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

许多研究已经将不良生活事件与儿童情绪和行为问题的病因和维持联系起来。这些应激源可以启动生物过程，增加儿童这两种类型问题的风险，但尚未有研究证明炎症是应激源诱导的生物过程，可能会增加这种风险。炎症通常被认为是身体对身体伤害或感染的主要反应。然而，现在有大量证据表明，应激源也会引发炎症活动的显著增加，这可能解释了外部应激源是如何“深入皮肤”的。炎症的增加反过来会导致行为的深刻变化，包括开始出现悲伤情绪、快感缺失、疲劳以及社交和行为退缩等症状。该项目将首次研究应激源诱导的儿童期炎症在儿童至青春期的情绪和行为问题的病因学和维持中的作用。这就是这个项目的主要目的，我们将使用雅芳父母和儿童纵向研究(ALSPAC)的数据来实现这一目标，该研究是英国的一项研究，在1991-2年间对14,000多名孕妇、因怀孕而产生的孩子及其伴侣进行了研究。鉴于有证据表明，产前和儿童期的逆境可以通过不同的机制影响儿童，将在产前和儿童期对不良生活事件进行衡量。我们还将探索事件相互作用以预测儿童结果的复杂方式，调查按类型区分事件的重要性(例如，依赖与独立；慢性与间歇性)，并检查其感知影响的作用。情绪和行为问题将在4岁、7岁、8岁、9岁、12岁、13岁和16岁左右用强项和困难问卷(SDQ)进行测量。在ALSPAC中，儿童的炎症在9岁左右被用白细胞介素6和C反应蛋白水平来测量。我们的分析将考虑两个重要的问题。首先，炎症可以由多种因素引起。因此，我们将控制各种健康危险行为(例如，不良饮食、缺乏锻炼、睡眠障碍)、环境挑战(例如，低社会经济地位)和围产期并发症，因为所有这些也会引发炎症，我们将排除少数在测量炎症时有感染的儿童。其次，炎症、压力源和情绪/行为问题之间的因果关系可能很复杂。例如，儿童的炎症被认为既是压力源的结果，也是情绪或行为问题的结果。因此，我们还将探讨：1.不良生活事件在炎症中的作用。在项目的这一部分，我们将重点关注炎症测量之前的不良生活事件(即发生在产前和0-9岁左右的事件)，以及II。情绪/行为问题在炎症中的作用。为此，我们将把重点放在炎症测量之前的情绪/行为问题上(即在4-9岁左右)。还有另一个相关的目标：考察不良生活事件和情绪/行为问题之间相互影响的性质。不利的生活事件可能是这些问题的起因，也可能是结果。我们将能够使用不良生活事件的子集来检验这种联系的方向，即在评估情绪/行为问题时重复测量的那些事件。这将使我们能够测试两个相互竞争的假设，即炎症在不良生活事件和童年情感/行为问题之间的纵向联系中所起的作用。也就是说，a)问题引起炎症，导致生活事件，或者b)生活事件引起炎症，导致问题。

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.