Despite the alarming increase in the prevalence of depression during adolescence, particularly among female adolescents, the pathophysiology of depression in adolescents remains largely unknown. Event-related potentials (ERPs) provide an ideal approach to investigate cognitive-affective processes associated with depression in adolescents, especially in the context of negative self-referential processing biases. In this study, healthy (n = 30) and depressed (n = 22) female adolescents completed a self-referential encoding task while ERP data were recorded. To examine cognitive-affective processes associated with self-referential processing, P1, P2, and late positive potential (LPP) responses to negative and positive words were investigated, and intracortical sources of scalp effects were probed using low-resolution electromagnetic tomography (LORETA). Additionally, we tested whether key cognitive processes (e.g., maladaptive self-view, self-criticism) previously implicated in depression related to ERP components. Relative to healthy female subjects, depressed females endorsed more negative and fewer positive words, and free recalled and recognized fewer positive words. With respect to ERPs, compared with healthy female adolescents, depressed adolescents exhibited greater P1 amplitudes following negative words, which was associated with a more maladaptive self-view and self-criticism. In both early and late LPP responses, depressed females showed greater activity following negative versus positive words, whereas healthy females demonstrated the opposite pattern. For both P1 and LPP, LORETA revealed reduced inferior frontal gyrus activity in response to negative words in depressed versus healthy female adolescents. Collectively, these findings suggest that the P1 and LPP reflect biased self-referential processing in female adolescents with depression. Potential treatment implications are discussed. (PsycINFO Database Record
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