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

拟议的研究是关于什么的？精神疾病，如抑郁症、精神分裂症、双相情感障碍和焦虑症，影响着世界各地数百万人。它们扰乱思维、情绪和行为，并可能干扰日常生活，造成破坏性影响。它们通常在年轻时发作，了解在个体生命的早期我们仍然能够干预和改变发展这些疾病的风险是非常重要的。例如，经历过创伤和逆境的人以及生活在贫困社会条件下的人的风险更高。然而，我们不知道那些处于逆境的青少年的大脑发育是否不同，这是否解释了为什么他们更容易经历某些类型的心理健康问题。此外，我们也不知道在一个非常支持的家庭环境中成长，或者拥有更高的一般智力，是否可以保护一些青少年免受早期逆境的影响，防止大脑以不同的方式发育，防止以后出现精神症状。我们知道，遭受创伤经历的人，以及那些有心理健康问题的人，大脑结构会发生变化。例如，与记忆有关的区域（额叶、海马体）体积较小。然而，我们不知道这些变化何时开始，或者它们是否在整个青春期保持不变。此外，我们不知道它们是否特别发生在那些对压力有身体反应的青少年身上。事实上，压力系统的激活会触发“免疫系统”的反应，该系统致力于对抗我们体内的感染。抑郁症和精神分裂症患者也会出现这种情况，他们的身体表现得好像在与感染因子作斗争，即使他们没有持续的感染。因此，有可能社会逆境和这种免疫反应与大脑中潜在的脆弱性相互作用，导致大脑在青春期的发育不同，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。这项研究将涉及什么？我们建议评估和随访440名在校青少年（年龄11-14岁），有或没有逆境的经验，谁已经参加了其他研究的风险因素，心理健康状况不佳。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，我们都将评估大脑结构和免疫反应。我们将使用一种称为“磁共振”的方法，它允许我们在不使用辐射的情况下观察大脑结构，并观察大脑如何随时间变化。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，即超过一半的青少年已经在两项研究中进行了这些评估，我们将简单地访问现有的评估。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受到心理健康问题影响的时间，当干预措施（谈话治疗或药物）可以降低不良心理健康结果的风险时。

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.