Associations Between Sensory Processing and Irritability in Prader-Willi Syndrome: Beyond Genetic Subtypes and Clinical Backgrounds.

Irritability is a core challenge in Prader-Willi syndrome (PWS). This study investigated the independent contribution of sensory processing to irritability while controlling for clinical and genetic backgrounds in a cohort of 101 individuals with PWS (77 deletion, 24 maternal uniparental disomy [mUPD]). Caregivers completed the Japanese version of the Short Sensory Profile (SSP-J) and the irritability subscale of the Aberrant Behavior Checklist (ABC-J). Hierarchical multiple regression analysis was performed. In Step 1, age, sex, genetic subtype, and psychotropic medication use explained 22.3% of irritability variance (R 2 = 0.223, p < 0.001). Adding sensory variables in Step 2 explained an additional 38.2% (ΔR 2 = 0.382, p < 0.001), totaling 60.6% (R 2 = 0.606). Auditory filtering (β = 0.262), under-responsiveness/seeking sensation (β = 0.201), and visual/auditory sensitivity (β = 0.194) were significant independent predictors (p < 0.05). Notably, the effect of the mUPD subtype became non-significant after accounting for sensory variables. Sensory processing is a robust predictor of irritability, independent of genetic subtype and medication. Evaluating sensory profiles is essential for environmental adaptations and behavioral interventions in PWS.