Project Summary Children with Callous-Unemotional (CU) traits, which are defined by impairments in empathy, prosociality, and guilt, represent a uniquely at-risk subset of children with conduct disorder. These children have worse prognoses and response to treatments than children with conduct disorder alone. As a result, many of them suffer from poor educational achievement, substance use disorders, and antisocial behaviors. Genetic and environmental factors both affect the development of CU traits, which can occur as early as age 3 years. Twin studies place the heritability of CU traits around 58-81%, with the most implicated genes coding for neurotransmitter receptor variants. Due to the potential genetic effect on brain development, prior studies in adolescents have investigated and found alterations in emotion processing and emotion regulation areas of the brain. However, it is unknown whether these brain changes precede the early development of CU traits or occur later as a result of the pathology. To address this gap, we will leverage a unique, prospective, longitudinal cohort of 385 mother-infant dyads (recruited through R01 MH113883) that includes state-of-the-art neonatal neuroimaging, parental measures of CU traits (added by the applicant), and measures of offspring CU traits at age 3 years (added by the applicant). We hypothesize that altered functional brain connectivity in the newborn period, which occurs prior to postnatal environmental exposures, will mediate the heritable link between parent’s and children’s CU traits. To test this hypothesis, we plan to link CU traits in both mothers and fathers to CU traits in their children at age 3 years. Second, we will explore the relationship between neonatal functional connectivity in emotion processing and emotion regulation regions and CU traits at age 3 years. Finally, we will examine the role of neonatal functional connectivity in mediating heritable relationships between parent and children CU traits. Critically, this proposed project builds upon the candidate’s strong background and experience in neuroimaging analyses and behavioral assessments, enabling development of new skills across the domains of quantitative methods and atypical child development. Finally, not only will this project improve the understanding of aberrant brain development underlying early CU traits, but it will also provide the necessary background for the candidate to become a highly successful academic physician-scientist investigating the biological underpinnings of CU traits and treating patients with externalizing disorders.