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Individuals with Prader–Willi syndrome (PWS) exhibit complex behavioral characteristics, including hyperphagia, autistic features, and subsequent age-related maladaptive behaviors. While this suggests functional involvements of subcortical, limbic, and brainstem areas, developmental abnormalities in such structures remain to be investigated systematically. Twenty-one Japanese individuals with PWS and 32 healthy controls with typical development were included. T 1 -weighted three-dimensional structural magnetic resonance images were analyzed for subcortical, limbic, and brainstem structural volumes, with age as a covariate, using a model-based automatic segmentation tool. Correlations were determined between each volume measurement and behavioral characteristics as indexed by questionnaires and block test scores for hyperphagia (HQ), autistic and obsessional traits, non-verbal intelligence (IQ), and maladaptive behavior (VABS_mal). Compared with the control group, the PWS group showed significantly reduced relative volume ratios per total intracranial volume (TIV) in thalamus, amygdala, and brainstem structures, along with TIV and native volumes in all substructures. While the brainstem volume ratio was significantly lower in all age ranges, amygdala volume ratios were significantly lower during early adulthood and negatively correlated to HQ and VABS_mal but positively correlated to Kohs IQ. Thus, limbic and brainstem volume alterations and differential volume trajectories may contribute to the developmental and behavioral pathophysiology of PWS.

Differential volume reductions in the subcortical, limbic, and brainstem structures associated with behavior in Prader–Willi syndrome