Proposal summaries
B4130 - Cognihoods Measuring our mental maps of the mosaic of social worlds - 08/09/2022
This project will transform our understandings of how neighborhoods “work” by developing a systematic and representative national study to understand neighborhood structure, function, and evolution, the first of its kind in the world. Neighborhoods are fundamental social and built environments for cities. They form the backbone of place-based policy and urban planning, nucleate our urban social communities, and have profound effects on peoples’ health, wealth, voting, and beyond. Often, policymakers and social scientists use administrative areas to stand in for our “neighborhoods,” but studies persistently show that these areas do not reflect peoples’ actual lived experiences. This mismatch between concept and measure reduces the effectiveness of place-based policy and confounds social science. Convenience samples (e.g. hoodmaps.com) or small-scale focus groups have sought to resolve this, but these are often unrepresentative—challenging to validate, reproduce, and generalize.
Instead, I will develop a novel social survey method that is socially-representative, reproducible, and generalizable. First, I will develop an open and reproducible neighborhood survey module with the Avon Longitudinal Study of Parents and Children (ALSPAC). Respondents will be able to draw their neighborhoods, describe them, and relate them to other parts of respondents’ lives. Then, I will seek to understand how potential mis-matches between these lived neighbourhoods and zones used in urban planning may affect political, social, and health inequalities and outcomes. Finally, I will work with the Cohort and Longitudinal Enhancement Resources (CLOSER), the UK’s world-leading network of cohort and longitudinal studies, to deploy this nation-wide and examine both the generality and stability of these lived neighborhoods over time. In addition, I will seek to develop statistical learning techniques that can predict where these communities might arise directly from information on the built environment. Altogether, this will provide the first socially-representative longitudinal study of neighborhood structure and function in the world.
B4128 - Interplay between genetic risk for metabolic syndrome and mental illness on childhood development outcomes - 15/08/2022
Individuals with a mental health condition are more likely to develop metabolic syndrome, which is a collection of risk factors for heart disease like elevated blood sugar, cholesterol, and blood pressure. Conversely, those with metabolic syndrome are also at higher risk of mental illness. This relationship can be partially explained by factors like lifestyle and medication; however, shared biology also influences the cardiovascular system and brain. For example, there is emerging evidence that there are genetic risk factors that are related to both mental health and cardiovascular disease. The impact of this genetic risk for both disorders remains poorly understood in children and adolescents. Given early intervention is important for both mental illness and heart disease, understanding these relationships may assist to identify how best to implement early intervention. This study will investigate individuals with high genetic risk for both mental health conditions and heart disease to establish whether this impacts their psychological and physical development.
B4129 - Characteristics of Converters to and Deconverters from Traditional Religious Beliefs and Behaviours - 15/08/2022
Our Co-investigator, Ralph Hood, has undertaken studies of individuals who have left their religion and those who have stayed or converted using longitudinal data in two countries – Germany and the USA. ALSPAC provides a valuable data set to investigate whether the factors that predict such events are similar in the UK, and whether the individual that makes such a change benefits psychologically in the longer term.
B4125 - Determining the association between trauma HPA axis dysregulation and mental health using robust measures - 01/09/2022
Poor mental health affects more than one billion people worldwide but despite this frequent occurrence and the potential personal burden, treatment options are scarce and not always effective. There is a need, therefore, for a better understanding of the environmental and biological causes of mental health problems, so that new treatments can be developed.
It is known that stressful or traumatic situations can increase an individual’s chance of developing a range of mental health problems. In response to a stressful situation, whether psychological or physical, the human body activates processes that aim to increase the chance of survival. These responses are referred to as “fight-flight-freeze” and can result in giving the body energy, making you feel more, and reducing the sensation of pain. One key hormone involved in this response is cortisol. Although the release of cortisol in response to stress is initially beneficial, evidence has shown that experiencing severe or ongoing stressful events can lead to abnormal cortisol levels, which in turn has been linked to harmful outcomes, including obesity, cancer, heart disease, susceptibility to infection, and poor mental health.
Mental health problems that have been linked to cortisol levels include psychosis, depression, anxiety, and post-traumatic stress disorder (PTSD). For example, studies have shown that individuals diagnosed with depression or schizophrenia have higher levels of cortisol in their blood or saliva when compared to individuals without a psychiatric illness, while individuals with PTSD have lower levels. Some studies also show that high cortisol levels in early life associate with developing a mental health problem later in life, indicating that stress response abnormalities may cause mental health problems. However, findings are not always consistent, and results are hard to compare as the time of day the cortisol measure is taken and the material used for measurement (e.g., saliva, blood, urine) vary across studies.
One way in which cortisol may be causally linked to mental health problems is through inflammation. In normal conditions, cortisol reduces inflammation (e.g., it’s commonly used to treat inflammatory diseases such as arthritis and asthma), however, studies have shown that under abnormal conditions (e.g., during ongoing stress), the relationship changes and high levels of cortisol are associated with increased inflammation. An increase in inflammation can be harmful to neurons in the brain by affecting neuron functioning and decreasing neuron repair. As such, studies have linked stress-related inflammation to poor mental health, however, the size of these studies are small and, again, studies are hampered by inadequate measures of cortisol and inflammation.
As can be seen, there is a need for large studies using improved measures of cortisol to investigate the causal link between stress response and mental health. In this project we therefore aim to generate reliable, robust measures of cortisol and inflammation using serum measures, genetic data and hair samples, to investigate whether cortisol levels lie on the pathway between early life trauma and mental health and whether they influence inflammation.
This work will inform whether interventions targeting the stress response system have the potential to prevent or treat psychiatric disorders.
B4126 - The ALSPAC variable search tool - 15/08/2022
Creating a search tool for researchers to browse the available data within ALSPAC, and to provide an R package for direct users to extract data in a reproducible manner
B4124 - Utilising Epigenetics as a Platform for Precision Medicine - 15/08/2022
Complex disorders such as psychiatric conditions often arise from varying combinations of genetic and environmental factors. This represents a major problem for drug development, as the cause of the disease is highly variable from person to person, and as such, drug response rates vary significantly. By examining an individual’s unique genetic risk factors, treatment response rates could theoretically be increased by improving subcategorization of individuals and personalising the administration of appropriate medications. Although genetic risk scores have been developed for this purpose, the use of epigenetic information in the form of DNA methylation remains relatively underexplored, despite the fact this epigenetic modification can simultaneously index both genetic and environmental risk factors. In this study, we will examine whether DNA methylation can be used to refine the classification individuals with complex disorders and better match affected individuals to personalised medications. In addition, we will also explore the relationship between epigenetic risk for complex disorders and measures of biochemical and metabolic traits to determine whether the epigenetic component of complex disorders is associated with changes in druggable, blood-based biomarkers.
B4115 - Adverse Childhood Experiences and Violent Offending - 09/08/2022
Our proposed project is primarily centred on the research topic of diversion away from the criminal justice system. Specifically, we will chart the developmental interplay between person-centred clusters of adverse childhood experiences (ACEs) and violent offending (assault and use of a weapon) during adolescence. In doing this we hope to identify which clusters of ACEs are most salient for subsequent violent offending. We will also investigate whether these differ for marginalised groups.
B4123 - Climate change sustainable diets and religion - 09/08/2022
Human activity is having a dramatic impact on our planet's climate, and measures to reduce carbon emissions to limit to extent of this climate change are urgently needed. In this project, using the recently-collected climate change data in ALSPAC we aim to explore the factors associated with climate change beliefs and behaviours, with a specific focus on both behaviours relating to sustainable diets (i.e., reduction of meat and/or dairy consumption) and religious/spiritual beliefs and behaviours (RSBB).
B4122 - AMOUNT An investigation of changes in young peoples substance use - 15/08/2022
Substance use (SU) by young people (YP; YPSU) can lead to short- and long-term harms. Although YPSU has been falling over the past 20 years in the UK, evidence suggests that it is now increasing again among some groups. Studies suggest that these changes may depend on where YP live, how they socialise, the health/social challenges that they face, and the ways in which they access and use substances.
This project is part of a larger study that is working with YP and other experts to understand in what ways and for which groups of YP SU is changing. We are developing and testing new theories to help us understand the most important factors that underpin these increases. Some factors relate to individuals, including mental health or experiences of the care system; others will relate to wider contexts such as communities, policy, and youth culture, including how drug markets have changed, changes in leisure and recreation, or shifts in attitudes towards SU; and others depend on the interactions between all of these.
In this project we will first examine whether there is evidence that YP may be using drugs to help cope with mental health problems. We will then explore whether YP who use alcohol and have mental health problems have worse outcomes if they also use drugs such as cannabis.
B4103 - Quantifying the multi-system impact of antenatal maternal wellbeing across generations - 01/08/2022
Maternal antenatal anxiety, depression, and stress increase the risk for socioemotional and behavioral problems in childhood, effects which persist into early adulthood (O’Donnell et. al, 2014; Pearson et. al, 2013; Robinson et. al, 2008). These findings are consistent with the fetal origins of mental health hypothesis, which posits that exposures in utero contribute to individual differences in mental health outcomes across the lifespan (O’Donnell, Meaney, 2017).
While the association between antenatal maternal wellbeing and child development is well-established, much less is known about the multi-generational impact of antenatal maternal wellbeing on child health and development. Existing findings from multigenerational studies focus on birth weight (Lahti-Pulkkinen et. al, 2018; Drake et. al, 2015), and antenatal lead (Sen et. al, 2015) or diethylstilbestrol exposure (Kioumourtzoglou et. al, 2018). Interestingly, mouse models have shown the multi-generational effects of stress or dietary manipulations on molecular characteristics of the offspring across multiple generations (Ward et. al, 2013; Radford et. al, 2014; Jawaid, Roszkowski, Mansuy, 2018).
In this proposal, we examine multi-generational effects of maternal well-being (encompassing mental and physical health) in an index pregnancy across 2 or more generations. Our analysis framework will consider important confounds including maternal and child genetic variation and will examine candidate biological processes for the transmission of risk e.g. variation in DNA methylation.
B4114 - Social determinants of mental health and cognition in adolescence - 01/08/2022
One quarter of the world’s population is affected by a mental or neurological disorder at some point in their life (WHO, 2001), and depression alone is predicted to be the leading burden of disease globally by 2030 (Malhi & Mann, 2018). These disorders typically manifest early in life, with 74% of diagnoses first occurring under the age of 18 years, and 50% before 15 years (Kim-Cohen et al., 2003). Understanding risk and protective factors underlying mental ill-health, and how these might develop over time, is crucial for the creation of effective prevention and intervention.
As children mature into adolescents, they increasingly interact with, and become more sensitive to evaluation and rejection by peers. Increased sensitivity to social rejection during this period has been associated with decreased mental health (Gao et al., 2017), while the opposite has been found for increased social support (van Harmelen et al., 2017). The environment in which these interactions occur is also changing, with adolescents spending an average of 6 hours each day online, the majority of which is spent on social media sites (Anderson & Jiang, 2018). Exploring these effects cross-sectionally, we found that increased social rejection sensitivity and decreased perceived social support were associated with increased negative mood in adolescents (11-24 years; Grunewald, Deng, Wertz & Schweizer, Under review), and now seek to further investigate these effects longitudinally.
B4121 - Mechanisms linking the natriuretic peptide receptor-C gene to elevated blood pressure Genetic epidemiology study - 01/08/2022
Previous research has identified several regions of the human genome associated with high blood pressure. One such region is the NPR3 gene, encoding the natriuretic peptide receptor-C. Whilst genetic variants in this region are associated with high blood pressure, it is not known which variant/s drive the association or whether the effect on blood pressure occurs through altered expression of the NPR3 gene. This study will use existing ALSPAC data to investigate the association between the NPR3 gene and high blood pressure.
B4118 - Intergenerational gut bacterial strain transfer - 15/09/2022
The gut microbiome is important for human health, supporting nutrition, pathogen defence and immune homeostasis, with more than 200 species inhabiting each human gut. The majority of the hundreds of microbial species (Bacteria, Archaea, Fungi typically) colonizing each human gut were only recently characterized from metagenomic assembled genomes and new taxa are still being discovered. Systematic studies investigating how these diverse microbial ecosystems are transferred between humans and adapt to their hosts are so far large lacking. Describing dispersal strategies and microbial adaptation to the human host will significantly contribute to understanding and manipulating the gut microbiome to re-set the host health.
B4120 - Investigation of impacts of colour blindness on educational and psychological outcomes - 22/08/2022
Colour blindness (CVD) is a congenital condition affecting 8% of men (0.4% of women). Depending on type and severity, affected individuals have significant difficulties discriminating a wide range of colours facing wide-ranging challenges on a day-to-day basis (e.g. interpreting colour-coded information at the workplace or recreational environments). A growing impact is expected in educational settings due to an increasing reliance on colour resources in schools. Unfortunately, a study using a birth cohort from 1958 (Cumberland et al, 2004) has reported a lack of impact of colour blindness on Maths and reading ability but fails to account for the increase in colour in classrooms in recent years. Regrettably the publication led to the cessation of CVD school screening in 2009, preventing children from accessing more appropriate resources.
In contrast, a number of authors have argued that CVD can increase difficulties experienced in a range of school subjects including Sciences, Maths, Art, PE and Geography as such subjects may use colour to explain concepts, give instructions and require it in problem solving tasks. Alongside any academic implications, CVD has been found to have an effect on social, psychological and emotional outcomes. For example CVD children may experience teasing from classmates.
We here propose to investigate the potential impacts of CVD on education and emotional outcomes in a more recent cohort.
B4092 - The Relationship Between Identifiable Health Risk Behaviours And the Development of Severe Mental Illness Within A Syndemic Fram - 22/08/2022
We want to find out in what way everyday habits and behaviours actually can change how people with a severe mental illness experience this illness, and, by finding that out, how we can possibly advise people, GPs, and the government in helping people feel better and live a better life they enjoy more in the long term. To do that, we are collecting information on how active a person with one of three specific mental illnesses keeps; how often they spend time outside, like in a garden, park or forest; how well and how much they sleep; whether they smoke or drink alcohol, and if so how much and when or when not; and how resilient they are personally to the bad or sad things that can happen in life, like having to move or losing their job or a loved one dying. We then try to find out how likely for example a highly active person with for example bipolar disorder is to also spend a lot of time outside in a park or garden, and how likely they are to sleep better and more hours during the night, and whether they smoke or drink alcohol (a lot) or not. And then we check whether them being so active changes how bad they feel with regards to their mental illness, and how their mental illness affects them. And we do the same thing for people with schizophrenia and severe depression. The idea behind it is that all these habits and behaviours make another habit or behaviour more or less likely to happen, so a person who is highly active would technically also be less likely to smoke a lot. And smoking a lot makes it very likely that if you have depression, you don't feel very good and experience a lot of negative feelings, more so than a person with depression who doesn't smoke. We'll be working on this for three years, building a blueprint-model on this collection of information, and then test how strong this model is on other datasets. And if we're right and we can find a strong model of influencing behaviours and habits, then we can use this model to help councils and the government give out better information on how to help make people live a healthier and better life for themselves.
B4119 - Genetic environmental and pharmacological determinants of telomere attrition rates - 04/11/2022
The UK Office for National Statistics estimates that in 50 years’ time, there will be an additional 8.6 million people aged 65 years and over. Longer lifespan has clear benefits, but when it is associated with an increased proportion of the population suffering from age-related diseases, it can pose a burden to individual sufferers and to the economy.
Telomeres are ‘DNA tails’ at the end of chromosomes that shorten as we age, in accordance with the number of cell divisions. The rate at which telomeres shorten is also affected by genetic, environmental and pharmacological factors, which is important because premature telomere shortening is hypothesized to predispose to multiple age-related diseases, including coronary artery disease and rheumatoid arthritis. This is because cells with very short telomere lengths are less able to divide, leading to the accumulation of old, damaged or unhealthy cells within a tissue, and subsequently an increased risk of disease. A deeper understanding of which specific factors affect rates of telomere shortening might allow us to identify who is most at risk for premature telomere shortening and what sort of interventions may be effective at preventing age-related diseases.
This project will use the rich phenotype data within ALSPAC to define genetic, environmental and pharmacological factors associated with telomere length and its rate of attrition.
B4109 - Childhood adverse events and breastfeeding associations with pregnancy behaviour and infant outcomes - 29/07/2022
Adverse childhood experiences have been associated with unfavorable health behaviours, somatic and psychological complaints in pregnancy. Beyond pregnancy experiences, a large body of research highlights intergenerational effects of maternal history of early trauma on their offspring. Given the growing interest on early adversity consequences during the perinatal phase, we aim to examine the associations between traumatic childhood events and pregnancy health behaviour, psychological symptoms, birth outcomes, sociodemographics and breastfeeding. For this we intend to include mother-infant pairs from the Avon Longitudinal Study of Parents and Children. Adverse childhood events consist of abuse (e.g. emotional, physical and sexual), neglect, (e.g. emotional and physical) and household dysfunction (e.g. parental mental illness, divorce or incarceration). We measure pregnancy health behaviour (e.g. exercise, smoking, alcohol, BMI), psychological symptoms (e.g. anxiety and depressive symptoms), sociodemographics (e.g. education, social class) and breastfeeding (e.g.initiation and duration).
B4113 - Exploring the epigenetic profiles of vapers smokers dual users abstainers and never users in ALSPAC - 20/09/2022
DNA methylation is an epigenetic change that can influence how our genes are expressed. Smoking has been found to influence DNA methylation, and these changes could be responsible for some of the negative health consequences of smoking. In comparison, the epigenetic changes associated with e-cigarette use are not well known. In this project, we will explore how e-cigarette use is associated with DNA methylation.
B4111 - Research methods in human epigenetics - 18/07/2022
This project looks at methods used in research on human epigenetics, particularly around uses of
sociological and psychological data in devising research questions.
All paperwork stored in relevant B number folder
B4107 - Fathers preconception smoking and offspring DNA methylation A population-based two generation study - 18/07/2022
Animal experiments suggest that exposure to toxins such as found in cigarette smoke may impact respiratory health across generations. Studies in humans are however limited. In this study, we ask if gene activity differs in children whose fathers smoked prior to them being conceived. Differences have been observed in participants of the RHINESSA study. Here we ask if similar differences are observed in ALSPAC participants.