Altered brain function associated with non-suicidal self-injury in adolescents with major depressive disorder: An rs-fMRI study

BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent and harmful among adolescents with major depressive disorder (MDD), threatening mental and physical health. This study aims to elucidate the poorly understood neural mechanisms underlying NSSI behaviors and motivations in this group. METHODS: 133 adolescent participants were recruited, comprising 45 MDD with NSSI, 46 MDD without NSSI, and 42 age- and sex-matched healthy controls. All underwent resting-state functional MRI, from which low-frequency amplitude fluctuations (ALFF) were assessed and regions showing group differences were used as seeds for functional connectivity (FC) analyses. Associations between ALFF/FC values and NSSI behaviors and motivations were then evaluated via a cross-validation prediction method for robustness and generalizability. RESULTS: Adolescents with MDD who engaged in NSSI showed increased ALFF in the left precuneus, significantly associated with NSSI behaviors, and increased left precuneus-left cuneus FC, significantly associated with behaviors and intrapersonal negative reinforcement motivations. Prediction analyses confirmed the robustness of these associations, with ALFF (r(predicted, observed) = 0.653, p = 0.001) and FC (r(predicted, observed) = 0.601, p = 0.001; r(predicted, observed) = 0.587, p = 0.001). CONCLUSION: Our study identified key alterations in brain activity associated with NSSI behaviors and motivations in adolescents with MDD, providing neural markers for NSSI prediction and diagnosis and targets for precision interventions.