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

Background Adverse 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.

Using data from the Adolescent Brain Cognitive Development (ABCD) Study (N≈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).

Boys 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).

Boys 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was supported by the NIH K01MH122774 and the Brain and Behavior Research Foundation NARSAD Young Investigator (Dr. Zhu Xi) Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of the University of California, San Diego gave ethical approval for the Adolescent Brain Cognitive Development (ABCD) Study. Use of this dataset was approved through data use certification from the NIMH Data Archive (NDA). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Revised stats result in abstract; Co-author and co-last author notation revision. Data Availability The data used in this study are publicly available from the Adolescent Brain Cognitive Development (ABCD) Study through the National Institute of Mental Health Data Archive (NDA) at https://nda.nih.gov/abcd. Access requires data use certification.