Clinical and Biomarker-Based Trajectories of Psychosis-Risk Populations in Kenya

肯尼亚精神病风险人群的临床和基于生物标记的轨迹

• 批准号: 10671487
• 负责人: DANIEL MAMAH
• 金额: $ 62.63万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-18 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671487
• 关键词: Address; Adolescent and Young Adult; Affective Symptoms; Africa; Africa South of the Sahara; African; Asia; Attenuated; Auditory; Australia; Biological Markers; Bipolar Disorder; Brain; Brain Diseases; Brain Mapping; Clinical; Clinical Trials; Cognition; Cognitive deficits; Computer software; Country; Data; Delusions; Development; Diffusion; EP300 gene; Early identification; Early treatment; Electroencephalography; Electrophysiology (science); Ethnic Origin; Ethnic Population; Europe; Functional Magnetic Resonance Imaging; Funding; Future; Genetic; Goals; Hallucinations; Heterogeneity; Human Resources; Hydrocortisone; Image; Individual; Infrastructure; International; Intervention; Kenya; Knowledge; Magnetic Resonance Imaging; Maps; Measures; Methods; Nerve Degeneration; North America; Oceania; Outcome; Outcome Study; Participant; Pathogenicity; Patients; Persons; Population; Prognostic Marker; Psychopathology; Psychoses; Psychotic Disorders; Research; Research Training; Risk Reduction; Sampling; Schizoaffective Disorders; Schizophrenia; Site; Slice; Structure; Syndrome; Testing; Thinness; Time; Training; Training and Infrastructure; United States National Institutes of Health; Variant; Work; Youth; aged; behavioral outcome; blood oxygenation level dependent imaging; brain behavior; brain magnetic resonance imaging; clinical effect; clinical heterogeneity; clinical high risk for psychosis; clinical risk; clinically relevant; cohort; diagnostic strategy; early psychosis; effective therapy; equipment acquisition; experience; frontal lobe; functional decline; functional disability; functional improvement; healthy volunteer; high risk; high risk population; imaging capabilities; insight; magnetic resonance imaging/electroencephalography; multimodality; neuroimaging; personalized medicine; predictive marker; psychosis risk; psychotic symptoms; risk variant

PROJECT SUMMARY Worldwide, up to 3% of people will experience psychosis, a heterogeneous neurodevelopmental and neurodegenerative brain disorder typically characterized by delusions, hallucinations, and functional decline. Currently, clinicians can identify adolescents and young adults who are at clinical high risk (CHR) for developing psychosis. However, as the mechanisms leading to development of psychosis are not fully known, we have limited ability to predict who will develop psychosis. Safe intervention in this population requires high confidence in predictive biomarkers that can stratify individuals into likely clinical trajectories, and match them with effective treatments. Africa has a very limited early psychosis research effort, resulting in a substantial gap in our knowledge about the ethnic heterogeneity of the high-risk state. Recently, a multi-site international effort, the Psychosis-Risk Outcomes Network (ProNET), was funded by the NIH to analyze variation in a diverse set of biomarkers to predict individual CHR clinical trajectories. However, while countries in North America, Europe and Asia are included in this landmark effort, it includes no African country. This is relevant, as risk genes for psychosis as well as the clinical and cultural presentation of psychosis often differ across ethnic groups. This proposal aims to build research capacity in Kenya, using state-of-the-art multimodal methods in Kenya identical to that applied in the ProNET study, in order to map clinical outcomes in CHR populations (Aim 1). This involves building ERP/EEG infrastructure in Nairobi, by acquiring research grade acquisition equipment and software; MRI upgrades, including advanced diffusion and fMRI BOLD imaging capability; and elaborate research training. In Aim 2, we will collect multi-modal biomarkers over 24 months (eight timepoints) from 100 CHR participants (aged 15-22) including brain MRI, ERP/EEG, psychopathology, cognition, genetics, and cortisol. Healthy volunteers (N=50) will complete baseline assessment to quantify typical variation. Aim 3 will test the hypothesis that psychosis outcomes in Kenyan CHR populations will differ from the international ProNET CHR cohort, including a lower rate of psychosis conversion and improved functioning. MRI and ERP analyses are expected to find orbitofrontal cortical thinning and reduced P300 (auditory P3b) amplitude with psychosis progression. Together, this work would address key existing knowledge gaps in global CHR research and provide insights into ethnic heterogeneity of outcomes among CHR patients. By building capacity in CHR clinical and biomarker- based research in Kenya, we will facilitate sub-Saharan Africa joining future international research efforts.

项目概要 在世界范围内，多达 3% 的人会经历精神病，这是一种异质性神经发育和疾病 神经退行性脑部疾病的典型特征是妄想、幻觉和功能衰退。 目前，临床医生可以识别处于临床高风险（CHR）的青少年和年轻人 精神病。然而，由于导致精神病发展的机制尚不完全清楚，我们有 预测谁会患上精神病的能力有限。对这一人群的安全干预需要高度信心 预测性生物标志物可以将个体分层到可能的临床轨迹中，并将其与有效的 治疗。非洲的早期精神病研究工作非常有限，导致我们在 关于高风险国家的种族异质性的知识。最近，通过多地点的国际努力， 精神病风险结果网络 (ProNET) 由 NIH 资助，用于分析不同群体的变异 预测个体 CHR 临床轨迹的生物标志物。然而，虽然北美、欧洲国家 这一具有里程碑意义的努力包括亚洲和非洲，但不包括非洲国家。这是相关的，因为风险基因 不同种族的精神病以及精神病的临床和文化表现通常有所不同。这 该提案旨在利用肯尼亚最先进的多式联运方法建设肯尼亚的研究能力 与 ProNET 研究中应用的方法相一致，以便绘制 CHR 人群的临床结果（目标 1）。这涉及到 通过购买研究级采集设备和软件，在内罗毕建设 ERP/EEG 基础设施； MRI 升级，包括先进的扩散和 fMRI BOLD 成像能力；和精心的研究培训。 在目标 2 中，我们将从 100 名 CHR 参与者收集超过 24 个月（八个时间点）的多模式生物标志物 （15-22 岁）包括脑 MRI、ERP/EEG、精神病理学、认知、遗传学和皮质醇。健康 志愿者（N = 50）将完成基线评估以量化典型变化。目标 3 将检验假设 肯尼亚 CHR 人群的精神病结果将不同于国际 ProNET CHR 队列， 包括降低精神病转化率和改善功能。预计 MRI 和 ERP 分析 发现随着精神病进展，眶额皮质变薄和 P300（听觉 P3b）振幅降低。 总之，这项工作将解决全球 CHR 研究中现有的关键知识差距，并提供见解 CHR 患者结局的种族异质性。通过建设 CHR 临床和生物标志物方面的能力 基于肯尼亚的研究，我们将促进撒哈拉以南非洲地区加入未来的国际研究工作。