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

描述（由申请人提供）：在成年早期的主要精神疾病中，精神分裂症谱系障碍（SSD）患者（即，精神分裂症、情感障碍、精神分裂症样障碍）表现出社会功能连续性损伤。治疗效果甚微，而且损害往往会持续存在。社会认知（SCog）过程障碍的神经生物学知识将促进治疗发现。在我们的每个研究中心，试点数据显示，社交障碍最严重的SSD患者功能恢复的可能性很低，并且已知参与健康个体SCog过程神经生物学的离散脑回路明显受损。利用我们的试点数据，这是一致的三个网站，和我们的团队在SSD研究的专业知识与现象学，结果，多站点神经影像学，和治疗创新，我们建议使用研究领域标准（RDoC）的研究框架与SSD的人，以全面和明确地描绘SCog过程损伤的神经生物学。我们的方法将采用先进的结构和功能神经成像方法来识别神经回路（沿着从健康对照到SSD患者的连续体），预测SCog过程和伴随的社会功能的损伤。我们计划使用先进的神经影像学和网络分析方法，包括：1）灰质形态学方法来映射皮层厚度并检查皮层厚度网络拓扑结构，2）DTI采集和分析方法来映射大脑中的白色物质回路; 3）基于fMRI的方法来参与这些相同的回路，包括功能连接测量以获得回路功能的详细测量。然后，我们将利用我们小组在复杂的多变量神经成像统计（偏最小二乘法）方面的专业知识，提取与大脑结构->大脑功能->行为相关的维度特征，并提供对正常和异常（SSD）领域从电路到行为的社会过程的神经生物学的全面理解。我们的建议直接在RDoC框架内建模;具体而言，我们使用分析矩阵作为指导结构，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。我们预计识别实质上异常的大脑行为的关系，从电路表征的水平。我们合作团队的最终目标是确定新的治疗靶点， 通过识别潜在的神经回路和受损的社会功能的病理生理学来评估社会功能障碍。

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.