Adverse childhood experiences (ACEs, e.g. family violence, parental mental health problems, bullying) carry a higher risk of anxiety-related disorders, yet the underlying mechanisms remain unclear. We will use cohort studies in the UK and Brazil to assess the mechanisms linking ACEs to anxiety-related disorders.

The depth and breadth of measurements in the cohorts enables us to examine: 1) multiple levels of explanation: social, cognitive, psychological, biological, plus within- and between-level interactions, 2) the developmental trajectory of onset and persistence of anxiety, and how this can be prevented or interrupted, 3) the role of commonly co-occurring conditions (e.g. depression, neurodivergence), and 4) consistency/specificity of mechanisms across ACEs and anxiety-related disorders.

Comparisons across generations and the UK and Brazil, where social contexts and levels of ACEs vary, will enable assessment of the degree to which interventions need to be culturally/generationally specific.

Multiple analysis approaches will support causal inference: difference-in-difference, sensitivity analyses to assess environmental and genetic confounding, and causal mediation analysis. Where possible, we will triangulate cohort analyses with Mendelian randomization studies using large biobanks.

The research has been co-designed, and will be co-produced by, UK-based people with lived experience of anxiety. We will develop and evaluate lived experience involvement in Brazil.

DNA methylation is the addition of a methyl group to DNA. Patterns of DNA methylation have a variety of roles cells, the most well-known is determining the activity of genes. These patterns are known to change in response to lifestyle factors such as cigarette smoking and diet and to be useful in diagnosing disease and predicting future disease risk. Measuring patterns of DNA methylation is challenging as there are about 28 million locations in the human genome that can be methylated. Fortunately, we can obtain useful information about health from a small subset of these locations. A new method for cheaply measuring a small, selected subset uses a system that captures DNA fragments containing specific nucleotide subsequences and then measures the methylation patterns on those fragments by DNA sequencing. A couple of ALSPAC DNA samples have had DNA methylation measured using more expensive methods (beadchip and nanopore sequencing). We would like to evaluate the performance of our new method by applying it to these samples and then comparing the results to these other methods.

Attention Deficit Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental condition, characterized by difficulties in behavioural and neurocognitive functioning. Many studies have suggested that some maternal factors during pregnancy are associated with ADHD in the offspring. However, the mechanisms and whether the associations are causal is still unclear. This project will be conducted to understand the impacts of maternal hypertensive disorders during pregnancy on attention deficit hyperactivity disorder (ADHD) in offspring as little is known about this. As ADHD is becoming more prevalent, more research is needed to thoroughly understand factors that may increase risk of this disease. We will investigate the role of hypertension during pregnancy in ADHD using genetic, clinic and questionnaire data from the ALSPAC cohort.

Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.

Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.

Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.

Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.

We will investigate associations between religious/spiritual beliefs and behaviours (RSBB) and DNA methylation at specific CpG sites. We will perform epigenome-wide associations (EWAS's) of RSBB in the G0 mothers and fathers/partners and in the G1 offspring. The primary RSBB variables that we will use are religious/spiritual beliefs and religious attendance. There is not currently any good evidence to show if DNA methylation is associated with religiosity/spirituality. The aim of this research is to answer this knowledge gap.

Autoimmune conditions affect around 13% of women in the UK (1) and are often diagnosed during their potentially reproductive years, including conditions like multiple sclerosis and rheumatoid arthritis. These conditions can be managed using monoclonal antibodies, a relatively new category of drug which has grown rapidly over the past two decades and are tailor-made to bind to particular protein targets.

Randomised clinical trials provide the gold-standard of evidence on how effective and how safe drugs are, but since pregnant participants are typically excluded from these trials, there is often a lack of evidence available for clinicians and doctors on how well drugs work and how safe they are for pregnant patients. This is the case for monoclonal antibodies, and particularly since many of these drugs have been developed very recently there is also limited evidence on their safety from observational studies which follow participant’s pregnancies over time. The limited evidence is particularly challenging since having an unmanaged autoimmune condition can increase your risk of an adverse pregnancy outcome, for instance inflammatory bowel disease is linked to increased risk of early pregnancy loss (2).

This project aims to understand how underlying autoimmune conditions and using monoclonal antibodies to treat them may cause adverse pregnancy events such as pregnancy loss, low birth weight, and pre-term birth, by examining natural genetic variation between participants within existing databases including ALSPAC.

First, the genetic variation associated with seven common autoimmune conditions will be used to assess if differences in participant’s genetic predisposition to an autoimmune condition may have a causal effect on adverse pregnancy outcomes. Second, to mimic how monoclonal antibodies work, the same method will be used but this time taking advantage of genetic variation in protein levels in blood to mimic the effects of these drugs which each target very specific proteins involved in the immune response. The project will assess whether variation in these proteins has a causal effect on adverse pregnancy outcomes, to provide evidence on whether monoclonal antibody drugs are safe to be used by pregnant patients to manage their autoimmune conditions.

1. Conrad, N. et al. (2023) ‘Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK’, The Lancet, 401(10391), pp. 1878–1890. Available at: https://doi.org/10.1016/S0140-6736(23)00457-9.
2. Nielsen, O.H. et al. (2022) ‘Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis’, Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 20(1), pp. 74-87.e3. Available at: https://doi.org/10.1016/j.cgh.2020.09.021.