Brain ageing in schizophrenia and as a marker of physical and mental well-being

精神分裂症患者的大脑老化以及作为身心健康的标志

• 批准号: 2573882
• 金额: --
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2573882
• 关键词: Brain; ageing; schizophrenia; marker; physical

Background and context: The structure of the human brain changes as we age, and these changes are associated with cognitive decline and brain diseases. Individual differences exist in the brain ageing process and, potentially, deviations from healthy brain ageing trajectories could indicate underlying problems in apparently healthy people and relate to the risk and progression of disease and mortality [1]. Alternatively, the presence of a disease may result in progressive acceleration of the brain ageing process. For example, findings from several recent studies indicate significantly accelerated structural brain ageing in schizophrenia [2-4]. Furthermore, individuals with schizophrenia have a reduced life expectancy of up to 15 years, however, it is not well understood (i) whether this is driven by poor physical health or also through accelerated brain ageing and (ii) which genetic and/or modifiable lifestyle factors influence this acceleration. Aims and objectives: This project focuses on healthy brain ageing in the general population and in individuals with schizophrenia. We will develop a novel signature of accelerated brain age (derived from structural MRI scans) to: 1. Investigate how brain age links to a large number of traits in the general population, including physical health (e.g. immune and cardiometabolic traits) (Study 1). Study 1 will be based on data from UK Biobank (subset with brain imaging data, n=21,915). We will derive a brain age measure based on a pipeline developed as part of the Enhancing Neuro-Imaging Genetics through Meta-Analysis (ENIGMA) Brain Age working Group (https://www.photon-ai.com/enigma_brainage) and test associations with all traits in UK Biobank (n=23,004). This will allow us to identify how brain ageing associates with a wide range of traits related to physical and mental health. 2. Shed light into the genetic architecture of brain ageing (Study 2). Study 2 will also be based on UK Biobank data. We will carry out a genome-wide association analysis to identify genetic variants associated with brain ageing, which could then be used as instrumental variables in a Mendelian randomization analysis to assess causality of associations identified in Study 1 [5]. 3. Identify how schizophrenia (SZ) and linked modifiable lifestyle factors (e.g. cannabis use, smoking, BMI) impact accelerated brain ageing (Study 3). We will generate the largest study of brain ageing in SZ. Data will be analysed from the ENIGMA-SZ Group, which includes 39 well-characterized cross-sectional samples worldwide with brain imaging data (n=10,132, age 10-87). We will investigate brain age difference in patients and controls and how lifestyle factors might affect these differences.

背景和背景：人脑的结构随着年龄的增长而变化，这些变化与认知能力下降和大脑疾病有关。大脑老化过程中存在个体差异，可能偏离健康的大脑老化轨迹可能表明表面上健康的人存在潜在问题，并与疾病和死亡的风险和进展有关[1]。或者，疾病的存在可能会导致大脑老化过程的逐步加速。例如，最近几项研究的结果表明，精神分裂症患者的结构性脑老化速度显著加快[2-4]。此外，精神分裂症患者的预期寿命减少了长达15年，然而，尚不清楚(一)这是由于身体健康状况不佳还是大脑老化加速所致，以及(二)哪些遗传和/或可改变的生活方式因素影响了这种加速。目的和目的：该项目关注普通人群和精神分裂症患者的健康脑老化。我们将开发一个新的大脑年龄加速的标志(来自结构磁共振扫描)：1.研究大脑年龄如何与普通人群中的大量特征联系起来，包括身体健康(例如，免疫和心脏代谢特征)(研究1)。研究1将基于英国生物库的数据(带有脑成像数据的子集，n=21,915)。我们将基于一条管道推导出大脑年龄测量，该管道是通过荟萃分析(Enigma)增强神经成像遗传学(Enigma)脑年龄工作组(https://www.photon-ai.com/enigma_brainage))的一部分开发的，并在英国生物库(n=23,004)中测试与所有特征的关联。这将使我们能够确定大脑老化是如何与与身心健康相关的一系列特征相关联的。2.揭示大脑老化的遗传结构(研究2)。研究2还将基于英国生物库的数据。我们将进行全基因组关联分析，以确定与大脑老化相关的遗传变异，然后将其用作孟德尔随机化分析的工具变量，以评估研究1[5]中确定的关联的因果关系。3.确定精神分裂症(SZ)和相关的可改变的生活方式因素(例如，大麻使用、吸烟、体重指数)如何影响大脑加速老化(研究3)。我们将在深圳开展最大规模的大脑老化研究。数据将来自Enigma-SZ小组，该小组包括全球39个具有良好特征的横断面样本和脑成像数据(n=10,132，年龄10-87岁)。我们将调查患者和对照组的大脑年龄差异，以及生活方式因素如何影响这些差异。

项目成果

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

• DOI: 10.1038/s41380-022-01897-w
• 发表时间: 2023-03
• 期刊: MOLECULAR PSYCHIATRY
• 影响因子: 11
• 作者: Constantinides, Constantinos;Han, Laura K. M.;Alloza, Clara;Antonucci, Linda Antonella;Arango, Celso;Ayesa-Arriola, Rosa;Banaj, Nerisa;Bertolino, Alessandro;Borgwardt, Stefan;Bruggemann, Jason;Bustillo, Juan;Bykhovski, Oleg;Calhoun, Vince;Carr, Vaughan;Catts, Stanley;Chung, Young-Chul;Crespo-Facorro, Benedicto;Diaz-Caneja, Covadonga M.;Donohoe, Gary;Du Plessis, Stefan;Edmond, Jesse;Ehrlich, Stefan;Emsley, Robin;Eyler, Lisa T.;Fuentes-Claramonte, Paola;Georgiadis, Foivos;Green, Melissa;Guerrero-Pedraza, Amalia;Ha, Minji;Hahn, Tim;Henskens, Frans A.;Holleran, Laurena;Homan, Stephanie;Homan, Philipp;Jahanshad, Neda;Janssen, Joost;Ji, Ellen;Kaiser, Stefan;Kaleda, Vasily;Kim, Minah;Kim, Woo-Sung;Kirschner, Matthias;Kochunov, Peter;Kwak, Yoo Bin;Kwon, Jun Soo;Lebedeva, Irina;Liu, Jingyu;Mitchie, Patricia;Michielse, Stijn;Mothersill, David;Mowry, Bryan;de la Foz, Victor Ortiz-Garcia;Pantelis, Christos;Pergola, Giulio;Piras, Fabrizio;Pomarol-Clotet, Edith;Preda, Adrian;Quide, Yann;Rasser, Paul E.;Rootes-Murdy, Kelly;Salvador, Raymond;Sangiuliano, Marina;Sarro, Salvador;Schall, Ulrich;Schmidt, Andre;Scott, Rodney J.;Selvaggi, Pierluigi;Sim, Kang;Skoch, Antonin;Spalletta, Gianfranco;Spaniel, Filip;Thomopoulos, Sophia, I;Tomecek, David;Tomyshev, Alexander S.;Tordesillas-Gutierrez, Diana;van Amelsvoort, Therese;Vazquez-Bourgon, Javier;Vecchio, Daniela;Voineskos, Aristotle;Weickert, Cynthia S.;Weickert, Thomas;Thompson, Paul M.;Schmaal, Lianne;van Erp, Theo G. M.;Turner, Jessica;Cole, James H.;Dima, Danai;Walton, Esther
• 通讯作者: Walton, Esther

Association between polygenic risk for schizophrenia and brain age in a population-based of young adults: a recall-by-genotype-based approach

基于人群的年轻人精神分裂症多基因风险与脑年龄之间的关联：基于基因型的回忆方法

• 发表时间: 2022
• 作者: Constantinides C