furthermore, we plan to evaluate the biochemical effects of genes and/or DNA methylation marks associated with longitudinal physical fitness and mental health, by studying their associations with levels of different biochemicals (called ‘metabolites’) in child and mother’s blood samples using the metabolomics data in ALSPAC.
B4377 - Lifecourse MR Consortium - 11/08/2023
The aim of the Lifecourse-MR consortium is to collate data capturing life-stage specific exposures and investigate their effect on disease risk. As a contributing study in the consortium, GWAS summary statistics will be generated on the ALSPAC cohort for a variety of variables measured in early life and in adulthood. The data generated in this study will be used to help establish putative causal effects of life-stage specific exposures on health and disease.
B4361 - Young onset colorectal cancer and childhood exposures to the microbiome YOUTHCLUB - 18/08/2023
Colorectal cancer incidence in individuals younger than 50, referred to as early-onset colorectal cancer (eoCRC), has doubled in many countries. Over the next decade, deaths due to eoCRC are expected to rise globally, with eoCRC accounting for over 20% of all colorectal cancers and becoming the leading cause of cancer-related deaths in 20-49 year olds. However, the factors leading to this increase are uncertain. The gut microbiome, which comprises millions of bacteria, fungi and viruses that are housed naturally within our digestive system, may influence the development of colorectal cancer, whereby some microbiota play a role in inflammation, DNA damage and production of cancer-promoting molecules. Recent studies have shown that there are specific genetic mutations associated with colorectal cancer risk, which occur more often in people of younger ages than in older ages. These mutations are also caused by the toxin called colibactin, which is produced by certain gut microbial bacteria. Our study aims to understand whether these bacteria, if present in early life, cause these mutations within our DNA (via colibactin production) and therefore increase the risk of eoCRC.