Abstract Non-Suicidal Self Injury (NSSI) is a common clinical problem can lead to severe negative outcomes and has limited treatment options. Advancement of new interventions for NSSI is hindered by a lack of knowledge about its neural mechanisms. Neurobiological research on NSSI should ideally incorporate approaches promoted by the NIMH Research Domains Criteria (RDoC) initiative, i.e. examination of brain-behavior relationships outside of the confines of traditional psychiatric diagnoses. Since individuals primarily use NSSI to regulate negative affect and are characterized by interpersonal disturbances and negative self-conceptions, candidate RDoC domains for further study include Negative Valence and Social Processes. NSSI usually emerges during adolescence, a time period notable for significant developmental changes in brain and behavior. The over-arching goal of this research is to characterize the abnormal development of neural systems underlying NSSI in adolescence. New data from our group has revealed clues about brain-behavior relationships implicated in adolescent NSSI. Neuroimaging, self-report and endocrine data from two pilot studies suggest two RDoC constructs most relevant to adolescent NSSI: Sustained Threat (Negative Valence; an aversive emotional state caused by prolonged exposure to stimuli that signal danger that involves amygdala-frontal circuitry and neuroendocrine response to stress) and Self-Knowledge (Social Processes; the ability to judge one's states, traits, and abilities that involves the medial cortical network [MCN] including rostral anterior cingulate and posterior cingulate/precuneus). We found (a) NSSI-related abnormalities in multi-modal measures of these constructs, (b) within-construct and across-construct links among their measurements, and (c) a suggestion of aberrant neurodevelopmental trajectories in adolescents with NSSI. We now propose to more fully examine Sustained Threat and Self-Knowledge in 152 post-menarchal adolescent girls 12-14 years old who represent a continuum of NSSI [no NSSI (N=38); transient NSSI experimentation (N=38); moderate/chronic NSSI (N=38); and severe/chronic NSSI (N=38)], utilizing multiple units of analysis (self- reports, circuits, physiology) and a longitudinal design (with two follow-up assessments at 18 year intervals) to measure developmental trajectories across mid-adolescence. Our first aim is to examine baseline coherence across measurements of Sustained Threat and Self Knowledge. Our second aim will examine developmental change in Sustained Threat and Self-Knowledge across mid-adolescence, and how developmental trajectories are influenced by NSSI. Our third aim is to examine how Sustained Threat and Self Knowledge neural systems interact over time. These results will guide foundational knowledge needed to create targeted early interventions for adolescents with NSSI that promote healthy neurodevelopment. Additionally, this research will provide a method of interrogating the development of Negative Valence and Social Process systems under typical and atypical conditions, which will likely have implications for a broader array of psychopathology.