Adolescent Neural Substrates of Risk for Schizophrenia

描述（由申请人提供）：本职业发展计划的主要目的是为候选人提供所需的培训、支持和资源，使其成为神经精神病学研究领域的独立研究者。候选人的长期目标是通过建立一个结合流行病学、发育学和神经影像学方法的多学科研究项目来推进对精神分裂症发育神经病理学的认识。候选人在本奖项期间的短期目标是在以下领域发展专业知识：(1)磁共振成像（MRI）研究的方法、设计和分析；(2)认知神经科学与神经心理学；(3)纵向研究方法与设计。这些培训目标将通过课程作业、咨询这些领域的知名研究科学家，以及在麦克林医院脑成像中心完成一项研究学习计划来实现。拟议研究的设计和假设是基于越来越多的工作（包括候选人之前的研究），这些工作表明遗传和产科因素可能以一种易患精神分裂症的方式破坏大脑发育。也有初步证据表明，青春期后期精神病发作的特征性时间可能与这一时期前额叶和颞边缘皮层发生的成熟大脑变化有关。据此，本研究计划对精神分裂症遗传风险高（HR）和低（LR）的青少年进行纵向病例对照调查。该研究的第一个主要目的是检查遗传风险状态和OCs对预测认知功能的神经心理学测量和区域脑容量的结构MRI测量的贡献。第二个主要目的是评估HR和LR受试者在基线和2年随访评估之间的脑结构和认知功能的年龄相关变化。这项研究的结果有望增加我们对青春期大脑正常成熟变化的理解，这是一个相对研究不足的领域，尽管它与精神分裂症和其他神经精神疾病有潜在的关联。此外，这项研究与精神分裂症的病理生理学和疾病高风险个体的发病前识别有关。

DESCRIPTION (provided by applicant): The principal aim of this career development plan is to provide the candidate with the training, support, and resources required to develop as an independent investigator in the field of neuropsychiatric research. The candidate's long-term goals are to advance knowledge of the developmental neuropathology of schizophrenia by establishing a multidisciplinary research program that combines epidemiologic, developmental, and neuroimaging methods. The candidate's short-term goals for the duration of this award are to develop expertise in the following areas: (1) methods, design, and analysis of magnetic resonance imaging (MRI) studies; (2) cognitive neuroscience and neuropsychology; (3) longitudinal research methods and design. These training goals will be met through a combined program of coursework, consultation with established research scientists in these fields, and completion of a research study plan at McLean Hospital's Brain Imaging Center. The design and hypotheses of the proposed study were based on a growing body of work (including the candidate's prior research) indicating that genetic and obstetric factors may disrupt brain development in a manner that predisposes to schizophrenia. There is also preliminary evidence that the characteristic timing of psychosis onset in late adolescence may relate to maturational brain changes that occur around this period in prefrontal and temporal-limbic cortices. Accordingly, the research plan proposes a longitudinal, case-control investigation of adolescents at high (HR) and low (LR) genetic risk for schizophrenia. The first major aim of the study is to examine the contributions of genetic risk status and OCs to the prediction of neuropsychological measures of cognitive function and structural MRI measures of regional brain volume. The second major aim is to assess age-related changes in brain structure and cognitive function between the baseline and 2-year follow-up assessments in the HR and LR subjects. The results of this study are expected to increase our understanding of the normative brain maturational changes of adolescence, which has been a relatively under-studied area despite its potential relevance to schizophrenia and other neuropsychiatric disorders. In addition, this study has relevance to the pathophysiology of schizophrenia and to the premorbid identification of individuals at heightened risk for the disorder.