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

• 批准号: 8644920
• 负责人: STEVEN M SILVERSTEIN
• 金额: $ 42.99万
• 依托单位: RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS
• 依托单位国家: 美国
• 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/8644920
• 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

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计划阐明了与治疗开发最相关的认知功能领域，旨在改善精神分裂症患者的认知和功能。这些项目还确定了特定的任务，这些任务在心理测量学上是合理的，在患者群体中得到了很好的验证，并且在CNTRICS的情况下，已经很好地理解了神经生理学。最近，人们对确定符合这些标准并且对治疗效果敏感的任务的兴趣有所增加。识别这些任务对于我们在认知神经科学框架内理解疾病进展和恢复过程非常重要。这些信息还将允许基于认知神经科学的治疗反应性指标，从而更有针对性的药物开发工作和药物反应的早期预测。这种类型的任务有希望的候选人是感知组织的措施。知觉组织的选定测试符合心理测量学健全性（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，尽管此时关于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，在这项研究中，精神分裂症患者从急性期到稳定期再到稳定期进行随访，以确定知觉组织功能障碍是否在恢复过程中正常化。我们还将确定知觉组织指数是否与以病前功能差、预后差和症状紊乱为特征的疾病亚型最相关--这是过去研究提出的关系。此外，我们将研究知觉组织的过程中的第一集人口，这是以前没有描述过。一些证据表明，知觉组织在第一次发作时是正常的或被夸大了。我们将澄清是否在首次发作时存在损害，或是否在首次住院后15个月内发展。对于在随访期间开始表现出损害的患者，我们将确定新出现的异常与哪些临床和功能变化相关。我们将使用随访设计来探索这些问题，其中我们将招募首次发作和后期发作的精神分裂症患者（以及健康对照组），在入院和出院时进行测试，然后在15个月内每3个月进行一次测试。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（生物标志物）和行为指标; 2）战略2.1：定义精神障碍的发展轨迹。本研究将确定在何种程度上表现为基础的指标，从有前途的知觉组织任务作为一般精神分裂症的疾病过程的生物标志物，或严重残疾的疾病亚型。