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

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

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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的一致努力，将性作为人类的生物变量研究神经科学通过全球大脑倡议。我们创建了它是为了响应NIH的授权以解决关于为什么某些脑部疾病在女性中比男性更普遍，反之亦然，反之亦然。男女在衰老趋势方面有所不同，重度抑郁症，焦虑症，底物的流行滥用障碍（SUD），酒精中毒，精神病，创伤后应激障碍（PTSD）和神经退行性阿尔茨海默氏病等疾病。脑疾病的平均年龄有很大的性别差异发作，治疗反应，症状严重程度和疾病轨迹。然而科学对为什么。为了回应这一点，我们发起了一项新的全球大脑计划：“ Enigma-SD：了解性别通过谜团在全球大脑健康方面的差异”。谜的性别差异计划池数据全球旨在解决功能不足的研究的“可重复性危机”（Ioannidis 2014）。我们带两个创新来源：（1）在35个国家 /地区进行全球研究的巨大，前所未有的力量对性别差异和（2）寿命的敏感性非常敏感，以列出整个疾病的出现生活，在发病，严重程度和脑部疾病轨迹的时代拾起性别特定的“转移”。我们将一贯分析来自数百个机构的成像，基因组和临床数据 - 了解（1）跨越生命的大脑结构和功能的性别差异；（2）大脑异常如何因五个性别而异常重大精神病：严重抑郁症（MDD），躁郁症（BD），精神分裂症（SCZ），PTSD，和泡沫。我们将利用我们的谜联盟的成功 - 对18种主要脑部疾病的全球研究。我们的目标是：目标1。一生中大脑衰老的性别差异。建立在我们有史以来最大的基础上在10,144人中对大脑的正常研究（Enigma-Lifespan; Dima 2017），我们将创建特定的性别寿命“图表”显示了大脑在女性和男性中的平均年龄。使用MRI，DTI和休息在全球范围内，我们的状态fMRI，我们测量皮质/皮质下脑结构，白质区和年龄 - 功能性脑同步的敏感指标。我们根据年龄和性别制定统计规范；我们测试生物性别与脑老化指标之间的相互作用。目标2。确定性别差异 MDD，BD，SCZ，PTSD和成瘾中大脑缺陷的轨迹。建立我们的全球神经影像学对5种流行脑部疾病的研究 - 我们会问：（1）大脑在患有的男女中的定义相同每种疾病？（2）在相同临床严重程度上，女性的大脑差异是否更大？目标3。性和遗传风险。在我们5个全球宪法的独特合作中 - Enigma -MDD，-bd，-scz，-ptsd和 - suds - 我们将计算每种疾病的多基因风险评分，并询问：对大脑的影响是什么对其中一种疾病承担更高的遗传风险？这会因性别而不同吗？我们将进行基础工作在2022年提交有关脑部疾病性别差异的全谜U01。