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

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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.