PROJECT SUMMARY / ABSTRACT Depression is one of the major contributors to the global burden of disease, with the World Health Organization (WHO) ranking it as the number one non-fatal contributor. Most cases of depression appear by an individual’s third decade of life, which is classified as early onset depression. The long-term effects of early onset depression extend well into adulthood, usually leading to a high rate of recurrence and significant health concerns. Research has shown that early intervention prior to disease onset leads to the best outcomes. Therefore, detecting early markers of depression risk would help mitigate the disease. Previous investigations have looked at the effect of environmental exposures or genetic influences separately, with studies beginning to examine the interactive effects of genes and the environment on risk for depression. Though, few studies have been done examining how gene-by-environment interactions may map onto prodromal brain and behavioral biomarkers of risk for early onset depression, which could greatly assist in early detection and treatment. Specifically, select brain structure and functional networks as well as distinct emotional behaviors – such as, positive affect and withdrawal symptoms – have been consistently associated with early onset depression. Ultimately, it suggests that these may be important biomarkers in studying how gene-by-environment may contribute to risk for depression that emerges prior to disease onset. Thus, this study will examine whether the well-known environmental predictor of family income-to-needs may have independent and/or interactive effects along with an individual’s polygenic risk score for depression on the development of emotional brain structure and function from pre- to early adolescence. To accomplish this goal, the current study will leverage existing longitudinal data from approximately 5,000 subjects 9-10 year-of-age at baseline to 11-12 year-of-age at the 2-year follow-up from across the United States as part of the larger Adolescent Brain Cognitive Development? Study (ABCD Study®). Using two time point data for the brain imaging and up to three time points for emotional behavior outcome data, we will examine how gene-by-environment interactions effect changes in brain size and function. Aim 1 and Aim 2 will examine the independent and interactive effect of an individual’s income-to-needs and polygenic risk for depression on functional brain connectivity and brain structure of key emotional regions previously associated with depression, respectively. Aim 3 will further test whether the income-to-needs and polygenic risk score relate to established prodromal emotional behaviors. Ultimately, the findings from this project hold the potential to identify potential brain-behavior biomarkers that may be important to consider in establishing risk for early onset depression, ultimately helping to improve early detection and treatment.