PROJECT SUMMARY/ABSTRACT This K23 proposal integrates research and training to characterize how genetic, neural, and environmental risk factors impact treatment outcomes for adolescents using substances and engaged in related externalizing behaviors. While substance problems and associated externalizing behaviors (i.e., violence, delinquency) have a significant negative impact on health and development, empirically-supported treatments are time- and resource-intensive, placing a high burden on youth and families engaged in treatment as well as the therapists providing these services. Using knowledge from neuroimaging and psychiatric genetics can inform personalized clinical practice, ultimately improving the precision and potency of treatment for these youth. The training in advanced network neuroscience methods, advanced quantitative and statistical genetic methods, and clinical and translational research, complement the research aims, which examine how neural and genetic risk markers, identified from a large sample of adolescents, can be evaluated as targets and moderators of treatment outcomes for youth with substance problems. The candidate will work towards this goal through the completion of a research project with three parts. The first aim focuses on using data from the Adolescent Brain Cognitive Development (ABCD) study to identify key neural networks associated with early externalizing and examining how genetic and environmental risk are associated. The second part (Aims 2 & 3) involves collecting neuroimaging, genetic, and phenotypic data from youth enrolled in Multisystemic Therapy (MST), an empirically-supported treatment for substance problems in youth with severe behavior problems. Third, comprehensive pilot data on family trios will be used to support future grant submissions examining transmission of risk and impact of treatment on family systems. Etiologic findings from ABCD, will be translated and applied in this clinical sample, addressing the following research aims: 1) Identify the neural networks and genetic and environmental factors that relate to externalizing outcomes in youth, 2) Examine the impact of MST on multimodal indices of inhibitory control, reward responsivity, and socioemotional functioning in treatment seeking youth, and 3) Examine how genetic and environmental risk are associated with MST treatment outcomes and 4) Examine the impact of MST on the family system. The following training objectives will be completed during the award period to equip the candidate to carry out the proposed project and establish herself as an independent investigator ready to conduct future projects following from this work: 1) Training in advanced multivariate network neuroscience methods; 2) Training in advanced quantitative and statistical genetics methods; 3) Further develop clinical and translational research skills; 4) Improving professional skills essential for an independent patient-oriented investigator. The proposed K23 ...