プラダー･ウィリ症候群

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder classically defined by hyperphagia and obesity. However, its profound psychiatric phenotype offers a unique genetic framework for understanding major mental illnesses. This review positions PWS as a potentially informative biological model for psychosis and obsessive-compulsive disorder (OCD), bridging the gap between 15q11-q13 imprinting defects and neural circuit dysfunction. We synthesize evidence demonstrating that psychosis in PWS is not a uniform trait but is disproportionately linked to the maternal uniparental disomy (mUPD) subtype. This genotype-phenotype correlation suggests that overexpression of maternally imprinted genes and loss of paternal expression disrupt cortical excitatory-inhibitory balance, resembling the "schizophrenia-bipolar" genomic architecture. Furthermore, synthesized evidence characterizes the repetitive, ritualistic behaviors in PWS not merely as behavioral challenges, but as a developmentally arrested OCD-spectrum phenotype driven by distinct serotonergic-oxytocinergic imbalances and hypothalamic-limbic dysconnectivity. Mechanistic insights from preclinical models of MAGEL2, SNORD116, and NDN deficiency are integrated with clinical findings to highlight shared neurobiological substrates. Finally, we outline a roadmap for precision psychiatry in PWS, emphasizing the necessity of pharmacogenomics in antipsychotic management and the potential of targeted circuit-based therapeutics. By deconstructing the psychiatric comorbidities of PWS, we provide a framework for translating genomic architecture into mechanistic understanding and targeted treatment for complex neuropsychiatric disorders.

The purpose of the present study was to investigate the effects of a sleep treatment package on the frequency of night awakenings, bedtime resistance, and caregiver stress with the caregivers of three child participants diagnosed with Prader-Willi syndrome (PWS) using a multiple baseline across subjects design. During baseline, child participants were not exposed to any procedure. During intervention, caregivers implemented a treatment package including graduated extinction, bedtime routines, and bedtime fading without response cost. All interventions were previously successful with children diagnosed with autism spectrum disorder but had not been attempted with this population. Correct responding was defined as zero instances of night awakenings, zero instances of bedtime resistance (different for each child participant) and decreases in caregiver-reported stress. In addition, social validity was assessed using a Likert-style questionnaire. The results show that the treatment package had varying success across all participants, with the most success being for reducing behaviors at bedtime. These results will provide further understanding of the effect behavior-analytic approaches can have on children diagnosed with Prader-Willi syndrome, increasing the number of applications of applied behavior analysis and the supports available for caregivers of children diagnosed with PWS.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder with hyperphagia, hypothalamic dysfunction, and severe behavioral dysregulation. Empirical descriptions of integrated inpatient treatment models remain limited. We examined multidomain outcomes during interdisciplinary inpatient stabilization in PWS. METHODS: This exploratory retrospective cohort included nine adolescents and young adults with genetically confirmed PWS admitted for severe behavioral dysregulation to a specialized interdisciplinary inpatient program. Behavioral, functional, anthropometric, and fasting metabolic outcomes were assessed at admission and discharge; medication profiles were recorded descriptively and three-month follow-up obtained via caregiver interview. Within-subject change was analyzed with Wilcoxon signed-rank tests. RESULTS: Token engagement increased (median 8 percentage points, p < 0.05) and aggression resolved: every patient had incidents in the first week, none in the final week (p = 0.004). Agitation showed a non-significant decrease (p = 0.063, floor effect) and global behavioral disturbance was non-significant (p = 0.24). Walk distance and functional independence improved (both p < 0.05). Weight decreased 73 lbs (1.2% per week) and BMI by 11.9 kg/m2 (both p < 0.05), with improvements in triglycerides, HbA1c, HDL, LDL, and total cholesterol (all p < 0.05). No behavioral-metabolic correlations survived false discovery rate adjustment. At three months, 89% remained in the community without rehospitalization and 77% rated global well-being as good or excellent. CONCLUSIONS: Structured interdisciplinary inpatient treatment for severe behavioral dysregulation in PWS was associated with multidomain improvement across behavioral, functional, and cardiometabolic domains. Behavioral and metabolic changes were not directly coupled; causality cannot be inferred. These findings support prospective investigation of integrated treatment models.