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

项目摘要 在世界范围内，高达3%的人会经历精神病，这是一种异质性的神经发育和 神经退行性脑障碍，通常以妄想、幻觉和功能衰退为特征。 目前，临床医生可以确定青少年和年轻人谁是在临床高风险（ESTA）发展 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 预测谁会患上精神病的能力有限对这一人群进行安全干预需要高度信心 在预测性生物标志物中，可以将个体分层为可能的临床轨迹，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，导致我们在这方面的巨大差距。 了解高风险国家的种族异质性。最近，一个多地点的国际努力， 精神病风险结果网络（ProNET）由NIH资助，用于分析一组不同的 生物标志物来预测个体的乳腺癌临床轨迹。然而，尽管北美、欧洲和 和亚洲都参与了这一具有里程碑意义的努力，但没有非洲国家。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 该提案旨在建立肯尼亚的研究能力，在肯尼亚使用最先进的多式联运方法， 应用于ProNET研究，以绘制临床研究人群的临床结果（目标1）。这涉及 通过购置研究级采集设备和软件，在内罗毕建立ERP/EEG基础设施; MRI升级，包括先进的扩散和fMRI BOLD成像能力;以及精心设计的研究培训。 在目标2中，我们将在24个月（8个时间点）内从100名受试者中收集多模式生物标志物 (aged 15-22），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 肯尼亚青少年人群的精神病结局将不同于国际ProNET青少年队列， 包括降低精神病转化率和改善功能。预期进行MRI和ERP分析 发现眶额皮质变薄和P300（听觉P3 b）振幅降低与精神病进展。 总之，这项工作将解决全球可持续发展研究中现有的关键知识差距，并提供见解。 种族异质性的结果之间的神经系统疾病患者。通过建立临床和生物标志物方面的能力- 我们将在肯尼亚的基础上开展研究，促进撒哈拉以南非洲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.