Sex-Specific Effects of Adverse Childhood Experiences on Adolescent Brain Development: Insights from the ABCD Study

BackgroundAdverse Childhood Experiences (ACEs) are established risk factors for physical and mental health outcomes, yet their associations with pediatric brain development remain underexplored, particularly regarding sex differences. Most studies treat ACEs as a single construct, overlooking the distinct effects of specific subtypes (e.g., sexual abuse, physical neglect) on brain structure and function. This study examines how ACE subtypes and their interaction with sex are linked to brain development in 9-10-year-olds. MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study (N{approx}12,000, ages 9-10), we assessed the links between emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect and structural brain measures in the hippocampus, amygdala, lateral orbital frontal cortex (lOFC), medial orbitofrontal cortex (mOFC), and rostral anterior cingulate cortex (rACC). Mixed-effects linear models tested ACE subtype, sex, and interaction effects, adjusting for multiple comparisons (Benjamini-Hochberg FDR correction). ResultsBoys reported higher exposure to emotional abuse (p =.01), emotional neglect (p = .037), and physical neglect (p< .001), while girls had greater exposure to sexual abuse (p < .001). Significant ACE-by-sex interactions emerged: sexual abuse was associated with smaller hippocampal volume in boys (p = .003) but showed no significant effect in girls (p = .433). Emotional abuse was linked to reduced lOFC volume in boys (p = 0.024), while in girls, it was associated with a marginal increase (p = .048). Physical neglect was associated with reduced hippocampal volume regardless of sex (pFDR = .05). ConclusionBoys may be particularly vulnerable to hippocampal and lOFC changes following sexual and emotional abuse, while physical neglect broadly impacts hippocampal development. These findings highlight sex-specific neurodevelopmental effects of ACE subtypes, emphasizing the need for tailored interventions and possible biomarkers for treatment and prevention of sequelae.