Major depressive disorder (MDD) is the most common mental illness and is the single leading cause of years lived with disability. Depression that begins early (by the early 20s) predicts particularly poor mental health and social outcomes and a chronic and relapsing course of symptoms over time. The strongest and most common risk factor for early-onset MDD is depression in a parent – this risk is likely to involve both environmental and inherited components.

In this project, we will characterise the trajectory of depressive symptomatology over adolescence and early adult life. We will test whether antecedent risk and protective factors identified in previous work influence the trajectory of symptoms over time. We will develop an algorithm to quantify individual risk for early-onset depression.

Previous research has shown detrimental offspring outcomes for children prenatally exposed to alcohol. However, uncertainty remains as to whether these negative offspring outcomes are due to the intrauterine environment, or environmental influences after birth, for example parental lifetime drinking. Further investigation is required to assess the impact of parental alcohol use on offspring outcomes. The research that has been previously conducted in this area has focused on academic outcomes, with less focus on the influence maternal and partner drinking may have on offspring mental health.
In addition, valid reports of alcohol use may be affected by under-reporting. Using parental methylation markers that are predictive of alcohol use, could be a more biologically valid method for assessing alcohol consumption. These methylation-based biomarkers were developed by Liu et al (2018) and are currently being validated by co-applicants (LZ) in ALSPAC. The proposed study will use such biomarkers to assess if this produces a stronger signal, in comparison to self-reported alcohol use.

Observing that an exposure (e.g. higher meat intake) is associated with an outcome (e.g. higher BMI) does not necessarily mean that the exposure caused the outcome. Other factors may "confound" the association by causing both the exposure and the outcome. Such confounding can be difficult to detect if the factors responsible have not been measured. A recent study proposed a method to detect confounding by unmeasured variables if they cause discontinuous variation in the exposure. We intend to develop this method further and apply it to the question of whether eating meat affects a person's BMI. The method should tell us whether simple observation of people's meat intake and BMI reveals the causal effect or is confounded.

A single mutation within the genome (called rs71564871 near a gene called BEND6) has been previously linked to fat distribution in the body, specifically the proportion of fat stored across the waist compared to the hips, in women of the ORCADES study and UK Biobank. Within this study, we want to assess whether this single mutation is similarly related to the same pattern of fat deposition in the Avon Longitudinal Study of Parents and Children.

Socioeconomic disparities in health across the life-course are well-documented, long-standing, and consequential. Research suggests that a significant proportion of the social gradient in health is due to SES differences in health-risk behaviors. Scholarship investigating the underlying mechanisms whereby lower SES increases health-risk behavior points to the mediating role of risk-increasing (or ‘riskogenic’) psychosocial schemas. Specifically, evidence suggests that social context and experiences in development, which are patterned by one’s social position, calibrate psychosocial orientations, including impulsivity or self-control, sensation seeking, and hostile views of relationships, which influence health-risk behaviors and health outcomes. Although the past decade has seen a spate of published GE-health research, few studies have focused on the role of G-E interplay in shaping psychosocial schemas as mechanisms through which SES adversity shapes health disparities. This project will investigate the effects of SES adversity on changes in psychosocial schemas, conceived as socially-calibrated and genetically-influenced endophenotypes which link SES adversity to increased health risk-behaviors. Additionally, although we know that social experiences “get under the skin” to have enduring effects on health outcomes, we lack knowledge on the biological pathways through which such effects persist. Thus, second, and more innovatively, we will engage with the nascent field of social epigenetics to examine DNA methylation (DNAm) as a biological mechanism through which SES-adversity calibrates psychosocial schemas. In this project, we will investigate the DNAm patterns underlying psychosocial adaptations to SES adversity that increase health-risk behaviors, building on work that identifies DNAm as an important molecular underpinning of experience-dependent changes in cognitions, decision-making, and behavior.

There has been increasing research attention to the impact of in utero exposures to specific perinatal risk factors and their potential impact on diseases later in life. One of these is hypertensive disorders of pregnancy (HDP), a perinatal condition which affects up to 10% of pregnancies globally. Current evidence shows that HDP are associated with an increased risk of offspring cardiovascular, immune, metabolic disorders in later life. HDP are also responsible for various adverse perinatal outcomes such as preterm birth, low birth weight and intrauterine growth restriction, which are known risk factors for numerous mental health morbidities. In addition, HDP may also affect brain development via utero-placental vascular insufficiency and fetal malnutrition and lead to subsequent neurobehavioral difficulties. A lot of research has been conducted on the associations between HDP and cognitive functioning in offspring, however, evidence on the effect of intrauterine exposure to HDP on offspring mental and behavioural disorders is not well-established.
Two systematic reviews conducted by this team, one currently under review and the other one accepted by the British Journal of Psychiatry have shown that HDP had a negative impact for a range mental or behavioural disorders. Our finding showed that preeclampsia was associated with increased risk of offspring schizophrenia. The risk of Autism spectrum disorder was also 32% higher in offspring who had intrauterine exposure to preeclampsia as compared to those non-exposed. However, we found inconclusive finding on the effect of HDP and other mental and behavioural disorders, suggesting the need of further studies to progress this area of research. Following on from these findings, this PhD project aims to add to the existing evidence in a meaningful way by conducting a high quality, large sample, birth cohort study.

The proposal is to continue the collaborative work we have been doing with this Swiss group over the past few years. Ben Spycher was a Marie Curie Fellow who worked with ALSPAC data previously. Prof Kuehni leads eth Leicester Asthma Cohorts and has established the Swiss Paediatric Airway Cohort (SPAC). OUr joint objective is to discover influences that determine the onset and progression of asthma in children, how asthma varies between individuals in type and severity and whether we can predict the outcome of asthma using individuals' information. The data in eth Leicester adn Swiss cohorts is complementary to data held in ALSPAC and we have had joint publications where ALSPAC is able to replicate findings in the other cohorts run by the Swiss group.

Intimate Partner Violence (IPV) is defined as any violent behavior within an intimate relationship or any other controlling behavior that is conducted by a current or former partner. It is the most common form of violence in women which constitutes a major public health problem worldwide. The current explanatory theories of IPV perpetration can be summarized as feminist/sociocultural, social learning theory-based intergenerational transmission and psychological/psychosocial. According to the feminist/sociocultural theory, domestic violence is a consequence of “patriarchy”. From this view, violence is used as a form of power and control of women by men. The intergenerational transmission theory asserts that domestic violence is based on the exposure to, or observation of, violence in the family of origin. Psychological theories propose that there are psychological, psychiatric, behavioural and neurological risk factors for domestic violence perpetration. In the study of IPV perpetration, it is important to consider the variables addressed by such theories as a whole and from a developmental perspective and there is no study that simultaneously considers all the variables of these explanatory theories. The general aim of our study is to identify those etiological mechanisms linking risk factors for IPV perpetration across development. This study will be the first one that sheds light on which the origins of IPV perpetration are by knowing how IPV perpetration develops. Implications in terms of prevention and treatment will be of a great relevance for public health.

Growing evidence points to a role of epigenetic alterations in the development of psychiatric disorders. DNA methylation – an epigenetic mechanism sensitive to both genetic and environmental influences – has been linked to a wide range of emotional and behavioral problems in childhood, including anxiety, depression, conduct problems and attention-deficit hyperactivity. However, findings to date have been primarily drawn from candidate gene studies, or EWAS studies investigating single sites across the genome. As a result, how much of the variance in psychiatric phenotypes is collectively explained by the methylome as a whole is currently unknown.