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.

摘要 双相情感障碍(BD)是一种毁灭性的疾病，人们对此知之甚少。它的负担每年超过2020亿美元 直接治疗、社会和家庭费用。由于没有已知的治愈方法和有限的治疗选择，50%的患者 至少尝试自杀一次；高达30%的患者对一线治疗没有反应-即使是最新的 药物和心理社会治疗--然而，双相情感障碍只接受了 对严重的非精神疾病的研究关注。BD与重度抑郁症的区别是 对了解BD的病理生理学至关重要。成像技术的进步开始提供第一个详细的、 关于BD的脑部变化及其进展情况的可重复、可靠的数据，但缺乏全球倡议 双相情感障碍的研究已经停滞不前。数据收集的高成本-很少有研究扫描超过100 患者--导致了动力不足的研究，其结果往往无法复制，无法充分建模 混淆，而且往往缺乏能力来确定调节疾病进展或康复的因素。我们的谜团 两极倡议提供了一种新的、具有成本效益的、创新的全球方法--一种新的力量来源 整合领先业务发展中心的资源、资本基础设施和人才，包括来自 世界各地的48个队列。Enigma公司双相世界成像基因组学全球联盟 混乱-建立在我们欣欣向荣的谜团之上。Enigma的方法合并了数万个数据 个人和“给予我们从未有过的力量”，并且正在“打破神经科学的僵局”(纽约 次数)。《柳叶刀》将谜团誉为“众包遇神经科学”。在设计谜-双极中 倡议，我们确定了谜双极工作组中最有成效的活动，并组织了这些活动 分成3个主题--成像、基因组学和交叉紊乱比较。这一全球倡议解决了关键问题 BD的问题：这种疾病是如何影响大脑的？哪些成像和基因组生物标记物有助于诊断， 监测治疗并预测结果？BD遗传易感基因是如何影响大脑的？通过全球 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的问题具有前所未有的力量。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--我们的大脑有哪些可重复的差异 在BD中检测(使用结构/弥散磁共振成像、连接学和静息状态功能磁共振成像)？它们在生活中是如何变化的， 疾病持续时间、人口统计学、女性与男性、发病年龄、亚型和治疗？vbl.使用 Enigma的协调协议，我们将分析BD中最大的多点神经成像数据集合- 在年龄、种族、治疗反应方面的多样性--以跟踪世界各地的疾病。在一个新的跨障碍合作伙伴关系中 对于Enigma-BD和MDD，我们使用Enigma的数据驱动模型来检测成像和基因组生物标记物 区分这两种疾病并确定其亚型。在协调跨障碍的数据元素之后，我们将 创建影响BD预后的可操作因素的排序列表。