Cortical Thinning in Adults with Prader-Willi Syndrome: Distribution Across Functional Networks and Associations with BMI and the GH/IGF-1 Axis
Abstract
Prader-Willi syndrome (PWS) is a rare neurogenetic disorder associated with neuropsychiatric, metabolic, endocrine, and physical abnormalities. Although previous neuroimaging studies have identified regional gray matter alterations, cortical thickness (CT) abnormalities and their distribution across large-scale functional brain networks remain poorly characterized in adults with PWS. We investigated cortical morphology in 23 adults with PWS and 22 age- and sex-matched healthy controls who underwent structural MRI. Cortical reconstruction and surface-based morphometric analyses were performed using FreeSurfer. Between-group differences in CT were assessed using age, sex, and intracranial volume as covariates. Associations between CT and clinical, cognitive, anthropometric, and endocrine measures were examined using Spearman correlations. Significant cortical regions were further mapped onto an a priori functional network atlas. Adults with PWS showed reduced CT in a left-hemispheric cluster involving the inferior precentral gyrus, insula, inferior temporal cortex, and orbitofrontal cortex. This cluster overlapped predominantly with the somatomotor, auditory, cingulo-opercular, language, and frontoparietal networks. Within the PWS group, lower CT was associated with higher body mass index and poorer global functioning. CT was positively associated with IGF-1 levels and was greater in participants with a history of growth hormone therapy during childhood. These findings indicate cortical thinning across regions belonging to multiple functional networks involved in sensorimotor, attentional, language, and executive processes, extending previous volumetric findings. The associations with body mass index, functional measures, and the GH/IGF-1 axis suggest that cortical morphology may reflect an interplay between genetic vulnerability and potentially modifiable metabolic and endocrine factors, raising the possibility of a neuroprotective role for GH/IGF-1 signaling.
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BibTeX
@misc{morenoarmengol2026cortical,
title = {{Cortical Thinning in Adults with Prader-Willi Syndrome: Distribution Across Functional Networks and Associations with BMI and the GH/IGF-1 Axis}},
author = {A. Moreno-Armengol and L. Blanco-Hinojo and L. Casamitjana and O. Gimenez-Palop and J. Cobo and J. Pujol and G. Martinez-Vilavella and J. Deus and S. Esteba-Castillo and R. Pareja and A. Caixas and C. Pena-Gomez},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.26367090},
url = {https://www.medrxiv.org/content/10.64898/2026.11.04.26367090v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cortical Thinning in Adults with Prader-Willi Syndrome: Distribution Across Functional Networks and Associations with BMI and the GH/IGF-1 Axis
AU - A. Moreno-Armengol
AU - L. Blanco-Hinojo
AU - L. Casamitjana
AU - O. Gimenez-Palop
AU - J. Cobo
AU - J. Pujol
AU - G. Martinez-Vilavella
AU - J. Deus
AU - S. Esteba-Castillo
AU - R. Pareja
AU - A. Caixas
AU - C. Pena-Gomez
PY - 2026
DA - 2026/11/04
PB - medRxiv
DO - 10.64898/2026.11.04.26367090
UR - https://www.medrxiv.org/content/10.64898/2026.11.04.26367090v1
AB - Prader-Willi syndrome (PWS) is a rare neurogenetic disorder associated with neuropsychiatric, metabolic, endocrine, and physical abnormalities. Although previous neuroimaging studies have identified regional gray matter alterations, cortical thickness (CT) abnormalities and their distribution across large-scale functional brain networks remain poorly characterized in adults with PWS. We investigated cortical morphology in 23 adults with PWS and 22 age- and sex-matched healthy controls who underwent structural MRI. Cortical reconstruction and surface-based morphometric analyses were performed using FreeSurfer. Between-group differences in CT were assessed using age, sex, and intracranial volume as covariates. Associations between CT and clinical, cognitive, anthropometric, and endocrine measures were examined using Spearman correlations. Significant cortical regions were further mapped onto an a priori functional network atlas. Adults with PWS showed reduced CT in a left-hemispheric cluster involving the inferior precentral gyrus, insula, inferior temporal cortex, and orbitofrontal cortex. This cluster overlapped predominantly with the somatomotor, auditory, cingulo-opercular, language, and frontoparietal networks. Within the PWS group, lower CT was associated with higher body mass index and poorer global functioning. CT was positively associated with IGF-1 levels and was greater in participants with a history of growth hormone therapy during childhood. These findings indicate cortical thinning across regions belonging to multiple functional networks involved in sensorimotor, attentional, language, and executive processes, extending previous volumetric findings. The associations with body mass index, functional measures, and the GH/IGF-1 axis suggest that cortical morphology may reflect an interplay between genetic vulnerability and potentially modifiable metabolic and endocrine factors, raising the possibility of a neuroprotective role for GH/IGF-1 signaling.
ER -