<p>Heightened error-related negativity (ERN), a neural marker of error sensitivity and trait defensive reactivity, and maladaptive appraisals of interpersonal events have each been linked to adolescent internalizing symptoms. Few studies have evaluated a developmental mechanistic model to test whether enhanced ERN might prospectively predict more negative perceptions of peer and family events, and if through this pathway, internalizing symptoms increase. The present study tested this hypothesis in a sample of 79 female adolescents (ages 11–16 years old), of whom 36 adolescents had mothers with histories of internalizing disorders. At baseline, the participants’ ERN was measured through electroencephalogram recordings while completing a computerized flanker task. At baseline and 6-month follow-up, participants completed self-report measures of adolescent perceptions of family and peer events and internalizing symptoms. Analyses were conducted within a structural equation modeling framework to capitalize on the full dataset. Three competing models (correlated outcomes, negative perceptions of interpersonal events mediation, reverse internalizing symptoms mediation) were tested and relative model fit comparisons were made to determine which model fit the data better. We found partial support for our hypotheses. For the family events models, there was stronger evidence that baseline ERN predicted increases in internalizing symptoms via increases in negative perceptions of family events. However, for the peer events models, there was stronger evidence that internalizing symptoms mediated the prospective associations between baseline ERN and increases in negative perceptions of peer events. Future research should consider reciprocal effects among these pathways and how these processes could be targeted by preventive interventions.</p>