Project Summary Many psychiatric disorders, ranging from major depressive disorder to substance use and delinquency, emerge or worsen during adolescence. These disorders are quite prevalent and associated with substantial distress and impairment. They jeopardize one's trajectory towards a productive adulthood, and increase suicide risk and involvement in crime. Because adolescence is characterized by dramatic physical development and the onset of menses in females, this critical developmental period is also associated with increased risk for iron deficiency (ID). Iron deficiency has been associated with neuropsychiatric impairment, including depressive and attention deficit hyperactivity symptoms. This is not surprising, given iron's role in dendritic mitochondrial motility during hippocampal neuron development, monoaminergic signaling, and myelination. In fact, across independent samples of otherwise medically-healthy adolescents, we have found prevalent ID and an inverse association between iron stores and the severity of psychiatric symptoms. Moreover, our preliminary evidence suggests that body iron stores are associated with brain morphometry and connectivity, as captured by magnetic resonance imaging. This work has resulted in a R01 award (1 R01 MH124848) to further examine how body iron stores relate to brain iron stores, brain function, and psychopathology. Only a few studies have examined the association between body iron stores and psychopathology in adolescents and those that have suffer from substantial limitations. As such, this Small Grant (R03) application seeks funding to use several waves of data from the National Health and Nutrition Examination Survey (NHANES). This data set offers a unique opportunity given the availability of information on a large number of adolescents (~900/wave) for several markers of body iron stores, depressive symptoms, inattention, substance use, sexual activity, and sexually transmitted infections. As such, we will be examine the association of body iron stores with depressive symptoms (Aim 1a) and with a composite score of externalizing behavior (Aim 1b). More importantly, we also seek to determine the level of body iron stores at which problematic mental health-related behaviors emerge (Aim 2). This is critical given that the ID has been defined by the medical field based on anemia-related outcomes; however, preclinical and clinical data suggest that brain iron is depleted before anemia emerges. In sum, taking advantage of several NHANES data waves, this proposal will be the first to examine the clinical correlates of body iron stores in a large group of adolescents, accounting for various confounders. Moreover, it has the potential to make a substantial impact on the field by highlighting ID's neuropsychiatric effects at levels of body iron stores higher than what has so far been considered medically problematic, requiring repletion.