Mapping Abnormal Neurodevelopment in Schizophrenia

描述（由申请人提供）：脑结构和功能的缺失是精神分裂症的关键神经生物学特征之一。在精神分裂症受试者中，神经结构回路内存在组织体积损失、神经元密度变化和功能激活缺陷。这个康特精神疾病神经科学中心（CCNMD）的中心科学目标是更精确地定义这些大脑结构和功能异常的解剖模式，调查其可能的原因（即，遗传的和/或环境的）和发病机理，并建立这些结构异常和认知功能异常之间的功能联系（例如，工作记忆和情景记忆），这可能是精神病理学和残疾的基础。我们的总体假设是，精神分裂症的遗传易感性可能部分由特定脑区网络内神经解剖结构和功能的变化来表达，并且这些相同的结构可能在早期发育期间受到环境损伤的影响，最终导致目前定义疾病的认知和临床异常。 CCNMD将1）对精神分裂症受试者、他们的非精神病同胞、健康对照及其同胞的脑结构和功能进行综合研究。2）研究胎儿环境损伤猕猴模型中脑结构变化的发育过程。（3）再次利用猕猴阐明工作记忆神经回路的细胞成分。最后，我们将使用重组的近交系小鼠来鉴定影响这些神经解剖学和行为表型的基因。 为中心提出的各个项目都有几个主题。结合共享的技术和资源，总体假设和这些主题代表了作为一个中心而不是一系列R 01项目资助这项研究的强烈理由。

DESCRIPTION (provided by applicant): Abnormalities of brain structure and function are one of the key neurobiologic characteristics of schizophrenia. In schizophrenia subjects, losses of tissue volume, changes in neuronal density, and deficits of functional activation are present within a circuit of neural structures. The central scientific goals of this Conte Center for the Neuroscience of Mental Disorders (CCNMD) are to more precisely define the anatomical pattern of these abnormalities in brain structure and function, to investigate their possible causes (i.e., genetic and/or environmental) and pathogenesis, and to establish functional links between these structural abnormalities and abnormalities of cognitive function (e.g., working and episodic memory) that may underlie psychopathology and disability. Our overarching hypothesis is that genetic liability for schizophrenia may be expressed in part by variation in neuroanatomical structure and function within a network of specific brain regions and that these same structures may be impacted by environmental insult during early development, ultimately leading to the cognitive and clinical abnormalities that currently define the disease. The proposed CCNMD will 1) carry out an integrated investigation of brain structure and function in schizophrenia subjects, their non-psychotic siblings, healthy controls and their siblings.2) Study the developmental progression of changes in brain structure in a macaque model of fetal environmental insult. and 3) elucidate the specific cellular elements of the neural circuit underlying working memory again using macaques. Finally, we will use recombinant, inbred strains of mice to identify genes that influence these neuroanatomical and behavioral phenotypes. Several themes are carried across the individual Projects proposed for the Center. Taken together with shared technologies and resources, the overarching hypothesis and these themes represent a strong rationale for the funding of this research as a Center, rather than a series of R01 projects.