Center Overview Abstract The University of Pittsburgh Autism Center of Excellence (ACE) directly addresses the Interagency Autism Coordinating Committee’s call for research on adult mental health to improve safety and quality of life, and to reduce premature mortality. We do so by generating the measures and mechanistic targets needed to improve mental health and reduce suicide risk in autistic adults. We address this understudied and critical topic in authentic partnership with autistic adults and their allies. We emphasize mechanistic translation, bring new researchers to work on autism, and provide an academic home for junior researchers getting started in this area. We will assemble a Pittsburgh ACE cohort of 200 autistic and 100 non-autistic 18- to 65-year-old adults (≥ 50 with recent suicidality in each group) who will complete three projects that are focused on different units of analysis (self-report, behavior and ambulatory physiology, and neural circuits), time scales, and primary outcomes, all related to adult mental health. Project 1 will provide the first dimensional self-report questionnaire of suicidality developed for ASD and the first longitudinal characterization of suicidality in autistic adults. Project 2’s innovative physiologically-triggered ecological momentary design will characterize proximal risk processes for suicidal ideation, non-suicidal self-injury, and impulsive aggression in a temporally sensitive manner to allow for future interventions prior to escalation of emotion dysregulation and harmful outcomes. Project 3 tests a neural mechanistic model of early neural hyper-reactivity to stimuli followed by decreased recruitment of regulatory resources and consequent physiological, subjective, and behavioral hypo-reactivity. Our Clinical Core provides data to all of the projects to characterize the sample, including novel phenotypic measures (e.g., a biomarker of aging based on structural brain images). Our Center structure enables us to integrate data from all sources to enhance the impact of individual projects. For example, we will speed translation by connecting a biological causal mechanism to lived experience and longitudinal outcomes. We will pool all data to identify the most salient predictors of suicidality trajectories, providing a significant advance over approaches that consider small sets of predictors and enabling determination of relative contributions to risk. We will shed light on heterogeneity in outcomes by connecting subgroups based on daily dynamics of emotion and physiological reactivity and regulation to neural reactivity and suicidality. Our age range and transdiagnostic, suicidal comparison group allows us to determine what is unique about mental health in ASD and how aging may play a role. We will employ novel means to disseminate this critical information to the community with the help of our team of autistic partners from diverse backgrounds. This process will ensure that our Center will not only engage individuals from groups that have been marginalized, but will also create and maintain mutually beneficial and rewarding relationships that will enhance and enrich our research sample, outcomes, and overall impact.

Narrative The University of Pittsburgh Autism Center of Excellence will fill a void in research on autistic adults and their mental health needs, including risk for suicide. We address this critical topic in authentic partnership with autistic adults and their allies, emphasize mechanistic translation, bring new researchers to work on autism, and provide an academic home for junior researchers getting started in this area. We will generate measures and mechanistic treatment targets that can be applied to improve safety and quality of life, and to reduce premature mortality for autistic adults.