Neural Mechanisms of Depressive Symptoms in Youth with Autism SpectrumDisorder

项目摘要/摘要 自闭症谱系障碍(ASD)很常见(每59名美国儿童中就有一名)，并有损害。然而，同时发生的 自闭症患者的精神障碍--尤其是抑郁症--仍未得到充分研究，阻碍了临床护理。这个K23 寻求解决关于抑郁症潜在神经机制的知识的一个重要缺口 ASD的症状，这最终可能为新的治疗提供一种基于精确医学的方法 发展。我们的中心假设是患有自闭症的青少年的抑郁症状将与 额叶到边缘、额叶到额叶和额叶到丘脑的连接，这些连接反过来又与潜在的 白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)伴ASD者，n=40名年龄匹配的无ASD者。这款K23的研究目标是：(I) 确定静息状态功能磁共振成像(rs-fMRI)与抑郁症状的相关性 ASD；(Ii)调查与ASD抑郁症状有关的白质微结构变化；(Iii)利用 基于连接组的方法，以探索各种形式的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(以及对前景的更深理解 (2)扩散光谱成像/髓鞘成像；(3)研究-- ASD的分级诊断评估；(Iv)ASD患者的情绪障碍特征；以及(V) 专业发展，成为一名独立的调查员。这项提议意义重大，因为它将 满足NIMH战略计划目标1.3，以表征潜在的神经电路机制中断 ASD的抑郁症状，使用神经成像和详细的精神病理学表型。这台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、扩散光谱。 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 患有自闭症的青少年。利用这一K23的重要数据和职业发展，我将提交未来 R01s作为一名独立研究人员，专注于：(I)更深入地了解 共发抑郁障碍(包括重度抑郁障碍、持续性抑郁障碍) 患有自闭症的人，以及(Ii)检查神经回路如何在发育过程中变化(延长年龄 在患有或不伴有抑郁障碍的自闭症患者中)。

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.