Adverse life events, inflammation, and trajectories of emotional and behavioural problems in childhood

Lead Research Organisation: University College London
Department Name: Psychology and Human Development

Abstract

Much research has linked adverse life events to the aetiology and maintenance of emotional and behavioural problems in children. These stressors can initiate biological processes that increase risk for both types of problems in children but no study has yet examined inflammation as the stressor-induced biological process that can increase this risk. Inflammation is typically thought of as the body's primary response to physical injury or infection. However, there is now substantial evidence that stressors can also trigger significant increases in inflammatory activity which may account for how external stressors 'get under the skin'. Increases in inflammation can in turn elicit profound changes in behaviour, which include the initiation of symptoms such as sad mood, anhedonia, fatigue and social and behavioural withdrawal. This project will examine, for the first time, the role of stressor-induced inflammation in childhood in the aetiology and maintenance of emotional and behavioural problems from childhood to adolescence. This is the main aim of this project, which we will meet using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK study of more than 14,000 pregnant women in 1991-2, the children arising from the pregnancy, and their partners. Adverse life events will be measured at both the prenatal and the childhood period, in view of the evidence that prenatal and childhood adversity can affect children through different mechanisms. We will also explore the complex ways in which events may interact to predict child outcomes, investigate the importance of distinguishing events by type (e.g., dependent vs independent; chronic vs episodic), and examine the role of their perceived impact. Emotional and behavioural problems will be measured with the Strengths and Difficulties Questionnaire (SDQ) at ages around 4, 7, 8, 9, 12, 13 and 16 years. In ALSPAC, inflammation in childhood was measured at age around 9 years with levels of interleukin 6 and C-reactive protein.

Our analyses will consider two important issues. First, that inflammation can be caused by a number of factors. Therefore, we will control for a diverse range of health-risk behaviours (e.g., poor diet, lack of exercise, sleep disturbance), environmental challenges (e.g., low socio-economic status) and perinatal complications, as all these can also activate inflammation, and we will exclude a small number of children with an infection at the time inflammation was measured. Second, that causal associations between inflammation, stressors and emotional/behavioural problems may be complex. For example, inflammation in children has been implicated as both the outcome of stressors and the outcome of emotional or behavioural problems. Thus we will also explore:
i. the role of adverse life events in inflammation. For this part of the project, we will focus on adverse life events preceding the measurement of inflammation (that is, events that occurred at the prenatal period and at ages around 0-9 years), and
ii. the role of emotional/behavioural problems in inflammation. For this, we will focus on emotional/behavioural problems preceding the measurement of inflammation (that is, at ages around 4-9 years).

There is another, related, objective: to examine the reciprocal nature of the influences between adverse life events and emotional/behavioural problems. Adverse life events can be the cause but also the outcome of such problems. We will be able to examine the direction of this association using a subset of adverse life events, namely those that were measured repeatedly and at the time emotional/behavioural problems were assessed. This will enable us to test two competing hypotheses of the role of inflammation in the longitudinal link between adverse life events and emotional/behavioural problems in childhood. That is, that a) problems cause inflammation, leading to life events, or b) life events cause inflammation, leading to problems.

Planned Impact

Our project findings will be of interest and, we hope, use to a number of groups. The first group are those making decisions about preventive and early treatment interventions. If our main hypothesis that early (including prenatal) stressors can lead to inflammation in children in turn leading to emotional difficulties or behaviour problems is supported, then we will have shown what reduction in type and number of early stressors can benefit children, and what reduction in inflammation can benefit children at risk. But even if it is not, our research will have shown to what extent early adversity and emotional/behavioural problems can predict inflammation, a precursor of several medical conditions. From a practice perspective, our project findings may suggest that it can be valuable for researchers to incorporate assessments of inflammation into prevention-oriented intervention studies for high-risk children (such as those whose mothers were exposed to high levels of psychosocial stress in pregnancy or those exposed to adversity themselves). This will provide insight into whether it is possible to reverse or minimise dysregulated inflammatory processes. In the future, practitioners may be able to utilise biomarkers of inflammation to identify children at high risk for long-term health problems, or to evaluate the effectiveness of social interventions to prevent future chronic disease risk among high-risk children. Given the effects of psychosocial stressors on inflammation, improvements in social environments are likely to be beneficial. Emerging data indicate that exercise, weight loss, yoga and meditation may have anti-inflammatory effects, and these approaches may be particularly appropriate components of social interventions for children exposed to adversity. If our findings show that emotional or behavioural problems cause inflammation, then we would suggest that efforts to prevent or treat emotional and behavioural problems in childhood could help prevent disease risk.

A second group to whom results will be addressed are the general public, especially parents and expectant parents. Academic researchers are a third category of users, including those with a substantive interest in child emotional and behavioural development, those interested in stressor 'effects' and those interested in advanced longitudinal modelling. Finally, we hope to inform those commissioning research in child development, who, to a large extent, continue to underestimate or neglect the interaction between the body and the mind. Our project will show if compartmentalising the domains of child functioning (into the physical and the mental, for example) in training, funding, research and social services programmes may be contraindicated.

To reach these groups, we will organise a 1-day seminar, publish accessible research briefings and press release project findings, and engage with the social media (see also Pathways to Impact). The press releases on project findings attract significant media and government interest. The research briefings will include papers for magazines (such as the Psychologist) and reports that will be available on the UCL website to download at no cost, will be targeted not only at academics but also at policy makers and the public, and will summarise research findings in non-technical language.
 
Description We still have four papers under review.

Our main findings are as follows.

1. The association between adverse life events and children's emotional problems is bidirectional but inflammation (IL6) mediates the effect of events on emotional problems, not the reverse. This is in line with our hypotheses.

2. In the general child population, increasing adversity in childhood is associated with the early onset of depressive symptoms, partly via increasing levels of plasma IL-6.

3. Independently of prenatal adversity, the number and increase in number of adverse life events experienced in childhood are associated positively with plasma levels of inflammatory markers, such as IL-6, in girls. This gender specificity warrants further research.

4. Increases in emotional and social difficulties lead to elevated CRP in healthy children. This association suggests that successful interventions targeting children experiencing chronic emotional and social difficulties could also have physical health benefits. Elevated CRP has been found to be associated with early functional and structural atherosclerotic vascular changes in children, independently of conventional risk markers. To the extent that the level of CRP may ultimately represent an important therapeutic target, these findings suggest that successful interventions to prevent or reduce chronic emotional and social difficulties in childhood could have health benefits in childhood and beyond.
Exploitation Route If the association we are seeing is causal, ie stress causes child ill mental health at least partially by inflammation, then this identifies targets for prevention and treatment.
Sectors Communities and Social Services/Policy,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description British Academy Small Grants Scheme
Amount £10,000 (GBP)
Organisation The British Academy 
Department British Academy/Leverhulme Trust Senior Research Fellowships
Sector Charity/Non Profit
Country United Kingdom
Start 01/2018 
End 12/2019
 
Description Socioeconomic differences in child cognitive outcomes:The role of inflammation
Amount £71,000 (GBP)
Funding ID 1992039 
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 09/2017 
End 09/2020
 
Description ALSPAC papers - external collaborators 1. Oxford 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a collaboration with Oxford's psychiatry department (Minichino) which resulted in a paper (under review) linked to the grant (also using ALSPAC), on internalising and psychotic symptoms.
Collaborator Contribution Intellectual leadership and steer. The PDRA on our grant (Francesconi) is the first author.
Impact Paper is under review.
Start Year 2018
 
Description ALSPAC papers - external collaborators 2. Cambridge 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a collaboration with Cambridge's dept of psychiatry (Khandaker), also using ALSPAC, and linked to our project. The result of this collaboration is a paper, under review, which examines the association between inflammation and psychotic symptoms, building on Khandaker's and our own work on inflammation in the ALSPAC dataset.
Collaborator Contribution Intellectual leadership and steer. I am the senior (last author)
Impact paper is under review
Start Year 2018
 
Description ALSPAC papers - external collaborators 3. UCL 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a collaboration with UCL's department of psychiatry (Solmi), again using ALSPAC, which extends some of our grant findings. The result of this is a paper (under review) and capacity building for Solmi, the early career person who is the first author.
Collaborator Contribution Mentoring and steer. I also lead on cognition.
Impact Paper is under review.
Start Year 2018
 
Description Inflammation SNPs - the Young Finns study 
Organisation University of Helsinki
Country Finland 
Sector Academic/University 
PI Contribution This is a collaboration with LSHTM (Heikkila and Clemens) and the University of Helsinki (Elovainio) and extends some of our grant's findings, using the young finns study. The paper is being prepared and the first author is a masters student (Clemens), working under our guidance.
Collaborator Contribution The idea for the project was given by Flouri. Heikkila led on the data access and the day to day management of the work, and Elovainio facilitated data access
Impact Paper is being prepared.
Start Year 2018
 
Description Scientific advisory network for CLS cohorts 
Organisation University College London
Department Centre for Longitudinal Studies
Country United Kingdom 
Sector Academic/University 
PI Contribution I have been invited to join a new scientific advisory network to support the development of the CLS cohorts. I have joined a small and focussed group on the theme of 'Mental health across the life course'. The overall purpose of the network is as a resource for strategic advice and support for the development of the CLS cohorts.
Collaborator Contribution CLS runs most of the UK cohort studies. This will be a platform for discussions of the development of the cohorts. They will also call on my advice, on an ad hoc basis, for example to support the design of a new study sweep for one of their studies, or when they are developing strategic funding bids. As well as providing strategic advice and support to the cohorts, this will be a forum for developing new ideas, and collaborations.
Impact No outcomes yet. Yes, it will be multidisciplinary. The cohorts are of scientific interest to all the social sciences and most of the medical ones, too.
Start Year 2019