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）是一种毁灭性的和知之甚少的疾病。它的负担每年超过2020亿美元， 直接治疗、社会和家庭成本。由于没有已知的治愈方法和有限的治疗选择，50%的患者 至少有一次试图自杀;高达30%的患者对一线治疗没有反应-即使是最新的治疗。 药物和心理治疗-然而双相情感障碍只收到了一小部分的金额， 对严重非精神疾病的研究关注。BD与重度抑郁症的区别在于 对理解BD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大脑变化及其进展的可重复和可靠的数据，但缺乏全球倡议 双相情感障碍的研究陷入停滞。数据收集的高成本-很少有研究扫描超过一百个 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，并且通常缺乏能力来识别调节疾病进展或恢复的因素。我们的ENIGMA 双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， 通过合并资源，资本基础设施和领先的BD中心的人才，包括来自 全球48个国家ENIGMA全球双极成像基因组学联盟 无序-建立在我们蓬勃发展的谜财团。ENIGMA的方法融合了数万个 对个体的研究“给予了我们前所未有的力量”，并且正在“打破神经科学的僵局”（纽约 Times）。《柳叶刀》将ENIGMA誉为“众包与神经科学的结合”。在设计ENIGMA-Bipolar 在这一倡议下，我们确定了ENIGMA双极工作组中最富有成效的活动，并组织了这些活动 分为3个主题-成像，基因组学和交叉疾病比较。这一全球倡议解决了关键问题， BD中的问题：疾病如何影响大脑？哪些影像学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？与全球 数据和来自15个国家的专家团队（见支持信），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。巴西、日本、美国、加拿大、挪威、 荷兰、德国、法国、澳大利亚和南非--我们可以重现哪些大脑差异 检测BD（结构/扩散MRI，连接组学和静息状态fMRI）？它们在生命中是如何变化的， 与疾病持续时间，按人口统计学，女性与男性，按发病年龄，亚型和治疗？使用 ENIGMA的协调协议，我们将分析BD中最大的多站点神经成像数据集- 不同的年龄、种族、治疗反应--以跟踪全球疾病。在一个新的跨障碍伙伴关系中 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， 区分这两种疾病并确定亚型。在协调了各种疾病的数据元素后，我们将 创建影响BD预后的可操作因素的排名列表。