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

自闭症谱系障碍和抑郁症：大脑和行为的共同机制

• 批准号: 9119618
• 负责人: Katherine O Gotham
• 金额: $ 16.01万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9119618
• 关键词: Address; Adult; Advanced Development; Affect; Affective; Anxiety; Autistic Disorder; Behavioral; Blinking; Clinical; Clinical Research; Cognitive; Communities; Comorbidity; Control Groups; Cues; Depressed mood; Development; Development Plans; Disease; Electromyography; Emotional; Environment; Exhibits; Eye; Face; Future; General Population; Goals; Health; Image; Impairment; Individual; Individual Differences; Intervention; Intervention Studies; Knowledge; Lead; Link; Major Depressive Disorder; Measurement; Measures; Mental Depression; Mentors; Methods; Motivation; National Institute of Mental Health; Neurobiology; Neurologic; Outcome Study; Participant; Population; Positioning Attribute; Process; Prospective Studies; Protocols documentation; Psychometrics; Psychophysiology; Quality of life; Reflex action; Reporting; Research; Research Design; Research Personnel; Research Training; Sampling; Schizophrenia; Social Controls; Source; Stimulus; Thinking; Time; Training; Translating; Treatment outcome; Underserved Population; Visual; Work; analog; autism spectrum disorder; brain behavior; career; career development; clinically significant; cohort; comparison group; depressive symptoms; design; effective intervention; experience; improved; in vivo; mood symptom; named group; novel; peer; programs; response; screening; social; theories; therapy development

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.

描述（由申请人提供）：患有自闭症谱系障碍 (ASD) 的成年人是一个鲜为人知且服务不足的人群。共存抑郁症是该群体临床损伤的主要形式，但很少有研究探讨 ASD 抑郁症的潜在潜在机制和干预措施。临床迫切需要将抑郁症研究方法转化为自闭症谱系障碍（ASD），最终目标是开发有效的干预措施，提高这一特殊人群的生活质量。该培训计划的目标是将 PI 定位为独立研究者以及 ASD 和抑郁症研究之间的转化桥梁。 PI 的培训目标是 (1) 培养心理生理学方法方面的专业知识，可用于研究自闭症谱系障碍 (ASD) 抑郁症的候选机制，以及 (2) 获得自闭症谱系障碍 (ASD) 和抑郁症领域研究项目的工作知识，这些项目是专门组织的，旨在将机制研究的发现转化为治疗开发和结果研究。 PI 提出了一项职业发展计划，其中整合了指导研究经验、高级课程作业以及积极参与非常有利于前沿自闭症和抑郁症研究的机构环境。该培训将增强 PI 在行为方法、自闭症谱系障碍 (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自闭症谱系障碍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（患有自闭症谱系障碍的成年人、患有抑郁症的成年人、通常正在发育的成年人）的情感调节、社交动机和沉思的标记。这些结构已经过抑郁症的实证验证，并且在概念上与自闭症谱系障碍的核心特征相关；然而，不存在直接的组间比较。该候选人的初步研究已经确定，在患有自闭症谱系障碍的成人中，坚持同一性（IS）、沉思和抑郁症状之间存在密切关系，这表明 IS 可能是自闭症患者特有的持久思维过程的类似物，该过程已被证明在一般人群中先于并维持抑郁症。目标 2 将探讨患有自闭症谱系障碍 (ASD) 的成年人样本中的个体差异，比较目标 1 中抑郁相关标记（情感调节、社交动机、沉思）的高水平和低水平 IS 的参与者，以及通过经验抽样每天收集的社会参与和抑郁症状的重复测量。拟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，并完善有关可能导致自闭症谱系障碍抑郁症的潜在致病过程及其相互作用的假设。这项研究培训计划将加速候选人作为独立调查员的职业生涯，设计和评估自闭症谱系障碍社区内抑郁症的理论干预措施。因此，研究特殊人群中具有临床意义的健康问题的因果机制和干预措施与 NIMH 的目标完全一致。