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Self-referential processing (i.e., self-schemas that guide processing of self-descriptive information) emerges early in youth, with deeper encoding of negative self-descriptors and/or shallower encoding of positive self-descriptors causally linked to depression. However, the relationship between depressogenic self-schemas and brain structure is unclear. We investigated associations between self-schemas and regional grey matter volume (GMV) in 84 never-depressed preadolescents oversampled for depression risk based on maternal depression history. Self-schemas were assessed using a Self-Referent Encoding Task (SRET) and regional GMV was indexed via voxel-based morphometry analysis of structural magnetic resonance imaging data. Youths’ positive self-schemas were associated with greater regional GMV within the ventrolateral prefrontal cortex (vlPFC) and posterior cingulate cortex (PCC), while negative self-schemas were associated with smaller regional GMV within vlPFC and PCC, areas important to emotion regulation and self-referential processing. These associations remained significant after controlling for youths’ concurrent depressive symptoms. Exploratory mediation analysis suggested that adolescents’ depressogenic self-schemas may mediate associations between GMV and depressive symptoms. Our findings suggest that the observed GMV variations within vlPFC and PCC may serve as neurobiological markers of depressogenic self-schemas during preadolescence.