ENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMA

ENIGMA-SD：通过 ENIGMA 了解全球心理健康中的性别差异

基本信息

批准号：
9892045
负责人：
PAUL M THOMPSON
金额：
$ 59.51万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-23 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892045
关键词：
Address Age Age of Onset Aging Alcoholism Alzheimer&apos s Disease Alzheimer&apos s disease risk Anxiety Anxiety Disorders BRAIN initiative Big Data Biological Bipolar Disorder Brain Brain Diseases Brain imaging Clinical Clinical Data Collaborations Country Data Data Pooling Disease Drug Addiction Environment Extramural Activities Female Functional Magnetic Resonance Imaging Funding Genetic Genetic Risk Genome Genomics Grant Human Image Impaired cognition Individual Institutes Institution Knowledge Life Longevity Magnetic Resonance Imaging Major Depressive Disorder Measures Medicine Mental Depression Mental Health Mental disorders Neurobiology Neurodegenerative Disorders Neurosciences Outcome Pattern Phenotype Positioning Attribute Post-Traumatic Stress Disorders Power Sources Prevalence Psychotic Disorders Reproducibility Research Research Personnel Rest Risk Risk Factors Schizophrenia Science Severities Sex Differences Source Structure Substance Use Disorder Substance abuse problem Symptoms Syndrome Testing United States National Institutes of Health Validation Woman Work addiction aging brain base biological sex brain abnormalities brain health data centers disorder risk genomic data imaging study innovation male men neuroimaging polygenic risk score post-traumatic stress programs response risk variant sex sex risk success treatment response trend white matter

项目摘要

ABSTRACT This application is the first, large scale, concerted effort to study sex as a biological variable in human neuroscience through a worldwide brain initiative. We created it to respond to the NIH mandate to address major gaps in knowledge on why some brain disorders are more prevalent in women than men, and vice versa. Women and men differ in aging trends and in the prevalence of major depression, anxiety disorders, substance abuse disorders (SUDs), alcoholism, psychosis, post-traumatic stress disorder (PTSD), and neurodegenerative diseases such as Alzheimer's disease. There are significant sex differences in the brain disorders' mean age of onset, treatment response, symptom severity and disease trajectory. Yet science knows alarmingly little about why. To respond to this, we launch a new worldwide brain initiative: “ENIGMA-SD: Understanding Sex Differences in Global Brain Health through ENIGMA”. ENIGMA's Sex Differences Initiative pools data worldwide to address the “crisis of reproducibility” from underpowered studies (Ioannidis 2014). We bring two sources of innovation: (1) the vast, unprecedented power of a global study across 35 countries, yielding exceptional sensitivity to sex differences and (2) a lifespan approach, to chart disease emergence throughout life, to pick up sex-specific `shifts' in the age of onset, severity, and trajectory of brain disease. We will consistently analyze imaging, genomic, and clinical data from hundreds of institutes - to understand (1) sex differences in brain structure and function across life; and (2) how brain abnormalities differ by sex in five major psychiatric illnesses: major depression (MDD), bipolar disorder (BD), schizophrenia (SCZ), PTSD, and SUDs. We will leverage the success of our ENIGMA consortium - a global study of 18 major brain diseases. Our Aims are: Aim 1. Chart Sex Differences in Brain Aging throughout Life. Building on our largest-ever normative study of the brain in 10,144 people (ENIGMA-Lifespan; Dima 2017), we will create sex-specific lifespan “charts” showing how the brain ages, on average, in women and in men. Using MRI, DTI and resting state fMRI on a worldwide scale, we measure cortical/subcortical brain structures, white matter tracts, and age- sensitive metrics of functional brain synchrony. We develop statistical norms based on age and sex; we test interactions between biological sex and brain aging metrics. Aim 2. Determine Sex Differences in the Trajectory of Brain Deficits in MDD, BD, SCZ, PTSD, and Addictions. Building on our global neuroimaging studies of 5 prevalent brain disorders - we will ask: (1) Are the brain deficits the same in women and men with each disease? (2) Are brain differences greater in women at the same level of clinical severity? Aim 3. Sex and Genetic Risk. In a unique collaboration across our 5 global consortia – ENIGMA-MDD, -BD, -SCZ, -PTSD, and -SUDs – we will compute polygenic risk scores for each disease, and ask: What is the effect on the brain of carrying a higher genetic risk for one of these disorders? Does this effect differ by sex? We will do the groundwork to submit an ENIGMA-wide U01 on Sex Differences in Brain Disease, in 2022.

抽象的该应用是第一个大规模、共同努力研究性别作为人类生物变量的研究我们通过一项全球大脑计划创建它来响应 NIH 的任务，以解决这一问题。关于为什么某些脑部疾病在女性中比男性更常见，反之亦然，在知识上存在重大差距。女性和男性在衰老趋势以及重度抑郁症、焦虑症、物质障碍的患病率方面存在差异虐待障碍 (SUD)、酗酒、精神病、创伤后应激障碍 (PTSD) 和神经退行性疾病阿尔茨海默病等脑部疾病的平均年龄存在显着的性别差异。然而，科学对发病、治疗反应、症状严重程度和疾病轨迹知之甚少。为了应对这一问题，我们发起了一项新的全球大脑计划：“ENIGMA-SD：理解性”。 ENIGMA 的性别差异倡议汇集了全球大脑健康的差异。在世界范围内解决动力不足研究带来的“可重复性危机”（Ioannidis 2014）。创新来源：(1) 涵盖 35 个国家的全球研究具有巨大的、前所未有的力量，产生了对性别差异的异常敏感性以及（2）生命周期方法，以绘制整个过程中疾病出现的图表我们将在生活中发现脑部疾病的发病年龄、严重程度和轨迹方面的性别特异性“变化”。持续分析来自数百家机构的影像、基因组和临床数据 - 了解 (1) 一生中大脑结构和功能的性别差异；以及（2）五种性别的大脑异常有何不同主要精神疾病：重度抑郁症（MDD）、双相情感障碍（BD）、精神分裂症（SCZ）、创伤后应激障碍（PTSD）、我们将利用 ENIGMA 联盟的成功——一项针对 18 种主要脑部疾病的全球研究。我们的目标是：目标 1. 绘制一生中大脑老化的性别差异图。对 10,144 人的大脑进行规范性研究（ENIGMA-Lifespan；Dima 2017），我们将创建性别特异性使用 MRI、DTI 和休息的寿命“图表”显示女性和男性的大脑平均老化情况。在全球范围内进行功能磁共振成像，我们测量皮质/皮质下大脑结构、白质束和年龄我们根据年龄和性别制定了大脑功能同步的敏感指标；生物性别与大脑衰老指标之间的相互作用目标 2. 确定性别差异。 MDD、BD、SCZ、PTSD 和成瘾的大脑缺陷轨迹以我们的全球神经影像学为基础。对 5 种常见脑部疾病的研究 - 我们会问：(1) 女性和男性的脑部缺陷是否相同 (2) 在相同的临床严重程度下，女性的大脑差异是否更大？遗传风险是我们 5 个全球联盟（ENIGMA-MDD、-BD、-SCZ、-PTSD 和）的独特合作。 -SUD——我们将计算每种疾病的多基因风险评分，并询问：患有这些疾病之一的遗传风险是否因性别而异？于 2022 年提交关于脑部疾病性别差异的 ENIGMA 范围 U01。