Social Processes Initiative in Neurobiology of Autism-spectrum and Schizophrenia-spectrum Disorders(SPIN-ASD)

项目总结 描述：社会缺陷，自闭症谱系障碍(ASD)诊断的核心，持续存在 时间，影响功能，并预测长期结果。然而，一系列的社会损害 存在于受影响的人群中。迄今为止，社会认知受损背后的大脑变化并不是始终如一的 通过比较一组患有自闭症的人和一组健康的对照组的研究显示。同样， 精神分裂症谱系障碍(SSD)患者表现出一系列社会认知障碍 而且相关的大脑变化并不是一致的。成熟的生物学和临床 到目前为止，这些疾病的异质性一直是鉴定神经回路的主要障碍。 社会认知障碍的生物标志物。研究领域标准(RDoC)方法可以利用 临床和生物异质性，以确定可能跨越固态硬盘或 ASD诊断。我们的试点数据显示，关键社会认知回路的结构/功能特征是 健康对照(HCS)、自闭症(ASD)和固态硬盘(SSD)的社会认知表现与连续统一体的关系 (与仅在HCS和SSD中相比，变化范围更广)。在拟议的研究中，我们有一个 独特的机会-招募匹配的ASD患者样本，使用相同的神经成像和 在已资助的HCS研究的主要地点实施的行为评估 RDoC社交流程领域内的固态硬盘(1/3R01MH102324)。我们研究的第一个目的是确定 脑回路结构、脑回路功能和社会认知表现之间的维度关系 在整个HCS中，参与者使用固态硬盘和ASD。将患有自闭症的参与者包括在内将增强 整个样本的社会认知表现，并允许我们检测大脑-行为关系的全部范围 这是对HCS、ASD和SSD的社会认知的基础。此外，我们假设一些有 与一些ASD患者相比，SSD在神经回路和行为水平上的损害可能更相似， 而不是在他们自己的诊断组中。因此，我们还将应用一种新颖的数据驱动 一种称为相似性网络融合(SNF)的方法，用于识别具有相似特征的个体的亚组 神经回路和社会认知障碍的诊断超越了传统的诊断。该计划的最终目的 目前的建议是确定社会过程领域中跨越DSM的大脑-行为关系 诊断，并分析具有不同社会认知大脑行为特征的人的子集。如果成功， 当这两个目标结合在一起时，将加速相关的机制驱动的治疗开发 可以改善社会功能的ASD和SSD。

PROJECT SUMMARY DESCRIPTION: Social deficits, central to the diagnosis of autism spectrum disorders (ASDs), persist over time, influence functioning, and are predictive of long-term outcome. However, a range of social impairment exists among those affected. To date, brain alterations underlying impaired social cognition are not consistently shown across studies comparing a group of individuals with ASDs, to a group of healthy controls. Similarly, people with schizophrenia spectrum disorders (SSDs) demonstrate a range of social cognitive impairments and associated brain alterations have not been consistent. The well-established biological and clinical heterogeneity of these disorders has, thus far, been a major obstacle to the identification of neural circuit biomarkers of social cognitive impairment. The Research Domain Criteria (RDoC) approach can capitalize on clinical and biological heterogeneity to identify novel brain-behavior relationships that may cut across SSD or ASD diagnoses. Our pilot data show that structural/functional features of key social cognitive circuits are associated with social cognitive performance along a continuum in healthy controls (HCs), ASDs, and SSDs (and across a broader range of variation than in HCs and SSDs alone). In the proposed study, we have a unique opportunity – to recruit a matched sample of individuals with ASDs using identical neuroimaging and behavioral assessments as implemented at the lead site of an already funded study in HCs and people with SSDs, within the RDoC Social Processes Domain (1/3R01MH102324). The first aim of our study is to identify dimensional relationships, among brain circuit structure, brain circuit function, and social cognitive performance across HCs, participants with SSDs and ASDs. The inclusion of participants with ASDs will enhance variation in social cognitive performance across our sample and allow us to detect the full range of brain-behavior relationships that underpin social cognition across HCs, ASDs, and SSDs. Further, we hypothesize that some individuals with SSDs may be more similarly impaired at the neural circuit and behavioral level to some individuals with ASDs, as opposed to those within their own diagnostic group. Therefore, we will also apply a novel data-driven approach, known as Similarity Network Fusion (SNF), to identify subgroups of individuals with similar profiles of neural circuit and social cognitive impairment that cut across conventional diagnoses. The ultimate aim of the current proposal is to identify brain-behavior relationships in the Social Processes Domain that cut across DSM diagnoses, and also parse subsets of people with distinct social cognitive brain-behavior profiles. If successful, when taken together, these two aims will accelerate mechanism-driven treatment development relevant across ASDs and SSDs that can improve social function.