The mediating roles of self-esteem and psychopathology in sex and age differences in non-suicidal self-injury among adolescents with major depressive disorder

Non-suicidal self-injury (NSSI) is highly prevalent among adolescents with major depressive disorder (MDD), yet the developmental and sex-related mechanisms underlying its occurrence and severity remain poorly understood. This study examined the effects of age and sex on NSSI occurrence and frequency in a large clinical cohort (N = 2,343) of Chinese adolescents diagnosed with MDD. Mediation analyses assessed self-esteem, depression, and anxiety as potential pathways linking age and sex to NSSI. Females had significantly higher NSSI prevalence (OR = 2.53) and frequency than males, while NSSI engagement decreased with age (OR = 0.808/year for NSSI occurrence). Self-esteem and depression partially mediated the effect of sex on NSSI occurrence, whereas self-esteem largely explained sex differences in NSSI frequency. Age-related declines in NSSI were mediated by self-esteem only in early adolescence, suggesting distinct developmental mechanisms across age groups. In late adolescence, age was directly protective for NSSI occurrence, independent of psychological variables. These findings highlight self-esteem as a critical factor influencing NSSI severity, with implications for sex- and age-specific intervention strategies. Future research should explore longitudinal trajectories and causal relationships to refine targeted prevention efforts for adolescents at risk of NSSI.