2/3-Social Processes Initiative in Neurobiology of the Schizophrenia(s)

2/3-精神分裂症神经生物学社会过程倡议

• 批准号: 8758171
• 负责人: Anil K Malhotra
• 金额: $ 37.67万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8758171
• 关键词: Amygdaloid structure; Behavior; Biological Markers; Brain; Cognitive; Data; Disease; Dissociation; Emotions; Exhibits; Face; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Gold; Hospitals; Image Analysis; Impaired cognition; Impairment; Individual; Knowledge; Lead; Least-Squares Analysis; Major Mental Illness; Maps; Maryland; Measures; Mental disorders; Mind; Modeling; Morphology; Neurobiology; Neurocognition; Neurosciences Research; Normal Range; Outcome; Parietal; Participant; Pathway Analysis; Performance; Principal Investigator; Procedures; Process; Process Assessment; Psychopathology; Quality of life; Recovery of Function; Recruitment Activity; Relapse; Reporting; Research; Research Domain Criteria; Research Personnel; Resources; Rest; Sampling; Schizoaffective Disorders; Schizophrenia; Schizophreniform Disorder; Site; Social Functioning; Structure; Techniques; Therapeutic; Thick; Universities; base; behavior measurement; brain behavior; design; emerging adult; functional disability; functional outcomes; gray matter; improved; innovation; interest; mirror neuron; neural circuit; neuroimaging; new therapeutic target; patient population; public health relevance; simulation; social; social neuroscience; statistics; theories; white matter

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.

描述（由申请人提供）：在成年早期的主要精神疾病中，患有精神分裂症谱系障碍（SSD）（即精神分裂症、分裂情感性障碍、精神分裂样障碍）的人表现出社会功能的连续性损害。治疗效果甚微，而且损伤往往会持续存在。有关社会认知（SCog）过程障碍的神经生物学知识将促进治疗发现。在我们每个研究中心，试点数据显示，患有 SSD 的社交障碍最严重的人功能恢复的可能性很低，并且已知与健康个体 SCog 过程的神经生物学有关的离散大脑回路存在明显损伤。利用我们在三个中心一致的试点数据，以及我们小组在与现象学、结果、多中心神经影像和治疗创新相关的 SSD 研究方面的专业知识，我们建议在 SSD 患者中使用研究领域标准 (RDoC) 研究框架，以全面、明确地描述 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影像学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并检查皮质厚度网络拓扑，2）DTI采集和分析方法来绘制大脑中的白质回路； 3）基于功能磁共振成像的方法来参与这些相同的电路，包括功能连接测量以获得电路功能的详细测量。然后，我们将利用我们小组在复杂的多元神经影像统计（偏最小二乘）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。我们的提案直接在 RDoC 框架内建模；具体来说，我们使用分析矩阵作为指导结构，从整个精神分裂症谱系的正常对照中识别 SCog 过程构建的神经生物学。我们预计从电路特征层面开始识别显着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 通过识别社会功能受损的潜在神经回路和病理生理学来识别社交障碍。