Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults
Open accessAbstract
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a characteristic overeating disorder, mild to moderate intellectual disability, and a variable range of social and behavioral difficulties. Consequently, widespread alterations in neural structure and developmental and maturational trajectory would be expected. To date, there have been few quantitative and systematic studies of brain morphology in PWS, although alterations of volume and of cortical organisation have been reported. This study aimed to investigate, in detail, the structure of grey matter and cortex in the brain in a sample of young adults with PWS in a well-matched case-controlled analysis. 20 young adults with PWS, aged 19-27 years, underwent multiparameter mapping magnetic resonance imaging sequences, from which measures of grey matter volume, cortical thickness and magnetisation transfer saturation, as a proxy measure of myelination, were examined. These variables were investigated in comparison to a control group of 40 typically developing young adults, matched for age and sex. A voxel-based morphometry analysis identified large and widespread bilateral clusters of both increased and decreased grey matter volume in the brain in PWS. In particular, widespread areas of increased volume encompassed parts of the prefrontal cortex, especially medially, the majority of the cingulate cortices, from anterior to posterior aspects, insula cortices, and areas of the parietal and temporal cortices. Increased volume was also reported in the caudate, putamen and thalamus. The most ventromedial prefrontal areas, in contrast, showed reduced volume, as did the parts of the medial temporal lobe, bilateral temporal poles, and a small cluster in the right lateral prefrontal cortex. Analysis of cortical structure revealed that areas of increased volume in the PWS group were largely driven by greater cortical thickness. Conversely, analysis of myelin content using magnetisation transfer saturation indicated that myelination of the cortex was broadly similar in the PWS and control groups, with the exception of highly localised areas, including the insula. The bilateral nature of these abnormalities suggests a systemic biological cause, with possible developmental and maturational mechanisms discussed, and may offer insight into the contribution of imprinted genes to neural development.
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Prader-Willi syndrome is a disorder in which imprinted genes on chromosome 15 are affected and is characterized by increased volume of prefrontal subdomains important in the reward circuitry.
“Prader-Willi syndrome (PWS) is a disorder in which imprinted genes on chromosome 15 are affected and is characterized by increased volume of prefrontal subdomains important in the reward circuitry [300, 301].”
From Development of prefrontal cortex (2022) · cites this paper as [301]
The Introduction identifies PWS as a disorder of imprinted genes at chromosome 15q11–13, and the Results (VBM analysis) report increased volume in bilateral medial prefrontal cortex. The copy does not identify those prefrontal areas as reward circuitry; the Abstract also reports reduced volume in the most ventromedial prefrontal areas. (LLM, conf=0.85)
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Development of prefrontal cortex
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“Prader-Willi syndrome (PWS) is a disorder in which imprinted genes on chromosome 15 are affected and is characterized by increased volume of prefrontal subdomains important in the reward circuitry [300, 301].”
Background
- Authors
- Manning, K. E., Tait, R., Suckling, J., & Holland, A. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Manning, Katherine E.
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2018
- Volume
- 17
- Pages
- 899-909
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC5842730
- OpenAlex
- W2780291877
- Cited by
- 45
- References
- 60
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 14 · 2021: 10 · 2020: 1 · 2019: 4 · 2018: 1
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- BCU Open Access Repository (Birmingham City University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- National Institute for Health Research
- Health Foundation (RG34317)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- Prader-Willi syndrome, gray matter volume, cortical thickness, myelination, brain structure, prefrontal cortex, cingulate cortex, insula, caudate nucleus, putamen, thalamus, medial temporal lobe, genomic imprinting, brain development, young adults
- MeSH terms
- Adolescent, Adult, Brain Mapping, Cerebral Cortex, Female, Humans, Image Processing, Computer-Assisted, Intelligence Tests, Magnetic Resonance Imaging, Male, Prader-Willi Syndrome, Psychiatric Status Rating Scales, Body Mass Index, Young Adult, Gray Matter
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