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

• ACE scores were significantly associated with psychiatric diagnoses at baseline and 2-year follow-up (β = 0.14)
• Brain functional connectivity patterns modified the relationship between ACEs and psychiatric disorders (β = -0.02, P < .001)
• The protective effect of brain connectivity was stronger for threat-related ACEs (β = -0.04) than other types
• Girls showed a more pronounced protective effect of brain connectivity against ACEs than boys (β = -0.06 for girls)
• ACEs account for more than 25% of psychiatric disorders in youths, but mechanisms of resilience are poorly understood

Limitations

The study is observational and cannot establish causation. The findings are specific to a US population and may not generalize to other countries or cultural contexts.

Abstract

IMPORTANCE: 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. OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURE: Lifetime ACEs, assessed from child and parent reports, through 2-year follow-up. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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). CONCLUSIONS AND RELEVANCE: 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.