SUMMARY Autism Spectrum Disorder (ASD) is characterized by social impairments and restricted and repetitive behaviors. Those with a genetic liability for social deficits, including individuals with ASD and their unaffected relatives are also at high risk for internalizing and externalizing conditions. The presence of comorbid affective and behavioral conditions impairs adaptive functioning, increases family stress, and is associated with psychiatric hospitalizations and residential placement. Identification of risk factors for internalizing and externalizing disorders amongst young children with ASD and their siblings would improve diagnostic practices and promote implementation of preventative and early interventions. Extensive research in the general population indicates that precursors of internalizing and externalizing disorders can be identified in the first two years of life as indexed by elevated or attenuated levels of Emotional Reactivity (eReactivity), or intensity of emotional reactions in response to internal or external triggers. Extant, albeit limited, evidence suggests that toddlers with ASD and their unaffected siblings exhibit atypical eReactivity profiles both on the behavioral and physiological levels, though the evidence is incomplete and both their origins and the links with later psychopathology are largely unknown. To fill this gap, we propose to prospectively examine the development of eReactivity from 4 to 30 months in 150 younger siblings of children with ASD, who, due to familial factors, are at high risk for developing ASD (HR) and 30 low-risk (LR) siblings. We plan to examine eReactivity to real- world triggers aimed to elicit fear, anger, and joy, and to evaluate the effects of the social and nonsocial nature of the triggers on eReactivity across the three emotions using a state-of-the-art multi-method behavioral and physiological approach. Aim 1 will evaluate prospectively whether the HRASD group (siblings with ASD), HRATP (siblings with developmental challenges), and HRTD (siblings without developmental challenges) are characterized by distinct patterns of eReactivity to social vs nonsocial triggers as measured by behavioral and physiological indices between 4 and 30 months compared to the LRTD group. The aim will clarify if differential emotional reactivity to social and nonsocial triggers constitutes an emerging characteristic of the autism phenotype in ASD. Aim 2 will examine predictive relationships between development of eReactivity in infancy and severity of internalizing and externalizing symptoms at 30 months. Identification of early predictors of internalizing/externalizing problems will facilitate access to early interventions aimed at amelioration of behavioral and emotional challenges. Consistent with the Research Domain Criteria research framework recommendations, the project (1) employs multiple levels of analysis, (2) investigates negative and positive valence systems as well as arousal systems, and ...