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灰质标记物和进展预测因子。