Cumulative impacts of early life adversity and persistent/recurrent pain in children: A longitudinal normative modelling study from the ABCD Study cohort.

Background: Compared to typically developing children, those experiencing persistent/recurrent pain (PRP) often report increased exposure to early life adversity (ELA). Separate studies of children experiencing PRP or exposed to ELA show similar alterations in brain morphology. Despite the close relationship between ELA and PRP experiences, their combined effect on the brain remains poorly understood. Methods: Structural magnetic resonance imaging data at baseline and 2-year follow-up was accessed from the Adolescent Brain Cognitive Development cohort (N = 1,671). 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. Support vector machine was applied to perform group classification based on brain measures. Results: 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 to 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 to the control and PRP only groups Using all brain measures, support vector machine models could not identify group status better than 66.8% accuracy. Conclusions: Our findings provide evidence for unique brain signatures representing the combined effects of PRP and ELA in children during development. Understanding effects of PRP and ELA on the brain of children can inform on treatment options to reduce pain symptoms and improve psychological outcomes.