The Social Brain in Schizophrenia and Autism Spectrum Disorders

精神分裂症和自闭症谱系障碍的社交大脑

• 批准号: 8505543
• 负责人: Michal Assaf
• 金额: $ 49.84万
• 依托单位: HARTFORD HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-05 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8505543
• 关键词: Age; Anterior; Base of the Brain; Behavioral; Biological; Brain; Categories; Characteristics; Clinical; Clinical Research; Cluster Analysis; Cognitive; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Dimensions; Disease; Electroencephalography; Empathy; Etiology; Event-Related Potentials; Functional Magnetic Resonance Imaging; Functional disorder; Genetic; Genetic Risk; Goals; Group Identifications; Heterogeneity; Human; Image; Investigation; Joints; Judgment; Linear Models; Maintenance; Maps; Matched Group; Measures; Medial; Mental disorders; Methods; Mind; Modality; Nature; Neurodevelopmental Disorder; Neurons; Neurophysiology - biologic function; Pain; Participant; Pathology; Patient Self-Report; Patients; Pattern; Play; Prefrontal Cortex; Procedures; Process; Protocols documentation; Psychiatric Diagnosis; Questionnaires; Research; Resolution; Role; Schizophrenia; Severities; Social Functioning; Social Interaction; Subgroup; Symptoms; Techniques; Testing; autism spectrum disorder; base; behavior measurement; cingulate cortex; clinical Diagnosis; computerized; endophenotype; independent component analysis; innovation; neuroimaging; neuropathology; neurophysiology; outcome forecast; relating to nervous system; response; social; social cognition; theories; tool; treatment response; treatment strategy

DESCRIPTION (provided by applicant): Although traditionally considered 2 separate entities based on clinical symptoms and course, schizophrenia (SZ) and autism spectrum disorders (ASD) are heterogeneous, neurodevelopmental disorders with core deficits in social functions. Little is known, however, about the neuropathology associated with these abnormalities in these diagnoses or about the degree and nature of overlap between them. The aim of the current study is to investigate the neural correlates of 3 social cognitive processes, Theory of Mind (ToM), social judgment, and empathy, using a multimodal approach incorporating functional MRI (fMRI) and event related potential (ERP) data, in relation to the nosological diagnoses of ASD and SZ and their clinical and functional symptoms. Eighty SZ and 80 high-functioning ASD patients, ages 18-30, as well as matched healthy controls (HC) will complete the protocol. Participants' social functions will be characterized with self-report questionnaires, computerized tests, role-play and observational tools. Neuronally, ToM will be evaluated with a 2-player interactive fMRI Domino task, social judgment with an fMRI Trustworthiness task and empathy with an ERP Empathy to Pain task. We will (1) identify group differences based on categorical diagnostic mapping in social functions and social cognition-related neural deficits. We will further relate patients' social functions and symptoms to abnormal activation of specific brain circuits; (2) Identify patient sub-groups based on integrated multi-modal neural abnormalities related to social cognitive processes, independent of symptom-based diagnostic categories. We will first use an innovative data-driven method, joint independent component analysis (jICA), to fuse the data from all imaging tasks and to identify the upper 30% impaired patients (either SZ or ASD) and 30% of patients most similar to HC, based on brain activity during the different social tasks. The clinical characteristics of these subgroups will be further evaluated. Then the jICA most discriminative single or integrated components will be entered into a cluster ICA (cICA) to identify natural patient subgroups independently of formal clinical diagnosis. We hypothesize that while both SZ and ASD groups will show abnormal social functions and related brain activity compared to HC, some findings will overlap while others will be diagnosis specific. Importantly, we anticipate that the non-diagnostic based analyses (aim 2) will demonstrate the ability of brain based classifying procedures to identify neurobiologically-based patient subgroups that are more homogeneous than current symptom based categories with respect to clinical and behavioral characteristics. Such subgroups can then be evaluated with regard to differential treatment response and possible etiologies, such as genetic risk variables. If successful, the current study will support the emerging shift in clinical and research paradigms for ASD and SZ specifically and more generally for psychiatric illnesses, toward using dimensional biological (vs. categorical behavioral) measures to identify meaningful patient groups. This in turn will advance etiologic and treatment research for these illnesses.

描述（由申请人提供）：尽管传统上认为基于临床症状和过程的两个独立实体，但精神分裂症（SZ）和自闭症谱系障碍（ASD）是具有社会功能核心缺陷的异质性神经发育障碍。然而，关于这些诊断中这些异常或它们之间重叠的程度和性质相关的神经病理学知之甚少。当前研究的目的是研究3个社会认知过程，思想理论（TOM），社会判断力和同理心的神经相关性，使用纳入功能性MRI（FMRI）和事件相关潜力（ERP）数据的多模态方法，与ASD和SZ及其临床和他们的临床和功能性症状有关。 18-30岁的80 SZ和80名高功能的ASD患者以及匹配的健康对照组（HC）将完成该方案。参与者的社交功能将以自我报告问卷，计算机测试，角色扮演和观察工具来表征。神经统治，汤姆将通过两人互动fMRI多米诺骨牌任务，fMRI可信赖的任务和同理心评估汤姆，并具有对痛苦任务的ERP同理心。我们将（1）基于社会功能和与社会认知相关的神经缺陷的分类诊断映射确定群体差异。我们将进一步将患者的社会功能和症状与特定脑电路的异常激活联系起来。 （2）基于与社会认知过程有关的综合多模式神经异常确定患者子组，而与基于症状的诊断类别无关。我们将首先使用创新的数据驱动方法，即独立组件分析（JICA），融合所有成像任务中的数据，并确定30％受损的患者（SZ或ASD）和30％的患者与HC最相似的患者，基于不同社会任务期间的大脑活动。这些亚组的临床特征将得到进一步评估。然后，JICA最判别的单个或集成的组件将被输入ICA集群（CICA），以独立于正式的临床诊断而识别自然患者亚组。我们假设，尽管与HC相比，SZ和ASD组都会显示出异常的社会功能和相关的大脑活动，但一些发现将重叠，而另一些发现将是特定于诊断的。重要的是，我们预计基于非诊断的分析（AIM 2）将证明基于大脑的分类程序能够鉴定基于神经生物学的患者亚组，这些亚组比目前基于症状的类别在临床和行为特征方面更均匀。然后可以在差异治疗反应和可能的病因（例如遗传风险变量）方面评估此类亚组。如果成功，当前的研究将支持针对ASD和SZ的临床和研究范例的新兴转变，专门针对精神病疾病，更普遍地使用维度生物学（与分类行为）措施来识别有意义的患者群体。反过来，这将推动这些疾病的病因和治疗研究。