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灰质标记物和进展的预测因子。 越来越多的证据，包括来自我们的CIDAR研究人员的证据，指出了 精神分裂症（SZ）的事件相关电位（ERP）和MRI病理标志物，包括联合 Heschl回灰质丢失的进展和音高失配负波（MMN）的异常。 然而，SZ中的许多推定标记中的每一个的相对优点尚不清楚，而SZ中的标记 前驱期根本没有定义或仅最低限度地定义。 因此，本项目将研究一组选定的推定生物标志物的脆弱性进展， 3组受试者，每组有相同数量的对照受试者，年龄、性别和 父母的社会经济状况：1）75名有SZ前驱表现的受试者（PRO），在入组时研究， 在一年的纵向随访中，对于转换为SZ的转换者，当他们将 进入第一集协议。2)首发精神分裂症（FESZ）方案将包括预计的 24例转换者和80例首次发作精神分裂症的新受试者，操作上定义为首次 住院治疗的障碍。FESZ和对照将在入学时（t1）、入学后6个月（t2）和18个月进行研究 入组后3个月（t3），根据我们的初步数据，显示最大进展率的时间为 发病后即刻。3)慢性精神分裂症组（CSZ）将是42名有3或4年病史的个体。 住院次数更多且发病后持续时间至少为5年的患者将接受一次研究， 根据该模型的需要，确定推定的进展标志物是否存在于完全发育的 疾病，接近发展的末期。 我们将使用伽马波段振荡、不匹配负波（音高和持续时间）和P300的ERP， MRI测量新皮质灰质、脑沟和脑室CSF，以及特定区域的 感兴趣区域，包括上级颞回、Heschl回和前额皮质。我们预测 ERP振幅降低，新皮质灰质减少，CSF增加，两个时间点（持续时间 不匹配，P300，伽马，灰质测量）第一次发作（音高不匹配，伽马，灰质 措施）。我们预测前列腺增生和FESZ的进展程度梯度具有上级 (STG)>中回>颞下回，STG进展大于新皮质灰质。我们 预测海马区的进展比新皮质区要小。结合遗传学核心， 将决定特定基因与变化测量的关联。结合验尸报告 核心，我们将确定在GABA神经元和锥体细胞的表达数据是否一致 我们的模型的伽马振荡异常的来源，在这两种细胞类型的相互作用。