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: 8890889
• 负责人: Anil K Malhotra
• 金额: $ 37.91万
• 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 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8890889
• 关键词: Amygdaloid structure; Behavior; Biological Markers; Brain; Data; Disease; Dissociation; Emotions; Exhibits; Face; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Gold; Health; 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; 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; Social Processes; Structure; Techniques; Therapeutic; Thick; Universities; base; behavior measurement; brain behavior; cognitive performance; cognitive process; design; emerging adult; functional disability; functional outcomes; gray matter; improved; innovation; interest; mirror neuron; neural circuit; neuroimaging; new therapeutic target; patient population; phenomenological models; 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，精神分裂症谱系障碍（SSD）（即精神分裂症，精神分裂症，精神分裂症）的人表现出社交功能受损的连续性。治疗至少有效，损害往往会持续存在。关于社会认知（SCOG）过程障碍的神经生物学的知识将促进治疗发现。在我们的每个站点上，试点数据都表明，具有社会障碍最障碍的SSD的人的功能恢复的可能性很小，并且在离散的脑电路中显然障碍，这些脑电路中涉及健康个体中SCOG过程的神经生物学。利用我们的试验数据，这在三个站点之间是一致的，以及我们小组在SSD研究中的专业知识与现象学，结果，多站点神经影像学和治疗创新有关，我们建议使用研究领域标准（RDOC）研究型人与SSD的人进行综合和确定的neurobiology congienecrigair cond of neurobiogiy cond ocg cond ocgient of neurobiogy。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的人的连续体），以预测SCOG过程中的损害和随之而来的社会功能。我们计划使用先进的神经影像学和网络分析方法，包括：1）灰质形态学方法来绘制皮质的厚度并检查皮层厚度网络拓扑，2）DTI获取和分析方法以绘制大脑中的白质学电路； 3）基于fMRI的方法来参与这些相同的电路，包括功能连接度量，以获得详细的电路功能度量。然后，我们将在复杂的多元神经影像学统计（部分最小二乘）方面使用小组的专业知识来提取与大脑结构 - > Brai功能 - >行为相关的维度特征，并提供了对从电路到正常和异常（SSDS）领域行为的社会过程神经生物学的全面理解。我们的建议直接建立在RDOC框架内；具体而言，我们使用分析的矩阵作为指导结构来识别整个精神分裂症谱的正常对照的SCOG过程构建的神经生物学。我们预计从电路表征的水平开始，可以确定基本异常的脑行为关系。我们合作团队的最终目标是确定治疗的新治疗靶标 通过确定社会功能受损的基本神经回路和病理生理学，社会障碍。