Neurophysiological Studies of Schizophrenia

描述（由申请人提供）：精神分裂症和双相情感障碍是主要的精神疾病，造成他们的受害者和他们的家人非常痛苦，是一个主要的生产力损失和医疗费用的来源，我们的国家。然而，人们对它们知之甚少，特别是关于疾病过程中最有效的治疗干预时间。这项竞争性R 01更新申请的主要目标是推进我们对精神分裂症（SZ）神经生理学的了解，该申请采用了前瞻性纵向研究设计。（和情感性精神病）通过：1）评估EEG事件相关电位（ERP）的功能异常，其跨越处理的早期和晚期，特别关注早期听觉处理; 2）将这些信息与结构MRI解剖学相结合;以及3）将ERP和MRI测量与临床特征相结合。我们的研究结果以及其他研究结果表明，了解这种疾病的过程非常重要。我们对首次精神病发作受试者（FE，操作上定义为首次住院）进行的前瞻性纵向研究的初始数据显示，MRI/ERP功能缺陷的发作后进展，包括脑灰质丢失和伴随的ERP功能测量减少。在首次住院后的前1.5年内进展非常迅速，但在慢性患者中进展缓慢得多甚至不存在。本申请增加了第二纵向研究群体，即临床上为精神病前驱期（PRO）的受试者，我们建议在其中跟踪进展和转化为精神病，特别是SZ精神病的生物预测因子。统一我们的方法是我们的神经生物学模型的基础上，NMDA神经传递异常的复发性抑制的基本细胞缺陷。具体来说，我们假设这种异常可能是负责在这种疾病中观察到的发育异常以及前驱和发病后进展。这种基于细胞的模型和我们的初步数据已经导致越来越多地关注早期大脑处理，特别是听觉处理，因为来自早期处理范例的结果似乎特别适合于与大脑解剖缺陷和疾病进展的记录相关。最后，我们将使用这些措施来评估特异性FE精神分裂症精神病与FE情感性精神病（90%双极）。就意义而言，几乎不需要强调的是，如果我们预测的ERP/MRI异常在前列腺癌中的进展得到证实，并构成转换的预测因素，这些发现可能会形成心理社会和药物治疗干预的合理基础。此外，如果我们的初步发现得到证实-精神分裂症早期发病后进展迅速，随后发生的变化较小-这将立即形成强调早期治疗的科学基础，并可能预防疾病随时间的进展。

DESCRIPTION (provided by applicant): Schizophrenia and bipolar disorder are major mental illnesses that cause their victims and their families much anguish and are a major source of lost productivity and medical care expenses to our nation. Yet too little is known about them, especially about the most effective time of treatment intervention during the course of illness. The main goal of this competing R01 renewal application, which uses a prospective longitudinal study design, is to advance our knowledge of the neurophysiology of schizophrenia (SZ) (and affective psychosis) by: 1) evaluating functional abnormalities in EEG event-related potentials (ERPs) that span both early and late stages of processing, with a special focus on early auditory processing; 2) integrating this information with structural MRI anatomy; and 3) integrating both ERP and MRI measures with clinical features. Findings from our work, as well as others, suggest the importance of understanding the course of the disorder. Initial data from our prospective longitudinal study of first psychotic episode subjects (FE, operationally defined as first hospitalization)have shown which demonstrate post onset progression of MRI/ERP features deficits, including brain gray matter loss and concomitant reduction of ERP functional measures. Progression is very rapid in the first 1.5 years after initial hospitalization, but much slower or even absent in chronic patients. The present application adds a second longitudinally studied population, subjects who are clinically prodromal for psychosis (PRO) in whom we propose to track progression and biopredictors of conversion to psychosis, especially SZ psychosis. Unifying our approach is our neurobiological model of a fundamental cellular defect in recurrent inhibition, based on an NMDA neurotransmission abnormality. Specifically, we hypothesize that such an abnormality may be responsible for both the developmental abnormalities observed in this disorder as well as the prodromal and post-onset progression. This cellular- based model and our preliminary data have led to an increasing focus on early-stage brain processing, especially auditory processing, as results from early processing paradigms appear to be especially amenable to correlation with brain anatomical deficits and with documentation of progression of the disorder. Finally, we will use these measures to evaluate specificity to FE schizophrenic psychosis versus FE Affective Psychosis (90% biopolar). In terms of significance, it hardly needs emphasis that, should our prediction of progression of ERP/MRI abnormalities in prodromes be confirmed and constitute predictor(s) of conversion, such findings would likely form a rational basis for psychosocial and medication therapeutic interventions. Moreover, should our preliminary findings be confirmed -rapid post-onset progression in the early course of schizophrenia with lesser changes occurring later-this would immediately form a scientific foundation for emphasis on early treatment, and perhaps prevention of progression of illness over time.