Katherine O. Gotham, Ph.D. - US grants

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.

Project Summary/Abstract Adults with autism spectrum disorder (ASD) often have poor outcomes across a range of domains, particularly emotional health. Rumination, or repetitive negative thinking, is a cognitive characteristic of ASD that also appears to contribute to depression and anxiety. Rumination is linked to both poor emotional and physical health in the general population. However, as perseveration is a core feature of autism, repetitive thinking (RepT) within ASD appears to be a broader construct than general rumination. Better understanding of the phenomenon, mechanisms, and health states associated with RepT in autism could determine novel, specific targets to guide development of health interventions for adults with ASD. Our proposal seeks to characterize repetitive thinking within ASD and inform its psychometric measurement in this population (Aim 1); explore neural correlates of sustained cognitive-affective processing in adults with ASD using pupil methods, with comparisons to typically developing depressed adults (TD-dep) (Aim 2); and investigate relations between diverse forms of RepT and health and behavior in adults with ASD (Aim 3). This work is intended to shape precision hypotheses as to which specific RepT processes most impact which adverse health outcomes in this special population. Aim 1 takes a mixed-method approach, including: (1) structural analyses of survey data on various constructs related to RepT (e.g., rumination, worry, obsessive thoughts, circumscribed interests) to identify common patterns of repetitive thinking (e.g., by valence, function, intrusiveness) in a large sample of verbally-fluent adults with ASD, n=760 online + n=72 in lab; and (2) lab- based inductions of RepT, with pre-/post language samples coded for RepT features. Findings will be synthesized to inform understanding of the phenomenon and measurement of RepT in ASD. In Aim 2, patterns of pupil-indexed neural reactivity will be compared across diagnostic cohorts (ASD and TD-dep) and stimuli types (social, non-social, emotional, non-emotional), and assessed for relation to RepT features and other moderators. This is intended to illuminate patterns of sustained cognitive-affective processing in ASD, and thus refine future research into mechanistic ?points of entry? for treatment development. Aim 3 proposes to analyze both existing and novel markers of diverse forms of RepT for differential association with health and functioning in adults with ASD. A model will be tested in which negative RepT predicts poor emotional and physical health, whereas positive/neutral RepT predicts social deficits. This proposal applies an expert team and multi-method approach to the goal of identifying potential targets for intervention on emotional health problems, which are prevalent and largely untreated in adults with ASD. If successful, this also will structure empirical data collection on RepT, advance understanding of its mechanisms via a convergent physiological marker (sustained pupil responsivity), and help extend repetitive behavior research to internal thinking processes.