Amygdala Structure & Biochemistry in Adolescents with Autism

杏仁核结构

• 批准号: 7712456
• 负责人: Brendon Nacewicz
• 金额: $ 2.76万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7712456
• 关键词: Adolescence; Adolescent; Affect; Age; Age Distribution; Amygdaloid structure; Area; Atrophic; Autistic Disorder; Behavior; Behavioral; Biochemical; Biochemistry; Biological; Brain; Chemicals; Childhood; Chronic; Clinical; Cognitive; Control Groups; Custom; Data; Development; Diagnosis; Diagnostic; Dimensions; Dissection; Emotional; Emotions; Employee Strikes; Eye; Face Processing; Facial Expression; Fright; Future; Genetic; Glutamates; Goals; Growth; Heterogeneity; Hippocampus (Brain); Hyperactive behavior; Imaging Techniques; Impairment; Individual; Individual Differences; Knowledge; Laboratories; Link; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Modeling; Neurotransmitters; Participant; Pattern; Performance; Population; Procedures; Process; Property; Publishing; Relative (related person); Reporting; Research; Role; Sampling; Schedule; Severities; Social Behavior; Social Development; Spectrum Analysis; Structure; Symptoms; System; Techniques; Testing; Treatment Efficacy; Variant; Work; affective neuroscience; age related; allostatic load; autism spectrum disorder; base; behavior measurement; early childhood; excitotoxicity; gamma-Aminobutyric Acid; improved; in vivo; indexing; male; outcome forecast; response; showing emotion; social; tool; young adult

DESCRIPTION (provided by applicant): Autism encompasses a striking heterogeneity of behaviors, which has so far precluded development of biologically meaningful measures of severity. The lack of reliable symptom clusters or behavioral dimensions along which to characterize individuals is a major obstacle to research into the biological causes, prognosis, and treatment of autism. Put simply, without a severity scale, individuals can never be shown to improve. Beyond this, the period during which autistic symptoms evolve and are probably most amenable to treatment is markedly understudied. Despite the dramatic cognitive and emotional changes during childhood and adolescence, little is known about the brain changes that underlie them. A number of studies have uncovered abnormalities in the emotional circuitry of the brain in autism, but results are inconsistent and have not been reliably linked to emotional and social behavior. The amygdala is known to be essential to fear behavior and to normal processing of facial expressions of emotion, but its role in autism is highly controversial. Using the tools of affective neuroscience and new magnetic resonance imaging techniques, we will focus on objective, quantitative measures of social and emotional deficits to characterize differences in amygdala structure, connectivity and biochemistry between individuals with autism. Our initial studies in this area showed amygdala volume to be strongly tied to these behavioral measures and to clinical diagnostic measures from early childhood. Importantly, this relationship was specific to nonverbal social and communicative impairments in autism. Our results were consistent with a model of chronic amygdala hyperactivity in autism that could resolve much of the inconsistency in previous analyses. This work will directly test several hypotheses from this model, including a longitudinal assessment of amygdala growth and the direct measurement of neurotransmitter levels in vivo. This work, focused on adolescence, will characterize the development of brain systems involved in emotion and affect and their dysregulation in autism. By tying autistic social impairments to specific brain differences, it will provide tools for future genetics studies, objective measures to gauge the efficacy of therapies, and knowledge of brain chemical abnormalities that will guide future pharmacological research.

描述（由申请人提供）：自闭症包括一个惊人的行为异质性，这到目前为止，排除了生物学意义的严重程度的措施的发展。缺乏可靠的症状群或行为维度沿着来表征个体是研究自闭症的生物学原因、预后和治疗的主要障碍。简而言之，如果没有一个严重程度的量表，个人永远不会被证明有所改善。除此之外，自闭症症状演变的时期以及可能最适合治疗的时期显然没有得到充分研究。尽管儿童和青少年时期的认知和情感发生了巨大的变化，但人们对这些变化背后的大脑变化知之甚少。许多研究已经揭示了自闭症患者大脑情感回路的异常，但结果并不一致，而且与情感和社会行为没有可靠的联系。杏仁核被认为是恐惧行为和情绪面部表情的正常处理所必需的，但它在自闭症中的作用是非常有争议的。利用情感神经科学和新的磁共振成像技术的工具，我们将专注于社会和情感缺陷的客观，定量的措施，以表征杏仁核结构，连接和生物化学自闭症个体之间的差异。我们在这一领域的初步研究表明，杏仁核体积与这些行为指标和儿童早期的临床诊断指标密切相关。重要的是，这种关系是特定于自闭症的非语言社交和沟通障碍。我们的研究结果与自闭症患者慢性杏仁核过度活跃的模型一致，这可以解决以前分析中的大部分不一致。这项工作将直接测试这个模型的几个假设，包括杏仁核生长的纵向评估和体内神经递质水平的直接测量。这项工作，集中在青春期，将表征大脑系统的发展涉及情绪和影响及其失调的自闭症。通过将自闭症社会障碍与特定的大脑差异联系起来，它将为未来的遗传学研究提供工具，客观衡量治疗效果的措施，以及指导未来药理学研究的大脑化学异常知识。