Neural Mechanisms of Depressive Symptoms in Youth with Autism SpectrumDisorder

项目总结/摘要 自闭症谱系障碍（ASD）是常见的（1/59的美国儿童）和损害。然而， ASD中的精神障碍-特别是抑郁症-仍然未得到充分研究，这阻碍了临床护理。K23 试图解决一个重要的知识空白的神经机制的基础抑郁症 ASD的症状，这可能最终提供一种基于精确医学的新治疗方法 发展我们的中心假设是青少年ASD患者的抑郁症状与 与额-边缘系统、额-额和额-丘脑的连接有关，反过来， 白色物质完整性和髓鞘形成的差异。我们的中心方法是扫描n=40名儿童（年龄 12-16）ASD和n=40年龄匹配的对照无ASD。本K23的研究目标是：（i） 确定静息态功能磁共振成像（rs-fMRI）与抑郁症状的相关性 ASD;（ii）研究与ASD抑郁症状相关的白色微结构改变;（iii）利用 基于连接组的方法来探索抑郁症状之间的相互作用。 我的职业发展目标是获得以下方面的专业知识：（i）rs-fMRI（以及对有前途的 （ii）扩散光谱成像/髓磷脂成像;（iii）研究- ASD的分级诊断评估;（iv）ASD个体中情绪障碍的表征;和（v） 专业发展，成为独立调查员。这一建议意义重大，因为它将 解决NIMH战略计划目标1.3，以表征神经回路机制中断的基础 ASD中的抑郁症状，使用神经影像学和详细的精神病理学表型。K23是 创新，因为它将是第一个使用多模式成像方法，包括rs-fMRI，扩散谱 成像和髓鞘成像，以确定性别平衡样本中抑郁症状的神经机制 自闭症的青少年。利用K23的重要数据和职业发展，我将提交未来 R 01作为一个独立的研究者，专注于：（一）更深入地了解神经机制， 合并抑郁障碍（包括重度抑郁障碍、持续性抑郁障碍）， ASD患者，以及（ii）检查电路如何在发育过程中发生变化（扩大年龄） 范围至幼儿期和青年期）。

PROJECT SUMMARY/ABSTRACT Autism spectrum disorder (ASD) is common (1 in 59 US children) and impairing. Yet, co-occurring psychiatric disorders—especially depression—in ASD remain understudied, hindering clinical care. This K23 seeks to address an important gap in knowledge about the neural mechanisms underlying depressive symptoms in ASD, which could ultimately provide a precision medicine-based approach to novel treatment development. Our central hypothesis is that depressive symptoms in adolescents with ASD will be associated with fronto-limbic, fronto-frontal and fronto-thalamic connectivity that, in turn, are related to underlying differences in white matter integrity and myelination. Our central methodology is to scan n=40 children (ages 12-16) with ASD and n=40 age-matched controls without ASD. The research goals of this K23 are to: (i) identify resting-state functional magnetic resonance imaging (rs-fMRI) correlates of depressive symptoms in ASD; (ii) investigate white matter microstructural alterations linked to depressive symptoms in ASD; (iii) utilize connectome-based approaches to explore the interaction between depressive symptoms across modalities. My career development goals are to gain expertise in: (i) rs-fMRI (and deeper understanding of promising circuit-based approaches to target engagement); (ii) diffusion spectrum imaging/myelin imaging; (iii) research- grade diagnostic evaluation of ASD; (iv) characterization of mood disorders in individuals with ASD; and (v) professional development to become an independent investigator. This proposal is significant because it will address NIMH Strategic Plan Objective 1.3 to characterize neural circuit mechanism disruption underlying depressive symptoms in ASD, using neuroimaging and detailed psychopathology phenotyping. This K23 is innovative because it will be the first to use multimodal imaging methods, including rs-fMRI, diffusion spectrum imaging, and myelin imaging, to define neural mechanisms of depressive symptoms in a sex-balanced sample of adolescents with ASD. Leveraging vital data and career development from this K23, I will submit future R01s as an independent investigator that focuses on: (i) deeper understanding of the neural mechanisms of co-occurring depressive disorders (including major depressive disorder, persistent depressive disorder) in individuals with ASD, and (ii) examination of how circuits change across development (expanding the age range to early childhood and young adulthood) in individuals with ASD with or without depressive disorders.