ENIGMA Bipolar Initiative: A Global Study of Imaging Genomics & Clinical Outcomes

ENIGMA 双极倡议：影像基因组学的全球研究

• 批准号: 10598611
• 负责人: Ole A Andreassen
• 金额: $ 58.95万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598611
• 关键词: Affect; Age; Age of Onset; Antidepressive Agents; Attention; Australia; Bayesian Method; Behavioral; Bipolar Disorder; Bipolar I; Brain; Brain imaging; Brain region; Brazil; Canada; Capital; Categories; Chronic; Clinical; Collection; Complex; Corpus Callosum; Country; Data; Data Collection; Data Element; Diagnosis; Diagnostic; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Dose; Emotions; Ethnic Origin; Evaluation; Family; First Degree Relative; France; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genomics; Germany; Image; Impairment; Individual; Infrastructure; International; Investigation; Japan; Letters; Life; Life Expectancy; Link; Longevity; Major Depressive Disorder; Manic; Maps; Measures; Mental Depression; Modeling; Monitor; Moods; Netherlands; Neurobiology; Neurosciences; New York; Norway; Obesity; Outcome; Patients; Pattern; Personal Satisfaction; Pharmaceutical Preparations; Phenotype; Power Sources; Predictive Value; Prefrontal Cortex; Productivity; Prognosis; Protocols documentation; Recovery; Reporting; Reproducibility; Research; Research Domain Criteria; Resources; Rest; Rewards; Risk; Sampling; Scanning; Severities; Site; Sleep disturbances; South Africa; Standardization; Structure; Suicide attempt; Susceptibility Gene; Symptoms; System; Talents; Testing; Therapeutic; Thick; Treatment outcome; Woman; Work; associated symptom; biomarker validation; biotypes; clinical imaging; cohort; comorbidity; comparison control; cost; cost effective; crowdsourcing; data harmonization; data-driven model; demographics; depressive symptoms; design; disorder subtype; emotion dysregulation; follow-up; functional disability; functional outcomes; genetic variant; genomic biomarker; genomic data; imaging biomarker; imaging detection; imaging study; improved; innovation; men; multimodality; neuroimaging; outcome prediction; patient subsets; polygenic risk score; psychosocial; resilience; social relationships; suicide rate; tool; treatment effect; treatment response; white matter; working group

ABSTRACT Bipolar disorder (BD) is a devastating and poorly understood illness. Its burden exceeds $202 billion a year in direct treatment, societal and family costs. With no known cure and limited therapeutic options, 50% of patients attempt suicide at least once; up to 30% of patients do not respond to first-line treatment - even with the latest medications and psychosocial therapy - yet bipolar disorder has only received a small fraction of the amount of research attention that goes into serious non-psychiatric illness. Differentiating BD from major depression is crucial for understanding BD pathophysiology. Advances in imaging are beginning to offer the first detailed, reproducible, and reliable data on brain changes in BD and how they progress, but the lack of global initiatives in bipolar disorder has stalled research. The high cost of data collection - few studies scan more than a hundred patients - has led to underpowered studies whose findings often fail to replicate, cannot adequately model confounds, and often lack power to identify factors that modulate disease progression or recovery. Our ENIGMA Bipolar Initiative offers a new, cost-effective, innovative global approach - a new source of power to unblock this logjam by merging resources, capital infrastructure and talents of leading BD centers including data from 48 cohorts across the world. ENIGMA’s Global Alliance for Worldwide Imaging Genomics in Bipolar Disorder - builds on our thriving ENIGMA Consortium. ENIGMA’s approach merges data from tens of thousands of individuals and “gives us a power we have not had”, and is “breaking the logjam in neuroscience” (New York Times). The Lancet hailed ENIGMA as “Crowdsourcing meets Neuroscience”. In designing the ENIGMA-Bipolar initiative, we identified the most productive activities in the ENIGMA Bipolar working group, and organized them into 3 themes - imaging, genomics, and cross-disorder comparisons. This global initiative tackles key questions in BD: how does the illness affect the brain? What imaging and genomic biomarkers assist diagnosis, monitor treatment, and predict outcomes? How do BD genetic susceptibility loci affect the brain? With global data and expert teams from 15 countries (see Support Letters), we tackle imaging, genomic, and predictive questions about BD with unprecedented power. Across Brazil, Japan, the US, Canada, Norway, The Netherlands, Germany, France, Australia, and South Africa - what brain differences do we reproducibly detect in BD (with structural/diffusion MRI, connectomics and resting state fMRI)? How do they vary across life, with illness duration, by demographics, in women versus men, by age of onset, subtype and treatment? Using ENIGMA’s harmonized protocols, we will analyze the largest collection of multisite neuroimaging data in BD - diverse in age, ethnicity, treatment response - to track disease worldwide. In a new Cross-Disorder partnership of ENIGMA-BD and MDD, we use ENIGMA’s data-driven models to detect imaging and genomic biomarkers to distinguish the 2 disorders and identify subtypes. After harmonizing data elements across disorders, we will create a ranked list of actionable factors that affect prognosis in BD.

抽象的 双相情感障碍（BD）是一种毁灭性的疾病，理解不足。它的燃烧超过每年202亿美元 直接治疗，社会和家庭成本。没有已知的治愈方法和有限的治疗选择，有50％的患者 至少尝试自杀一次；多达30％的患者对一线治疗没有反应 - 即使是最新的 药物和社会心理疗法 - 但双相情感障碍仅收到的一小部分 研究严重的非精神病患者的注意力。将BD与大抑郁症区分开来 对于理解BD病理生理学至关重要。成像的进步开始提供第一个详细的信息， 可再现的，可靠的，可靠的关于BD大脑变化及其进步的数据，但缺乏全球计划 在躁郁症中，研究陷入僵局。数据收集成本高 - 很少有研究扫描一百多个 患者 - 导致了能力不足的研究，其发现通常无法复制，无法充分建模 混淆，通常缺乏识别调节疾病进展或康复的因素的能力。我们的谜 双极倡议提供了一种新的，具有成本效益的创新全球方法 - 取消阻止此的新力量来源 合并资源，资本基础设施和领先BD中心的才能的logjam，包括来自 48个在世界各地。 Enigma的全球全球成像基因组学联盟在双极 障碍 - 建立在我们繁荣的谜团的基础上。 Enigma的方法合并了数以万计的数据 个人和“赋予我们我们没有拥有的力量”，并且正在“破坏神经科学的logjam”（纽约 时代）。柳叶刀称呼为“众包遇到神经科学”。在设计谜团时 主动性，我们确定了谜躁郁症工作组中最有生产力的活动，并组织了它们 分为3个主题 - 成像，基因组学和跨二项比较。这项全球倡议解决了关键 BD中的问题：疾病如何影响大脑？哪些成像和基因组生物标志物有助于诊断， 监测治疗并预测结果？ BD遗传易感性位置如何影响大脑？与全球 来自15个国家 /地区的数据和专家团队（请参阅支持信），我们处理成像，基因组和预测 关于BD具有前所未有的权力的问题。在巴西，日本，美国，加拿大，挪威， 荷兰，德国，法国，澳大利亚和南非 - 我们可重复地有什么大脑差异 在BD中检测（具有结构/扩散MRI，连接组学和静止状态fMRI）？它们如何在生活中变化， 随着疾病的持续时间，按人口统计，在女性与男性中，按发病，亚型和治疗年龄？使用 Enigma的协调协议，我们将分析BD中最大的多站点神经影像学数据集合。 年龄，种族，治疗反应的潜水员 - 追踪全球疾病。在新的跨界合作伙伴关系中 在Enigma-BD和MDD中，我们使用Enigma的数据驱动模型来检测成像和基因组生物标志物 区分两种疾病并识别亚型。在跨疾病统一数据元素之后，我们将 创建一个可行的因素的排名列表，以影响BD中的提示。