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）和分裂情感障碍（SAD）是核心的严重精神疾病（SMIs），给个人、他们的照顾者和更广泛的社会带来了巨大的负担。在英国每年约1180亿英镑的精神疾病费用中，它们占了四分之一以上，与预期寿命缩短有关，这与医学上一些最严重的慢性疾病相似。然而，与其他医学领域不同，几十年来没有开发出真正新颖的治疗方法来治疗重度精神分裂症，因此自20世纪中叶以来，现实世界的结果和治愈率几乎没有变化。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、心理或社会原因对患者进行分类，也无法以任何方式了解他们为什么会出现这种情况，这阻碍了发现新的机械治疗方法。相反，我们依赖的是基于症状的诊断，而这些诊断与潜在的生理机能并不相符。与精确治疗之前的癌症治疗相比，这种方法是不利的，在精确治疗之前，非特异性的，适度有效的治疗，有严重的副作用，主要是根据组织起源而不是患者特异性的癌症分析来选择的。我一定有别的办法。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关系和机制信息诊断方法迈进，这将推动精神病学和改善这些疾病患者的生活。为了实现这一目标，我们创建了一个杰出的跨学科网络，由来自南威尔士（卡迪夫斯旺西）和英格兰西南部（巴斯，布里斯托尔，埃克塞特）的早期，中期和高级职业研究人员和有生活经验的人组成。利用我们世界领先的12,000多名BD-SAD-SZ患者队列，我们的SW2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展数据，用我们在先进表观遗传学方面的世界领先专业知识来询问这些因素的生物学相关性。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方法来改进我们对SZ-BD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地接触到黑暗基因组。数据的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，并且对于机器学习模型的更广泛应用至关重要。由SW2 Hub生成和整理的各种表型数据将向学术界公开提供，为国际研究人员开发新方法提供独特的数据资源，用于复制结果和组合数据集，以获得更强大的输出，从而为更好的诊断方法提供信息。这些工作计划将为该领域创造丰富的资源，支持培训和优秀研究的交付，作为UKRI心理健康研究平台的一个关键方面，但更重要的是，将为推进精神病学和改善一些最严重的精神疾病患者的生活提供一条途径。

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.