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