Neurobiological pathways from trauma exposure to child mental health outcomes in a high adversity South African Birth Cohort

在许多低收入和中等收入国家（LMIC）环境中长大的儿童遭受创伤的风险很高，例如家庭或社区暴力、儿童虐待或严重伤害。暴露在这样的逆境中已被确定为儿童心理障碍的主要因素。儿童创伤暴露的负面影响已被发现持续到成年，具有广泛的个人和社会后果。事实上，遭受童年创伤的个人在全世界社会中最脆弱的群体中所占的比例过高（例如，无家可归者）。尽管有确凿的证据表明创伤暴露会产生有害影响，但我们对这个问题的理解仍有一些关键的局限性。首先，大多数相关证据来自高收入国家，而不是中低收入国家，在中低收入国家，儿童创伤暴露更为普遍，许多儿童经历多重逆境。因此，我们对世界上大多数儿童所处的各种环境中所经历的童年创伤的影响了解有限。这反过来又破坏了在这种情况下进行有针对性的预防或干预的能力。其次，对早期创伤与负面心理健康结果之间联系的潜在机制的理解极其有限，特别是考虑到生物过程。我们对创伤是如何在儿童的大脑和身体中扎根的，以及这反过来又如何导致多种心理障碍的风险的理解尤其有限。我们计划通过利用和扩展一项关键的南非出生队列——德拉肯斯坦儿童健康研究（DCHS），来解决我们对创伤对儿童心理健康影响的理解的局限性。在南非，童年创伤是一个与心理健康有关的主要问题，特别是由于人际暴力程度高（包括社区暴力、亲密伴侣暴力和虐待儿童发生率高）。我们建议在这一队列中对儿童创伤的心理健康影响进行深入研究，这将解决我们理解中的局限性，并在对低收入和中等收入国家背景至关重要的领域实现知识的重大改变。儿童健康中心的特殊之处在于，它在生命的最初几年反复测量儿童的创伤暴露，并在多个时间点同时完成了儿童心理健康的生物学评估和测量。DCHS中儿童的高创伤暴露率意味着它提供了一个研究儿童创伤影响的机会，这是基于高收入国家背景的出生队列所没有的，在这些国家中，很少有儿童暴露于严重或复发性创伤。我们计划在8-9岁时随访DCHS队列中的儿童，这是许多常见心理障碍首次在儿童中表现出来的年龄。因为我们有暴露于创伤和随时间重复的生物过程的测量方法，我们将能够了解创伤如何影响与压力相关的生物系统，以及这些影响如何反过来导致儿童的心理障碍。我们将能够研究人体对压力反应的关键生物系统，免疫系统（越来越多地被认为与压力密切相关）和大脑发育。通过确定儿童从创伤到心理障碍的途径，这项工作可能会改变我们未来提供干预措施的方式。

Children growing up in many low and middle income country (LMIC) contexts are at high risk of exposure to trauma, such as domestic or community violence, child abuse, or severe injury. Exposure to such adversity has been identified as a major contributor to psychological disorders in children. The negative impacts of childhood trauma exposure have been found to persist into adulthood, with wide ranging individual and societal consequences. Indeed, individuals exposed to childhood trauma are disproportionately represented among the most vulnerable groups in societies worldwide (e.g., the homeless). Despite this robust evidence of the detrimental effects of trauma exposure, there are key limitations to our understanding of this problem. First, the majority of relevant evidence derives from high income countries, rather than from LMICs, where exposure to childhood trauma is substantially more common and many children experience multiple adversities. Consequently, we have limited knowledge of the impact of childhood trauma as experienced in the types of contexts in which the majority of the world's children live. This, in turn, undermines capacity for targeted prevention or intervention in such settings. Second, there is extremely limited understanding of the underlying mechanisms that link early trauma with negative mental health outcomes, particularly considering biological processes. Our understanding of how trauma becomes embedded in the brain and body in children, and how that, in turn, confers risk of multiple psychological disorders, is particularly limited. We plan to address limitations in our understanding of the mental health consequences of trauma in children through capitalizing on and extending a key South African birth cohort, the Drakenstein Child Health Study (DCHS). Childhood trauma is a major mental health related concern in South Africa, particularly due to high levels of interpersonal violence (including high rates of community violence, intimate partner violence and child maltreatment). We propose to conduct an in depth study of the mental health impacts of childhood trauma in this cohort, which will address limitations in our understanding and achieve a major change in knowledge in an area of key importance for LMIC contexts. The DCHS is exceptional in having repeatedly measured child trauma exposure during the first years of life, and having simultaneously completed biological assessments and measures of child mental health at multiple times points. High rates of trauma exposure among children in the DCHS mean that it provides an opportunity to study the impact of childhood trauma which is not afforded by birth cohorts based in high income country contexts, in which very few children are exposed to severe or recurrent trauma. We plan to follow-up children in the DCHS cohort at age 8-9 years, when many common psychological disorders manifest for the first time in children. Because we have measures of both exposure to trauma and biological processes which are repeated over time, we will be able to understand how trauma influences stress-related biological systems, and how those effects, in turn, may lead to psychological disorder in children. We will be able to study key biological systems involved in the body's response to stress, the immune system (which is increasingly being understood to be closely related to stress), and brain development. Through identifying pathways from trauma to psychological disorders in children, this work may change the way we provide interventions in the future.