Brain Functional Connectivity Mediates the Association Between Adverse Childhood Experiences and Conduct Problems.

Background: Adverse childhood experiences (ACEs) are key risk factors for adolescent mental health problems, including conduct problems (CPs). While ACEs may impact CPs through neurobiological pathways, it is unclear whether brain functional connectivity (FC) acts as the neurobiological link.

Methods: We included 11,868 children from the baseline sample of the Adolescent Brain Cognitive Development (ABCD) Study. First, the continuous association between ACEs and CP severity was analyzed using linear mixed-effects (LME) modeling. Next, connectome-based predictive modeling (CPM) was used to predict CP scores and identify the CP-related connections, which were validated in 174 Healthy Brain Network (HBN) clinical participants. Finally, mediation analyses assessed whether the strength of CP-related connections mediated the association between ACEs and CP scores collected at baseline, 2 years, and 4 years after the ACEs report in the ABCD sample.

Results: LME modeling showed total ACEs and all 10 ACE categories were associated with increased CP scores (d = 0.056-0.465, false discovery rate-corrected p < .01). CPM significantly predicted CP scores (ρ = 0.128, p < .001), validated in the HBN dataset (ρ = 0.148, p = .048). The identified CP-related connections are involved in sensorimotor processing, emotional cognition, and impulsivity. Mediation analysis revealed that the strength of CP-related connections partially mediated the association between ACEs and CP scores at baseline, 2-year follow-up, and 4-year follow-up (β = 0.0086-0.015, p < .01).

Conclusions: This is the first study to our knowledge to suggest that FC provides a biological link between ACEs and subsequent CPs. ACEs may impact the strength of CP-related connections, in turn increasing risk of CPs. These findings highlight the importance of early assessment of ACEs and suggest CP-related connections as potential biomarkers.