Modification of Brain Connectome on Association Between Adverse Childhood Experiences and Development of Mental...

Adverse childhood experiences (ACEs) are common and account for more than 25% of psychiatric disorders in youths, but the underlying neurobiological mechanisms associated with risk and resilience among children exposed to ACEs are poorly understood.

To examine associations between ACEs and transdiagnostic psychopathology during the transition to adolescence and to test whether these associations are modified by whole-brain functional connectivity.

This cohort study used data from the longitudinal Adolescent Brain Cognitive Development (ABCD) Study's baseline through 2-year follow-up assessments. A total of 6813 children aged 9 to 11 years at baseline were recruited from 21 US sites between June 1, 2016, and October 31, 2018. Data were analyzed from September 2023 to April 2025.

Lifetime ACEs, assessed from child and parent reports, through 2-year follow-up.

Cumulative number of current DSM-5 psychiatric disorders obtained from the computerized self-administered Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 (KSADS-5) through 2-year follow-up and a machine learning-based latent connectome variate (CV) score derived from baseline resting-state functional magnetic resonance imaging data.

Among 6813 children (mean [SD] age at baseline, 10.0 [0.6] years; 3413 girls [50.1%]) with available baseline neuroimaging, behavioral, and covariate data, the mean (SD) ACE score was 2.3 (1.7) at baseline. ACE scores were significantly associated with the cumulative number of KSADS-5 diagnoses at baseline (β = 0.11; 95% CI, 0.10-0.12; P < .001) and 2-year follow-up (β = 0.14; 95% CI, 0.12-0.15; P < .001). Baseline CV score modified associations between ACEs and psychiatric disorders across the 2 years (β = -0.02; 95% CI, -0.03 to -0.01; t = -3.34; P < .001). Post hoc investigation showed that the modification of the CV score on associations between ACEs and psychopathology was specific to the threat-related ACEs (β = -0.04; 95% CI, -0.06 to -0.02; t = -3.67; P < .001) and was pronounced for girls (β = -0.06; 95% CI, -0.09 to -0.02; t = -3.33; P < .001).

In this cohort study of children, a whole-brain functional connectivity score derived from neuroimaging data modified the association between ACEs and psychiatric disorders. This modification was particularly seen against threat-related ACEs and was pronounced for female youths. These findings suggest that functional connectivity strength in a broad system relevant to cognitive control may protect preadolescents who have experienced lifetime ACEs-especially girls and those experiencing threat-related ACEs-from developing transdiagnostic psychopathology.