ABSTRACT Adolescent concussion is a major public health concern, affecting nearly 2 million children and adolescents in the U.S. each year. These injuries result from biomechanical forces acting on the brain. Primarily invovled in emotion processing and regulation, midline brain regions −including the fronto-limbic system and hypothalamus/pituitary− are particularly vulnerable to these forces. The reporting of transient psychological symptoms is common following a concussion; h owever, adolescent g persistent psychological problems (e.g., anxiety) irls are at a greater risk for after injury. It is important to note that adolescence is a period marked by hormone-dependent mechanisms of brain plasticity that open a window of heightened sensitivity to the influences of endogenous and exogenous factors on the brain. Thus, it is conceivable that a concussion during this period may increase risk for psychiatric morbidity, especially in girls who, having a more rapid transition through puberty, may have a limited time to heal. If puberty has an effect on concussion, concussion is also likely to affect puberty. Intriguing evidence of post-concussion hypopituitarism are emerging; yet the underlying mechanisms are unknown. Filling this knowledge gap is important because a better understanding of the pathophysiologic mechanisms of adolescent concussion can aid in early identification of risk and provides new targets for the development of future interventions. The objective of this application is to investigate the pathophysiologic mechanisms of persistent psychological symptoms in adolescent concussion and to further un- derstand the role of pubertal hormones across sexes and pubertal stages, when neurodevelopmental changes with potential downstream consequences for psychiatric vulnerability may occur. By prospectively characterizing 6-month trajectories of psychological symptoms in 10- to 18-year-olds with and without concussion, this proposal aims to ex- amine if a) hormonal changes and/or b) concussion-related lesions in midline brain regions can help explain the persistence of these symptoms across different pubertal stages and sexes and to further determine c) the contribution of pubertal maturity and sex on these relationships. To this end, we will use a combination of hormonal profiles, capturing changes in pubertal hormones for up to 3 months after injury, state-of-the-art neuroimaging methods, al- lowing to detect indirect indices of brain injury in subacute and chronic phases of concussion, and statistical methods designed to model different effects of complex developmental processes during adolescence. This is innovative be- cause no study has used such a highly integrative approach to examine the influence of hormones and MRI abnor- malities in adolescent concussion and how these relate to pathophysiologic mechanisms underlying the persistence of psychological symptoms in 10- to 18-year-olds. This contribution is anticipated to be significant ...