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) 是一种破坏性且人们对其知之甚少的疾病，其每年造成的负担超过 2020 亿美元。 50% 的患者没有已知的治疗方法且治疗选择有限。 至少尝试自杀一次；高达 30% 的患者对一线治疗没有反应 - 即使采用最新的治疗 药物和心理社会治疗 - 然而双相情感障碍只接受了一小部分治疗 研究关注的是如何区分严重的非精神疾病和重度抑郁症。 影像学的进步对于理解 BD 病理生理学至关重要。 关于 BD 大脑变化及其进展的可重复且可靠的数据，但缺乏全球倡议 双相情感障碍的研究因数据收集成本高昂而陷入停滞——很少有研究会扫描超过一百个数据。 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 我们的 ENIGMA 令人困惑，并且常常缺乏识别调节疾病进展或恢复的因素的能力。 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——一种打破这一障碍的新力量来源 通过合并领先 BD 中心的资源、资本基础设施和人才（包括来自 ENIGMA 全球双相情感基因组学全球联盟有 48 个队列。 Disorder - 建立在我们蓬勃发展的 ENIGMA 联盟的方法之上，合并了数以万计的数据。 个人的力量，“赋予我们一种我们从未有过的力量”，并且“打破神经科学的僵局”（纽约 《柳叶刀》称赞 ENIGMA 是“众包与神经科学的结合”。 倡议中，我们确定了 ENIGMA 双极工作组中最具成效的活动，并将其组织起来 分为 3 个主题——成像、基因组学和跨疾病比较。这项全球倡议解决了关键问题。 BD 中的问题：这种疾病如何影响大脑？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 遗传易感性位点如何影响大脑？ 来自 15 个国家的数据和专家团队（请参阅支持信），我们解决成像、基因组和预测问题 有关 BD 的问题在巴西、日本、美国、加拿大、挪威等国家具有前所未有的影响力。 荷兰、德国、法国、澳大利亚和南非——我们可以重现哪些大脑差异 BD 中的检测（通过结构/扩散 MRI、连接组学和静息态 fMRI）它们在生命过程中有何变化？ 疾病持续时间、人口统计、女性与男性、发病年龄、亚型和治疗？ ENIGMA 的统一协议，我们将分析 BD 中最大的多站点神经影像数据集 - 年龄、种族、治疗反应不同——在新的跨疾病伙伴关系中追踪疾病。 ENIGMA-BD 和 MDD 的结合，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，以 在协调不同疾病的数据元素后，我们将区分这两种疾病并确定亚型。 创建影响 BD 预后的可行因素的排名列表。