Autism Spectrum Disorders and Depression: Shared Mechanisms in Brain and Behavior

描述(由申请人提供)：患有自闭症谱系障碍(ASD)的成年人代表了一个缺乏了解和服务的人群。共生抑郁是这一群体临床损害的主要形式，但很少有研究探索ASD抑郁的潜在潜在机制和干预。临床上有必要将抑郁症的研究方法转化为自闭症，最终目标是开发有效的干预措施，旨在提高这一特殊人群的生活质量。本培训计划的目标是将PI定位为独立的调查者和ASD和抑郁症研究之间的转换桥梁。PI的培训目标是(1)发展可用于研究ASD抑郁候选机制的心理生理学方法方面的专业知识，以及(2)从ASD和抑郁症领域获得研究计划的实用知识，这些研究计划是专门组织的，将机制研究的结果转化为治疗发展和结果研究。PI提出了一项职业发展计划，该计划整合了有指导的研究经验、先进的课程工作，以及积极参与强烈有利于尖端自闭症和抑郁症研究的机构环境。这项培训将增强PI在行为方法、ASD临床研究和抑郁症理论方面的背景。拟议的研究计划旨在探索ASD可能导致抑郁倾向增加的可能机制。在目标1中，将比较三组(患有自闭症的成年人、患有抑郁症的成年人，通常是发育中的成年人)在情绪调节、社会动机和沉思方面的标志。这些结构已经过抑郁症的经验性验证，在概念上也与ASD的核心特征有关；然而，不存在组间直接比较。这位候选人的初步研究发现，在患有自闭症的成年人中，坚持相同(IS)、沉思和抑郁症状之间存在强烈的联系，这表明IS可能是自闭症特有的类似于持之以恒的思维过程，已被证明在普通人群中先于并维持抑郁。目标2将探索成人自闭症患者样本中的个体差异，比较目标1(情绪调节、社交动机、沉思)中IS水平高和低的参与者，以及通过经验抽样每天收集的社交参与和抑郁症状的重复测量。建议的研究旨在为候选人提供与抑郁症研究相关的心理生理学方法的直接经验，并完善关于可能导致自闭症抑郁的潜在致病过程及其相互作用的假说。这项研究培训计划将加速候选人作为一名独立调查员的职业生涯，具备设计和评估ASD社区内抑郁症理论上的基础干预措施的能力。因此，研究特殊人群中临床重大健康问题的因果机制和干预措施与NIMH的目标很好地一致。

DESCRIPTION (provided by applicant): Adults with autism spectrum disorder (ASD) represent a poorly understood and underserved population. Co- occurring depression is a leading form of clinical impairment for this group, yet few studies have explored potential underlying mechanisms of and intervention for depression in ASD. There is a significant clinical need to translate methods from depression research to ASD, with the ultimate goal of developing effective intervention aimed at improving quality of life in this special population. Th goal of this training plan is to position the PI as an independent investigator and translational bridge between ASD and depression research. The PI's training goals are (1) to develop expertise in psychophysiological methods that can be used to study candidate mechanisms of depression in ASD, and (2) to gain a working knowledge of research programs from the ASD and depression fields that are specifically organized to translate findings from mechanistic studies into treatment development and outcome studies. The PI has proposed a career development plan that integrates mentored research experience, advanced coursework, and active involvement in an institutional environment strongly conducive to cutting-edge autism and depression research. This training will augment the PI's background in behavioral methods, ASD clinical research, and depression theory. The proposed research plan is designed to explore possible mechanisms by which ASD may confer increased propensity for depression. In Aim 1, three groups (adults with ASD, adults with depression, typically developing adults) will be compared on markers of affect modulation, social motivation, and rumination. These constructs have been empirically validated for depression and also are conceptually related to core features of ASD; however, no direct between-group comparison exists. The candidate's preliminary studies have identified a strong relationship between insistence on sameness (IS), rumination, and depressive symptoms in adults with ASD, suggesting that IS may be an autism-specific analogue of the perseverative thought process that has been shown to precede and maintain depression in the general population. Aim 2 will explore individual differences within a sample of adults with ASD, comparing participants who have high versus low levels of IS on depression-related markers from Aim 1 (affect modulation, social motivation, rumination) and on repeated measures of social engagement and depressive symptoms collected daily via experience sampling. The proposed studies are designed to provide the candidate with direct experience in psychophysiological methods relevant to the study of depression, as well as to refine hypotheses about potential pathogenic processes and their interactions that may lead to depression in ASD. This research training plan will accelerate the candidate's career as an independent investigator equipped to design and evaluate theoretically grounded interventions for depression within the ASD community. As such, it is well-aligned with NIMH goals to study both causal mechanisms and intervention for a clinically significant health problem in a special population.