Connectome-based Brain Marker Moderates the Relationship between Childhood Adversity and Transdiagnostic Psychopathology during Early Adolescence.

ABSTRACT

Importance Identifying brain-based markers of resiliency that reliably predict who is and is not at elevated risk for developing psychopathology among children who experience adverse childhood experiences (ACEs) is important for improving our mechanistic understanding of these etiological links between child adversity and psychopathology and guiding precision medicine and prevention efforts for reducing psychiatric impact of ACEs. Objective: To examine associations between ACEs and transdiagnostic psychopathology during the transition from preadolescence to early adolescence and test whether these associations are moderated by a hypothesized resilience factor, a previously identified connectome variate (CV) that is associated with higher cognitive function and lower psychopathology. Design Setting and Participants: This study was conducted in a longitudinal design based on multicenter data from a community cohort of U.S. youth aged of 9-11 at baseline, who participated in the Adolescent Brain Cognitive Development (ABCD) study (N=7,382 at baseline and 6,813 at 2-year follow-up). Linear regression models and moderation analyses were used to characterize concurrent and prospective associations between lifetime ACEs and number of DSM-5 psychiatric disorders (indexing transdiagnostic psychopathology) and to determine if individual variations in these associations were moderated by the CV derived from resting-state fMRI at baseline. Main Outcomes and Measures: Cumulative number of current DSM-5 psychiatric disorders assessed using the computerized self-admin version Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) and lifetime ACEs assessed from child and parent reports at baseline (9-10 years) and 2-year-follow-up (11-12 years). Results: ACE total scores correlated positively with the cumulative number of current DSM-5 psychiatric disorders at both baseline (r =.258, p < .001) and 2-year follow-up (r =.257, p < .001). The baseline CV score moderated the ACE-disorder associations at baseline (B = -0.021, p < .001) and at 2-year follow-up (B = -0.018, p = .008), as well as the association between the changes in ACE and in the number of disorders from baseline to year 2 (B = -0.012, p = .045). Post-hoc analyses further showed that the moderation effect of CV on ACE-psychopathology associations was specific to the threat-related ACEs and to female youth. Conclusions and Relevance These findings provide preliminary evidence for a connectome-based resiliency marker and suggest that functional connectivity strength in a broad system including frontal-parietal cortices and subcortical nuclei relevant to cognitive control may protect preadolescents who have experienced lifetime ACEs--especially females and those experiencing threat-related ACEs--from developing transdiagnostic psychopathology.