THE IMPACT OF EARLY ADVERSITY ON TRAJECTORIES OF BRAIN MATURATION AND MENTAL HEALTH IN YOUNG ADOLESCENTS

这项拟议的研究是关于什么的？精神障碍，如抑郁症、精神分裂症、躁郁症和焦虑症，影响着世界各地数百万人。它们会扰乱思维、情绪和行为，并会对日常生活造成毁灭性的影响。它们通常在年轻时发作，了解我们在一个人生命的早期仍然能够干预和改变发展这些障碍的风险，这是非常重要的。例如，那些经历过创伤和逆境的人，以及那些生活在贫困社会条件下的人，风险更高。然而，我们不知道那些遭遇逆境的青少年的大脑发育是否有所不同，以及这是否解释了为什么他们更有可能经历某些类型的心理健康问题。此外，我们不知道在非常支持的家庭环境中长大或拥有较高的一般智力等因素是否可以保护一些青少年免受早期逆境的影响，防止大脑发育不同，并在以后出现精神症状。我们对这一领域已知多少？我们知道，经历过创伤和精神健康问题的人，大脑结构会发生变化。例如，涉及记忆的区域(额叶、海马体)体积较小。然而，我们不知道这些变化是从什么时候开始的，或者它们是否在整个青春期都保持不变。此外，我们不知道它们是否特别发生在那些身体对压力的反应活跃的青少年中。事实上，压力系统的激活会触发免疫系统的反应，免疫系统是专门用来对抗我们体内感染的系统。这种情况也见于抑郁症和精神分裂症患者，他们的身体表现得就像是在与感染剂作斗争，尽管他们没有持续的感染。因此，社会逆境和这种免疫反应可能会与大脑的潜在脆弱性相互作用，导致大脑在青春期的发育方式不同，并使人更有可能经历某些心理健康问题，如抑郁症或精神病。不幸的是，整个青春期的大脑发育，以及它与环境和免疫系统的关系，在一般社区的青少年中从未被研究过。这就是我们在这项研究中计划做的事情。这项研究将涉及哪些方面？我们建议评估和跟踪440名在校青少年(年龄11-14岁)，他们有和没有经历过逆境，他们已经参与了其他关于心理健康不良风险因素的研究。这些研究正在英国和其他六个欧洲国家进行。我们将在几年内对这些青少年进行三次评估。每一次，我们都会评估大脑结构和免疫反应。我们将使用一种名为“磁共振”的方法，这种方法允许我们在不使用辐射的情况下观察大脑结构，并观察大脑如何随着时间的推移而变化。我们将测量血液样本中的免疫反应。这项研究有一个很大的优势，那就是在这两项研究中，超过一半的青少年已经接受了这些测量，我们只需访问现有的评估。这项研究将如何帮助有心理健康问题的人？我们相信，这项研究可以帮助我们了解青少年最容易出现心理健康问题的时间是什么时候，何时干预(谈话治疗或药物)可以降低不良心理健康结果的风险。

WHAT IS THE PROPOSED STUDY ABOUT?Psychiatric disorders, like depression, schizophrenia, bipolar disorder, and anxiety affect millions of people around the world. They disturb thinking, mood, and behaviour, and can interfere with daily life with devastating effects. They usually strike at a young age and it is very important to understand how early in the life of an individual we are still able to intervene and modify the risk of developing these disorders. For example, the risk is higher in those who have experienced trauma and adversity, and in those living in deprived social conditions. However, we do not know if the brain develops differently in those adolescents with adversity, and whether this explains why they are more likely to experience certain types of mental health problems. Furthermore, we do not know whether factors such as growing up in a very supportive family environment, or having higher general intelligence, may protect some adolescents from the effects of early adversity, preventing the brain from developing differently and from experiencing psychiatric symptoms later on. WHAT IS ALREADY KNOWN ABOUT THIS AREA?We know that individuals who have suffered traumatic experiences, and those with mental health problems, show alterations in the structure of the brain. For example, regions involved in memory (frontal lobe, hippocampus) are smaller in volumes. However, we do not know when these alterations start, or whether they stay the same throughout adolescence. Also, we do not know whether they particularly occur in those adolescents that have an activation of the body's response to stress. In fact, the activation of the stress system triggers a response in the "immune system", the system dedicated to fight infections in our body. This is a situation also seen in patients with depression and schizophrenia, whose bodies behave as if they were fighting an infective agent, even though they do not have an ongoing infection. Therefore, it is possible that social adversity and this immune response interact with an underlying vulnerability in the brain, causing the brain to develop differently across adolescence, and making the person more likely to experience certain mental health problems, such as depression or psychosis. Unfortunately, the development of the brain throughout the full adolescence, and its relationship with the environment, and the immune system, in adolescents from the general community has never been studied. This is what we are planning to do in this study.WHAT WILL THE STUDY INVOLVE? We propose to evaluate and follow up 440 school adolescents (age 11-14 years), with and without an experience of adversity, who are already participating in other studies on risk factors for poor mental health. These studies are being conducted in the UK and in six other European countries. We will evaluate these adolescents three times, over a few years. Each time, we will assess brain structure and immune response. We will use an approach called "magnetic resonance", which allows us to look at the brain structure without using radiations, and to look at how brain changes over time. We will measure immune response in a blood sample. This study has the big advantage that more than half of these adolescents have already been evaluated with these measures in the two studies, and we will simply access the existing assessments.HOW WILL THE STUDY HELP PEOPLE WITH MENTAL HEALTH PROBLEMS?We are confident that this study can help us understand what are the times when adolescents are most vulnerable to mental health problems, when interventions (talking therapy or medications) can reduce risk of adverse mental health outcomes.