Brain structural alterations in obese children with and withoutPrader‐Willi Syndrome

Abstract

Prader-Willi syndrome (PWS) is a genetic imprinting disorder that is mainly characterized by hyperphagia and childhood obesity. Previous neuroimaging studies revealed that there is a significant difference in brain activation patterns between obese children with and without PWS. However, whether there are differences in the brain structure of obese children with and without PWS remains elusive. In the current study, we used T1-weighted and diffusion tensor magnetic resonance imaging to investigate alterations in the brain structure, such as the cortical volume and white matter integrity, in relation to this eating disorder in 12 children with PWS, 18 obese children without PWS (OB) and 18 healthy controls. Compared with the controls, both the PWS and OB groups exhibited alterations in cortical volume, with similar deficit patterns in 10 co-varying brain regions in the bilateral dorsolateral and medial prefrontal cortices, right anterior cingulate cortex, and bilateral temporal lobe. The white matter integrities of the above regions were then examined with an analysis method based on probabilistic tractography. The PWS group exhibited distinct changes in the reduced fractional anisotropy of white matter fibers connected to the co-varying regions, whereas the OB group did not. Our findings indicated that PWS and OB share similar gray matter alterations that are responsible for the development of eating disorders. Additionally, the distinct white matter alterations might explain the symptoms associated with food intake in PWS, including excessive hyperphagia and constant hunger. Hum Brain Mapp 38:4228-4238, 2017. © 2017 Wiley Periodicals, Inc.

Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults

“…It was not possible, however to match participants for BMI or IQ, since BMI was significantly greater in the PWS group and IQ was significantly higher for the control group. A recent study by Xu et al (2017) identified a number of overlapping brain regions of decreased grey matter volume between children with PWS and children with severe obesity, suggesting shared effects or vulnerabilities. The strength of the associations of BMI and IQ with group was such that attempting to control for these factors during comparisons of the PWS and control groups was not possible.…”

“…Abnormal cortical gyrification with reduced cortical complexity particularly in frontal areas, including the insula and cingulate regions, as well as in parietal and temporal cortices has also been reported, alongside reduced total cortical surface area in children with PWS compared to sibling controls ( Lukoshe et al, 2013 , Lukoshe et al, 2014 ). Most recently, Xu et al (2017) reported reduced total cortical volume and reductions in the medial prefrontal cortex (PFC), dorsolateral PFC, right anterior cingulate cortex (ACC) and in temporal and occipital areas in children with PWS compared to healthy controls, however these alterations were also seen in a highly obese group.…”

Obesity management in Prader–Willi syndrome: current perspectives

“…Altered brain structures have been documented in PWS that may underlie the excessive hyperphagia and the constant hunger, including low number of oxytocin neurones in the hypothalamus 20 and reduced fractional anisotropy of white matter fibers. 21 More recently, it has been shown that selective disruption of Snord116 expression in the mediobasal hypothalamus models the hyperphagia of PWS. 22 However, body weight gain in mice lacking Snord116 is limited to the first 18 weeks of life.…”

Cerebellar Volumes Associate with Behavioral Phenotypes in Prader-Willi Syndrome

“…Previous magnetic resonance imaging (MRI) studies have noninvasively detected in vivo structural brain alterations in individuals with PWS. Morphometric analysis has demonstrated developmental abnormalities in cortical and subcortical brain structures on a macroscopic scale [ 8 , 9 ], and these findings have been supported by microstructural evidence of altered connectivity using diffusion tensor imaging [ 10 , 11 ]. In contrast, research on the contribution of the cerebellum in PWS remains sparse, despite evidence suggesting a significant role of the cerebellum in a wide variety of neurodevelopmental disorders [ 12 ].…”