Perceptual Organization Dysfunction as a Biomarker of Schizophrenia

知觉组织功能障碍是精神分裂症的生物标志

基本信息

批准号：
8689515
负责人：
STEVEN M SILVERSTEIN
金额：
$ 19.7万
依托单位：
RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-20 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8689515
关键词：
Acute Admission activity Behavioral Binding Biological Markers Brain region Characteristics Clinical Cognition Cognitive Control Groups Data Development Disabled Persons Disease Progression Enrollment Functional disorder Heterogeneity Hospitalization Hospitals Impairment Inpatients Laboratories Length of Stay Link Measurement Measures Mental disorders National Institute of Mental Health Outcome Outpatients Patients Performance Pharmaceutical Preparations Phase Population Process Psychometrics Recovery Reporting Sample Size Schizophrenia Severities Severity of illness Staging State Hospitals Strategic Planning Subgroup Symptoms Task Performances Testing Therapeutic Intervention Time United States National Institutes of Health Validation Variant base cognitive function cognitive neuroscience design drug development follow-up functional decline high risk improved indexing interest meetings neurophysiology older patient outcome forecast patient population perceptual organization public health relevance relating to nervous system response sound therapy development treatment effect

项目摘要

DESCRIPTION (provided by applicant): The NIMH MATRICS and CNTRICS initiatives have clarified the domains of cognitive functioning that are most relevant to treatment development targeting improved cognition and functioning in people with schizophrenia. These projects also identified specific tasks that are psychometrically sound and well validated in patient populations, and that, in the case of CNTRICS, have well understood neurophysiology. More recently, interest has increased in identifying tasks that meet these criteria and that are sensitive to treatment effects. Identification of such tasks is important for grounding our understanding of illness progression and recovery processes within a cognitive neuroscience framework. This information would also allow for cognitive neuroscience-based indicators of treatment responsiveness, and therefore for more targeted drug development efforts and early prediction of medication response. Promising candidates for this type of task are measures of perceptual organization. Selected tests of perceptual organization meet the criteria of psychometric soundness (including avoidance of generalized deficit confounds), validation in patient studies, and known neurophysiology, although evidence regarding treatment effects at this point comes from very limited data. We now propose to conduct the first study in which schizophrenia patients are followed-up from the acute to stabilization to stable phases of illness, to determine whether perceptual organization dysfunction normalizes over the course of recovery. We will also determine if perceptual organization indices are most relevant for an illness subtype characterized by poor premorbid functioning, poor prognosis, and disorganized symptoms - relationships suggested by past studies. In addition, we will examine the course of perceptual organization in a first-episode population, which has not been previously described. Some evidence suggests that perceptual organization is normal or exaggerated at first episode. We will clarify whether the impairment is present at first episode or whether it develops within 15 months after initial hospitalization. For patients who begin to demonstrate impairment during the follow-up period, we will determine with what clinical and functioning changes the emerging abnormality is associated. We will explore these issues using a follow-up design in which we will enroll first-episode and later-episode schizophrenia patients (and a healthy control group), test them at hospital admission and discharge, and then again every 3 months, over a 15-month period. We will also examine covariation between changes in perceptual organization and changes in symptoms and level of functioning. The proposed project is consistent with two objectives from the NIMH Strategic Plan: 1) Strategy 1.3: Identify and integrate biological markers (biomarkers) and behavioral indicators associated with mental disorders; and 2) Strategy 2.1: Define the developmental trajectories of mental disorders. This study will determine the extent to which performance-based indices from promising perceptual organization tasks serve as biomarkers of illness processes for schizophrenia in general, or for a severely disabled illness subtype.

描述（由申请人提供）：NIMH MATRICS 和 CNTRICS 计划阐明了与旨在改善精神分裂症患者认知和功能的治疗开发最相关的认知功能领域。这些项目还确定了在心理测量上合理且在患者群体中得到充分验证的具体任务，并且就 CNTRICS 而言，这些任务具有很好的神经生理学知识。最近，人们越来越关注确定满足这些标准并且对治疗效果敏感的任务。识别此类任务对于在认知神经科学框架内奠定我们对疾病进展和恢复过程的理解非常重要。这些信息还可以用于基于认知神经科学的治疗反应指标，从而实现更有针对性的药物开发工作和药物反应的早期预测。此类任务的有前途的候选人是感知组织的衡量标准。选定的知觉组织测试符合心理测量健全性（包括避免广义缺陷混淆）、患者研究验证和已知神经生理学的标准，尽管目前有关治疗效果的证据来自非常有限的数据。我们现在建议进行第一项研究，对精神分裂症患者从疾病的急性期到稳定期进行随访，以确定感知组织功能障碍是否在康复过程中恢复正常。我们还将确定感知组织指数是否与以病前功能不良、预后不良和紊乱症状为特征的疾病亚型最相关——过去的研究表明这些关系是存在的。此外，我们将研究第一阶段人群的知觉组织过程，这在之前没有被描述过。一些证据表明，感知组织在第一次发作时是正常的或夸大的。我们将澄清该损伤是否在首次发作时就存在，或者是否在初次住院后 15 个月内出现。对于在随访期间开始表现出损伤的患者，我们将确定新出现的异常与哪些临床和功能变化相关。我们将通过后续设计来探讨这些问题，其中我们将招募首发和后期精神分裂症患者（以及健康对照组），在入院和出院时对他们进行测试，然后每 3 个月进行一次测试，持续时间超过15个月的期限。我们还将研究知觉组织变化与症状和功能水平变化之间的协变。拟议的项目符合 NIMH 战略计划的两个目标： 1）战略 1.3：识别和整合与精神障碍相关的生物标志物（biomarkers）和行为指标； 2）策略2.1：定义精神障碍的发展轨迹。这项研究将确定来自有希望的感知组织任务的基于绩效的指数在多大程度上作为一般精神分裂症或严重残疾疾病亚型疾病过程的生物标志物。