Cumulative impacts of early-life interpersonal adversity and persistent/recurrent pain in children: a longitudinal normative modelling study from the ABCD study cohort

ABSTRACT: Children experiencing persistent/recurrent pain (PRP) report increased exposure to early-life adversity (ELA), often accompanied by more severe pain and worse mental health outcomes. Separate studies of PRP and ELA show similar alterations in brain morphology, yet their distinct and cumulative contributions remain poorly understood. Structural magnetic resonance imaging data at baseline and 2-year follow-up were accessed from the Adolescent Brain Cognitive Development cohort (N = 1671). Linear mixed models were used to determine the main effects of group (control, PRP only, ELA only, and PRP + ELA) and group-by-time interaction on measures of subcortical volume, cortical thickness, and surface area. In addition to determining brain morphological differences between the groups, support vector machine was applied to perform group classification based on brain measures to assess translational relevance of brain-based markers. The PRP + ELA group showed more pronounced reduction in left hippocampal volume and sensorimotor surface area and increase in left precuneus and right frontal pole surface area over time compared with all other groups. In addition, independently of time, the ELA only group showed overall smaller accumbens, thicker right prefrontal, and thinner left postcentral gyrus compared with the control and PRP only groups. Using all brain measures, support vector machine models could not identify group status better than 66.8% accuracy. Our findings provide evidence for unique brain signatures representing the cumulative effects of PRP and ELA in children during development. Identification of these brain markers can inform the choice of interventions in this population.