fMRI Studies in Adolescents At-Risk for Schizophrenia

描述(由申请人提供)：这项职业发展提案的目的是让申请人获得必要的技能，以表征与精神分裂症风险青少年相关的神经发育异常。 精神分裂症是一种高度虚弱和复杂的疾病，其特征是认知功能，特别是工作记忆的严重异常。这种疾病可能是由神经发育异常和遗传因素引起的。对青少年一级亲属神经发育的研究有望帮助更好地阐明疾病的发病前疾病。这项提议将使用功能磁共振成像来研究精神分裂症患者的青少年一级亲属的工作记忆异常。功能磁共振成像的使用将有助于了解这些受试者功能神经结构的变化，并填补目前对疾病前兆的理解的空白。对fMRI数据的分析将集中在识别异常激活的区域，以及探测大脑区域之间的功能断开。还将探索异常的功能磁共振成像激活与大脑结构变化之间的关系。 在获奖期间，申请者将获得以下方面的培训：1)了解青春期发育神经科学，2)使用功能磁共振成像对青少年高危人群进行研究，3)了解与精神分裂症有关的临床问题，特别是其发病前和先兆阶段，4)了解与实地神经精神病学研究相关的统计、伦理和流行病学问题。到奖项结束时，申请者希望成为一名将神经成像应用于精神分裂症神经生物学先兆研究的专家。该提案的重点有望为疾病的发育神经生物学以及发育和遗传学的贡献提供更好的见解。这些数据将帮助申请者在获奖期的最后几年制定更大的项目，这些项目可能有助于在有精神分裂症风险的青少年中制定心理社会和精神药理学干预措施。

DESCRIPTION (provided by applicant): The aim of this career development proposal is to allow the applicant to acquire the skills necessary to characterize neurodevelopmental abnormalities associated with adolescents at risk for schizophrenia. Schizophrenia is a highly debilitating and complex disorder marked by severe abnormalities in cognitive function, particularly working memory. The illness may be mediated by neurodevelopmental abnormalities and by genetic factors. Studies of neurodevelopment in adolescent first-degree relatives who are at significantly elevated risk for developing the illness promise to help better elucidate the premorbid diatheses of the illness. This proposal will use fMRI to investigate working memory abnormalities in adolescent first-degree relatives of schizophrenia patients. The use of fMRI will facilitate an understanding of alterations in the functional neuroarchitecture of these subjects and fill a lacuna in the present understanding of the precursors of the illness. The analysis of the fMRI data will focus on identifying regions of aberrant activation, as well as probing functional disconnections between regions of the brain. Relationships between aberrant fMRI activation and structural alterations in the brain will also be explored. During the course of this award, the applicant will obtain training in: 1) understanding developmental neuroscience during the period of adolescence, 2) the use of fMRI for the study of adolescent high-risk populations 3) understanding of the clinical issues associated with schizophrenia, particularly its premorbid and prodromal phases, 4) understanding of statistical, ethical and epidemiological issues associated with the field neuropsychiatric research. By the conclusion of the award, the applicant expects to emerge as an expert on the application of neuroimaging to the study of the neurobiological precursors of schizophrenia. The proposal's focus promises to provide better insights into the developmental neurobiology of the illness and the contributions of development and genetics. The data will help the applicant develop larger projects during the concluding years of the award period that may help in the development of psychosocial and psychopharmacologic interventions in adolescents at risk for schizophrenia.