There has a great deal of research that has shown that maternal depression has a long-term effect on the child. Longitudinal studies have also shown that maternal anxiety can affect the child, including recent studies from ALSPAC that have shown that maternal anxiety during pregnancy can have a long term effect on the child.

There is considerable interest in the idea that pregnancy and the postnatal period represent a "critical period" of development for the mother-infant relationship and for the infant. If the "critical period" idea is correct, then maternal mental health problems that occur during this period should be particularly harmful to the infant compared to maternal mental health problems that occur at other periods of the child's life. Other studies, however, have shown that chronic and recurring forms of maternal mental health problems have a stronger and more lasting effect than "critical periods" of maternal poor mental health.

In this proposal, we aim to investigate longitudinal PATTERNS of maternal anxiety. A patterns approach to mental health may be helpful in understanding what kinds of individuals struggle most, and if there are particular patterns or timepoints that are particularly important for child outcomes.

We expect that within mothers who experience anxiety, the pattern of anxiety across time will differ. We will use newer statistical procedures to model these different groups, or classes, of patterns. For example, some mothers may have chronic anxiety, some may have recurring patterns, and some may have episodic patterns. Other studies of patterns or trajectories of mental health problems (primarily depression) have detected low, high, decreasing and increasing patterns across time. Once we have established a well-performing model of maternal anxiety, we want to assess whether there are individual factors that predict the type of pattern of anxiety mothers have. For example, are mothers who live in poverty more likely to experience recurring or chronic patterns of anxiety? We also want to see if the pattern of anxiety varies based on other factors that might be happening for mothers. For example, we expect that stressful life events and depression may vary across time with anxiety, although one may precede the other in time. We will use lagged analyses to examine these effects. We also think that some baseline factors might change how closely life events, anxiety and depression co-vary. Women who have a history of abuse, for instance, may have a stronger link between life events and anxiety over time than those who don't have that history. Lastly, and importantly, we want to see if different patterns of anxiety predict child outcomes. We will use cross-lagged analyses to examine if there are reciprocal effects of child behaviours on maternal anxiety, and vice versa.

Self-harm is common in adolescence with community studies reporting lifetime rates of 13-18%. Self-harm is distressing for the individual, their friends and family and leads to considerable healthcare costs for the NHS. It is associated with a range of poor outcomes in early adulthood including mental health problems, substance use, and educational and occupational difficulties, and is the strongest risk factor for suicide. Self-harm is therefore a major public health concern.

Early intervention and treatment strategies for those who self-harm are important, however, only one in eight individuals who self-harm seek medical help. This means the majority of self-harm episodes remain hidden from health services. There is an urgent need to develop interventions for young people who self-harm that are effective, accessible and engaging, and for their wider dissemination beyond those seeking medical treatment.

There is increasing interest in using technology (such as the Internet and mobile phones) to educate, monitor, and treat a variety of mental and physical health problems. Several recent government and NHS strategies have highlighted the potential for technologies to transform the delivery of mental health care and improve patient outcomes. E-health interventions have been shown to be effective for a number of different mental health problems, including depression and suicidal thoughts, but few have been developed specifically for individuals who self-harm.

The aim of the research is to is to develop an innovative and user-friendly E-health package for self-harm that is specifically targeted at young people (aged 15-25). Development of the package will be informed by:
• A thorough review of the literature on i) theories for the persistance of self-harm and for help-
seeking and ii) existing E-health interventions for self-harm and suicidal behaviour.
• Analyses of new data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth
cohort examining i) the functions of self-harm, ii) the reasons for stopping self-harm, iii)
preferred sources of help and iv) exploring how young people use technologies.
• Interviews and focus groups with potential users, parents/carers and peers, and professionals
working with young people who self-harm.

Prenatal exposure to tobacco through maternal smoking during pregnancy increases the risk of many negative health and behavioural outcomes. Across human populations, smoking during pregnancy remains above 10%. To better discover and apply effective interventions, it is important to determine the exposure of each child. Unfortunately, simply asking mothers about their smoking behaviour is not sufficient due to lapses in memory, reluctance to admit smoking or failure to accurately define smoking behaviour. Measurement of cotinine in maternal blood, urine or saliva can improve detection but may miss cases of intermittent smoking because cotinine is cleared quickly during pregnancy. Fortunately, children retain evidence of prenatal tobacco exposure in the DNA methylation of their blood even beyond the age of 17. However, since blood collections are a precious and finite resource many cohort studies have derived lymphoblastoid cell lines (LCLs) from blood samples. LCLs are B cells that have been transformed to spontaneously replicate, thereby providing a constant supply of new biological material. Although the transformation process is known to disrupt DNA methylation marks, a recent study has reported associations between LCL DNA methylation and present tobacco smoking. We would like to test associations of prenatal tobacco exposure in LCL DNA methylation and determine the extent to which the transformation process has modified these associations by comparing them to associations in B cells isolated from matching blood samples. B cell isolation is necessary because each of the many cell types found in blood has a unique DNA methylation profile.

ALSPAC has generated many cell lines from white blood cells. We would like to exploit this resource by treating some of the cell lines in a specific way to produce induced pluripotent stem cells (also known as iPS cells or iPSCs). iPS cells can be programmed to take up characteristics of different cell types, for example cardiac or skin cells. Producing such cells from the ALSPAC participants will enable researchers to look the effects of different genetic variants or environmental exposures on different types of cells helping to determine the mechanisms of disease. The aim of this project is to establish procedures and processes for creation and use of iPS cells from the ALSPAC cohort to enhance future research.

We are proposing to synthesize the current available evidence in the literature regarding the association between vitamin D and myopia.

Essential fatty acids and risk of psychotic symptoms in the ALSPAC cohort outline

Aim:

To investigate whether essential fatty acids intake both perinatally and in childhood and is associated with the later development of psychotic symptoms or disorder in adolescence.

Genome-wide association studies (GWAS) have uncovered multiple single nucleotide polymorphisms (SNPs) that are associated with height[1], adiposity[2, 3], cardiometabolic diseases[4] and intermediate cardiometabolic phenotypes.[5, 6] However, most GWAS have been carried out in caucasian adults, and the association between the SNPs and phenotypes in different ethnic groups and at different stages of the life course remains uncertain.

Within epidemiology, observational data are often used to assess the association between an exposure and a health outcome of interest in situations where a randomized controlled trial (which provides stronger evidence of causality) is not possible or not ethical. These studies are, however, plagued with difficulties due to bias and confounding.[7, 8] Mendelian Randomization[9] (MR) is a technique that uses genetic variants related to an exposure of interest to obtain an estimate of the exposure-outcome association that is not affected by confounding or reverse causality.

This PhD proposal will 1) further understanding of the genetic architecture of anthropometry and cardiometabolic traits, and 2) use MR to advance understanding of the causal relationships between anthropometry and cardiometabolic health.

The proposed research aims to answer the following questions: 1) Do children of parents with high levels of depressive symptoms score lower on measures of academic achievement and positive school behaviours? 2) Does parenting and chronicity of parental depressive symptoms explain the link between parental depression and children's outcomes? 3) Does children's intellectual functioning moderate the link between parental depressive symptoms and child outcomes so that children with higher IQ do better at school despite exposure to parental depression?

Preterm birth, i.e. birth before 37 completed weeks of pregnancy, is a major public health concern that complicates on average 11.1% of the pregnancies worldwide. Preterm infants are at increased risk of short-term consequences but are also more susceptible to severe life-long diseases. Majority of the preterm births occur after a spontaneous onset of labor, and currently, there are no effective strategies to prevent preterm birth.

According to current understanding, both maternal and fetal factors may influence the risk of spontaneous preterm birth. These risk factors include environmental (pregnancy related) risk factors, as well as a genetic predisposition. Twin studies and segregation analyses indicate that 30-40% of the variation in birth timing is heritable.

In this work, we plan to improve our understanding of the biology of birth timing by identifying genes involved in spontaneous preterm birth. This will allow more effective preventative strategies to be developed. We will accomplish this by comparing data we have previously collected on families with preterm birth that occurs for no identifiable reason to this important genotyped Avon longitudinal mother-child data set.