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

点击翻译按钮获取中文摘要

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.