Aberrant functional connectivity in psychosis

精神病中的异常功能连接

• 批准号: 6989204
• 负责人: KENT A KIEHL
• 金额: $ 31.28万
• 依托单位: HARTFORD HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-27 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989204
• 关键词: biomarker; bipolar depression; brain circulation; brain electrical activity; brain imaging /visualization /scanning; brain mapping; clinical research; data collection methodology /evaluation; early diagnosis; electrophysiology; evoked potentials; frontal lobe /cortex; functional ability; functional magnetic resonance imaging; human subject; intercellular connection; longitudinal human study; mental disorder diagnosis; neuropsychological tests; parietal lobe /cortex; schizophrenia; synapses; temporal lobe /cortex

DESCRIPTION (provided by applicant): Schizophrenia and psychotic bipolar disorder are debilitating mental illnesses characterized by diffuse emotional and cognitive impairment in many domains of mental function. One of the most pressing needs in psychiatry is the development of procedures to aid in the differential diagnosis of these two disorders at early stages. Accumulating evidence suggests that a cardinal abnormality in schizophrenia is aberrant connections between brain regions (i.e., functional connectivity). Aberrant functional connectivity has been observed in frontal and temporal lobes in schizophrenia during performance of target detection of low probability events. Patients with bipolar illness show impairments in multiple frontal circuits, basal ganglia, parietal cortex and cerebellum during target detection but show greater activity in temporal lobe regions compared to patients with schizophrenia. These results suggest psychotic bipolar illness may be associated with aberrant functional connectivity between frontal, striatal, and temporal lobe circuits - but in a pattern opposite to that observed in schizophrenia. The present proposal seeks to test the hypothesis that event related potential (ERP) topography, patterns of hemodynamic activity, and measures of functional connectivity, will reliably differentiate patients with schizophrenia from patients with psychotic bipolar illness during performance of target detection. High temporal resolution electrophysiological techniques and high spatial resolution hemodynamic imaging will be used to map the functional neural architecture associated with target detection. Independent Component Analyses will be used to examine the patterns of aberrant functional connectivity. Patients with clear diagnoses of schizophrenia or psychotic bipolar illness will be studied during the first week of a relapsing psychotic episode and again at 3 months and at 6 months postepisode. The longitudinal design will permit evaluation of state and trait markers of the two disorders. It is hypothesized that patients with schizophrenia will be reliably differentiated from patients with psychotic bipolar illness based on the pattern of hemodynamics and functional connectivity measures in frontal, temporal and subcortical structures. This work will be an important step in developing procedures to aid in the differential diagnosis of schizophrenia or psychotic bipolar illness at early stages of the disorder. The data also will permit an examination of psychotic symptoms (i.e., disorganization, reality distortion, and psychomotor poverty) associated with electrophysiological and hemodynamic measures of brain function.

描述（由申请人提供）：精神分裂症和精神病性双相情感障碍是使人衰弱的精神疾病，其特征是精神功能许多领域的弥漫性情绪和认知障碍。精神病学最紧迫的需求之一是开发有助于在早期阶段鉴别诊断这两种疾病的程序。越来越多的证据表明，精神分裂症的一个主要异常是大脑区域之间的异常连接（即功能连接）。在执行低概率事件的目标检测过程中，精神分裂症患者的额叶和颞叶存在异常的功能连接。双相情感障碍患者在目标检测过程中表现出多个额叶回路、基底神经节、顶叶皮层和小脑的损伤，但与精神分裂症患者相比，颞叶区域表现出更大的活动。这些结果表明，精神病性双相情感障碍可能与额叶、纹状体和颞叶回路之间的异常功能连接有关，但其模式与精神分裂症中观察到的相反。本提案旨在检验以下假设：事件相关电位（ERP）地形、血流动力学活动模式和功能连接测量将在目标检测过程中可靠地区分精神分裂症患者与精神病性双相情感障碍患者。高时间分辨率电生理技术和高空间分辨率血流动力学成像将用于绘制与目标检测相关的功能神经结构。独立组件分析将用于检查异常功能连接的模式。明确诊断为精神分裂症或精神病性双相情感障碍的患者将在精神病复发发作的第一周进行研究，并在发作后 3 个月和 6 个月再次进行研究。纵向设计将允许评估两种疾病的状态和特征标记。据推测，根据额叶、颞叶和皮质下结构的血流动力学模式和功能连接测量，可以将精神分裂症患者与精神病性双相情感障碍患者可靠地区分开来。这项工作将是开发有助于在精神分裂症或精神病性双相情感障碍早期进行鉴别诊断的程序的重要一步。这些数据还将允许检查与脑功能的电生理学和血流动力学测量相关的精神病症状（即紊乱、现实扭曲和精神运动贫困）。