Alteration of brain nuclei in obese children with and without Prader-Willi syndrome

Abstract

Introduction: Prader-Willi syndrome (PWS) is a multisystem genetic imprinting disorder mainly characterized by hyperphagia and childhood obesity. Extensive structural alterations are expected in PWS patients, and their influence on brain nuclei should be early and profound. To date, few studies have investigated brain nuclei in children with PWS, although functional and structural alterations of the cortex have been reported widely.Methods: In the current study, we used T1-weighted magnetic resonance imaging to investigate alterations in brain nuclei by three automated analysis methods: shape analysis to evaluate the shape of 14 cerebral nuclei (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens), automated segmentation methods integrated in Freesurfer 7.2.0 to investigate the volume of hypothalamic subregions, and region of interest-based analysis to investigate the volume of deep cerebellar nuclei (DCN). Twelve age- and sex-matched children with PWS, 18 obese children without PWS (OB) and 18 healthy controls participated in this study.Results: Compared with control and OB individuals, the PWS group exhibited significant atrophy in the bilateral thalamus, pallidum, hippocampus, amygdala, nucleus accumbens, right caudate, bilateral hypothalamus (left anterior-inferior, bilateral posterior, and bilateral tubular inferior subunits) and bilateral DCN (dentate, interposed, and fastigial nuclei), whereas no significant difference was found between the OB and control groups.Discussion: Based on our evidence, we suggested that alterations in brain nuclei influenced by imprinted genes were associated with clinical manifestations of PWS, such as eating disorders, cognitive disability and endocrine abnormalities, which were distinct from the neural mechanisms of obese children.

MRI Volumetric Analysis of the Hypothalamus and Limbic System across the Pediatric Age Span

“…The volumes of components of the limbic system have been studied in numerous case-control studies in the context of different conditions in childhood including Prader–Willi syndrome [ 4 , 5 ], schizophrenia [ 11 , 12 , 16 , 18 ], bipolar disorder [ 13 ], depression [ 14 ], anxiety [ 31 ], autism spectrum disorder [ 32 , 33 ], attention deficit hyperactivity disorder [ 32 , 33 ], and children with obsessive-compulsive disorder [ 32 , 33 ]. However, normal values of the structures of the limbic system across the pediatric age range specific to sex and age are scarce.…”

“…Knowledge of the intricate structural and functional anatomy of the limbic system, its connectedness, and relationships to other brain regions is essential to better understand various disorders including schizophrenia, epilepsy, limbic encephalitis, dementia, anxiety disorders, and others [ 1 ]. Recently, Wu et al showed that automated volumetry of T1-weighted MR images can help elucidate the neuroanatomical correlate of Prader–Willi syndrome [ 4 ]. Prader–Willi syndrome is a genetic obesity disease characterized by an insatiable appetite, hyperphagia, and morbid to life-threatening obesity [ 4 ].…”

“…Recently, Wu et al showed that automated volumetry of T1-weighted MR images can help elucidate the neuroanatomical correlate of Prader–Willi syndrome [ 4 ]. Prader–Willi syndrome is a genetic obesity disease characterized by an insatiable appetite, hyperphagia, and morbid to life-threatening obesity [ 4 ]. In a cohort of 12 children with Prader–Willi syndrome, 18 obese children without Prader–Willi syndrome, and 18 healthy controls, Wu et al showed that children with Prader–Willi syndrome have a significantly smaller thalamus, globus pallidus, hippocampus, amygdala, nucleus accumbens, deep cerebellar nuclei, and hypothalamus [ 4 ].…”

“…Prader–Willi syndrome is a genetic obesity disease characterized by an insatiable appetite, hyperphagia, and morbid to life-threatening obesity [ 4 ]. In a cohort of 12 children with Prader–Willi syndrome, 18 obese children without Prader–Willi syndrome, and 18 healthy controls, Wu et al showed that children with Prader–Willi syndrome have a significantly smaller thalamus, globus pallidus, hippocampus, amygdala, nucleus accumbens, deep cerebellar nuclei, and hypothalamus [ 4 ]. Brown et al found similar differences with regard to the atrophy of hypothalamic nuclei, but they also showed that a lower whole hypothalamus volume was significantly associated with higher body mass index in Prader–Willi syndrome [ 5 ].…”

“…In addition, there is a large body of case-control studies assessing components of the limbic system in children in the context of different conditions. Several studies have assessed the hippocampus [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], amygdala [ 6 , 14 , 15 ], cingulate gyrus [ 16 , 17 , 18 ], and hypothalamus [ 4 , 5 ]. However, these studies include only a limited number of healthy children, and do not report the sex-specific change of volume across the entire pediatric age span.…”