Investigating psychosis in Prader-Willi syndrome: developing cognitive, electrophysiological and neuroimaging approaches
type: CreativeWork
description: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder resulting from the absent expression of maternally imprinted, paternally expressed genes located in the chromosomal region 15q11-13. This absence of expression is usually either due to a paternal deletion or maternal uniparental disomy (mUPD). Both genetic subtypes share the same core clinical symptoms, such as developmental delays, intellectual disability, hyperphagia, behavioural and social difficulties, and a heightened risk for anxiety and depression. However, only people with PWS due to mUPD seem to be at particularly high risk for developing psychosis. Research on the causes of this differential risk is very scarce. This PhD study aims to propose potential mechanisms of psychosis in PWS and design and develop a study to test them. I hypothesised that the GABA/glutamate equilibrium is disrupted in PWS due to the absence of paternal expression. In addition, the overexpression of maternal genes on chromosome 15 would cause cholinergic dysfunction in people with mUPD and further disrupt GABAergic, glutamatergic, dopaminergic and cholinergic functions, increasing the probability of psychotic symptoms. In line with the predictive processing model of psychosis, the neurotransmitter disruptions proposed would cause a reduction in the use of priors to formulate predictions, detect and generate prediction errors, and update the prediction system. A case-control study comprising clinical, cognitive, neuroimaging, and remote behavioural testing was designed to investigate the hypotheses. The study was organised into four modules. The EEG module comprised the Global-Local paradigm, a sensory gating paradigm, and resting state. The MRS module measured metabolites in the anterior cingulate cortex, the auditory and visual cortex. The cognitive module contained measures of IQ, processing speed and working memory. The behavioural module was added during the COVID-19 pandemic to enable online data collection and focuse…
abstract: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder resulting from the absent expression of maternally imprinted, paternally expressed genes located in the chromosomal region 15q11-13. This absence of expression is usually either due to a paternal deletion or maternal uniparental disomy (mUPD). Both genetic subtypes share the same core clinical symptoms, such as developmental delays, intellectual disability, hyperphagia, behavioural and social difficulties, and a heightened risk for anxiety and depression. However, only people with PWS due to mUPD seem to be at particularly high risk for developing psychosis. Research on the causes of this differential risk is very scarce. This PhD study aims to propose potential mechanisms of psychosis in PWS and design and develop a study to test them. I hypothesised that the GABA/glutamate equilibrium is disrupted in PWS due to the absence of paternal expression. In addition, the overexpression of maternal genes on chromosome 15 would cause cholinergic dysfunction in people with mUPD and further disrupt GABAergic, glutamatergic, dopaminergic and cholinergic functions, increasing the probability of psychotic symptoms. In line with the predictive processing model of psychosis, the neurotransmitter disruptions proposed would cause a reduction in the use of priors to formulate predictions, detect and generate prediction errors, and update the prediction system. A case-control study comprising clinical, cognitive, neuroimaging, and remote behavioural testing was designed to investigate the hypotheses. The study was organised into four modules. The EEG module comprised the Global-Local paradigm, a sensory gating paradigm, and resting state. The MRS module measured metabolites in the anterior cingulate cortex, the auditory and visual cortex. The cognitive module contained measures of IQ, processing speed and working memory. The behavioural module was added during the COVID-19 pandemic to enable online data collection and focuse…
author: Aman, Lucie
language: eng
keywords: Prader-Willi syndrome, Psychosis, genetic cause of psychosis, Predictive coding, EEG, Global-Local paradigm, Mismatch negativity, P50 sensory gating, MRI, MRS, Online assessments
license: https://www.repository.cam.ac.uk/bitstreams/12b508f3-2423-4250-a7c3-bfff240b1233/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-01-18
date modified: 2026-07-24T01:33:03Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.97021