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

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.