The South Wales and South West England Mental Health Platform Hub

南威尔士和英格兰西南部心理健康平台中心

• 批准号: MR/Z503745/1
• 负责人: James Walters
• 金额: $ 471.84万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FZ503745%2F1
• 关键词: South; Wales; West; England; Mental

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.

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巨大负担，占其中的四分之一以上。英国每年因精神疾病造成的费用约为 1180 亿英镑，并且与预期寿命的缩短有关，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，尚未开发出真正新颖的治疗方法。对于 SMI 来说，自二十世纪中叶以来，现实世界的结果和康复率几乎没有变化，造成这种停滞的根本原因是缺乏对因果关系的了解，我们无法根据生物学、心理对患者进行分类。或他们症状的社会原因，或者以任何方式了解他们为什么会出现这种情况，这阻碍了新的机械治疗方法的发现。相反，我们依赖于与潜在生理学表现出不良对应性的基于症状的诊断。已经与精准治疗之前的癌症治疗相比，这是不利的，在精确治疗之前，主要根据组织起源而不是患者特异性癌症分析来选择非特异性、不太有效的治疗方法，并且具有严重的副作用。我们必须采取另一种方法。将跨多个领域（例如临床、认知、发育、免疫和代谢、基因组和脑成像）大规模获取的丰富表型数据与复杂的分析相结合，我们将能够为 SMI 开发一种新的因果和机制诊断方法，将推进精神病学并改善患有这些疾病的人的生活。为了实现这一目标，我们创建了一个由来自南威尔士（卡迪夫斯旺西）和南威尔士的早期、中期和高级职业研究人员以及具有生活经验的人员组成的杰出跨学科网络。西英格兰（巴斯、布里斯托尔、埃克塞特）我们的 SW2 中心将利用由 12,000 多名 BD-SAD-SZ 患者组成的世界领先队列，建立一个由 600 名代表组成的前所未有的详细队列。我们还将访问威尔士 SAIL 数据库，整合丰富的环境和发展数据，利用我们在机器学习和大数据分析方面的世界领先的专业知识来探究这些因素的生物学相关性。然后应用先进的分析来改进我们对 SZ-BD 谱系患者的分组方式。在尖端基因组学应用的支持下，我们将首次大规模地共享严重精神疾病的数据和复制队列。对成功至关重要SW2 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。开发新方法，复制结果并组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，支持培训和提供优秀的研究。 UKRI 的关键方面更重要的是，心理健康研究平台将为推进精神病学和改善患有一些最严重精神疾病的人们的生活提供一条途径。