Psychosis is a severe mental illness. An example is schizophrenia. Symptoms of psychosis can include hearing voices and having strange and fixed ideas. It is not rare. Each person has a three in one hundred chance of developing psychosis over their lifetime. Psychosis has a very destructive effect on people's lives because the first episode often happens during late teens or early adulthood, at a time when people are finishing education or starting careers and forming long-term meaningful relationships. Psychosis can interrupt these important processes making it difficult for sufferers to catch up with the progress of their peers. It is also extremely expensive for the NHS to treat because it often requires lifetime medication and periods in psychiatric hospital. A recent study in England reported annual costs of £2 billion. Unfortunately, the outcomes for people with psychosis are often poor. About 25% of people relapse within 3 years of recovery, are likely to be unemployed long-term and have a poor quality of life. Relapses are very distressing for the patient and their family and increase treatment costs for the NHS.

Men have a higher risk of psychosis than women when young, but women are more at risk in later middle age. It has been suggested that this might be because a female sex hormone called oestrogen, protects women from psychosis from when they start their periods (when oestrogen levels rise) until the menopause (when oestrogen levels drop). Currently, there is not enough good quality evidence to know if this is correct. It is very important to find out whether this is true because an understanding of the underlying causes of a new episode of psychosis will help us to predict who is most risk and get them the help they need as soon as possible. This will, in turn, improve outcomes by reducing the
chance of a relapse and therefore reduce treatment costs for the NHS. I will use data from population-based long-term studies to see whether the age at which women start their periods, or experience menopause, is associated with risk of psychosis. If the oestrogen theory is correct, a later age of starting periods and an earlier age of experiencing the menopause will be linked to increased risk of psychosis. I will also use NHS prescription data to see if taking hormonal contraceptives and hormone replacement therapy, affect psychosis risk. Both these medications contain either oestrogen, or progesterone (another important female sex hormone) or both. Therefore, if the oestrogen theory is correct,
they may reduce the risk of psychosis. We will also be able to find out if progesterone has a role in risk of psychosis. This study proposes a new way to investigate this question using population-based data linked to NHS data.

Population data and NHS data are useful to researchers because they contain very large numbers of participants but there are also problems such as missing data and inaccurate recording, which can make the findings difficult to understand. To strengthen our findings in population data, we will also use genetic data which contains information about individual risk of psychosis and a woman's reproductive stage in life. These data have smaller numbers of participants than the population data and NHS data, but they do not have the same problems with missing data or inaccurate recording. Therefore, if we can find the same result in both types of data, we can be more confident that lower levels of oestrogen increase psychosis risk. We will also use population data from Sweden to find out whether the findings are the same outside the UK. The findings from this work will help doctors to identify women at greater risk of psychosis much earlier than happens now and provide opportunities for offering treatments that might prevent psychosis developing, like psychological or hormone-based drug therapies.

Streptococcal infection is common, but occasionally serious. In the winter of 2022, a large increase in severe streptococcal infection due to invasive Group A Streptococcus (also known as S.pyogenes) was identified in the U.K. and elsewhere in Europe, leading to a number of childhood deaths. The human genetic determinants of streptococcal infection are as yet largely unknown, with previous research only identifying associations at one area of the genome (the Human Leukocyte Antigen region). In this project, we want to perform a genome wide association study of Scarlet Fever, a form of infection caused by Group A streptococci. There are approximately 150 cases of self-reported Scarlet Fever in ALSPAC. The summary statistics from this GWAS (not the raw data) will be shared and meta-analysed with other GWAS of scarlet fever (e.g. UK Biobank, 23andMe), in order to help develop an understanding of the determinants of invasive group A streptococcus. This research is a priority for the UK Health Security agency.

Researchers suspect that children born to mothers who were abused by their partner during pregnancy are disadvantaged in terms of their development. They are more likely to experience mental health and cognitive problems over their life and an increased risk of neuro-developmental problems like Attention deficit hyperactivity disorder, Autism Spectrum Disorder, and Dyspraxia. In order to design effective interventions to help children whose mothers were abused while pregnant with them, it is essential for us to understand the pathways that link abuse during pregnancy to child outcomes. ALSPAC has the data needed to understand these kinds of pathways. Our project seeks to use the data to test which pathways are most important, helping us to understand the kind of support that abused mothers need to minimise the long-term effects of abuse on their child.

A healthy diet in childhood is really important for growth and development. Habits formed in childhood can persit into adulthood. It has been shown that variety in the diet (i.e. the different types of foods consumed) is relatively low at 2 years of age but increases by the age of 4.

These changes could be due to lots of factors such as environmental and social aspects of a child’s upbringing. For example, low socioeconomic status of the mother is associated with a low dietary variety score, whilst a higher dietary variety score is associated with children being less picky with their food choices.

A healthy diet consists of a variety of fruit and vegetable sources, carbohydrates, and low saturated fat, sugar and salt consumption.Vitamin D is a necessary vitamin needed for bone strength and development, however low levels in childhood is a common issue within the UK.

This project will look to see how dietary variety in childhood is associated with nutrient intakes (saturated fat, salt, sugar, fibre and vitamin D). It will also see whether dietary variety is associated with dietary pattern scores that have been created at age 7 (dietary patterns are healthy, processed).

Intimate partner violence is a recognized human rights, development, and public health issue, with one in three women globally estimated to have experienced physical and/or sexual violence by their partner during their lifetime. One of the times in life when women are believed to be spared from violence is pregnancy, a period when the well-being of the women and their unborn children is often prioritized. Yet, the reality is different. Worldwide, the prevalence of physical intimate partner violence during pregnancy ranges from 1 to 28 percent, with one in four women reporting that the violence was explicitly directed at their pregnant abdomen. The overarching aim of this proposal is to understand the risk and protective factors to mitigate the intergenerational transmission of violence during pregnancy and its short and long-term effects of violence during pregnancy. This will be achieved by firstly investigating the short and long-term social and health effects of violence during pregnancy on women and on their male and female children, secondly establishing that violence during pregnancy is a marker for severe violence during the lifetime and thirdly, exploring the maternal and paternal risk and protective factors for the intergenerational transmission of violence during pregnancy. Information on short and long-term health consequences will be based on both biomarkers and self-reported health assessments of mothers, daughters and sons.

Obsessive-compulsive disorder (OCD) is common and often debilitating, yet it remains under-researched and poorly
understood. OCD usually develops during childhood or adolescence, often amidst stressful environments. This raises the
possibility that OCD emerges as a psychological strategy aimed at reducing the anxiety caused by unavoidable stressful
situations (such as domestic violence). I term this strategy “excessive rationalisation”. Neurologically, excessive
rationalisation might be related to prefrontal “control” brain regions trying too hard to calm down “anxious” limbic regions.
Previous research suggests that people who show these patterns of brain activity may get less benefit from OCD
treatment. Therefore improved understanding of these patterns of brain activity and related psychological mechanisms
could help the 30-40% of people whose OCD doesn’t respond to treatment. This project will therefore investigate the novel
concept of excessive rationalisation and how it relates to brain activity in people with OCD.

Growing up with OCD has given me a passion to advance our scientific understanding of this debilitating condition. The
initial idea for this research came from my perspective as a person with OCD. I then drew on my expertise in mental health
and neuroscience to translate the idea into a research proposal, and showed it to three external advisors who also have
OCD. They wrote that focusing on early life stress and treatment-resistance is a “really important” endeavour which could
plug a significant gap in our understanding and treatment of OCD. After reading the proposal one person wrote, “this
research gives people like me some hope.”

About 1% of babies are born with a developmental disorder which affects mental or physical development, such as intellectual disability or congenital heart defects. Many of these disorders are at least partly genetic, often due to a rare change in a single gene. However, we also know that common genetic variants that influence cognitive ability, educational attainment and mental health traits in the general population affect risk of rare neurodevelopmental disorders too. We are exploring the genetic basis of rare neurodevelopmental disorders (NDDs) in two large cohorts of patients, Deciphering Developmental Disorders (DDD) and the Genomics England 100k Genomes project (GEL). We wish to use ALSPAC families as population-based controls in these analyses, since most of them do not have NDDs. We will calculate polygenic scores for different traits (including cognitive ability, educational attainment and schizophrenia), which summarise the level of genetic risk an individual has for a given trait based on the common genetic variants in their DNA, and compare these between NDD cases and ALSPAC participants. We will also make use of the trio data (children plus both parents) to investigate whether the genetic background of individuals’ parents influences the risk of NDDs independently of the individuals’ own genetic background (“genetic nurture”). Finally, we will compare the burden of rare genetic variants that affect gene function between NDD cases and ALSPAC controls.

Social anxiety is characterised by avoidance of social situations and excessive fear of embarrassment. It can interfere with a person’s social life in a major way. People struggling with social anxiety report the feelings of nervousness while interacting with people of opposite gender for the first time and are judged as less likeable after the initial contact. They can also be seen as shy or withdrawn in a social setting, potentially disrupting their chances at initiating a conversation with a potential partner. All those traits can therefore make it difficult to enter a romantic relationship. Once they enter a romantic relationship, these traits might show a smaller or null effect on their relationship satisfaction, as the familiarity and closeness with their partner would make them less likely to struggle; however, all the traits characterising social anxiety may still negatively impact the relationship. To answer the question of whether social anxiety traits impact adult romantic relationships, the current study will investigate the effects of social phobia at age 17.5 on the participant’s satisfaction with their romantic relationship at 25.

A low cardiorespiratory fitness (CRF, measured as peakVO2) increases the risk of future development of disease, in particular diseases related to metabolic and cardiovascular dysregulation. Undertaking physical activity (PA) can boost peakVO2 and is protective against cardiometabolic diseases. However, it is not known whether there are time-sensitive periods in life where the benefits of PA are greatest and whether these periods differ in men versus women. Establishing the patterns of PA through life that optimise CRF would permit more targeted interventions to be designed.

It is likely that pathological processes begin much earlier in life than the development of clinical disease. Perturbations in skeletal muscle, specifically the energetics of muscle cells (governed by mitochondrial processes), have been implicated in early cardiometabolic disease processes. The relationship between early physiological differences in skeletal muscle energetics and predictors of future disease, such as a low peak VO2, are incompletely understood. This proposal aims to investigate whether or not differences in skeletal muscle energetics are related to differences in circulatory capacity, whether the relationship between them differs in men and women and the extent to which they are impacted by different patterns of physical activity throughout early life.