Brain Function and Structure in Young Children at Familial Risk for Schizophrenia

描述（由申请人提供）：识别预测精神病的标志物是发展精神分裂症早期干预和预防策略的核心。尚未尝试针对精神病前期和前驱期的一级或二级预防策略，因为在出现轻度精神病症状之前的青春期之前的时期缺乏生物标志物或对病理生理学的扎实了解（即，在假定的“前驱症状”之前）。因为有一致的证据表明，在后来发展为精神分裂症的人中，从儿童早期开始就存在明显的神经心理和社会缺陷，所以有充分的理由相信，大脑异常存在于青春期前，但迄今为止还没有证据表明这一时期存在这种异常。本提案旨在开始填补这一重要的知识空白。事实上，精神分裂症的一些早期症状，如自我意识障碍，以及那些反映受损的元认知，如受损的自我-他人边界，经常出现在我们打算研究的年龄范围内的精神分裂症（ARS）风险人群中。我们假设，“早期发病前”时期的神经生物学特征是大脑发育不良，反映在皮质厚度改变，海马和内侧前额叶皮质体积减少，信息处理异常和连接功能障碍。这项初步研究重点关注8- 11岁有精神分裂症风险的儿童，旨在以横断面设计测试有关大脑功能、结构和认知的假设，这将为后续旨在研究大脑纵向演变的赠款奠定基础青春期前ARS儿童的结构和功能。该项目将专注于一个新的，但非常有前途的新研究领域;处于危险中的儿童的内在经验的神经基质，通过评估（使用功能性MRI）：1）。大脑功能的“默认模式”; 2）.“自我反思”（对自己或他人的反思）背后的神经网络。此外，我们将把我们以前在青少年中的工作扩展到童年; 3）。工作记忆中的脑功能改变; 4）。结构异常研究目标与R21指南一致，强调在幼儿中进行这些成像研究的可行性方面的新奇和创新性。此外，该研究与2008年NIMH战略计划一致，其中预测和预防精神分裂症和残疾的风险是NIH的重点。

DESCRIPTION (provided by applicant): The identification of markers for the prediction of psychosis is central to the development of early intervention and prevention strategies for schizophrenia. Primary or secondary prevention strategies oriented to the pre-psychosis and pre-prodromal periods have not been attempted because of an absence of biomarkers or solid knowledge of pathophysiology in the period before adolescence prior to the emergence of mild psychotic symptoms (i.e., prior to the putative "prodrome"). Because there is consistent evidence of significant neuropsychological and social deficits beginning in early childhood of people who later develop schizophrenia, there is strong reason to believe that brain abnormalities are present in the preteen years, but there is no evidence as yet about such abnormalities in that period. The present proposal aims to begin to fill that critical gap of knowledge. Indeed, some of the earliest symptoms of schizophrenia such as disturbances in the sense of self, and those that reflect impaired metacognition such as impaired self-other boundaries are frequently present in those at risk for schizophrenia (ARS) in the age range we intend to study. We hypothesize that the neurobiology of the "early premorbid" period, is characterized by brain dysmaturation, reflected in altered cortical thickness, volume reduction in hippocampus and medial prefrontal cortex, abnormal information processing and dysfunctional connectivity. This preliminary study, focused on children at risk for schizophrenia, ages 8- 11, is designed to test hypotheses about brain function, structure, and cognition in a cross-sectional design that will lay a foundation for subsequent grants designed to study the longitudinal evolution of brain structure and function in prepubertal ARS children. This project will focus on a novel, but highly promising area of new research; the neural substrates of the inner experience of the child at risk, by evaluating (using functional MRI): 1). the "default mode" of brain function and; 2). the neural network underlying 'self reflection' (reflection about oneself or others). Moreover, we will extend to childhood our previous work in adolescents demonstrating; 3). altered brain function during working memory and 4). structural abnormalities. The study goals are consistent with the R21 guidelines emphasizing novelty and innovation, in regard to the feasibility of conducting these imaging studies in young children. Moreover, the study is consistent with the 2008 NIMH Strategic Plan in which prediction and prevention of schizophrenia and disability in those at risk for the illness are key NIH priorities.