Investigating the Mechanisms underlying Psychosis Associated with Childhood Trauma (IMPACT

精神病是一种潜在的严重疾病，涉及恐惧感、听力和对现实的感知改变。在英国，精神病占成人心理健康和社会护理服务总支出的30%，并因生产力丧失而造成巨大的经济成本。精神病的潜在神经原因尚不清楚。越来越多的证据表明，童年时期的心理创伤经历会增加成年后患精神病的风险，约占病例的三分之一。这些心理创伤经历包括身体、性和情感虐待和忽视。由于这些经历可以改变大脑和心理发育，它们可以被称为发育创伤。然而，我们目前并不确切地了解童年创伤如何改变大脑的工作方式，从而导致成年人精神错乱。到目前为止，研究表明，发育创伤会影响涉及特定功能的大脑区域，包括大脑如何处理情绪，如感受到威胁和记忆。这些大脑功能在精神病患者中也受到影响，这表明发育创伤可能通过改变大脑功能的这些方面而导致精神病。同时，还有一种关于大脑如何工作的解释，叫做“分层预测编码”。分层预测编码是一种理解大脑如何对外部世界做出预测的方法。越来越多的证据表明，精神病患者做出预测的方式会导致他们曲解现实，这可能与精神病症状有关。重要的是，分层预测编码涉及大脑如何处理威胁，记忆对于分层预测编码也是必不可少的。也有证据表明，经历过发育创伤的人的大脑中参与分层预测编码的部分发生了变化。因此，这项研究将调查大脑处理威胁、记忆和分层预测编码的方式的变化是否会导致发育创伤增加成年人患精神病的风险。这项研究将通过三种方式来实现这一点。这项研究的第一部分将涉及使用问卷、基于计算机的心理学任务、临床评估和一种名为功能磁共振成像(FMRI)的大脑扫描。这项研究将在六组人中进行：有或没有发展性创伤的健康人，有或没有发展性创伤的亚临床精神病症状的人，以及有或没有经历过发展性创伤的精神病患者。这项研究的第二部分将涉及作为雅芳父母和孩子纵向研究(ALSPAC)研究的一部分收集的数据，该研究对1万多人进行了研究。这部分研究将涉及ALSPAC研究中大脑结构和功能的测量，该研究包含不同时间点的发育创伤和大脑功能测量。这项研究的第三部分将涉及与临床前研究人员合作，首先在人类身上进行翻译研究。临床前数据已经确定，在脆弱的青春期前经历的创伤将扰乱电路功能，导致与精神病一致的损害，并损害个体成年后处理应激源的方式。这项研究有可能改善目前对童年创伤如何影响大脑处理信息的方式，进而导致成年人精神病的潜在机制的理解。这将有助于开发有针对性的治疗方法，包括药物和谈话疗法，以降低暴露在创伤后的精神病风险，并改善对经历过创伤的精神病患者的治疗。

Psychosis is a potentially severe illness involving feelings of fear, hearing voices, and having an altered perception of reality. In the UK, psychosis contributes to 30% of the total expenditure on adult mental health and social care services and is responsible for substantial economic costs from lost productivity. The underlying neural cause of psychosis is unknown. There is growing evidence that psychologically traumatic experiences in childhood increase the risk for psychosis later in adult life, contributing to around a third of cases. These psychologically traumatic experiences include physical, sexual and emotional abuse and neglect. Since these experiences can alter brain and psychological development, they can be called developmental traumas. However, we currently do not understand precisely how childhood trauma can change how the brain works in order to cause psychosis in adults. To date, studies have shown that developmental trauma can affect brain regions involved in specific functions, including how the brain processes emotions, like feeling threatened, and memories. These brain functions are also affected in individuals with psychosis, suggesting that developmental trauma may contribute to causing psychosis by altering these aspects of brain function. At the same time, there is an explanation for how the brain works called "Hierarchical Predictive Coding". Hierarchical predictive coding is a way of understanding how the brain can make predictions about the outside world. There is growing evidence that people with psychosis make predictions in such a way as to lead them to misinterpreting reality which may be linked to symptoms of psychosis. Importantly, hierarchical predictive coding is involved in how the brain processes threats, and also memory is essential for hierarchical predictive coding. There is also evidence that people who have experienced developmental trauma have changes in parts of the brain involved in hierarchical predictive coding. This study will therefore investigate whether changes in the way the brain processes threat, memory and hierarchical predictive coding, underlie how developmental trauma increases the risk of psychosis in adults.This study will do this in three ways. The first component of the study will involve the use of questionnaires, computer-based psychological tasks, clinical assessments and a type of brain scan called functional magnetic resonance imaging (fMRI). This research will take place in six groups of people: healthy individuals with or without developmental trauma, individuals with subclinical psychosis symptoms with or without developmental trauma, and patients with psychosis who have or who have not experienced developmental trauma. The second part of the study will involve data that has already been collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) study of over 10,000 people. This part of the study will involve looking at measures of brain structure and function in the ALSPAC study, which has measures of developmental trauma and brain function taken across different time points. The third part of the study will involve working in collaboration with preclinical researchers to conduct translational research initially in humans. Preclinical data has identified that trauma experienced during the vulnerable prepubertal period will disrupt circuit functioning in a way that leads to damage consistent with psychosis, as well as impairing how the individual deals with stressors as an adult.The study has the potential to improve current understanding of the mechanisms underlying how trauma in childhood can affect the way the brain processes information and in turn cause psychosis in adults. This will assist in the development of targeted treatments, including medicines and talking therapies, to reduce the risk of psychosis following trauma exposure and improve treatments for people with psychosis who have experienced trauma.