Longitudinal trajectories in treated and untreated schizophrenia

对未经治疗的非情感性精神病的研究主要限于城市样本， 短期未经治疗的精神病（DUP）（少于5年）。我们建议利用一个独特的， 有时间限制的机会，研究精神病患者中延长的未治疗精神病病程 (IWP)DUP时间很长（>30年），主要分布在中国农村地区。我们的第一个目标是发展 关于未经治疗的持续性精神病的过程和相关神经生物学的知识， 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， IWP在成年后期仍不接受治疗。本R 01建议对400例未经治疗的IWP进行3年随访， 400名治疗的IWP和400名健康对照（HC），主要来自广西和湖南的农村地区 省（关键变量匹配）。我们主要关注的是认知表现，但我们也会比较 其他症状和功能领域的3组。此外，长期未治疗的 接受治疗的IWP（即，“新处理的”）与垃圾处理（即，“正在进行的未处理”）将 提供了关于在IWP伴扩展DUP患者中开始抗精神病药物治疗的影响的关键信息。 我们的具体目标包括：目标1）比较从基线到3年随访的认知表现变化 在3组中：正在进行的未经治疗的IWP、匹配的经治疗的IWP和匹配的HC。1a）我们假设 通过MATRICS测量的3年随访期间认知表现下降的主要分析 共识认知成套测验（MCCB）在正在进行的未治疗组中最高，在 匹配的治疗组，HC最少。1b）二次分析将类似地比较特定 认知领域和那些谁显示进行性认知下降之间的3组，在相同的 在1A中假设的顺序）。目的2）进行二次分析，以比较 从基线到基线的精神病理学、社会和职业功能、医学共病和社会负担 3-目标1中规定的相同3组中的1年随访。目的3）进行二次分析，比较 正在进行的未治疗组和新治疗组的以下方面：3a）认知表现的变化; 3b） 精神病理学、功能、医学共病和社会负担的变化。在目标3a）和3b）中，我们 确定对治疗无反应的新治疗IWP的特征。3c）识别患者， 家庭和其他与686计划药物摄取相关的患者水平因素。目标4）通过 能力建设，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“大脑 年龄差距”（即，脑年龄减去实足年龄的成像测量）在3年期间的一个子集中， 每个群体的人。我们建议在一个大样本的长期， 未经治疗的精神病，从而促进对中国、其他中低收入国家和全球精神病的理解。

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.