Amygdala Structure & Biochemistry in Adolescents with Autism

描述(由申请人提供)：自闭症包括行为的显著异质性，到目前为止，这排除了具有生物学意义的严重程度的发展。缺乏可靠的症状群或行为维度来表征个体，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，没有严重程度的衡量，个人永远不会有改善的迹象。除此之外，对自闭症症状演变和最容易接受治疗的时期的研究明显不足。尽管儿童和青春期的认知和情感发生了戏剧性的变化，但人们对这些变化背后的大脑变化知之甚少。许多研究都发现了自闭症患者大脑情绪回路的异常，但结果并不一致，也没有可靠的证据表明自闭症患者的情绪和社交行为存在关联。众所周知，杏仁核对恐惧行为和面部表情的正常处理是必不可少的，但它在自闭症中的作用存在很大争议。利用情感神经科学的工具和新的磁共振成像技术，我们将专注于社会和情绪缺陷的客观、定量测量，以表征自闭症患者之间在杏仁核结构、连接性和生化方面的差异。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，这种关系与自闭症患者的非语言社交和沟通障碍有关。我们的结果与自闭症慢性杏仁核过度活动的模型一致，该模型可以解决之前分析中的大部分不一致之处。这项工作将直接测试该模型的几个假设，包括对杏仁核生长的纵向评估和对体内神经递质水平的直接测量。这项以青春期为重点的研究，将描述涉及情绪和情感的大脑系统的发展及其在自闭症中的失调。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，为衡量治疗效果的客观措施，以及指导未来药理学研究的大脑化学异常知识提供工具。

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.