MRC Centre for Neuropsychiatric Genetics and Genomics

MRC 神经精神遗传学和基因组学中心

• 批准号: MR/L010305/1
• 负责人: Michael Owen
• 金额: $ 237.86万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL010305%2F1
• 关键词: MRC; Centre; Neuropsychiatric; Genetics; Genomics

The main goal of the Centre is to understand how genes are involved in a range of common psychiatric and neurological disorders, and to use this knowledge to improve our understanding of how these diseases arise and to develop new approaches to diagnosis and treatment. We have known for a long time that genes play an important role in disorders such as schizophrenia, bipolar disorder, depression, attention deficit hyperactivity disorder (ADHD), Alzheimer disease and Parkinson disease. Now, using modern genetic technologies, we have begun to identify some of the specific genes involved. Centre scientists have been at the heart of these exciting developments, which have begun to yield novel insights into the brain mechanisms involved, and which have also raised important questions about the validity of current diagnostic approaches. For example our work has shown that intellectual disability, autism, ADHD and schizophrenia are likely to be much more closely related than previously believed. Our success with existing methods, together with the development of new approaches particularly the ability to determine the sequence of DNA (the genetic code) in large numbers of patients, means that we are confident that further work will allow us to identify more of the genes involved in these disorders and that this will deliver greater understanding into how these diseases arise and the relationships between them. Thus a major focus of ours over the next 5 years will be to continue our work aimed at identifying disease genes in these disorders and in understanding how genetic risk operates both across and within current diagnostic categories.The second major focus of our work will be look at how risk genes lead to illness. This will be essential if we are to understand the mechanisms by which these diseases come about. This work will use a variety of approaches. First, we will look at the impact of risk genes in the general population for example on indexes of brain and cognitive development in the case of psychiatric disorders and on markers of inflammation, and cardiovascular health in the case of Alzheimer disease. This will help us understand how disease develops across the lifespan, and identify potentially modifiable risk factors or makers of those at increased risk of subsequent disease. The latter will be important for future studies aimed at early intervention. Second, we will develop animal and cellular models allowing us to study in detail the impact of risk genes on the function of nerve cells and brain circuits and on behaviour. Finally, we will study in human volunteers and patients how risk genes impact on brain structure and function using brain imaging methods. By studying cells, animals and patients we will be able to link abnormalities in brain function and behaviour seen in patients to abnormalities in cells and brain circuits. This will help us develop methods to stratify patient populations into specific groups for treatment studies as well to understand the mechanisms by which these diseases develop. These advances will be essential if we are to develop novel and more effective treatments for these disabling conditions.

该中心的主要目标是了解基因如何参与一系列常见的精神和神经系统疾病，并利用这些知识来提高我们对这些疾病如何发生的理解，并开发新的诊断和治疗方法。我们早就知道基因在精神分裂症、双相情感障碍、抑郁症、注意力缺陷多动障碍（ADHD）、阿尔茨海默病和帕金森病等疾病中起着重要作用。现在，利用现代遗传技术，我们已经开始确定一些相关的特定基因。中心的科学家们一直处于这些令人兴奋的发展的核心，这些发展已经开始对所涉及的大脑机制产生新的见解，并且也对当前诊断方法的有效性提出了重要的问题。例如，我们的工作表明，智力残疾，自闭症，多动症和精神分裂症可能比以前认为的更密切相关。我们在现有方法上的成功，以及新方法的开发，特别是确定大量患者DNA序列（遗传密码）的能力，意味着我们相信进一步的工作将使我们能够识别更多与这些疾病有关的基因，这将使我们更好地了解这些疾病是如何发生的，以及它们之间的关系。因此，我们在未来5年的主要重点将是继续我们的工作，旨在确定这些疾病中的疾病基因，并了解遗传风险如何在现有诊断类别中发挥作用。我们工作的第二个主要重点将是研究风险基因如何导致疾病。如果我们要了解这些疾病发生的机制，这将是至关重要的。这项工作将采用各种方法。首先，我们将研究风险基因在一般人群中的影响，例如在精神疾病的情况下对大脑和认知发展的指标以及在阿尔茨海默病的情况下对炎症和心血管健康的标志物的影响。这将有助于我们了解疾病在整个生命周期中是如何发展的，并确定潜在的可改变的风险因素或导致后续疾病风险增加的因素。后者将是重要的，为未来的研究，旨在早期干预。其次，我们将开发动物和细胞模型，使我们能够详细研究风险基因对神经细胞和大脑回路功能以及行为的影响。最后，我们将使用脑成像方法研究人类志愿者和患者的风险基因如何影响大脑结构和功能。通过研究细胞、动物和患者，我们将能够将患者的脑功能和行为异常与细胞和脑回路异常联系起来。这将有助于我们开发将患者人群分为特定组进行治疗研究的方法，以及了解这些疾病发展的机制。如果我们要为这些致残性疾病开发新的、更有效的治疗方法，这些进展将是必不可少的。

项目成果

Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE).

• DOI: 10.1136/bmjopen-2015-008312
• 发表时间: 2015-05-25
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Absoud M;Gadian J;Hellier J;Brex PA;Ciccarelli O;Giovannoni G;Kelly J;McCrone P;Murphy C;Palace J;Pickles A;Pike M;Robertson N;Jacob A;Lim M
• 通讯作者: Lim M

Understanding de novo onset of anxiety during COVID-19: Pre-pandemic socio-emotional functioning in vulnerable children.

• DOI: 10.1002/jcv2.12076
• 发表时间: 2022-06
• 期刊: JCPP advances
• 作者: Adegboye, Dolapo;Lennon, Jessica;Batterbee, Olivia;Thapar, Anita;Collishaw, Stephan;Shelton, Katherine;Langley, Kate;Hobson, Christopher;Higgins, Andrea;van Goozen, Stephanie
• 通讯作者: van Goozen, Stephanie

Understanding why the COVID-19 pandemic-related lockdown increases mental health difficulties in vulnerable young children.

• DOI: 10.1111/jcv2.12005
• 发表时间: 2021-04
• 期刊: JCPP advances
• 作者: Adegboye D;Williams F;Collishaw S;Shelton K;Langley K;Hobson C;Burley D;van Goozen S
• 通讯作者: van Goozen S

Psychopathology in adults with copy number variants.

• DOI: 10.1017/s0033291721005201
• 发表时间: 2023-05
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Adams, Rachael L.;Baird, Alister;Smith, Jacqueline;Williams, Nigel;van den Bree, Marianne B. M.;Linden, David E. J.;Owen, Michael J.;Hall, Jeremy;Linden, Stefanie C.
• 通讯作者: Linden, Stefanie C.