PROJECT SUMMARY/ABSTRACT By the time they are typically detected, attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are already challenging to treat. ADHD is characterized, in part, by deficits in self-regulation, while social communication deficits are a hallmark of ASD. Although traditional diagnostic definitions imply distinct phenotypes, co-occurrence is common with evidence of shared heritability, but little is known about overlapping versus unique markers and mechanisms early in development. Putative shared processes include dysregulation of attention and affect. Based on links with these processes, respiratory sinus arrhythmia (RSA), an index of parasympathetic nervous system (PNS) functioning reflecting effort allocation and emotion regulation, has been suggested as a potential transdiagnostic biomarker. No prior studies have examined shared versus distinct contributions of atypical infant PNS functioning, attention regulation, and affect regulation to later self-regulation and social communication deficits in infants at genetic risk for such challenges. Moreover, few studies have characterized continuity of symptoms across early childhood in high-risk samples, nor have infant predictors of symptom continuity been examined. Addressing these points is imperative to enhancing early detection efforts, delineating mechanisms underlying symptom development, identifying targets and time points for prevention and intervention, and determining novel markers of treatment efficacy. This proposal seeks to better understand developmental pathways to the Research Domain Criteria (RDoC) domains of cognitive systems (cognitive control/self-regulation) and social processes (social communication) across early development in a sample enriched for such challenges: infants at familial risk for ASD (n = 60), familial risk for ADHD (n = 60), and low risk for both (n = 40). We aim to: (1) identify shared and distinct early behavioral and physiological markers of, and mechanisms underlying, self-regulation and social communication problems among infants at risk, and (2) evaluate continuity of self-regulation and social communication problems across early childhood, including delineation of infant predictors of such continuity. Leveraging previous NIH support (K99/R00 MH106642) and employing a multi-method, multi-informant, multi-dimensional design, infants will be evaluated at 6 or 9, 12, 18, 24, and 36 months of age with a focus on trajectories and mediational mechanisms. This R01 proposal responds to the NIMH Strategic Plan to “Define the Mechanisms of Complex Behaviors” and “Chart Mental Illness Trajectories to Determine When, Where, and How to Intervene.” Exploring shared versus distinct mechanisms underlying the development of self-regulation and social communication symptoms will improve early identification of disorders like ADHD and ASD and encourage the development of transdiagnostic, process-focused early interventions,...