Restricted Repetitive Behavior in Autism

自闭症患者的限制性重复行为

• 批准号: 8451908
• 负责人: James William Bodfish
• 金额: $ 39.17万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-13 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8451908
• 关键词: Adult; Affect; Affective; Age; Anxiety; Area; Attention; Autistic Disorder; Behavior; Behavior Therapy; Biological; Brain; Candidate Disease Gene; Characteristics; Child; Clinical; Cognitive; Complex; Corpus striatum structure; Detection; Development; Developmental Delay Disorders; Diagnostic; Diagnostic and Statistical Manual; Disease; Etiology; Eye; Functional Magnetic Resonance Imaging; Funding; Future; Genetic; Goals; Heterogeneity; Image; Impairment; Incentives; Individual; Measures; Mediating; Mood Disorders; Motivation; Neurobiology; Neurodevelopmental Disorder; Obsessive-Compulsive Disorder; Outcome Measure; Participant; Pattern; Persons; Phenotype; Relative (related person); Research; Rewards; Ritual compulsion; Sampling; Stimulus; Symptoms; System; Visual; Visual attention; Work; affective neuroscience; clinically significant; functional disability; indexing; interest; neural circuit; neuropsychiatry; novel; programs; relating to nervous system; response; reward processing; social; therapy development; treatment response; treatment strategy

DESCRIPTION (provided by applicant): During the previous funding cycle of this project (R01 MH073402) we identified distinct subtypes of repetitive behavior validated by the presence of subtype-specific clinical correlates. The potential impact of this finding is that these distinct repetitive behavior subtypes could be leveraged to help parse the biological, behavioral, and treatment-response heterogeneity that heretofore has constrained research on the etiology and treatment of autism. This idea is the focus of our next round of studies in this systematic program of research on repetitive behaviors: By focusing on specific subtypes of repetitive behaviors, can we identify unique pathophysiologic factors that could be used to guide the development of novel treatment strategies? Our focus in this application is on one of these distinct subtypes of repetitive behavior - unusual and intense interests, preoccupations, and attachments - that has received virtually no attention in autism. In recent studies we have found that these so-called "Circumscribed Interests" (CI) appear to impart significant added impairment in autism over and above other core deficits. Clinically, CI seem to be associated with strong positive affect and anticipatory motivation in contrast to repetitive behaviors in other disorders such as obsessive compulsive disorder (OCD) that seem to be associated with negative affect and anxiety-reduction (e.g. rituals, compulsions, insistence on sameness). The heightened interest and restricted focus that are characteristic of CI suggest that the functioning of neural circuitry that mediate reward processing may be altered in persons with autism. Consistent with this, we hypothesize that the development of CI in autism is mediated by an underlying cognitive-affective reward system that is "biased" away from social information and towards nonsocial information and thus that a unique cognitive-attentional phenotype may characterize CI. The goals of the proposed continuation of this project are to elucidate the clinical significance of CI in autism and to identify cognitive and neurobiological markers of this subtype. We propose to compare children (ages 12 - 18 years) with low-functioning (n = 40) and high-functioning autism (n = 40) to individuals with obsessive-compulsive disorder (n = 40), developmental delay (n=40) and typically developing controls (n = 40) on (a) a standardized assessment battery for measuring CI and the other varieties of repetitive behavior (Aim 1); (b) a passive visual exploration, eye-tracking task that measures differential attention to CI and non-CI images (Aim 2); and (c) to compare the HFA and TYP samples on two fMRI tasks comparing brain activation to CI versus non-CI images under conditions of reward anticipation and target detection (Aim 3).

描述（由申请人提供）：在该项目的先前资金周期（R01 MH073402）期间，我们确定了通过存在亚型特异性临床相关性验证的重复行为的不同亚型。这一发现的潜在影响是，可以利用这些独特的重复行为亚型来帮助解析迄今为止迄今为止对自闭症的病因和治疗的研究的生物学，行为和治疗反应异质性。这个想法是我们下一轮研究的重点在这个关于重复行为的系统研究计划中的重点：通过关注重复行为的特定亚型，我们可以确定可用于指导新治疗策略发展的独特病理生理因素吗？我们在此应用中的重点是重复行为的这些独特的亚型之一 - 异常和强烈的兴趣，关注和依恋 - 几乎没有引起自闭症的关注。在最近的研究中，我们发现这些所谓的“限制利益”（CI）似乎超过了自闭症的显着损害，而不是其他核心缺陷。在临床上，与其他疾病的重复行为相比，CI似乎与强烈的积极影响和预期动机有关，例如强迫症（OCD）似乎与负面影响和减少焦虑（例如仪式，强迫症，坚持，坚持相同性）有关）。 CI特征的兴趣和受限重点的提高表明，自闭症患者可以改变介导奖励处理的神经回路的功能。与此相一致，我们假设自闭症中CI的发展是由一种潜在的认知影响奖励系统介导的，该系统“有偏见”远离社会信息和非社会信息，因此，一种独特的认知 - 意识 - 注意表型可能会表征CI的特征。该项目拟议延续的目标是阐明CI在自闭症中的临床意义，并确定该亚型的认知和神经生物学标记。我们建议将儿童（12-18岁）与低功能（n = 40）和高功能自闭症（n = 40）与具有强迫症的强迫症（n = 40），发育延迟（n = 40）的人进行比较（n = 40），通常在（n = 40）上（n = 40）在（a）上进行标准化的评估电池，以测量CI和其他品种的标准化电池。 （b）一个被动视觉探索，令人眼花tract乱的任务，该任务衡量了对CI和非CI图像的不同关注（AIM 2）； （c）在两个fMRI任务上比较了HFA和键入样本，将大脑激活与CI与CI与非CI图像进行比较，在奖励预期和目标检测条件下（AIM 3）。