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Published on: June 9, 2018
In vivo neuroimaging evidence of hypothalamic alteration in Prader-Willi syndrome
Stephanie S G Brown1, Katherine E Manning1, Paul Fletcher1
1Department of Psychiatry, University of Cambridge, Addenbrookes Hospital, Cambridge CB2 0QQ, UK.
Insights
Prader-Willi syndrome (PWS) involves smaller hypothalami, impacting eating behavior. This neurodevelopmental difference is distinct from general obesity, suggesting altered brain development in PWS.
Area of Science:
- Neuroscience
- Genetics
- Endocrinology
Background:
- Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder characterized by neonatal hypotonia, failure to thrive, hyperphagia, and obesity.
- Hypothalamic dysfunction is implicated in PWS, but whether it stems from pathway disruption or developmental failure is unclear.
Purpose of the Study:
- To investigate hypothalamic structure and connectivity in individuals with Prader-Willi syndrome (PWS) compared to controls and obese individuals.
- To determine if observed hypothalamic alterations in PWS are neurodevelopmental and distinct from general obesity.
Main Methods:
- Structural MRI scans were acquired for 20 participants with PWS, 40 age-matched controls, and 42 obese participants.
- The hypothalamus and its subnuclei were segmented, and eating behavior was assessed using the Food-Related Problem Questionnaire.
- Hypothalamic connectivity was analyzed using fractional anisotropy.
Main Results:
- All hypothalamic nuclei were significantly smaller in the PWS group compared to controls (P < 0.01), except for the right anterior-inferior nucleus.
- Lower whole hypothalamus volume correlated with higher BMI in PWS (P < 0.05).
- Increased food preoccupation was linked to smaller posterior and left tubular superior nuclei.
- Hypothalamic nuclei were also smaller in PWS compared to obese participants (P < 0.001).
- Altered hypothalamic connectivity (fractional anisotropy) was associated with impaired satiety in PWS (P < 0.05).
Conclusions:
- Hypothalamic structure is significantly altered in Prader-Willi syndrome (PWS).
- The observed hypothalamic dysfunction related to eating behavior in PWS is likely neurodevelopmental.
- These hypothalamic alterations in PWS are distinct from those seen in general obesity.
Abstract:
Prader-Willi syndrome is a genetic neurodevelopmental disorder with an early phenotype characterized by neonatal hypotonia, failure to thrive, and immature genitalia. The onset of hyperphagia in childhood and developmental, physical and neuropsychiatric characteristics indicate atypical brain development and specifically hypothalamic dysfunction. Whether the latter is a consequence of disruption of hypothalamic pathways for genetic reasons or due to a failure of hypothalamic development remains uncertain. Twenty participants with Prader-Willi syndrome, 40 age-matched controls and 42 obese participants underwent structural MRI scanning. The whole hypothalamus and its subnuclei were segmented from structural acquisitions. The Food-Related Problem Questionnaire was used to provide information relating to eating behaviour. All hypothalamic nuclei were significantly smaller in the Prader-Willi group, compared with age and gender matched controls (P < 0.01) with the exception of the right anterior-inferior nucleus (P = 0.07). Lower whole hypothalamus volume was significantly associated with higher body mass index in Prader-Willi syndrome (P < 0.05). Increased preoccupation with food was associated with lower volumes of the bilateral posterior nuclei and left tubular superior nucleus. The whole hypothalamus and all constituent nuclei were also smaller in Prader-Willi syndrome compared with obese participants (P < 0.001). Connectivity profiles of the hypothalamus revealed that fractional anisotropy was associated with impaired satiety in Prader-Willi syndrome (P < 0.05). We establish that hypothalamic structure is significantly altered in Prader-Willi syndrome, demonstrating that hypothalamic dysfunction linked to eating behaviour is likely neurodevelopmental in nature and furthermore, distinctive compared with obesity in the general population.
