1/3 - Social Processes Initiative in Neurobiology of the Schizophrenia(s)

描述(申请人提供)：在成年早期的主要精神疾病中，患有精神分裂症谱系障碍(即精神分裂症、分裂情感障碍、分裂样障碍)的人表现出一系列的社会功能障碍。治疗效果微乎其微，而且损伤往往持续存在。社会认知(SCOG)过程损害的神经生物学知识将促进治疗发现。在我们的每个站点，试点数据显示，社交障碍最严重的SSD患者功能恢复和离散大脑回路明显受损的可能性较低，这些回路与健康个体的SCOG过程的神经生物学有关。利用我们在三个地点一致的试点数据，以及我们团队在与现象学、结果、多部位神经成像和治疗创新相关的SSD研究方面的专业知识，我们建议使用SSD患者的研究领域标准(RDoC)调查框架来全面和明确地描述SCOG过程损害的神经生物学。我们的方法将使用先进的结构和功能神经成像方法来识别神经回路(沿着从健康对照组到SSD患者的连续体)，预测SCIG过程中的损害和伴随的社会功能。我们计划使用先进的神经成像和网络分析方法，包括：1)灰质形态学方法来绘制皮质厚度和检查皮质厚度网络拓扑；2)DTI获取和分析方法来绘制大脑中的白质电路；以及3)基于fMRI的方法来参与这些相同的电路，包括功能连通性测量以获得电路功能的详细测量。然后，我们将利用我们团队在复杂的多变量神经成像统计学(偏最小二乘法)方面的专业知识，提取与大脑结构-脑功能-行为相关的维度特征，并全面了解正常和异常(SSD)领域从电路到行为的社会过程的神经生物学。我们的建议直接在RDoC框架内建模；具体地说，我们使用分析矩阵作为我们的指导结构，以确定整个精神分裂症谱系中正常对照的SCOG过程结构的神经生物学。我们预计从电路特征的层面开始识别显著异常的大脑-行为关系。我们合作团队的最终目标是确定新的治疗靶点，用于治疗 通过识别社会功能受损的潜在神经回路和病理生理学，确定社会功能受损。

DESCRIPTION (provided by applicant): Among the major mental illnesses of early adulthood, people with schizophrenia spectrum disorders (SSDs) (i.e., schizophrenia, schizoaffective disorder, schizophreniform disorder) exhibit a continuum of impairment in social functioning. Treatment is minimally effective, and impairments tend to persist. Knowledge on the neurobiology of social cognitive (SCog) process impairment will foster therapeutic discovery. At each of our sites, pilot data show that people with SSDs who are among the most socially impaired have a low likelihood of functional recovery and manifest impairment in discrete brain circuits that are known to be involved in the neurobiology of SCog processes in healthy individuals. Leveraging our pilot data, which is consistent across three sites, and the expertise of our group in SSD research related to phenomenology, outcomes, multi-site neuroimaging, and treatment innovation, we propose to use the Research Domain Criteria (RDoC) investigational framework in people with SSDs to comprehensively and definitively delineate the neurobiology of SCog process impairment. Our approach will employ advanced structural and functional neuroimaging approaches to identify the neural circuitry (along a continuum from healthy controls to people with SSDs) that predict impairments in SCog processes and concomitant social function. We plan to use advanced neuroimaging and network analysis approaches including: 1) gray matter morphology approaches to map the thickness of the cortex and examine cortical thickness network topology, 2) DTI acquisition and analytic approaches to map white matter circuits in the brain; and 3) fMRI-based approaches to engage these same circuits, including functional connectivity measures to obtain detailed measures of circuit function. We will then use our group's expertise in sophisticated multivariate neuroimaging statistics (partial least squares), to extract dimensional features relating brain structure ->brai function -> behavior and provide a comprehensive understanding of the neurobiology of social processes from circuit to behavior across normal and abnormal (SSDs) domains. Our proposal is modeled directly within the RDoC framework; specifically, we are using a Matrix of Analysis as our guiding structure to identify the neurobiology of SCog process constructs from normal controls across the entire schizophrenia spectrum. We anticipate identifying substantially abnormal brain-behavior relationships starting from the level of circuit characterization. The ultimate goal of our collaborative team is to identify new therapeutic targets for the treatment of social impairments by identifying the underlying neural circuitry and pathophysiology of impaired social function.