Shyness is a temperamental trait characterized by an anxious preoccupation with the self and heightened reactivity in social situations. This trait is moderately stable across the childhood to adulthood [1]. Shy children often express social withdrawal and internalizing problems (i.e., loneliness, anxiety and depressive symptoms), if they have experienced negative peer experiences, such as peer rejection and victimization [2-6]. In contrast, mutual and high-quality friendships [6, 7] as well as parenting styles characterized by high warmth and autonomy [4, 8-10] buffer against social withdrawal and internalizing problems among shy youth. While the link between shyness and later socioemotional problems is well-documented, little is known about physical health outcomes of shy children even though epidemiologic studies suggest that childhood social withdrawal/isolation, an outcome of childhood shyness, is an independent risk factor for increased cardiovascular disease (CVD) risk in adulthood [11-13]. Similarly, studies using animal models show that rodents and dogs with stable neophobic/inhibited traits have shorter lifespan, dampened immune response, and elevated glucocorticoid production [14-17]. Yet, no studies in humans have identified whether early temperamental shyness plays a role in increased CVD risk in adulthood and how temperamental shyness, peer and parental relationships shape the development of physiological systems linked to CVD risk across the lifespan to confer later health risks. This research proposal aims to address these knowledge gaps by considering a broad range of negative and positive peer-experiences in relation to CV risk factors measured from childhood to adulthood, and the potential role of child mental health within this relationship. Using the ASLPAC cohort, we will address the following questions:

References
1. Pérez-Edgar, K. and N.A. Fox, Temperament and anxiety disorders. Child and Adolescent Psychiatric Clinics, 2005. 14(4): p. 681-706.
2. Boivin, M., S. Hymel, and W.M. Bukowski, The roles of social withdrawal, peer rejection, and victimization by peers in predicting loneliness and depressed mood in childhood. Development and Psychopathology, 1995. 7(4): p. 765-785.
3. Gazelle, H. and G.W. Ladd, Anxious solitude and peer exclusion: A diathesis–stress model of internalizing trajectories in childhood. Child development, 2003. 74(1): p. 257-278.
4. Booth-LaForce, C. and M.L. Oxford, Trajectories of social withdrawal from grades 1 to 6: Prediction from early parenting, attachment, and temperament. Developmental psychology, 2008. 44(5): p. 1298.
5. Tang, A., et al., Shyness trajectories across the first four decades predict mental health outcomes. Journal of abnormal child psychology, 2017. 45(8): p. 1621-1633.
6. Oh, W., et al., Trajectories of social withdrawal from middle childhood to early adolescence. Journal of Abnormal Child Psychology, 2008. 36(4): p. 553-566.
7. Fordham, K. and J. Stevenson-Hinde, Shyness, friendship quality, and adjustment during middle childhood. The Journal of Child Psychology and Psychiatry and Allied Disciplines, 1999. 40(5): p. 757-768.
8. Booth-LaForce, C., et al., Parent and peer links to trajectories of anxious withdrawal from grades 5 to 8. Journal of Clinical Child & Adolescent Psychology, 2012. 41(2): p. 138-149.
9. Kiel, E.J. and K.A. Buss, Prospective relations among fearful temperament, protective parenting, and social withdrawal: The role of maternal accuracy in a moderated mediation framework. Journal of abnormal child psychology, 2011. 39(7): p. 953-966.
10. Lewis‐Morrarty, E., et al., Infant attachment security and early childhood behavioral inhibition interact to predict adolescent social anxiety symptoms. Child development, 2015. 86(2): p. 598-613.
11. Caspi, A., et al., Socially isolated children 20 years later: risk of cardiovascular disease. Archives of Pediatrics & Adolescent Medicine, 2006. 160(8): p. 805-811.
12. Danese, A., et al., Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Archives of pediatrics & adolescent medicine, 2009. 163(12): p. 1135-1143.
13. Lacey, R.E., M. Kumari, and M. Bartley, Social isolation in childhood and adult inflammation: evidence from the National Child Development Study. Psychoneuroendocrinology, 2014. 50: p. 85-94.
14. Cavigelli, S.A., Behavioral Inhibition in Rodents: A Model to Study Causes and Health Consequences of Temperament, in Behavioral Inhibition. 2018, Springer. p. 35-58.
15. Cavigelli, S.A. and M. McClintock, Fear of novelty in infant rats predicts adult corticosterone dynamics and an early death. Proceedings of the National Academy of Sciences, 2003. 100(26): p. 16131-16136.
16. Corsetti, S., et al., Bold personality makes domestic dogs entering a shelter less vulnerable to diseases. PloS one, 2018. 13(3): p. e0193794.
17. Cavigelli, S.A., J.R. Yee, and M.K. McClintock, Infant temperament predicts life span in female rats that develop spontaneous tumors. Hormones and Behavior, 2006. 50(3): p. 454-462.

Poor quality diet is associated with increased risk of heart disease, stroke, type 2 diabetes, many forms of cancer and mental illness. Poor quality diet is the top contributor to mortality globally, and is estimated to cost the NHS £6billion per year.
The period of adolescence to early adulthood is the time when prevalence of overweight and obesity develops most rapidly, making this an important time to understand the contribution of diet to these developing risk factors. Adolescence and early adulthood is a time of rapid personal development and changing lifestyles. It also is the time when adult behaviours, including adult dietary patterns, are developed and established. Understanding the factors that influence development of adult diet is an important first step in developing strategies to change behaviour.
However, there has been little assessment of diet in young adults. Online tools (INTAKE24) are now available that make reporting on nutritional intake easier, allowing online completion of recalls of daily intake, and automated data processing. These validated tools make the collection of diet data in large samples more feasible, and are now being implemented in large-scale dietary surveys across many countries by researchers at the MRC Epidemiology Unit.
This application focusses on assessing the diet of young adults (age 28-30) in the ALSPAC cohort. This data will then be used together with other data collected within ALSPAC, or from linked datasets, to understand (1) the changes in environment and lifestyle which help to explain why individuals have adopted their current diets, and (2) the relationships between diet and measures of heart and blood health. The data will also be available for further research studying associations between diet at age 30 years and longer term measures of health and disease.

Mercury (Hg) is an environmental pollutant that can persist and bio-accumulates as methylmercury (MeHg) through the food chain. Foetuses are especially vulnerable to prenatal exposure since mercury can cross the placental barrier and the blood brain barrier is not fully developed until several months after birth. Prenatal exposure to Hg has been associated with impaired foetus development, such as reduced placental functioning and foetal growth. Prenatal exposure to Hg has also been associated with effects on child neuropsychological development. The specific mechanisms of toxicity related to these associations remain unclear, although some research has suggested that dramatic DNA methylation changes and epigenetic remodelling during early embryogenesis could be involved. Thus, cells and tissues acquire new methylation patterns that may persist in foetal development and childhood. To date, only three studies have been conducted relating Hg and epigenome-wide DNA methylation in cord blood with sample sizes between 138 and 321. These studies have identified altered expression in unique genomic regions as well as methylation changes in specific CpG sites. This study proposes to to investigate the association between prenatal Hg exposure and epigenome-wide methylation.

Maltreatment (physical, sexual and emotional abuse and neglect) in childhood is common and has both immediate and long-lasting negative effects. People who suffer maltreatment have a higher risk of many health conditions, including obesity, heart attack and stroke. However, it is not well understood why this is the case and at what age ill health starts to manifest. Unhealthy eating, smoking, physical inactivity and inadequate sleep may play a role in this relationship, but mental health issues, such as anxiety and depression, inflammation and other biological factors can also be involved. These factors might have separate effects but also act together, and these mechanisms might differ between men and women. This research aims to understand when the cardiovascular consequences of maltreatment appear, the pathways that link childhood maltreatment to heart disease in later life and whether these mechanisms differ by sex. This will help to identify potential targets for interventions to prevent heart disease in those who suffered maltreatment. We will use data from several British studies (ALSPAC, UK Biobank, the 1958 British Birth Cohort, Millennium Cohort and Growing up in Scotland), that have assessed maltreatment in early life and have measures of cardiovascular health indicators at different ages to understand when, why and how people who suffered maltreatment in childhood have a higher risk of heart disease in later life.

Adolescence is a key life course stage during which influences from the family of origin can influence later socioeconomic attainment and health and may be a particularly vulnerable time for the interaction between mental and physical health and social disadvantage. This project examines how circumstances from early-life such as family socioeconomic position and adverse childhood experiences shape the co-occurrence and co-development of depressive symptoms and overweight in adolescence and the socioeconomic consequences the comorbidity may have.

What a mother eats during pregnancy has previously been established to programme their infants health in later live, even tracking through to adulthood. However, despite compelling evidence to support foetal programming of physical health, neurodevelopment has remained understudied. Recently, autism has gained increased attention within this field of research. Although largely caused by genetic factors, it is now estimated that approximately 20% of the risk of developing autism relates to environmental factors, of which nutrition is a main focus. Preliminary evidence indicates that the risk of developing autism may be reduced through consumption of a nutritionally adequate diet or nutritional supplements. Furthermore, the presence of social patterning is unknown. Health inequities are observed in numerous health outcomes as low socioeconomic position groups experience more adversity including poorer diet quality. Thus, it is possible that, where an association existed between maternal diet and their child’s risk of autism, it may also be socially patterned.

Two datasets will be compared for this project, ALSPAC and a second dataset called the Norwegian Mother and Child Cohort Study. The data from each cohort will be analysed in the same way.
This project will apply statistical methods that estimate if there is an association between maternal nutritional intake during pregnancy and the child’s risk of developing autism. The project will apply ‘causal methods’ which are statistical methods which better estimate causal relationships from observation data when compared to conventional methods with measure ‘association’. A key way in which this occurs is through adjusting for confounders which vary over time, such as early infant nutrition. Both pregnancy and early infant nutrition such as breastfeeding, complementary feeding and nutrition in the early years have been associated with neurodevelopment and so the effects measured in pregnancy may be further altered by nutrition consumed in childhood. Lastly, results will be stratified by socioeconomic position to more clearly assess the presence and the degree of social patterning in this relationship.

Physical activity can be rewarding and lead to anxiety reduction, and physical activity levels in the general population are heritable, suggesting individual differences in the degree to which physical activity is reinforcing via biobehavioral pathways. Increases in physical activity are often associated with positive mental health outcomes, though more is not always better. For example, up to 40% of individuals with bulimia nervosa and up to 60% of those with anorexia nervosa present with driven exercise (exercising in a driven manner to control weight and shape). Driven exercise is a serious, concerning, and understudied eating disorder symptom. Existing research points towards compulsivity and general propensity to exercise as potential risk factors for driven exercise. At present, our understanding of the developmental etiology of driven exercise is poor, and the extent to which this symptom relates to patterns of PA during development is unknown.
We will examine risk for driven exercise in the ALSPAC cohort by identifying trajectories of physical activity during development and identifying whether these trajectories associate with driven exercise and eating disorder diagnoses in adolescence and emerging adulthood. We will then investigate the developmental timing and predictive strength of driven exercise in relation to eating disorder onset and maintenance. Finally, we will evaluate the degree to which genetic risk profiles inform risk for driven exercise.