Longitudinal trajectories in treated and untreated schizophrenia

对未经治疗的非情感性精神病病程的研究在很大程度上局限于城市样本 短期未经治疗的精神病(DUP)(少于5年)。我们建议利用一种独特的、 在精神病患者中研究延长的未经治疗的精神病病程的时间有限的机会 (IWP)具有很长的DUP(&gt；30年)，主要分布在中国的农村地区。我们的首要目标是发展 对未经治疗的持续性精神病的病程及相关神经生物学的了解 几十年。我们的第二个目标是扩大关于开始治疗(例如，抗精神病药物)的知识 到成年后期仍未接受治疗的IWP。这份R01报告建议对400名未治疗的IWP进行为期3年的随访， 来自广西和湖南主要农村地区的400名IWP治疗组和400名健康对照组(HC) 省(在关键变量上匹配)。我们的主要关注点是认知表现，但我们也会比较 3组在其他症状和功能领域。此外，长期未治疗的比较 接受处理(即“新处理的”)与垃圾处理(即“持续未处理的”)的IWP将 提供有关延长DUP的IWP患者开始抗精神病治疗的关键信息。 我们的具体目标包括：目标1)比较从基线到3年随访期间认知能力的变化 3组：持续未治疗的IWP、匹配的治疗IWP和匹配的HCS。1A)我们在假设中 初步分析通过Matrics测量的3年随访中认知能力的下降 共识认知电池(MCCB)，在正在进行的未治疗组中最大，在 相匹配的治疗组，HC组最少。1b)二次分析将类似地比较特定的 认知领域和那些在三组之间表现出进行性认知下降的人，在同一 1a中假设的顺序)。目的2)进行二次分析，以比较以下措施的变化 精神病理学、社会和职业功能、医疗并存和社会负担 在目标1中指定的相同3组中进行3年随访。目标3)进行二次分析比较 正在进行的未治疗组和新治疗组涉及：3a)认知表现的变化；3b) 精神病理、功能、医疗并存和社会负担方面的变化。在目标3a)3b)中，我们 确定新治疗的对治疗无效的IWP的特征。3C)识别患者-， 通过686计划与药物吸收相关的家庭和其他利益相关者层面的因素。目标4)通过 在能力建设方面，我们确定了一批新的临床研究人员，并通过这项大规模研究提供培训 引导他们走向可持续的研究事业。最后，在探索性分析中，我们将比较 年龄差距“(即脑部年龄减去按时间顺序排列的年龄的成像测量)在3年时间内 每组中的个人。我们建议在长时间的大样本中阐明认知过程， 未经治疗的精神病，从而促进了中国、其他LMIC和世界范围内对精神病的理解。

Studies of the untreated course of non-affective psychosis have been largely limited to urban samples with short duration of untreated psychosis (DUP) (less than 5 years). We propose to take advantage of a unique, time-limited opportunity to study the extended untreated course of psychosis among individuals with psychosis (IWP) with very long DUP (>30 yrs), in predominantly rural areas of China. Our first goal is to develop knowledge about the course of untreated ongoing psychosis and associated neurobiology over a span of decades. Our second goal is to expand knowledge about initiating treatment (e.g. antipsychotic medications) in IWP who remain untreated into late adulthood. This R01 proposes a 3-year follow-up of 400 untreated IWP, 400 treated IWP, and 400 healthy controls (HCs) from mainly rural areas of Guangxi Province and Hunan Province (matched on key variables). Our primary focus is on cognitive performance, but we will also compare the 3 groups on other symptomatic and functional domains. Moreover, comparisons of prolonged untreated IWP who accept treatment (i.e., the ‘newly-treated’) versus refuse treatment (i.e., the ‘ongoing untreated’) will provide crucial information about the effects of initiating antipsychotic treatment in IWP with extended DUP. Our specific aims include: Aim 1) compare change in cognitive performance from baseline to 3-year follow-up in 3 groups: ongoing untreated IWP, matched treated IWP, and matched HCs. 1a) we hypothesize in the primary analysis that decline in cognitive performance over 3-year follow-up, measured by the MATRICS Consensus Cognitive Battery (MCCB), will be greatest in the ongoing untreated group, intermediate in the matched treated group, and least in HC. 1b) a secondary analysis will similarly compare changes in specific cognitive domains and those who show progressive cognitive declines between the 3 groups, in the same order hypothesized in 1a). Aim 2) conduct secondary analyses to compare change in measures of psychopathology, social and vocational functioning, medical co-morbidity, and social burden from baseline to 3- year follow-up among the same 3 groups specified in Aim 1. Aim 3) conduct secondary analyses comparing the ongoing untreated and newly treated groups with respect to: 3a) change in cognitive performance; 3b) change in psychopathology, functioning, medical co-morbidity, and social burden. In Aims 3a) + 3b), we identify characteristics of newly treated IWP who remain nonresponsive to treatment. 3c) identify patient-, family-, and other stakeholder-level factors associated with medication uptake via the 686 Program. Aim 4) via capacity-building, we identify a cohort of new clinical researchers and provide training via this large-scale study in guiding them towards sustainable research careers. Finally, in exploratory analyses, we will compare “brain age gap” (i.e., an imaging measure of brain age minus chronological age) over the 3-year period in a subset of individuals from each group. We propose to illuminate the course of cognition in a large sample of prolonged, untreated psychosis, thus advancing understanding of psychosis in China, other LMICs, and worldwide.