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

项目总结 在世界范围内，高达3%的人将经历精神病，一种不同的神经发育和 神经退行性脑病以妄想、幻觉和功能衰退为特征的神经退行性脑病 目前，临床医生可以识别处于临床高危(Chr)的青少年和青壮年。 精神错乱。然而，由于导致精神病发展的机制尚不完全清楚，我们有 预测谁会发展成精神病的能力有限。对这一人群的安全干预需要高度的信心 在预测性生物标记物中，可以将个体分层为可能的临床轨迹，并将它们与有效的 治疗。非洲的早期精神病研究工作非常有限，导致我们的 了解高危州的种族异质性。最近，一项多地点的国际努力， 精神病-风险结果网络(ProNET)由美国国立卫生研究院资助，以分析一组不同的 用于预测个体CHR临床轨迹的生物标志物。然而，虽然北美、欧洲的国家 和亚洲都包括在这一里程碑式的努力中，不包括非洲国家。这是相关的，因为风险基因 精神病以及精神病的临床和文化表现往往因种族而异。这 该提案旨在建设肯尼亚的研究能力，在肯尼亚使用最先进的多式联运方法 与ProNET研究中应用的结果相同，以便绘制慢性阻塞性肺病人群的临床结果图(目标1)。这涉及到 通过购置研究级采购设备和软件，在内罗毕建立企业资源规划/脑电基础设施； MRI升级，包括先进的扩散和fMRI BOLD成像能力；以及精心的研究培训。 在目标2中，我们将从100名CHR参与者那里收集24个月(8个时间点)的多模式生物标志物 (15-22岁)，包括脑MRI、事件相关电位/脑电波、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，以量化典型的变异。目标3将检验这一假设 肯尼亚CHR人群中的精神病结果将不同于国际ProNet CHR队列， 包括较低的精神病转化率和改善的功能。预计将进行MRI和ERP分析 目的：观察随着精神病的进展，眶前叶皮质变薄和P300(听觉P3b)波幅降低的情况。 这项工作将共同解决全球气候变化研究中现有的关键知识差距，并提供见解。 慢性阻塞性肺病患者预后的种族异质性。通过建设CHR临床和生物标记物的能力- 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努力。

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.