The South Wales and South West England Mental Health Platform Hub

挑战：精神分裂症（SZ），双相情感障碍（BD）和情感障碍（SAD）是核心的严重精神疾病（SMI），给个人，他们的照顾者和更广泛的社会带来了巨大的负担。它们占英国每年约1180亿英镑精神疾病费用的四分之一以上，并与预期寿命的减少有关，类似于医学上一些最严重的慢性疾病。然而，与其他医学领域不同的是，几十年来没有为SMI开发出真正新颖的治疗方法，因此自世纪中期以来，真实世界的结局和恢复率几乎没有变化。这种停滞的根本原因是缺乏对因果关系的理解。因此，我们无法根据其症状的生物学，心理学或社会原因对患者进行分类，或者以任何方式告知他们为什么会发展出阻碍发现新的机械性知情治疗的疾病。相反，我们依赖于基于神经网络的诊断，这些诊断显示出与潜在生理学的对应性很差。与精确治疗之前的癌症治疗相比，这种方法是不利的，在精确治疗中，主要基于组织来源而不是患者特异性癌症特征来选择具有严重副作用的非特异性、适度有效的治疗。我们的愿景是，通过将在多个领域（如临床、认知、发育、免疫和代谢、基因组和脑成像）大规模获得的丰富表型数据与复杂的分析相结合，我们将能够朝着一种新的因果和机制上知情的诊断方法迈进，这将推动精神病学的发展，改善这些疾病患者的生活。为了实现这一目标，我们已经创建了一个优秀的跨学科网络的早期，中期和高级职业生涯的研究人员和人从南威尔士（卡迪夫斯旺西）和西南英格兰（巴斯，布里斯托，埃克塞特）的生活经验。基于我们世界领先的12，000多名BD-SAD-SZ患者队列，我们的SW 2中心将建立一个前所未有的600名代表性参与者的详细队列。我们还将访问威尔士SAIL数据库，以整合丰富的环境和发育数据，并利用我们在先进的表观遗传学方面的世界领先的专业知识来询问这些因素的生物相关性。利用我们在机器学习和大数据分析方面的专业知识，我们将应用先进的分析来改善我们在SZ-BD范围内对患者进行分组的方式。在尖端基因组学应用的支持下，我们将首次在严重精神疾病中大规模访问黑暗基因组。数据共享和复制队列的可用性对于精神病学遗传学的成功至关重要，对于机器学习模型的更广泛应用也至关重要。由SW 2 Hub生成和管理的各种表型数据将向学术界开放，为国际研究人员提供具有特殊价值的独特数据资源，以开发新方法，复制结果并结合数据集，以获得更强大的输出，从而为人们提供更好的诊断方法。这些工作计划将为该领域创造丰富的资源，以支持培训和提供优秀的研究，作为UKRI心理健康研究平台的一个关键方面，但更重要的是，将提供一条推进精神病学和改善生活的途径。

The Challenge: Schizophrenia (SZ), bipolar disorder (BD), and schizoaffective disorder (SAD) are core severe mental illnesses (SMIs) and place an enormous burden on individuals, their carers and wider society. They account for more than a quarter of the ~£118Bn annual UK costs of mental illness and are associated with a reduction in life expectancy similar to some of the most serious chronic illnesses in medicine. Yet, unlike other areas of medicine, no truly novel treatments have been developed for SMIs in decades and consequently real-world outcomes and recovery rates are little changed since the mid-twentieth century. The fundamental cause for this stasis is a lack of causal understanding. Consequently, we are unable to classify patients according to the biological, psychological or social causes of their symptoms, or in any way that is informed by why they have developed their condition which hampers the discovery of new mechanistically informed treatments. Instead, we rely on symptom-based diagnoses that show poor correspondence to underlying physiology. This approach has been unfavourably compared to cancer treatment prior to precision treatments where non-specific, modestly effective treatments, with severe side effects, were selected based largely on the tissue origin rather than patient-specific cancer profiling. There must me another way.Our vision is that by combining rich phenotypic data acquired at scale across multiple domains (e.g. clinical, cognitive, developmental, immune and metabolic, genomic and brain imaging) with sophisticated analysis, we will be able to move towards a new causally and mechanistically informed diagnostic approach for SMIs that will advance psychiatry and improve the lives of people with these disorders. To achieve this, we have created an outstanding interdisciplinary network of early-, mid- and senior-career researchers and people with lived experience from South Wales (Cardiff Swansea) and South-West England (Bath, Bristol, Exeter). Drawing on our world-leading cohorts of more than 12,000 patients with BD-SAD-SZ our SW2 hub will build an unprecedentedly detailed cohort of 600 representative participants. We will also access the Welsh SAIL Databank to incorporate rich environmental and developmental data, interrogate the biological correlates of these factors with our world-leading expertise in advanced epigenetic. Drawing on our expertise in machine-learning and big data analysis, we will then apply advanced analyses improve how we group patients across the SZ-BD spectrum. Underpinned by the application of cutting-edge genomics we will access the dark genome for the first time at scale in severe mental illness. Sharing of data and availability of replication cohorts has been critical to the success of psychiatric genetics and will be essential to the wider application of machine-learning models. The diverse range of phenotypic data generated and curated by the SW2 Hub will be made openly available to the academic community providing a unique data resource of exceptional value to international researchers to develop new methods, for replication of results and combining of datasets for more powerful outputs that will inform better ways of diagnosing people. These programs of work will create a rich resource for the field that will support training and the delivery of excellent research as a key facet of the UKRI Mental Health Research Platform but more importantly will offer a route to advancing psychiatry and improving the lives of people with some of our most serious mental illnesses.