CHECKPOINT: Finding immune & metabolic pathways to SMI

怎么啦？CHECKPOINT将成为科学家和有生活经验的人（PWLE）公开透明地共同工作的国家和国际中心。我们将利用大数据和先进的计算分析提供的前所未有的机会，找到连接身心健康的因果途径。这将加速个性化治疗的发展，针对那些最有可能受益的严重精神疾病（SMI）患者的免疫和代谢原因。为什么？研究表明，越来越多的证据表明，重度精神障碍患者的免疫系统也会发生不寻常的变化，比如炎症，而且由于体内不寻常的脂肪和糖代谢，他们患代谢紊乱（比如肥胖）的风险也会增加。这些生理和心理健康之间的联系表明了一个新的机会来理解、治疗和预防重度精神分裂症，并在以科学为基础的精确精神病学方法上取得重大进展。现在最根本的挑战是发现免疫和代谢因素是如何导致重度精神分裂症的。如果我们能找到这些因果关系，从身体到大脑再到精神，我们就能开发出针对免疫或代谢系统的治疗重度精神分裂症的新药。我们可以使用血液测试、脑部扫描和其他生物标记来确定哪些患者将从个性化治疗中受益。我们可以更精确地建议患者调整哪些生活方式，比如改变饮食习惯或多运动，最有可能有益于他们的心理健康。CHECKPOINT将通过汇集具有跨学科科学专业知识的不同研究人员和基于英国和欧洲5个卓越中心的PWLE来解决这些关键挑战。该团队将以三种主要方式使用大量现有数据，这些数据来自重度精神分裂症的基因研究和其他来源。第一种方法称为目标三角测量。我们将使用基因分析来筛选免疫和代谢系统中大量的分子和细胞，这些分子和细胞可以作为治疗的目标。我们希望找到一小部分筛选的靶点在精神分裂症或一系列重度精神障碍等疾病中具有因果作用。通过初步筛选的靶点将优先进行更深入的遗传、临床和纵向随访数据分析，通过对因果关系的多个趋同证据线进行三角测量，找到SMI的前几个免疫或代谢靶点。第二种方式被称为生物标志物创新。我们将分析从精神病患者收集的血液免疫细胞，并开始使用抗精神病药物治疗。我们还将分析大脑核磁共振扫描，设计视频游戏来衡量年轻人的思维和行为。我们将确定哪些潜在的生物标志物可用于识别SMI患者最有可能对针对免疫或代谢系统的治疗有反应。第三种方法被称为治疗性个性化。我们将发现哪些新药或已经获得许可的药物最有可能有效治疗SMI的免疫或代谢原因。科学家和PWLE还将共同制定两个项目：(i)开发更好的工具，用于预测与精神健康同时发生的不利身体健康，特别是由于抗精神病药物治疗；（ii）从健康数据和对患者的访谈中建立证据，证明哪种生活方式干预措施对重度精神分裂症患者最有可能有效和可及。

What? CHECKPOINT will be a national and international hub of scientists and people with lived experience (PWLE) working openly and transparently together. We will unlock the unprecedented opportunity provided by big data and advanced computational analysis to find causal pathways that connect physical and mental health. This will accelerate development of personalised treatments that work by targeting the immune and metabolic causes of severe mental illness (SMI) in those patients most likely to benefit.Why? There is growing evidence through research that people with SMI can also have unusual changes in their immune system, like inflammation, and have increased risk of metabolic disorders, like obesity, due to unusual fat and sugar metabolism in the body. These links between physical and mental health indicate a new opportunity to understand, treat and prevent SMI and make significant advances on a science-based approach for precision psychiatry. The fundamental challenge now is to discover how immune and metabolic factors can actually cause SMI. If we can find these causal links, from the body through the brain to the mind, we can develop new drug treatments for SMI that work by targeting the immune or metabolic systems. We can use blood tests, brain scans and other biomarkers to identify which patients will benefit from personalised treatment. We can advise patients more precisely about which lifestyle adjustments, such as eating a different diet or being more active, are most likely to be beneficial for their mental health.How? CHECKPOINT will address these key challenges by bringing together a diverse group of investigators with inter-disciplinary scientific expertise, and PWLE, based at 5 centres of excellence in the UK and Europe. The team will use large amounts of existing data, from genetic studies of SMI and other sources, in three main ways.The first way is called target triangulation. We will use genetic analysis to screen a large number of molecules and cells in the immune and metabolic systems that could be targeted for treatment. We expect to find a small proportion of screened targets will have a causal role in disorders like schizophrenia, or across a range of SMI disorders. Targets that pass preliminary screening will be prioritized for deeper analysis of genetic, clinical and longitudinal follow-up data, to find the top few immune or metabolic targets for SMI by triangulating multiple convergent lines of evidence for causality.The second way is called biomarker innovation. We will analyse blood immune cells collected from patients with psychosis and starting treatment with anti-psychotic drugs. We will also analyse brain MRI scans, and design video games to measure thinking and behaviour in young people. We will identify which of these potential biomarkers could be used to identify the patients with SMI most likely to respond to treatments targeting the immune or metabolic systems.The third way is called therapeutic personalisation. We will find which new drugs or already-licensed medications are most likely to be effective in treating the immune or metabolic causes of SMI. Scientists and PWLE will also co-produce two projects: (i) to develop better tools for predicting adverse physical health co-occurring with mental health, especially due to anti-psychotic drug treatment; and (ii) to build evidence from health data and interviews with patients about which lifestyle interventions are most likely to be effective and accessible for people with SMI.