Adolescence is a critical period for brain development, consolidation of self-understanding, and onset of non-suicidal self-injury (NSSI). This study evaluated the RDoC (Research Domain Criteria) sub-construct of Self-Knowledge in relation to adolescent NSSI using multiple units of analysis.

One hundred and sixty-four adolescents assigned female at birth (AFAB), ages 12–16 years with and without a history of NSSI entered a study involving clinical assessment and magnetic resonance imaging (MRI), including structural, resting-state functional MRI (fMRI), and fMRI during a self-evaluation task. For imaging analyses, we used an a priori defined Self Network (anterior cingulate, orbitofrontal, and posterior cingulate cortices; precuneus). We first examined interrelationships among multi-level Self variables. We then evaluated the individual relationships between NSSI severity and multi-level Self variables (self-report, behavior, multi-modal brain Self Network measures), then conducted model testing and multiple regression to test how Self variables (together) predicted NSSI severity.

Cross-correlations revealed key links between self-reported global self-worth and self-evaluation task behavior. Individually, greater NSSI severity correlated with lower global self-worth, more frequent and faster negative self-evaluations, lower anterior Self Network activation during self-evaluation, and lower anterior and posterior Self Network resting-state connectivity. Multiple regression analysis revealed the model including multi-level Self variables explained NSSI better than a covariate-only model; the strongest predictive variables included self-worth, self-evaluation task behavior, and resting-state connectivity.

Disruptions in Self-Knowledge across multiple levels of analysis relate to NSSI in adolescents. Findings suggest potential neurobiological treatment targets, potentially enhancing neuroplasticity in Self systems to facilitate greater flexibility (more frequently positive) of self-views in AFAB adolescents.