Final Report Summary - DEVHEALTH (UNDERSTANDING HEALTH ACROSS THE LIFECOURSE:<br/>AN INTEGRATED DEVELOPMENTAL APPROACH)
The DEVHEALTH project has the ambitious objective to combine insights from the social and the biomedical sciences in order to develop an integrated developmental approach to health throughout the lifecourse, and to devise policies to prevent, rather than to just cure, disease. The first part of the project has been focused on two main strands: understanding the importance of the early life years for the formation of health, and advancing the use of genetic data for social science research.
First, while there is now a consolidated body of evidence that early conditions matter for health, knowledge on the mechanisms is still scarce. Our work in DEVHEALTH has contributed to our understanding of how the circumstances in which the children are born and raised “get under the skin” and affect the biological development of the brain and of the rest of the body. Identifying the mechanisms is vital to design policies that are effective at reducing health inequalities. However, one major obstacle when undertaking this endeavor is that in humans it is not easy to separate out biological effects from behavioral responses that might alleviate or exacerbate the effects of early conditions. The use of animal models might provide a useful complement to the human evidence, since external manipulation of the environment and controlled experimental conditions allow analyzing the long-term effects of early circumstances which occur because of biological embedding. However, most of the animal work is conducted in labs on species which are – both genetically and socially – quite different from humans. In path-breaking work conducted on an experiment in non-human primates, the DEVHEALTH team has shown that adverse early-life conditions (non-maternal rearing) in rhesus monkeys have long-term negative effects on both physical and mental health; that they are not ameliorated by a normal social environment later in life; and that they operate at least in part through stress-response pathways and changes in the expression of leukocyte genes related to immune function. These findings provide robust evidence that the environment can causally affect the biology of the body – and that at the same time intervention is possible at a biological level before diseases becomes manifest. It also provides sounds biological foundations for the overwhelming human evidence that lack of maternal care in the early years carry long-term health effects. Complementary to the innovative animal work, we have also pursued analysis of both existing and recently collected data on several early childhood interventions aimed at enriching the environment of disadvantaged children. Our results to date show not only that high-quality interventions are effective in producing consistent patterns of successful outcomes for treatment group members as compared to control group members for both boys and girls (in terms of higher levels of education and wages, lower crime and welfare dependence) – a fact remarked by the President of the United States Barack Obama in his 2013 and 2014 State of the Union Addresses. They have also contributed to our understanding of the mechanisms through which these impacts occur. Evidence from the Perry Preschool Program has revealed that the effects of the intervention on life outcomes has operated primarily through the reduction in child’s externalizing behavior. Before the work of the DEVHEALTH team, much less was known about the health effects of these interventions. The DEVHEALTH team has conducted important work which has significantly reduced this gap in knowledge. An extensive analysis of all the health information available in the Abecedarian and Perry interventions, since childhood, has uncovered statistically significant and economically important treatment effects which survive stringent econometric methods. The Perry participants show a significant reduction in unhealthy behaviors, in particular smoking; the Abecedarian participants (who attended a childcare center which also provided nutrition and pediatric care) had a leaner physical constitution in childhood. Additionally, unique biomarkers data collected for the first time in an early childhood intervention when the participants were aged 35 have revealed that the treated group was in better health also in middle adulthood: in particular, the treated males were less likely to have hypertension and dyslipidemia, and to be affected by the metabolic syndrome, as compared to the males in the control group. Finally, complementary evidence on prenatal home-visiting programs such as the Nurse-Family Partnership and Preparing for Life (which has also been designed by members of the team) reveals the health-improving potential of interventions able to reach at the same time both mothers and children, improving the fate of this generation, and guaranteeing the best to the future one. Overall the DEVHEALTH team work has showed the potential for early life interventions to constitute an unexplored avenue for health policy.
Second, the DEVHEALTH team has been at the forefront on the use of genetic data for social science research. Members of the team have been involved in a pathbreaking analysis that has identified the first three genetic variants associated with educational attainment and duration of schooling. Second, the use of genetic variants known to be associated with risk factors for disease to make causal inference has led to important findings in relation to maternal behaviors in pregnancy and child outcomes. One major finding related to the use of genetic variants associated with alcohol consumption has shown evidence that moderate alcohol consumption can reduce offspring IQ. Finally, the DEVHEALTH team has produced the first epigenome-wide scan of DNA methylation in human tissue, building on the unique resource of the ALSPAC data. These scans are currently being used to investigate how the epigenome correlates with human characteristics and environmental determinants of ill health and disease.
First, while there is now a consolidated body of evidence that early conditions matter for health, knowledge on the mechanisms is still scarce. Our work in DEVHEALTH has contributed to our understanding of how the circumstances in which the children are born and raised “get under the skin” and affect the biological development of the brain and of the rest of the body. Identifying the mechanisms is vital to design policies that are effective at reducing health inequalities. However, one major obstacle when undertaking this endeavor is that in humans it is not easy to separate out biological effects from behavioral responses that might alleviate or exacerbate the effects of early conditions. The use of animal models might provide a useful complement to the human evidence, since external manipulation of the environment and controlled experimental conditions allow analyzing the long-term effects of early circumstances which occur because of biological embedding. However, most of the animal work is conducted in labs on species which are – both genetically and socially – quite different from humans. In path-breaking work conducted on an experiment in non-human primates, the DEVHEALTH team has shown that adverse early-life conditions (non-maternal rearing) in rhesus monkeys have long-term negative effects on both physical and mental health; that they are not ameliorated by a normal social environment later in life; and that they operate at least in part through stress-response pathways and changes in the expression of leukocyte genes related to immune function. These findings provide robust evidence that the environment can causally affect the biology of the body – and that at the same time intervention is possible at a biological level before diseases becomes manifest. It also provides sounds biological foundations for the overwhelming human evidence that lack of maternal care in the early years carry long-term health effects. Complementary to the innovative animal work, we have also pursued analysis of both existing and recently collected data on several early childhood interventions aimed at enriching the environment of disadvantaged children. Our results to date show not only that high-quality interventions are effective in producing consistent patterns of successful outcomes for treatment group members as compared to control group members for both boys and girls (in terms of higher levels of education and wages, lower crime and welfare dependence) – a fact remarked by the President of the United States Barack Obama in his 2013 and 2014 State of the Union Addresses. They have also contributed to our understanding of the mechanisms through which these impacts occur. Evidence from the Perry Preschool Program has revealed that the effects of the intervention on life outcomes has operated primarily through the reduction in child’s externalizing behavior. Before the work of the DEVHEALTH team, much less was known about the health effects of these interventions. The DEVHEALTH team has conducted important work which has significantly reduced this gap in knowledge. An extensive analysis of all the health information available in the Abecedarian and Perry interventions, since childhood, has uncovered statistically significant and economically important treatment effects which survive stringent econometric methods. The Perry participants show a significant reduction in unhealthy behaviors, in particular smoking; the Abecedarian participants (who attended a childcare center which also provided nutrition and pediatric care) had a leaner physical constitution in childhood. Additionally, unique biomarkers data collected for the first time in an early childhood intervention when the participants were aged 35 have revealed that the treated group was in better health also in middle adulthood: in particular, the treated males were less likely to have hypertension and dyslipidemia, and to be affected by the metabolic syndrome, as compared to the males in the control group. Finally, complementary evidence on prenatal home-visiting programs such as the Nurse-Family Partnership and Preparing for Life (which has also been designed by members of the team) reveals the health-improving potential of interventions able to reach at the same time both mothers and children, improving the fate of this generation, and guaranteeing the best to the future one. Overall the DEVHEALTH team work has showed the potential for early life interventions to constitute an unexplored avenue for health policy.
Second, the DEVHEALTH team has been at the forefront on the use of genetic data for social science research. Members of the team have been involved in a pathbreaking analysis that has identified the first three genetic variants associated with educational attainment and duration of schooling. Second, the use of genetic variants known to be associated with risk factors for disease to make causal inference has led to important findings in relation to maternal behaviors in pregnancy and child outcomes. One major finding related to the use of genetic variants associated with alcohol consumption has shown evidence that moderate alcohol consumption can reduce offspring IQ. Finally, the DEVHEALTH team has produced the first epigenome-wide scan of DNA methylation in human tissue, building on the unique resource of the ALSPAC data. These scans are currently being used to investigate how the epigenome correlates with human characteristics and environmental determinants of ill health and disease.