Cognitive and behavioural correlates of psychosis in genetic subtypes of Prader-Willi syndrome.

BACKGROUND

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder resulting from the loss of paternally expressed, maternally imprinted genes within the chromosome 15q11-q13 region. While core features such as hyperphagia and developmental delay are nearly universal, the maternal uniparental disomy (mUPD) subtype carries a significantly higher risk of psychosis compared to the paternal deletion subtype. This study investigated the neurocognitive and behavioural mechanisms driving this genotype-specific vulnerability within a predictive processing framework.

METHODS

Individuals with genetically confirmed PWS (n = 30; 13 mUPD, 16 deletions, 1 unknown case) completed assessments of intellectual ability, executive functioning, and processing speed. A subset of participants (n = 13; 7 mUPD, 6 deletions) completed additional online behavioural tasks assessing reaction time, probabilistic reasoning, and perceptual inference. Results were compared across subtypes and against 10 neurotypical controls to identify markers of psychosis risk.

RESULTS

Participants with the mUPD subtype exhibited exploratory trends towards greater impairments in executive control, processing speed, and mentalisation when compared to the deletion group. Within the mUPD cohort, preliminary associations were found between psychosis markers and reduced cognitive flexibility, impaired error monitoring, and heightened self-referential bias. These patterns align with predictive processing models of psychosis.

CONCLUSION

The findings from the study indicate that mUPD is associated with a distinct neurocognitive profile that may increase psychosis liability. Although preliminary, the study supports using predictive processing frameworks to understand genotype-specific risks. PWS remains a vital model for researching psychosis-related processes, though larger studies are essential to confirm these mechanisms and develop targeted interventions.