O1042: Morphological and Connectomic Brain Correlates of Constipation in 9- to 10-year-olds in the US

Background: Constipation is commonly encountered in children with urinary incontinence. Previous studies on adults reported altered cortical morphometry of the prefrontal cortex and supplementary motor area as well as functional connectivity (FC). However, whether and what structural and functional changes are present in pediatric patients with constipation remains unclear.

Methods: Using the population-based Adolescent Brain Cognitive Development (ABCD) Study that recruited over 11,000 9- to 10-year-olds across the US, we compared structural and resting-state functional magnetic resonance imaging (MRI) parameters of children with constipation to healthy controls. Inclusion in the case group required a record of constipation according to the child behavioral checklist (“Constipated, doesn't move bowels”). The healthy reference had no history of constipation, urinary incontinence, encopresis and mental health diagnoses as well as no parental drug use and mental health comorbidities. MRI regions of interest included thickness, volume, surface area and sulcus depth of 26 cortical regions, volume of 19 subcortical regions, FC within and between 6 cortical networks (cingulo-opercular, salience, dorsal and ventral attention, default and fronto-parietal networks) as well as FC from 6 cortical networks to 19 subcortical regions. Univariate logistic regression models determined differences in MRI parameters between the two groups with correction for multiple testing using Benjamini and Hochberg. Similarly, we also compared the following covariates between the two groups: gender, age, race/ethnicity and diagnosis of ADHD, depression, oppositional defiant behavior and anxiety. Covariates with a p-value below the significance level of p=0.05 in the univariate regression were included in multivariate models.

Results: The final cohort consisted of 712 children with constipation (411 (57.7%) females and 301 (42.3%) males) and 488 healthy controls (257 (52.7%) females and 231 (47.3%) males). There was no significant gender difference between the two groups. The mean age of all participants was 10.0 (±0.6) years. Only race/ethnicity were included in the multivariate model. After covariate adjustment, children with constipation had higher cortical thickness of bilateral pars triangularis (p≤0.014), left-sided isthmus of the cingulate cortex (p=0.044), insula (p=0.015) and lateral orbitofrontal (p=0.009) as well as right-sided pars orbitalis (p=0.005), precuneus (p=0.004), rostral middle frontal (p=0.017) and superior frontal (p=0.021) regions. Furthermore, the case group showed reductions of cortical surface area in bilateral pars orbitalis (p≤0.018), pars triangularis (p≤0.003) and precuneus (p≤0.034) as well as left insula (p=0.039), lateral orbitofrontal (p=0.036) and rostral middle frontal (p=0.021) regions. Additionally, our analysis showed lower volume of bilateral cerebellum cortex (p≤0.021) and increased FC of the dorsal attention network to the left amygdala (p=0.016) in the constipation group.

Conclusion: Our analysis provides multimodal neuroimaging evidence on brain morphology and FC alterations, especially in the prefrontal cortex and supplementary motor area, in association with pediatric constipation, which portrays important clues for improving new treatment strategies.