A prospective longitudinal study of transactional associations between social, neural, and hormonal changes and adolescent girls' mental health trajectories - ABSTRACT Internalizing problems are common, harmful, and sharply increasing amongst adolescent girls – creating a public health imperative to identify mechanisms as well as markers of risk or resilience, spanning from biology to behavior. It is also essential to identify for whom these issues will be adolescent-limited versus indicative of persistent or worsening mental health, and understand the reasons why. Core biological and social processes of adolescence, such as puberty, brain development, and peer relationships, are promising targets. Socially, building and strengthening close friendships and romantic relationships are central developmental tasks in mid-to-late adolescence. The quality of close peer relationships in mid-to-late adolescent girls is known to have bidirectional and nuanced associations with emergence and recurrence of depression, anxiety, and self-harm. Interrogating this dual nature of close relationships, across timescales from days to years, is critical to begin addressing the emerging mental health crisis in adolescent girls. Furthermore, it is necessary to also account for the extended influence of pubertal processes, as puberty itself is strongly implicated in adolescent girls’ mental health. Ongoing maturation of sex hormones as well as brain structure, function, and connectivity through late adolescence makes it vital to integrate the contribution of developmental change in these biological factors to social processes and internalizing problems. The Transitions in Adolescent Girls (TAG) study, launched in 2015 (R01/R56 MH107418), was designed as a comprehensive multilevel investigation of the connections between biological and social changes during early-to-mid adolescence, as mechanisms of risk for the emergence of depression, anxiety, and self-harm. We enrolled a community sample of N=174 girls (initial ages 10-13 years) into a longitudinal study, with three waves of data collected every 18 months, including two laboratory visits at each wave. The first phase of the TAG study focused on early-to-mid adolescent mental health, as shaped by pubertal, neural, and social development (self-perception and social cognition). We propose to collect three additional waves of data, approximately 18 months apart, extending the cohort’s age range to 21 years. This new phase of the TAG study will have a developmentally-appropriate multilevel emphasis on close peer relationships, assessed via established questionnaires, daily self-reports, and novel paradigms that tap into intimate self-disclosure behavior and brain function. It will conduct innovative analyses to relate daily positive and negative experiences in close friendships and romantic relationships, with changes in well-being. Finally, it will continue to deeply phenotype ongoing biological (neural, hormonal, and pubertal) changes, and relate these to antecedent and subsequent social processes and mental health. We propose that close relationship quality and neurodevelopment during mid-to-late adolescence is not only predictive of concurrent and near-future mental health, but also part of a cascading series of developmental and risk processes that are set into motion by earlier biological and psychosocial changes.