PROJECT SUMMARY/ABSTRACT Rates of suicide, self-harm, and depression are alarmingly high among adolescent girls, with a dramatic spike over the last decade, yet it is not clear which girls are at highest risk for these serious problems and when they might escalate. Some have argued that the dramatic rise in social media (SM) use may play a role, but more rigorous data are needed to evaluate the positive and negative effects of SM use in adolescent girls. Sensitivity to social evaluation, such as rejection or exclusion, is a potential cross-diagnostic risk factor for self-injurious thoughts and behaviors (SITB; including suicidal ideation and behavior and nonsuicidal self-injury) and de- pressive symptoms (DEPsx). This study examines how socially threatening and rewarding peer interactions— experienced online or in-person—contribute to real-time fluctuations in SITB, DEPsx, and well-being. The first aim is to use ecological momentary assessment (EMA) to identify how adolescent girls’ daily subjective experi- ence of online and in-person social threat and reward predict proximal within-person changes and longer-term between-person differences in SITB and DEPsx, along with wellbeing. The sample will include 177 adolescent girls (ages 13-17), with 75% of the sample at high-risk for suicide (e.g. active ideation within past 6 weeks, at- tempt in past year, or ≥ five episodes of nonsuicidal self-injury in past year), with at least half of high-risk par- ticipants also reporting elevated DEPsx. Girls will complete three 10-day bursts of EMA and will also provide access to passively obtained data on SM use and digital social interactions (i.e. text, video-chat). Multilevel modeling analyses will be used to identify predictors of near-term changes in SITB, DEPsx, and positive affect (PA), as well as long-term outcomes assessed at 6- and 12-month follow-up. A second aim is to identify which girls are at highest risk for DEPsx and/or SITB when exposed to near-term precipitants, focusing on differences in brain activation to social evaluation within an affective salience network (ASN) that includes the amygdala, anterior insula, dorsal and subgenual anterior cingulate cortex, and nucleus accumbens. Building on the differ- ential susceptibility to context theory, the study proposes that heightened ASN activation to social evaluation is a susceptibility factor that could amplify both the positive and negative effects of daily social experience on SITB and DEPsx. Girls will complete neuroimaging tasks that assess brain response to social evaluation from virtual peers. It is hypothesized that within-person increases and higher rates of peer social threat experiences (online and in-person) will be most strongly associated with SITB and DEPsx for girls with heightened ASN activation to social evaluation, and that within-person increases and higher rates of peer social reward experi- ences will also be more strongly associated with PA/wellbeing and more protective ...