Brain markers of early life adversity in children who develop sustained pain in the ABCD Study
Poster No:
948
Submission Type:
Abstract Submission
Authors:
Tong En Lim1, Sylvia Gustin1, Yann Quide1
Institutions:
1UNSW Sydney, Sydney, NSW
First Author:
Co-Author(s):
Introduction:
Early life adversity (ELA) is a risk factor for the development of chronic pain (Nicolson et al., 2023). Both ELA exposure and chronic pain are associated with similar brain alterations in stress-sensitive regions (i.e., prefrontal cortex, hippocampus, amygdala), but the effects of ELA exposure on brain morphology in children who will later develop sustained pain remains unclear. This study aims to determine how ELA exposure moderates the brain alterations of children who will develop sustained pain. We hypothesized that ELA exposure will be associated with stronger corticolimbic alterations in children experiencing sustained pain.
Methods:
A total of 2628 children were included from the Adolescent Brain Cognitive Development (ABCD) study, year 2 follow-up (FU2; 10-13 years old, 52% males; see Figure 1). Sustained pain (Pain+; N=876) was defined as reporting "sometimes true" or "often true" to any ache or pain over the past six months on the parent-reported Child Behaviour Checklist at FU2 (Achenbach, 2001); the Pain- group (N =1752) reported none of these experiences. ELA exposure (ELA+) was measured at baseline (age 8-11) and defined as experiencing at least one of the following: emotional, physical, sexual abuse or emotional and physical neglect (Hoffman et al., 2019); the ELA- group reported none of these experiences. Structural T1-weighted scans (at FU2) were processed using FreeSurfer (v7.1.1) and quality assessed according to ABCD standardised protocols. Indices of subcortical volume, cortical thickness and surface area (Desikan-Killiany atlas) were extracted and harmonised for scanning site differences using ComBat. Two-way multivariate analyses of covariance were used to determine the main effects of ELA exposure, sustained pain, and their interaction on indices of brain morphology (separate models for subcortical volumes, cortical thickness and surface area). Age, sex, socio-economic status, puberty, diagnoses of mental health conditions and total intracranial volume (for volumetric analyses only) were used as covariates. Significant multivariate analyses (p < 0.05) were followed by univariate analyses adjusted for the number of regions included using False-Discovery rate (FDR; q < 0.05). Indices of effect sizes were reported as a partial eta-squared (η2).
·Figure 1. Inclusion/exclusion flowchart
Results:
4.6% of the Pain+ (N=40 Pain+/ELA+, N= 836 Pain+/ELA-) and 5.1% of the Pain- group (N=89 Pain-/ELA+, N= 1663 Pain-/ELA-) reported ELA exposure. Subcortical multivariate analyses revealed significant ELA-by-pain interaction (p=0.025) and main effect of ELA (p=0.003), but no significant main effect of sustained pain. No univariate analyses survived FDR correction for the interaction, but ELA+ children had smaller left (η2=0.004) and right (η2=0.006) caudate volumes than ELA- children (see Figure 2A). Cortical thickness multivariate analyses revealed a significant ELA-by-pain interaction (p=0.029), but no significant main effects of ELA or sustained pain. Univariate analyses showed significant interaction effect on the left frontal pole thickness (η2=0.004; see Figure 2B); Pain+/ELA+ children showed thicker left frontal pole than Pain+/ELA- children (p=0.047), and Pain-/ELA+ children (p=0.007). Surface area multivariate analyses revealed significant main effects of ELA (p=0.022) and sustained pain (p=0.010), but no significant interaction. No univariate analyses survived FDR correction.
·Figure 2. Graphical representation of the results. (a) Univariate analyses for left frontal pole thickness, (b) Univariate analyses for bilateral caudate volume
Conclusions:
This study provides preliminary evidence for the role of ELA exposure to moderate changes in brain morphology in children who later developed sustained pain. Smaller caudate volumes could represent early markers of resilience to ELA exposure (Cohen et al., 2006). Thicker left frontal pole associated with ELA exposure in children who developed sustained pain may reflect abnormal neurodevelopment processes such as pruning and dendrite growth in this population. Future multimodal studies will determine the relationship of these morphological alterations with brain function and behaviors.
Lifespan Development:
Early life, Adolescence, Aging 1
Modeling and Analysis Methods:
Multivariate Approaches
Novel Imaging Acquisition Methods:
Anatomical MRI 2
Keywords:
Development
Pain
PEDIATRIC
STRUCTURAL MRI
Trauma
1|2Indicates the priority used for review
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Cohen, R. A., Grieve, S., Hoth, K. F., Paul, R. H., Sweet, L., Tate, D., Gunstad, J., Stroud, L., McCaffery, J., Hitsman, B., Niaura, R., Clark, C. R., McFarlane, A., Bryant, R., Gordon, E., & Williams, L. M. (2006). Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biological psychiatry, 59(10), 975–982. https://doi.org/10.1016/j.biopsych.2005.12.016
Hoffman, E. A., Clark, D. B., Orendain, N., Hudziak, J., Squeglia, L. M., & Dowling, G. J. (2019). Stress exposures, neurodevelopment and health measures in the ABCD study. Neurobiology of stress, 10, 100157. https://doi.org/10.1016/j.ynstr.2019.100157
Nicolson, K. P., Mills, S. E. E., Senaratne, D. N. S., Colvin, L. A., & Smith, B. H. (2023). What is the association between childhood adversity and subsequent chronic pain in adulthood? A systematic review. BJA open, 6, 100139. https://doi.org/10.1016/j.bjao.2023.100139