PROJECT 3: ELECTROPHYSIOLOGICAL & GRAY MATTER MARKERS & PREDICTORS OF PROGRESSION

项目 3：电生理学

• 批准号: 8136028
• 负责人: Robert W McCarley
• 金额: $ 12.53万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8136028
• 关键词: Affect; Age; Anatomy; Area; Auditory; Auditory Hallucination; Autopsy; Biological Markers; Brain; Chronic Schizophrenia; Clinical; Data; Defect; Development; Disease; Documentation; EP300 gene; Event-Related Potentials; Frequencies; Gender; Gene Expression; Generations; Genes; Genetic; Glutamates; Gray unit of radiation dose; Hippocampus (Brain); Hospitalization; Incipient Schizophrenia; Individual; Left; Link; Magnetic Resonance Imaging; Matched Group; Measures; Medial; Methods; Modeling; Neurobiology; Neurons; Parietal; Pathology; Play; Prefrontal Cortex; Process; Protocols documentation; Pyramidal Cells; Recording of previous events; Recurrence; Relative (related person); Research Personnel; Role; Schizophrenia; Site; Socioeconomic Status; Source; Staging; Structure; Structure of inferior temporal gyrus; Superior temporal gyrus; Temporal Lobe; Time; Ventricular; Visual; Visual Hallucination; Work; association cortex; base; cell type; first episode schizophrenia; follow-up; gamma-Aminobutyric Acid; gray matter; interest; neocortical; neural circuit; programs; progression marker; research study

Project 3. Electrophysiological and MRI gray matter markers and predictors of progression. Increasing evidence, including that from our CIDAR investigators, points to a post-onset progression of event-related potential (ERP) and MRI markers of pathology in schizophrenia (SZ), including a conjoint progression of gray matter loss in Heschl gyrus and abnormalities of pitch mismatch negativity (MMN). However, the relative merit of each of the many putative markers in SZ is not clear, while markers in the prodromal period are not at all or only minimally defined. Accordingly, this project will study a selected set of putative biomarkers of vulnerability to progression in 3 sets of subjects,each with an equal number of control subjects, group matched for age, gender and parental socioeconomic status: 1) 75 subjects with prodromal manifestations of SZ (PRO), studied at entry, at one year longitudinal follow-up, and, for converters to SZ, immediately post conversion when they will enter the first episode protocol. 2) The first episode schizophrenia (FESZ) protocol will include the projected 24 converters and 80 new subjectswith first episode schizophrenia, operationally defined as first hospitalization for the disorder. FESZ & controls will be studied at entry (t1), 6 months post-entry (t2) and 18 mo post-entry (t3), timing based on our preliminary data showing the maximal rate of progression is immediately post-onset. 3) The chronic schizophrenia group (CSZ) will be 42 individuals with a history of 3 or more hospitalizations and a minimum 5 year post-onset duration who will be studied on one occasion to determine if the putative progression markers are, as needed in this model, present in the fully developed illness, near the end stage of progression. We will use ERPs of gamma band oscillations, mismatch negativity (pitch and duration) and P300, with MRI measuresof neocorticalgray gray matter, sulcal and ventriciular CSF, as well as specific regions of interest, including superior temporal gyrus, Heschl gyrus, and prefrontal cortex. We predict progression of reduced ERP amplitude, decreased neocortical gray matter and increased CSF in both prodromes (duration mismatch, P300, gamma, gray matter measures) first episode (pitch mismatch, gamma, gray matter measures). We predict a gradient of degree of progression in both prodromes and FESZ with superior (STG) > middle > inferior temporal gyri, and with STG progression greater than neocortical gray matter. We predict lesser progression in hippocampus than neocortical areas. In conjunction with the genetics core we will determine association of change measures with particular genes. In conjunction with the post-mortem core we will determine if expression data in parvalabumin GABA neurons and pyramidal cells are consistent with our model of the source of gamma oscillation abnormality in the interaction of these two cell types.

项目3。电生理和MRI灰质标记和进展的预测指标。 越来越多的证据，包括我们的CIDAR研究人员，指出了发病后的进展 精神分裂症（SZ）的事件相关电位（ERP）和病理学的MRI标记，包括联合 heschl回的灰质损失的进展和音高不匹配负性（MMN）的异常。 但是，SZ中众多推定标记中每个标记的相对优点尚不清楚，而标记中的标记 前驱周期根本没有或最少定义。 因此，该项目将研究一套选择的推定生物标志物 3组受试者，每个受试者数量相等，组为年龄，性别和 父母的社会经济状况：1）75个在进入时研究的SZ前驱表现（Pro）的受试者 在一年的纵向后续行动中，对于转换为SZ，在转换后立即进行转换 输入第一集协议。 2）第一集精神分裂症（FESZ）协议将包括投影 24个转换器和80个新主题WESTSWITH第一集精神分裂症，在操作上定义为第一 该疾病的住院。 Fesz＆Controts将在入口（T1），入门后6个月（T2）和18个研究中进行研究 进入后（T3），基于我们的初步数据，表明进展的最大速率为 立即发生后。 3）慢性精神分裂症组（CSZ）将是42个患者，有3个或3个 更多的住院和至少5年后持续时间将有一次研究 在此模型中，确定假定的进程标记是否存在于全面开发中 疾病，近乎进展的阶段。 我们将使用伽马频段振荡，不匹配的负性（音高和持续时间）和p300的ERP，并使用 新皮质灰质，沟和心室CSF以及特定区域的MRI测量 兴趣，包括上颞回，赫希尔回和前额叶皮层。我们预测 ERP幅度降低，新皮层灰质减少和CSF增加（持续时间） 不匹配，P300，伽玛，灰质措施）第一集（音调不匹配，伽玛，灰质 措施）。我们预测前驱体和Fesz的进展程度梯度 （STG）>中间>次次回旋，并且STG进展大于新皮层灰质。我们 预测海马比新皮质区域的进展较少。与遗传学核心结合在一起 将确定变化措施与特定基因的关联。与验尸结合 核心我们将确定Parvalabumin Gaba神经元和锥体细胞中的表达数据是否一致 通过我们在这两种细胞类型的相互作用中γ振荡异常的模型。