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

项目3：电生理和核磁共振灰质标记物和进展预测因子。 越来越多的证据，包括我们CIDAR调查人员的证据，指出了发病后的进展 精神分裂症(SZ)的事件相关电位(ERP)和MRI病理标记物 进行性Heschl回灰质丢失和基音不匹配负波(MMN)异常。 然而，SZ中许多推定标记的相对优劣尚不清楚，而SZ中的标记 前驱期根本没有或只有最低限度的定义。 因此，该项目将研究一组假定的易患疾病进展的生物标记物。 3组受试者，每组有相同数量的对照受试者，年龄、性别和年龄相匹配的小组 父母社会经济状况：1)75名先兆表现为SZ(PRO)的受试者，在入院时进行研究， 在一年的纵向跟踪中，对于到深圳的转换者，当他们愿意时，立即进行转换期 进入第一集方案。2)首发精神分裂症(FESZ)方案将包括 24名转化者和80名新受试者，首发精神分裂症，手术定义为首发 因这种疾病住院治疗。FESZ和对照将在进入(T1)、进入后6个月(T2)和18个月进行研究 进入后(T3)，基于我们的初步数据显示最大进展速度的计时是 在发病后立即发生。3)慢性精神分裂症组(CSZ)为42人，有3年或3年以上病史 更多的住院和至少5年的发病后病程，将在一次情况下研究 确定假定的进展标记是否如该模型中所需要的那样存在于完全发育的 疾病，接近发展的末期。 我们将使用伽马频段振荡、失配负波(音高和持续时间)和P300的ERP， 新皮质灰质、脑沟脑脊液和脑室脑脊液的MRI测量 兴趣区包括颞上回、Heschl回和前额叶皮质。我们预测的是 两个先兆的事件相关电位波幅降低、新皮质灰质减少和脑脊液增加(持续时间 不匹配，P300，伽马，灰质测量)第一集(音调不匹配，伽马，灰质 措施)。我们预测了先兆和FESZ的进展程度的梯度 (STG)中、下回，且STG进展大于新皮质灰质。我们 预测海马区的进展慢于新皮质区域。与遗传学核心一起，我们 将确定变化措施与特定基因的关联。结合验尸报告 核心我们将确定GABA神经元和锥体细胞中的Parvalabumin表达数据是否一致 用我们的模型研究了这两种细胞类型相互作用中伽马振荡反常的来源。

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.