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Distinct Neurodevelopmental Phenotypes in Pediatric Daytime Urinary Incontinence: A Neuroimaging Study of Isolated DUI and Comorbid ADHD
Chino Eke, Bachelors of Arts (BA)1, Jordan Gitlin, Doctorate of Medicine2, Huang Lin, Doctorate of Medicine3, Israel Franco, Doctorate of Medicine4.
1Warren Alpert School of Medicine, Providence, RI, USA, 2NYU Langone Health Grossman School of Medicine, New York City, NY, USA, 3RWTH University, Aachen, Germany, 4Yale University School of Medicine, New Haven, CT, USA.
BACKGROUND: Daytime urinary incontinence (DUI) has traditionally been considered a problem of delayed maturation with or without problems with constipation or an isolated bladder problem. Over the last 20 years there has been increasing evidence that this is not just a bladder issue or a maturational delay. The adult literature has begun to enlighten us with regards to the areas in the brain involved with DUI. These areas encompass many areas that are associated with neuropsychiatric (NP) problems. These findings have lent support to the ever increasing findings that DUI in children is not just an unexplained comorbid problem but one in which there is a dysfunction in the areas of urination control which happen to be associated NP problems. We have learned that there are distinct phenotypes of DUI which can be classified as Urge and without awareness dominant with the latter primarily seen in children with ADHD. Our aim was to identify if there is a difference in the neurocorrelates associated with DUI with and without ADHD.
METHODS: Baseline multimodal neuroimaging data from the Adolescent Brain Cognitive Development (ABCD) Study were analyzed, including structural MRI, diffusion MRI, and resting-state functional MRI. Four cohorts were defined: neurotypical controls (n=5,947), DUI without ADHD (n=82), DUI with ADHD (n=16), and ADHD without DUI (n=1,266). ADHD status was defined using CBCL DSM-5 ADHD T-scores ≥65. ANCOVA models adjusted for age, sex, handedness, and intracranial volume for volumetric/surface area analyses. Estimated marginal means with Tukey-adjusted post-hoc contrasts were generated. False discovery rate (FDR) correction was applied across imaging metrics.
RESULTS: Children with isolated DUI demonstrated significantly increased cortical thickness and volume within frontal, insular, precuneus, and putaminal regions compared with controls. In contrast, ADHD without DUI demonstrated increased mean diffusivity (Elevated MD typically indicates reduced tissue density or compromised microstructural integrity) within the putamen and thalamus with reduced cortical surface area within the precuneus. Direct comparisons showed significantly greater frontal, insular, and precuneus thickness in isolated DUI compared with ADHD without DUI. The co-morbid DUI and ADHD cohort demonstrated attenuation of hypertrophic structural profile observed in isolated DUI, with imaging measures trending towards control values. These findings identify two distinct neurodevelopmental phenotypes: a structurally hypertrophic salience and interoceptive network phenotype in isolated DUI and a predominantly subcortical microstructural phenotype in ADHD (Table 1).
CONCLUSIONS: Children with isolated DUI demonstrate structural alterations involving the insula, frontal cortex, precuneus, and putamen, paralleling previously described salience and urgency networks implicated in adult urge urinary incontinence. In contrast, ADHD associated findings were characterized primarily by thalamic and putaminal microstructural abnormalities. These findings suggest that pediatric DUI with and without ADHD represent two biologically distinct neurodevelopmental phenotypes rather than a single shared disorder and may correspond clinically to separate continence phenotypes including urgency-driven incontinence versus impaired sensory awareness. Understanding these difference may help direct treatment with the appropriate medications.
Neuroimaging Differences between DUI with and without ADHD| Metric | DUI without ADHD | ADHD without DUI | Key Difference |
| Frontal thickness | Increased | Near-control values | DUI > ADHD (p=0.0036) |
| Insula thickness | Increased | Near-control values | DUI > ADHD (p=0.0241) |
| Precuneus thickness | Increased | Near-control values | DUI > ADHD (p=0.00009) |
| Putamen volume | Increased | Near-control values | DUI > ADHD (p=0.0018) |
| Putamen mean diffusivity | Mild change | Increased | ADHD-driven abnormality (p=0.00001) |
| Thalamus mean diffusivity | Mild change | Increased | ADHD-driven abnormality (p=0.0027) |
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