Amygdala Structure & Biochemistry in Adolescents with Autism

描述（由申请人提供）：自闭症包含了惊人的行为异质性，迄今为止，这阻碍了生物学上有意义的严重程度测量的发展。缺乏可靠的症状集群或行为维度来描述个体特征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，没有严重程度量表，个体永远无法得到改善。除此之外，自闭症症状发展和可能最适合治疗的时期显然没有得到充分的研究。尽管儿童和青少年时期的认知和情绪发生了巨大的变化，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，也没有可靠地将其与情感和社会行为联系起来。众所周知，杏仁核对恐惧行为和情绪面部表情的正常处理至关重要，但它在自闭症中的作用却备受争议。利用情感神经科学和新型磁共振成像技术的工具，我们将重点关注社会和情感缺陷的客观定量测量，以表征自闭症个体之间杏仁核结构，连通性和生物化学的差异。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,这种关系是特定于语言的社会和交际障碍自闭症。我们的研究结果与自闭症患者的慢性杏仁核过度活跃的模型一致，这可以解决之前分析中的大部分不一致。这项工作将直接测试该模型的几个假设，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。这项工作的重点是青少年，将描述自闭症中涉及情感和情感的大脑系统的发育及其失调。通过将自闭症社交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，为衡量治疗效果提供客观措施，并为指导未来的药理学研究提供大脑化学异常的知识。

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.