Maternal postnatal depression is estimated to affect 6 – 38% of women in high income countries. Not only is it by nature distressing, it is also associated with health risks to the child. We need to know more about what causes postnatal depression in order to inform policy to prevent it.

One set of factors which could be important are aspects of the city environment such as noise, air polution and access to natural spaces. The period following birth is a particular vulnerable time and these factors could have a negative impact on maternal mental health. For example, air polution could affect the brain which could lead to an increased risk of depression. Road traffic noise could disrupt sleep leading to increased stress, and a lack of access to natural spaces could reduce opportunities to socialise and relax.

Whilst there is some evidence that these aspects of the city environment are related to depression in adults, very few studies have explored their relevance for postnatal depression. In this study we aim to use a large data resource including many European cities to investigate whether exposure to these different aspects of the city environment increases the risk of postnatal depression.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic condition of childhood, but remains a relatively rare condition. Whilst there is growing knowledge about JIA disease management, we have very limited knowledge about the wider impacts of the condition, particularly in adolescence and adult life. For example observational data suggests that JIA patients have adverse educational attainment levels and employment outcomes. There is also growing concern about wider health implications of JIA such as cardiovascular disease risk, similar to that seen for adult rheumatoid arthritis patients, although long term follow-up data of JIA patients into adulthood is very limited. Within this PhD a range of different techniques are being used to explore causes and effects of JIA across the life course using observational and ‘omic data. Our earlier work has shown associations between JIA and a number of other health outcomes, however outcome datasets have all derived from older adult populations. Building on earlier work, this project aims to examine the association between the level of the genetic risk of JIA (using polygenic risk scoring) and a range of clinical (e.g. cardiovascular risk factors), biological (e.g. circulating CRP levels), metabolic (eg circulating lipids) and molecular (e.g. changes to DNA methylation) outcomes during childhood and early adulthood. This will allow us to identify potential JIA associated comorbidity earlier in disease to a) allow earlier risk stratification of patients and b) allow underlying mechanisms of comorbidity to be explored.

Certain behavioural (e.g. diet, smoking, physical activity) and physiological (e.g. obesity, cholesterol, glycaemic control, blood pressure) risk factors have long been known to increase risk of atherosclerotic CVD in later life. Although clinical events rarely occur prior to middle-age, our group have previously shown that early signs of damage to the vasculature can be detectable from as early as childhood (Charakida et al 2012 JACC; Dangardt et al 2019 Lancet Child and Adolescent Health; Chiesa et al JACC Imaging 2019), and that cumulative exposure to this damage across the lifespan likely represents one of the biggest causes of later-life events.

Intriguingly, recent research strongly suggests that these modifiable health behaviours and risk factors may also contribute to another of the world's most pressing global health crises – dementia. A wealth of recent research supports the concept that the development and progression of cognitive decline and eventual dementia can be slowed or perhaps even prevented by addressing various risk factors more commonly linked to CVD (Livingstone et al 2020 Lancet). The implementation of early-life prevention strategies to improve heart health may therefore also provide dual benefits for long-term brain health.

Our group and others have recently contributed to accumulating evidence suggesting that it is exposure to these CV risk factors earlier in the lifespan which appear to relate most strongly to risk of cerebral (i.e. brain) disease risk in later life. These findings suggest that although dementia diagnoses are almost exclusively made in older age, they may in fact represent the end result of cumulative damage to brain tissues which have been sustained over decades previously. However, how early this damage starts and what factors are responsible for its appearance is currently unknown, as very few populations are available in which detailed brain scans have been carried out on a young population with wide-ranging CVD risk factors.

Children with precocious puberty are defined as girls with breast development before age 8 years and boys with testicular enlargement before age 9 years (which corresponds to minus 2 standard deviations (SD) compared to the average age of these changes in both sexes). Earlier age at pubertal start has been associated with earlier age at first vaginal bleeding (menarche) in girls and earlier age at voice change in boys, and with long-term consequences, including shorter adult height and psychosocial adverse effects. Although more frequent in certain ethnicities, the prevalence of precocious puberty in girls is constantly increasing worldwide, following the increase in cases of pediatric obesity. Most children with precocious puberty do not present any endocrine, metabolic, neurologic or neurosurgical condition explaining their earlier pubertal start (these cases are defined as “idiopathic” precocious puberty), but extensive work up (including specific hormone measurements and radiological exams) is routinely performed to eliminate such conditions. An important portion of children with precocious puberty will be considered for treatment with puberty-blocking pharmacological agents, without clear evidence that these treatments will increase their adult height.
Late puberty is defined as an absence of breast development by age 13 in girls (or absence of menarche by age 15), and an absence of testicular enlargement before age 14 in boys. This phenomenon is more frequent in boys, in most of which no pathological cause is detected, and these children will end up developing a spontaneous puberty and achieve a normal adult height. Nonetheless, these children are often referred for endocrine evaluation and investigated to eliminate an underlying medical condition.
Given that age at pubertal start in the population follows a Gaussian distribution, 2.3% of normal healthy children will start their puberty at and age below 2 SD below the mean for each sex, and another 2.3% will start their puberty above 2SD above this mean. Defining which children with precocious or late puberty correspond to these 2.3% of the general population is important, since this would avoid unnecessary investigations and treatment in these patients.
Pubertal traits (age at breast development and menarche in girls, testicular enlargement and voice change in boys, age at pubertal growth spurt in both sexes), have a polygenic nature, and an overlapping genetic architecture in boys and girls. It has been estimated that about 50% of variation in age at menarche can be attributed to genetics. Polygenic risk scores (PRS) have been demonstrated to have an improving ability to identify individuals at significantly high/low predisposition towards complex diseases. Therefore, it has become possible to identify individuals who will lie at the extreme distribution of a trait, such as age at menarche in girls or age at voice change in boys.
Therefore, we posit that PRS for age at menarche in girls or age at voice change in boys, in combination with clinical risk factors (such as increased body mass index) may be able to effectively predict children diagnosed as having idiopathic precocious puberty and in which no further investigation or treatment would be required to achieve a normal adult height (within their parental target height). Also, the same scores could identify children in the opposite extreme of the normal distribution, ie children with late puberty.

Child maltreatment (CM) and domestic violence and abuse (DVA) are highly prevalent violations of human rights, recognised as being responsible for significant adverse short- and long-term impacts on the health, wellbeing and life opportunities of affected individuals. Multiple common risk factors are known to exist for CM and DVA, contributing to a high degree of co-occurrence. (1–3)

Understanding how these adversities interact and quantifying their individual and combined impacts is key to deriving accurate estimates of the burden that CM and DVA impose, both on services and on the individual throughout their life-course. Previous estimates of the economic burden of abuse were focused on either CM or DVA in isolation, which may fail to fully account for the intersection of CM and DVA and the relationships between exposure to multiple adverse childhood experiences and poor health. (4,5)

Study aims:
1) To estimate the impact on life outcomes (e.g. physical and mental health, healthy behaviours, employment and earnings, welfare use) resulting from exposure to CM and/or DVA, and to investigate the how this burden varies with household CM/DVA co-occurrence. This will inform parameters for the development of a multi-sectoral, incidence-based societal cost model and cost-effectiveness models for evaluation of relevant interventions.
2) To perform a comparative analysis with outcomes estimated from the Australian Longitudinal Study on Women's Health (ALSWH). (6) This will enable investigation of commonalities or differences between the UK and Australian cohorts with respect to the impact on life outcomes from exposure to abuse.

1. Herrenkohl TI, Sousa C, Tajima EA, Herrenkohl RC, Moylan CA. Intersection of Child Abuse and Children’s Exposure to Domestic Violence. Trauma, Violence, Abus. 2008;9(2):84–99.
2. Appel AE, Holden GW. The Co-Occurrence of Spouse and Physical Child Abuse: A Review and Appraisal. J Fam Psychol. 1998;12(4):578–99.
3. Edleson JL. The Overlap Between Child Maltreatment and Woman Battering. Violence Against Women [Internet]. 1999;5(2):134–54. Available from: https://doi.org/10.1177/107780129952003
4. Hughes K, Bellis MA, Hardcastle KA, Sethi D, Butchart A, Mikton C, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Heal [Internet]. 2017;2(8):e356–66. Available from: http://www.sciencedirect.com/science/article/pii/S2468266717301184
5. Bellis MA, Hughes K, Ford K, Ramos Rodriguez G, Sethi D, Passmore J. Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis. Lancet Public Heal [Internet]. 2019 Oct 1 [cited 2020 Apr 17];4(10):e517–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31492648
6. Loxton D, Dolja-Gore X, Anderson AE, Townsend N. Intimate partner violence adversely impacts health over 16 years and across generations: A longitudinal cohort study. PLoS One [Internet]. 2017;12(6):e0178138. Available from: https://doi.org/10.1371/journal.pone.0178138

DDepression affects up to 300 million people worldwide and is one of the greatest causes of disability in the world. While many aspects of depression trajectories from adolescence to adulthood are well understood, depression is still among the most unreliable diagnoses of all categorical mental disorders. Additionally, changes in symptom levels across adolescence and young adulthood are as yet poorly understood. This may result from nosological conceptualizations of mental disorders that do not vary for children as compared to adolescents or adults. Only the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders describes irritability rather than depressed mood as an additional core symptom for children and adolescents. In this vein, researchers and practitioners often apply sum score models that reflect these considerations. However, these models rely on strong assumptions and we therefore aim to use Avon Longitudinal Study of Parents and Children data to investigate depressive symptoms in more depth.

The benefits of physical activity (PA) for health are well established. However, limited evidence is available on the relative importance of specific intensities of PA as well as sedentary time for major health outcomes. In conventional analyses, accelerometer data are collapsed into only a few intensities (e.g. light, moderate-to-vigorous).This causes substantial loss of information and limits the detection of the relative importance of specific intensities. In this project we will use a novel multivariate pattern analysis approach to describe the entire PA intensity spectrum and examine the relative importance of different PA intensities on physical and mental health and mental wellbeing.