Characterization of Variability in Motivation and Reward in Psychosis

项目摘要/摘要 这是一项NIMH探索/发展研究资助计划(R21)提案，题为 “精神病患者在动机和报酬方面的可变性的特征。”动力不足是一个标志 精神分裂症和相关疾病，并与社区结果差和治疗减少有关 在认知补救等行为干预期间的依从性和有效性。激励和奖励 不是统一的结构，而是由可测量和可分离的域组成，如RDoC中所描述的 正价系统结构域，它可能与疾病特征、结果和 治疗反应。然而，使用多种测量方法对PVS领域的功能障碍进行表征 跨分析单位还没有在精神病中进行，以及缺陷的概况是否出现和 与临床和社区功能或预测治疗结果的不同相关尚未 已经测试过了。 在本提案中，我们的目标是使用 精神病患者交叉诊断样本中分析单元间的多变量组合 (n=200)和健康对照(n=50)，并使用主体检查该领域的结构 组件分析。我们将使用紧急因素来a)检验因素和 临床、认知和社区功能测量，以及使用验证的动机行为 方法；以及b)使用聚类分析确定具有相似PVS因素特征的患者组。 类似的方法已经成功地发现了以前被组级别遮挡的有意义的分组 使用这种技术的均值比较(5，8)，允许检查沿线患者的概况 与异质性相比，感兴趣的结构与结果和神经生物学相关性更紧密地映射 分组，如诊断(6，7)。这个项目的发现将使我们能够检查生物机制 巩固这些因素(3)，并--关键地--指导治疗努力，以针对这些特定的过程 我们正在进行的研究项目。PI是一名早期调查员和K23获奖者，专注于职业生涯 论认知、PVS等多维症状域的性质和过程表征 所有精神病的症状，以及针对这些症状的治疗，如认知补救 赤字。

Project Summary/Abstract This is an NIMH Exploratory/Developmental Research Grant Program (R21) proposal entitled, “Characterization of Variability in Motivation and Reward in Psychosis.” Motivational deficits are a hallmark of schizophrenia and related disorders and are associated with poor community outcomes and reduced treatment adherence and efficacy during behavioral interventions such as cognitive remediation. Motivation and reward are not unitary constructs but are comprised of measurable and separable domains, as delineated in the RDoC Positive Valence Systems Domain, which may be differentially associated with illness traits, outcomes, and treatment response. However, characterization of dysfunction across the PVS domain using multiple measures across units of analysis has not been undertaken in psychosis, and whether profiles of deficits emerge and are differentially associated with clinical and community functioning or predictive of treatment outcomes has not yet been tested. In the present proposal we aim to measure multiple constructs across the PVS Domain using a multivariate battery across units of analysis in a cross-diagnostic sample of patients with psychosis (n=200) and healthy controls (n=50), and examine the structure of this domain using principal components analysis. We will use emergent factors to then a) examine associations between factors and clinical, cognitive, and community functioning measures, and with motivated behaviors using validation measures; and b) identify groups of patients who share similar PVS factor profiles using cluster analysis. Similar approaches have successfully uncovered meaningful groupings previously obscured by group-level means comparisons (5, 8) using such techniques, permitting the examination of profiles of patients along constructs of interest map more closely to outcomes and neurobiological correlates than do heterogeneous groupings like diagnosis (6,7). Findings from this project will position us to examine biological mechanisms that underpin these factors (3), and – critically – guide treatment efforts toward targeting these specific processes in our ongoing program of research. The PI is an early stage investigator and K23 Awardee with a career focus on characterization of the nature and course of multidimensional symptom domains such as cognition and PVS symptoms across the psychosis spectrum, and treatments such as cognitive remediation to target these deficits.