Proposal summaries
B4446 - Predicting the risk of depression and anxiety in early life and adolescence - 02/11/2023
One in every eight people in the world have a mental health problem[1] and in 75% of these people their mental health problem develops before they are 18[2]. Depression and anxiety are the most common mental health problems and they often co-occur in the same individual. Early-life mental health problems, including depression and anxiety, can severely impact the lives of affected individuals including future health and wellbeing, education and jobs, and family and peer relationships. Therefore, research is needed to improve our understanding of why some people experience mental health problems while others don’t. While depression and anxiety symptoms are often time limited in some people, they are chronic in many, but currently there is no accurate/reliable way of predicting who might develop chronic/severe course of symptoms/illness. Identifying this subgroup would help in development of targeted prevention strategies.
Potential risk factors for mental illnesses include biological factors (e.g., genetics, epigenetics, low-grade inflammation), social factors (e.g., abuse, bullying, living in poverty) and psychological factors (e.g., internalising attributional style).
Evidence has shown that inflammation in the body is an important biological risk-factor[3, 4]. Inflammation can also be triggered or altered by other experiences (for example, eating certain foods, substance use or having an infection). Because of this, it is possible that modifying factors that cause inflammation (e.g., diet) may help to treat or prevent mental health problems.
An important group, who might have more inflammation, are people with food allergies, eczema and asthma. Allergy is very common; researchers predict that by 2025 half of all people living in Europe will have an allergy[5]. Psychosocial factors linked to allergy such as trauma associated with a severe allergic reaction, fear of experiencing a reaction, following a restricted diet, social exclusion, missing days from school, medication use and over-protective parenting styles might also influence a child’s mental health.
This project will use data collected from participants of the Avon Longitudinal Study of Parents and Children who answered questions about their mental health, and other life experiences, at different ages as they grew up. We will use these data to look at how bio-psycho-social risk factors in early life (e.g., gestation, childhood, adolescence) are linked to mental health in teenagers and young adults. Findings will enable us to identify and help children who are at high risk of developing a mental health problem before they have developed severe, adverse symptoms.
1. (WHO), W.H.O., Fact sheets: Mental Disorders. 2022.
2. England, M., Mental health statistics. 2020.
3. Milaneschi, Y., et al., Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts. Mol Psychiatry, 2021. 26(12): p. 7393-7402.
4. Foley, É.M., et al., Peripheral blood cellular immunophenotype in depression: a systematic review and meta-analysis. Molecular Psychiatry, 2023. 28(3): p. 1004-1019.
5. UK, A., Statistics and Figures. Allergy Prevalence: Useful facts and figures.
B4438 - How does adiposity distribution influence risk of obesity-driven cancers Exploring causality and mechanisms - 31/10/2023
Obesity, which is increasing worldwide, is known to increase a person’s risk of many health conditions. The amount of fat tissue that an individual has is often proxied using body mass index (BMI). BMI is cheap to measure and can be an effective measure of overall fat tissue when used at a population level. However, BMI cannot capture the full complexity of the distribution of fat tissue across the body. Recent research has highlighted that fat tissue at different locations throughout the body can have vastly different consequences for heart and blood outcomes, with more central fat tissue having negative consequences and more thigh and buttock fat tissue being beneficial. Whether similar effects of fat tissue distribution are also seen in cancer outcomes, particularly for cancers where there is a known link with obesity, is not yet unknown.
We aim to use ALSPAC data to gain a deeper understanding of the link between fat tissue distribution throughout the body and cancer risk. We will evaluate whether fat tissue distribution affects cancer risk and levels of certain molecular traits measured in blood samples at different ages using the latest statistical methods.
The proposed research will increase our understanding of how fat tissue distribution affects cancer risk. We will also unpick the potential biological mechanisms explaining these relationships and determine at what age the relationships may begin.
B4449 - Thermometer study - association between baby room temp and later asthma - 31/10/2023
During the last 6 months (may - Dec 1992) of recruitment to the study, mothers were randomised to receive a simple thermometer or not. Those who received one, were asked to place in the wall of the room where her baby slept. She was asked to record the temperature of the room twice a week for a year. This project will clean the data obtained and will derive a number of sumamry variables regarding temperature with a view to looking at later respiratory outcomes in the children up to the age of 18 years.
B4444 - Navigating reproductive events and autoimmune disorders - 31/10/2023
During pregnancy, many important biological and physiological changes occur to protect both mother and the growing baby, particularly related to hormones and the immune system. We also know that compared to men, women are more likely to have autoimmune disorders, where the body's defence system attacks itself. However, pregnant women are often excluded from studies because of safety implications. We now need to figure out how reproductive hormones might impact autoimmune disorders in both pregnant and non-pregnant people, as well as what other health behaviours may influence this.
B4437 - Synthetic Health Data for Research Support - an exemplar from a birth cohort - 31/10/2023
Electronic health records (EHRs) are a valuable resource in research, with the potential to increase sample size, reduce biases and improve representativeness, by being collected on national scale at the point of care by health care providers. Due to the personal and sensitive nature of EHRs, the confidentiality of these data is protected by strict regulatory frameworks. Accessing EHRs can take months or even years; this remains a major barrier for researchers gaining timely access to real world data. We propose to use the ALSPAC setting as an exemplar project synthesising EHRs in a cohort context. We will develop a roadmap of the key requirements for synthesising EHRs within a cohort setting.
B4442 - Genetic variation and alcohol use and smoking - contribution to GSCAN GWAS Sequencing Consortium of Alcohol and Nicotine use - 27/10/2023
In this study, we will be exploring the relationship between genetics and smoking and alcohol use. We will combine the findings with findings from other studies around the world. We will also explore whether our environment (based on year of birth) can impact this relationship.
B4436 - Epigenetic markers of gender domains distinct from biological sex - 27/10/2023
Sex and gender must be taken into account in health research and the provision of care. While sex refers to biological differences and gender refers to sociocultural effects, these terms are often used interchangeably, and most studies only consider their combined effects in a binary framework comparing two sexes/genders. We aim to develop a tool to distinguish gender from sex using epigenetic markers (chemical alterations to DNA that can be readily measured in biological samples such as blood). This will enable researchers and health care providers to go beyond simply dividing into two groups by sex (male vs female), and will recognize a continuum of masculinity and femininity, relevant to both cis and trans individuals. This tool will improve research into the social determinants of health, and help to tailor health care decisions and interventions to individuals.
B4443 - An examination of the association between school absence and exclusion and violent crime - 09/11/2023
Understanding the relationship between absence from school – unenforced, in the form of absence, or enforced, in the form of suspension or exclusion – and violence is a pressing issue. There are strong beliefs among some policy-makers and researchers that exclusions, in particular, are a direct cause of later offending and, on this basis, some school areas have moved to prohibit exclusions. While there are many harms associated with absence or exclusion, misconstruing the nature of the link between them and violence risks stigmatising those children and distracting attention from the underlying causes of violence. We seek to estimate the absence/exclusion-violence connections in a way that will inform school policies and guide the timing and context of violence prevention programmes for the future.
B4435 - Understanding the aetiology of Childhood self-harm in the general population An epidemiological approach - 30/10/2023
The prevalence of self-harm in young people is increasing whilst the age of self-harm onset is decreasing. Prevention and early identification of self-harm is critical to prevent additional adverse outcomes. The majority of research to date has focused on self-harm during adolescence and adulthood. Little is known about the prevalence of childhood self-harm in the general population, its risk factors, and likely outcomes. The CHARM project is uniquely positioned to answer these questions, with data on self-harm behaviours in children as young as three and longitudinally up to age 16 years. This is combined with a wealth of longitudinal data including questionnaires, linkage to national health registries, genetic data, parent data and detailed environmental exposure data. The CHARM project will leverage this amazing resource to build the most detailed picture to date of emergence, persistence and aetiology of childhood self-harm in the general population. Furthermore, we will apply genetic epidemiology techniques to strengthen causal inference, which increases the likelihood of interventions being effective. Together, these analyses will paint a rich picture of an understudied phenotype and help inform intervention design to prevent childhood self-harm and consequently prevent later adverse outcomes.
B4432 - The Impact of Adverse Childhood Experiences on Autonomic Functioning Across the Lifecourse - 23/10/2023
In the past 25 years, studies like the Welsh Adverse Childhood Experiences and Resiliency Survey (Public Health Whales 2018) and a representative British household survey (Bellis et al. 2014) have revealed that adverse childhood experiences (ACEs), such as abuse and neglect, are very common. They have highlighted an unfortunate truth that around 50% of children in England and Wales have experienced at least one form of adversity in childhood (Public Health Whales 2018, Bellis et al., 2014).
Traditionally, researchers have measured ACEs by summing up the total number of adversities experienced (cumulative risk models) across childhood and adolescence. Additionally, researchers have stressed the importance of investigating the individual impact of specific adversities, called specificity models. Both methods, however, have their weaknesses. Cumulative risk models do not account for the child’s experiences, and the duration and the timing of the experience. Conversely, examining individual adversities ignores the co-occurrence of these experiences and allows the relationship to potentially be confounded by other adversities.
In recent years, researchers such as Ellis and colleagues (2022) have introduced a new, comprehensive method to assess environmental adversity, known as dimensional models. A dimensional approach to measuring and classifying ACEs is a powerful tool as it recognises and evaluates a wide spectrum of negative experiences that differ in severity and timing. This enables researchers to delve into the ways and reasons by which negative environmental experiences affect developmental processes.
ACEs have been linked to many adverse cardiovascular health outcomes in every stage of the life span. In childhood 4 or more ACEs have been linked to increased resting heart rate (HR) in late childhood (12-14 years) (Petty et al., 2013) and enlarged arterial stiffness from childhood to young adulthood over time (Rafiq et al., 2020). Adults who experience a larger number and a greater impact to adverse life events in childhood demonstrated higher HR reactivity in response to an acute psychological stressor, indicating that life events are associated with elevated HR and reduced HR complexity in response to acute stress (Schneider et al., 2021). Moreover, these results indicate that poor cardiovascular outcomes appear earlier than expected in late childhood and early adolescence, stressing the importance of early intervention.
The connection between ACEs and cardiovascular health is not consistent because of the heterogeneity in ACEs definitions and study populations (Wesarg et al., 2022). To gain better insights into how a child’s unique vulnerability to adversity is mediated by individual characteristics, such as family factors, extrafamilial conditions, personality, or temperament (Belsky et al., 2013), a life course approach using birth cohort data is needed.
Sidonie Kilpatrick’s PhD dissertation investigates how ACEs impact heart-related automatic functions (i.e., autonomic functioning) throughout an individual’s life and identifies factors that can mitigate this impact. She will use data from two studies, the 1946 National Survey of Health and Development (NSHD) and the Avon Longitudinal Study of Parents and Children (ALSPAC), that collect information from the prenatal period to death. She plans to evaluate how ACEs influence resting blood pressure and heart rate across the life span and midlife heart rate variability. Additionally, she plans to evaluate how specific characteristics or interventions can influence resting HR and BP across the life course to better inform early intervention and policy.
References:
Bellis M A, Hughes K, Lechenby N, et al., . National household survey of adverse childhood experiences and their relationship with resilience to health-harming behaviors in England. BMC Med. 2014; 72(12): https://doi.org/10.1186/1741-7015-12-72
Belsky J, Pluess M. Beyond risk, resilience, and dysregulation: phenotypic plasticity and human development. Dev Psychopathol. 2013 Nov;25(4 Pt 2):1243–61.
Ellis BJ, Sheridan MA, Belsky J, McLaughlin KA. Why and how does early adversity influence development? Toward an integrated model of dimensions of environmental experience. Dev Psychopathol. 2022 May;34(2):447–71.
Pretty C, O’Leary DD, Cairney J, Wade TJ. Adverse childhood experiences and the cardiovascular health of children: a cross-sectional study. BMC Pediatr. 2013 Dec 17;13:208.
Public Health Whales, Sources of resilience and their moderating relationships with harms from adverse childhood experiences. Public Health Whales. 2018; https
://www.wales.nhs.uk/sitesplus/documents/888/ACE%20&%20Resilience%20Report %20(Eng_final2).pdf
Rafiq T, O’Leary DD, Dempster KS, Cairney J, Wade TJ. Adverse Childhood Experiences (ACEs) Predict Increased Arterial Stiffness from Childhood to Early Adulthood: Pilot Analysis of the Niagara Longitudinal Heart Study. J Child Adolesc Trauma. 2020 May 30;13(4):505–14.
Schneider M, Kraemmer MM, Weber B, Schwerdtfeger AR. Life events are associated with elevated heart rate and reduced heart complexity to acute psychological stress. Biol Psychol. 2021 Jul 1;163:108116.
Wesarg C, Van den Akker AL, Oei NYL, Wiers RW, Staaks J, Thayer JF, et al. Childhood adversity and vagal regulation: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022 Dec 1;143:104920.
B4439 - Scoping out the linked AWP data - 26/10/2023
We have a current ESRC-funded/ALSPAC-approved project (B3882)
This project will use linked data (with Jasmine and Jon accessing the data through the secure portal).
We are interested in families who have experienced services in relation to their study-child's behavioural problems. Up until recently the plan was to understand service-use through a combination of MHSDS, HES and GP records and we are working on an IRAS form for this, with support from Mark and Eleanor.
Very recently we learned that ALSPAC had obtained some new mental health data - the AWP dataset. We felt that this new data might be of use to us and help fill in some of the gaps left from using MHSDS etc.
Given our research group's clinical experience of MH services we felt it might be beneficial - both to us and to ALSPAC - if we put some effort into understanding these data and produced a data-note or some other kind of documentation for the use of ALSPAC and other interested data-users.
Mark felt it was a reasonable request for us to obtain these data in their entirety, but unlinked to other sources, through the linkage portal. We would then produce a data-note, and hopefully also some derived variable which could be checked before being incorporated into our main linkage data.
Any payments and data-agreements are ongoing and are all linked to the main project. Mark felt it sensible for us to submit a secondary project for this specific scoping aim.
B4440 - DNA methylation profiles in children in relation to pre- and postnatal exposure to environmental noise LongITools - 25/10/2023
This project will investigate the association between noise exposure during pregnancy and DNA methylation in children
B4433 - Association of ultra-processed food consumption with body composition and blood pressure in Brazilian and British adolescents - 23/10/2023
The consumption of ultra-processed foods (UPF) has been associated with various adverse health outcomes. However, the investigation of the effect of UPF consumption on obesity, body composition indicators, and blood pressure in adolescents, especially using longitudinal and high-quality studies, is still scarce in the literature. In this context, the present study aims to evaluate the effect of UPF consumption on body composition, obesity, and blood pressure in Brazilian and British adolescents. The comparison of data from adolescents in two countries with distinct socioeconomic and cultural backgrounds, such as Brazil and England, holds unique relevance for advancing knowledge in assessing the detrimental effect of UPF consumption on health, regardless of education or income and other differences between the countries. We hypothesise that there is an association between UPF consumption and body composition, obesity, and blood pressure of adolescents in both countries. The plausibility of this hypothesis is supported by existing evidence in the literature characterizing UPFs as rich in fats, sodium, sugar, and additives, being more high in calories and unhealthy. Therefore, it is likely that the higher consumption of these foods in the long term represents a risk factor for the development of the outcomes analyzed in the present proposal, even in young individuals.
B4434 - Body image and risky sun exposure in young people living in a developed country - 23/10/2023
This project is concerned with the rising incidence of skin cancer[1] and its primary causes, such as exposure to ultraviolet radiation (UVR), highlighting the role of body image on behaviours related to UVR exposure, including sunbathing and indoor tanning.
Body image incorporates body size estimation, evaluation of attractiveness, and emotional responses related to body shape and size[2]. A key aspect is the discrepancy between perceived societal body ideals and one's own appearance, which leads to body dissatisfaction[3]. The incidence of body dissatisfaction is on the rise among young populations in both developed and developing countries[3-4]. In addition, body image has been implicated in various unhealthy behaviours, like harmful weight control practices, disordered eating, smoking, excessive alcohol intake, and sunbed use, which are often interrelated[3].
The current proposal will examine the association between body dissatisfaction and tanning habits in ALSPAC young adults, aiming to identify targets for prevention of behaviours that increase risk for skin cancer in this population.
References
[1] Urban K, Mehrmal S, Uppal P, Giesey RL, Delost GR. The global burden of skin cancer: A longitudinal analysis from the Global Burden of Disease Study, 1990–2017. JAAD International. 2021;2: 98–108. doi:10.1016/J.JDIN.2020.10.013
[2] Grogan S. Body image and health: contemporary perspectives. J Health Psychol. 2006;11: 523–530. doi:10.1177/1359105306065013
[3] Strand M, Fredlund P, Boldemann C, Lager A. Body image perception, smoking, alcohol use, indoor tanning, and disordered eating in young and middle-aged adults: findings from a large population-based Swedish study. BMC Public Health. 2021;21: 128. doi:10.1186/s12889-021-10158-4
[4] Bornioli A, Lewis-Smith H, Smith A, Slater A, Bray I. Adolescent body dissatisfaction and disordered eating: Predictors of later risky health behaviours. Social Science & Medicine. 2019;238: 112458. doi:10.1016/j.socscimed.2019.112458
B4430 - CHARGE Metabolomics and Blood Pressure Replication - 23/10/2023
High blood pressure (BP) is a major risk factor for cardiovascular as well as non-cardiovascular diseases. Underlying molecular pathways related to BP regulation are not fully understood. The aim of the project is to identify ethnic-specific metabolites associated with cross-sectional measures of blood pressure levels and hypertension status. The project leaders have already found associations between specific metabolites and blood pressure levels or hypertension status in their discovery cohorts. Replication analyses will be conducted in several cohorts that are members of the CHARGE Metabolomics consortium, including ALSPAC.
B4431 - Diastolic blood pressure across the life course risk factors and consequences - 19/10/2023
High blood pressure is a risk factor for heart disease. Most research is carried out using systolic diastolic pressure - the pressure in the heart when the heart muscle contracts. Less is known about diastolic blood pressure - the pressure in the heart when the heart muscle relaxes. This project seeks to better understand diastolic blood pressure - what influences is, and what are its consequences for heart health.
B4425 - Menopause and depression assessing causation and identifying mechanisms - 10/10/2023
Despite the increasing media coverage concerning the impacts of the menopause on women’s mental health, this remains an under-researched area. Menopause affects quality of life, work, and relationships and is also a period of increased risk of depression. Depressive symptoms during menopause are often attributed to hormonal changes, but life stressors that coincide with the menopausal transition could also have a depressogenic effect. Earlier research, based mainly on cross-sectional data, has found that a later age at menopause and a longer reproductive period are associated with a lower risk of depression. This may reflect a greater lifetime exposure to oestrogen, which is thought to have an antidepressant effect in women. Limitations of previous studies include inadequate adjustment for confounders; lack of control for premenopausal depression, and failure to account for other factors affecting lifetime oestrogen exposure (e.g. oral contraceptives, breastfeeding, number of pregnancies) or hormone replacement therapy. Very few studies have sought to uncover the biopsychosocial mechanisms that might explain increased levels of depression during the menopausal transition. This project aims to advance understanding of women’s mental health during menopause by applying cutting edge causal inference methods.
B4426 - Investigating factors associated with within-individual variability in BMI from childhood through to early adulthood - 09/10/2023
Much research has indicated that obesity is associated with poorer health outcomes. Whilst these studies have tended to investigate average body weight (relative to height), more recently there has been interest in variation in body weight. This work has indicated that people whose body weight goes up and down a lot are more likely to experience future weight gain. This project will investigate variability in weight, using body mass index (BMI, a measure of weight which accounts for height), across the key developmental phase of childhood through to early adulthood. It aims to form a better understanding of the factors associated with variability in BMI across this time.
B4422 - A multi-cohort analysis of interacting prenatal and genomic risks in the development of childhood ADHD - 09/10/2023
Attention deficit hyperactivity disorder (ADHD) is the most common mental disorder in children worldwide, and can have lifelong health impacts, making it a major public health issue. Rates of ADHD have been increasing in Canada in recent years, particularly in Quebec, and increasing attention has been given to ADHD diagnosis around the world. Previous research suggests there is a significant gender gap in ADHD in children, with boys much more likely to be diagnosed than girls. However, reasons for this difference remain largely unknown. Genetic factors are known to play a key role in the development of ADHD. Yet, genes do not act in isolation. The early environment can also strongly influence brain development and may modify the risk of ADHD. Specifically, maternal stress may alter the prenatal environment to increase the risk of developing ADHD, which may be more likely to impact males due to genetic sex differences. The proposed research aims to analyze the relationship between prenatal maternal stress and offspring sex and genes in relation to the risk of later ADHD diagnosis. This analysis will be carried out in four large independent prenatal cohorts from Canada, the UK (ALSPAC), the Netherlands, and Singapore. Through the use of international, longitudinal data, the proposed project will be able to unpack the complex mechanisms that can result in the development of ADHD across different cohorts and settings. This will lead to a better understanding of the relevant genetic and environmental determinants of ADHD, to allow for better treatment options and identify potential areas of early intervention.
B4392 - Genetic risk scores for increased levels of endocrine disruptors and pubertal timing - 06/10/2023
Puberty is defined as the transition from infancy to reproductive maturity characterized by the acceleration of growth velocity and the development of secondary sexual characteristics and genitals. Normal puberty onset ranges between 8-13 years old for girls, and 9-14 years old for boys. It is clinically defined as the onset of Tanner stage 2 in thelarche for girls (development of breast buds) and by Tanner stage 2 in external genitalia development for boys (increase in testicular volume to >4mL). Age at menarche in girls and age at peak height velocity in both sexes are landmarks which can be used to evaluate pubertal timing.
Endocrine disrupting chemicals (EDCs) have become increasingly prevalent in the past century as manmade products and chemicals have been made essential in our daily lives. There are nearly 85 000 human-made chemicals in the world, and 1000 or more of those could be endocrine disruptors. There are two main types of EDCs: the persistent organic compounds with decade-long half-lives such as dichloro-diphenyl-trichloroethane (DDT) in pesticides and polychlorinated biphenyls (PCBs), and those that have a shorter half-life but can cause long-term health consequences such as phthalates and bisphenol A. EDCs disrupt the body’s delicate endocrine homeostasis by acting as an agonist or antagonist when binding to hormone receptors, thereby causing unwanted effects, such as earlier timing of puberty in girls and boys. The four EDCs of interest in our study are dibutyl phthalate, bisphenol A (BPA), dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyl (PCB).
Phthalates are a large group of omnipresent compounds used as liquid plasticizers. They are found in food packaging, cosmetic products, shampoo, children’s toys and medical device tubing. It was found that first and second-trimester exposure to Bis(2-ethylhexyl) phthalate (DEHP) was associated with increased peripubertal serum estradiol levels, whereas third-trimester exposure was associated to a delay of pubarche onset. BPA is used to make polycarbonate plastic and epoxy resin. It can be found in food packaging, toys, and canned beverages’ linings. At low concentrations, BPA and other phenol compete with endogenous estrogens for binding, whereas at higher concentrations they have anti-androgenic properties.
DDT was used in many organochlorine pesticides and insecticides before being banned in 1972 in multiple countries. In 2006 however, it was reintroduced in some areas by the World Health Organization in order to fight malaria and control other vector-borne diseases. DDT exposure begins prenatally and lasts throughout a lifetime, as it is found in abundance in consumed food products, and is found to have anti-androgenic properties. PCBs were found in lubricants, electrical equipment and plasticizers up until they were banned in 1979. Studies show that childhood exposures of PCBs are associated with earlier pubertal milestones in boys, such as earlier Tanner stages.
Although a large body of evidence from observational studies exists linking EDCs to pubertal timing variations, these associations can be confounded by factors such as low socio-economic status and obesity and cannot establish causality. In the absence of evidence from randomized controlled trials- which would be unethical to employ, the causal link between EDCs and pubertal timing remains undetermined. We have generated preliminary results using two-sample Mendelian randomization for 19 EDCs, most of which do not support a causal association of genetically determined levels of these EDCs with age at menarche in girls or age at voice change or facial hair in boys. Using genetic variants associated with levels of these EDCs, which are not influenced by environmental confounders, we aim to investigate if genetic predisposition to higher levels of these chemicals could affect pubertal timing in ALSPAC children.
In the proposed project, we hypothesize that genetic risk scores (GRS) composed of one to multiple single nucleotide polymorphisms (SNPs) associated with levels of 19 endocrine disrupting chemicals (dibutyl phthalate, BPA, DDT and 16 types of PCBs) in the largest available genome-wide association studies for EDC levels, could be associated to an altered age at menarche in girls or age at peak height velocity in both girls and boys (adjusting for sex) with and without adjusting for BMI SDS at age 8 and socio-economic status.