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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.

摘要