Depersonalisation disorder (DPD) is a distressing condition that typically emerges in young adulthood, characterised by detachment from one’s body and self, and/or one’s environment. Individuals with DPD retrospectively report adverse childhood experiences (ACEs) and are objectively evidenced to have a dysfunctional biological stress system. However, no research has looked at the biological mechanisms that translate ACEs into DPD later in life. Using self-report and biological data of parent-child dyads from the Avon Longitudinal Study of Parents and Children (ALSPAC), I aim to fulfil this research gap. Within the ALSPAC data, instances of childhood sexual, emotional, and physical abuse, emotional neglect and family dysfunction are reported separately by both parents (during annual assessment of the child’s development), and by the child (later in life), which can be combined, creating a measure of ACEs that doesn’t rely solely on retrospective reports. Stress system dysfunction is measured by cortisol (a stress hormone) level, interleukin-6 and C-reactive protein (measures of inflammation). At ages 12 (N = 6832), 17 (N = 5217) and 24 (N = 4021), symptoms of DPD were assessed. Using statistical modelling, I am examining whether the accumulation and the timing of childhood abuse translates into DPD symptoms, mediated by abnormal cortisol and inflammation levels. Additionally, factors with potential to provide risk for, or resilience against, developing DPD symptoms are also being evaluated to provide a comprehensive representation of how DPD symptoms may develop. These include sleep, drug use, attachment, maladaptive cognitions and social position.

In the United Kingdom, 10-15% of school-aged children have a special educational need (SEN). Children with SENs have impairments in language, learning, cognition, and social functioning. The diagnostic criteria for SENs are not, however, always fit for purpose. At-risk children can be missed or mislabelled meaning that they go without the support they need. This is compounded by the fact that SENs often co-occur with mental health difficulties but diagnostically they are usually considered separate. Therefore, a fundamental rethink of how children’s SENs and mental health difficulties are conceptualised is needed.
We will use data from two large UK-based datasets to 1) investigate the inter-relations between, and clustering of, SENs and mental health difficulties. Rather than looking at diagnoses, we will focus on how underlying strengths and difficulties in language, learning, cognition, social functioning, and mental health co-occur. In doing this, we will identify skills dimensions that map directly on to children’s needs, regardless of diagnostic label. Next, 2) we will investigate how these dimensions of skills cluster in children and how they compare with existing diagnostic labels in predicting children’s outcomes.
Finally, 3) we will identify environmental pathways through which risk is transmitted whilst controlling for genetic confounding. This will determine who and which environments should be the targets for early intervention to mitigate genetic risk for SENs and mental health difficulties.The proposed project will, therefore, mark a fundamental shift in how SENs and mental health difficulties are conceptualised, identified, and how at-risk children are supported.

Systemic inflammation is associated with increased risk in the development of atherosclerosis as well as other cardiovascular diseases (CVD). Recent trials have thus investigated whether immunotherapies may decrease the risk of CVD (Ridker et al. 2017; Tardif et al. 2019; Liberale et al. 2021). However, there remains a dearth of knowledge regarding which inflammatory proteins may play an aetiological and/or mediating role, and thereby may be potential therapeutic targets in the prevention of CVD. We seek to investigate the associations of the 92 Olink inflammatory proteins, measured in approximately 3000 mothers, 3000 children at age 9 and another 3000 children at age 24, with changes in carotid intima-media thickness (cIMT), pulse wave velocity (PWV) and blood pressures. We will also perform the analyses on the inflammatory biomarkers Glyoprotein Acetyls (GlycA) and C-reactive protein (CRP), as well as IL-6 measured in the 9-year-olds via clinical chemistry, since IL-6 is the only protein measured by Olink that has been measured previously in ALSPAC to be used as a validation.

Whole exome sequencing (WES) is a method used to generate the sequence of all protein encoding regions of the human genome. ALSPAC has already obtained WES data from all available DNA from G1 participants (original children) and a subset of G0 parents. ALSPAC has been included in an MRC funded initiative to complete WES sequencing in some cohort studies. This will fund generating WES on approximately 11,000 samples from the remaining G0 parents and G2 (CoCo90s). This, together with existing data, will ensure WES is available from all suitable ALSPAC DNA samples.

We have shown that spelling mistakes in a woman's genome can make her more likely to develop severe nausea and vomiting in pregnancy (also known as 'morning sickness') likely by altering the sensitivity to a hormone called GDF15. This hormone circulates in the blood and is well known to act on the brain known to to induce nausea and vomiting. GDF15 is made by the placenta in large amounts, and increases markedly in pregnancy, however, we do not understand how changes in the unborn baby's genes affect how much GDF15 the placenta makes or how this might alter the risk of nausea and vomiting in pregnancy.

The rationale for this project is to identify protein quantitative trait loci (pQTLs), which are robust connections between a gene variant and the levels of a protein, across the life course. We will conduct genome-wide association studies (GWAS’s) of protein levels at three separate timepoints and compare pQTLs at these different timepoints. Associations with independent lead variants within 300 kb window of the gene boundaries of the protein-coding gene are defined as cis-signals, and otherwise in trans. In this project, we will estimate the proportion of pQTLs that are in cis versus in trans at each of the three timepoints. We will investigate how much of the longitudinal correlation in inflammation levels is explained by genotype. We will also evaluate the relationship of pQTL with other down-stream phenotypes, including traits and diseases, and quantify the contribution made by pQTL to genetic variance in several common complex diseases that have previously been the subject of genome-wide association studies (GWAS).
This project will use the ALSPAC proteomic data, which consists of 92 proteins measured by Olink, measured in approximately 3000 mothers, 3000 children at age 9 and another 3000 children at age 24. We will also perform the analyses on the inflammatory biomarkers Glyoprotein Acetyls (GlycA) and C-reactive protein (CRP), as well as IL-6 measured in the 9-year-olds via clinical chemistry, since IL-6 is the only protein measured by Olink that has been measured previously in ALSPAC to be used as a validation.

Do official records and self-reports of offending identify the same individuals? And does this depend on the context and/or individual characteristics? These are critical questions at the heart of crime and violence research. Official records and self-reports represent the two primary methods for measuring offending. However, official records only capture the “tip of the iceberg” as not all crimes are reported to the police. Additionally, there is bias in which individuals and which offences are decided to be recorded as criminal incidents by the police, and there are examples of misidentification errors. On the other hand, self-reports of offending via confidential questionnaires or interviews can introduce different biases, including social desirability (e.g., response falsification), recall error, and selection bias – as individuals who have engaged in criminal activity are less likely to respond to research surveys and interviews.

Few studies have compared the two measures of offending, with most of these coming from the US. While this evidence suggests that both measures are generally concordant, self-reports identify higher rates of criminal offending and a significant proportion of individuals with criminal records fail to self-report. The strength of agreement between official records and self-report has been found to vary by crime types and sociodemographic groups. Cultural context may also represent an important factor influencing the agreement between official records and self-reports given known discrepancies in the prevalence of crime and violence in low- and middle-income countries (LMIC) compared to high-income countries (HIC). However, due to a lack of studies with both official records and self-reports of crime from countries outside of the US, the role of national context is poorly understood.

Family environments including relationships between parents and children are crucial for psychological adjustment and mental-health across childhood and adolescence. Parent reports as well as parent and child behaviours during their interpersonal interactions ("transactional" dynamics) are seen as particularly important. Moreover, the onset of mental health problems can disrupt previously healthy parent-child transactional dynamics. The aim of this project, which is an extension of the existing project B2159, is to explore family relationships (siblings and parents) from early to late development and their importance for children's adjustment.

Asthma is the most common chronic disease affecting children. Although we do not fully understand what causes asthma, there is good evidence that social conditions early in a child’s life play an important role in its development. Children from poorer backgrounds are more likely to develop asthma, suffer from asthma attacks, require hospitalisation and die from their asthma.
In this study I will unpick why asthma disproportionately impacts poorer children in the UK. I will explore the reasons for socio-economic differences in asthma outcomes in the UK and examine the conditions in children’s lives which gives rise to such differences, such as, exposure to second-hand smoke and poor housing conditions.
To do this, I will use data from ALSPAC and other UK birth cohorts that have collected detailed information on asthma and allergy from participating children at regular intervals in their lives.
Findings from this research will help to establish how to reduce unfair differences in asthma outcomes for children, informing policy and practice to deliver services and interventions in the populations that are most affected by asthma. The impact of this will be to reduce inequalities in children’s health over the lifecourse and costs to healthcare systems.