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

基本信息

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
项目类别：
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

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

展开

项目摘要

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.

项目摘要在全球范围内，多达3％的人会经历精神病，一种异质性神经发育和神经退行性脑疾病通常以妄想，幻觉和功能下降为特征。目前，临床医生可以识别出患有临床高风险（CHR）的青少年和年轻人精神病。但是，由于导致精神病发展的机制尚不完全了解，我们已经有限预测谁会发展精神病的能力有限。安全干预该人群需要高度信心在可以将个体分类为可能的临床轨迹的预测生物标志物中，并有效地匹配它们治疗。非洲的早期精神病研究工作非常有限，这导致了我们的差距很大有关高风险状态的种族异质性的知识。最近，是多站点的国际努力， NIH资助了精神病风险结局网络（PRONET），以分析一组多种多样的变化生物标志物预测单个CHR临床轨迹。但是，而北美的国家，欧洲这项具有里程碑意义的工作中包括亚洲，其中不包括非洲国家。这是相关的，作为风险基因精神病以及精神病的临床和文化表现在各个种族中常常有所不同。这提案旨在在肯尼亚使用最先进的多模式方法在肯尼亚建立研究能力为了绘制CHR人群中的临床结果（AIM 1），在PRONET研究中应用的。这涉及通过获取研究级获取设备和软件，在内罗毕建立ERP/EEG基础设施； MRI升级，包括高级扩散和fMRI大胆的成像能力；并详细的研究培训。在AIM 2中，我们将在100个CHR参与者的24个月内收集24个月（八个时间点）的多模式生物标志物（15-22岁）包括大脑MRI，ERP/EEG，心理病理学，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。 AIM 3将检验假设肯尼亚CHR人群中的精神病结果将与国际Pronet Chrort不同，包括较低的精神病转化率和改善的功能。预计MRI和ERP分析找到轨道额叶皮层稀疏和降低的p300（听觉P3B）幅度，随着精神病的进展。这项工作将解决全球CHR研究中现有的关键知识差距，并提供见解在CHR患者中成为结果的种族异质性。通过在CHR临床和生物标志物中建立能力基于肯尼亚的研究，我们将促进撒哈拉以南非洲加入未来的国际研究工作。