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Higher plasma orexin A levels in children with Prader-Willi syndrome compared with healthy unrelated sibling controls
Ann M Manzardo1, Lisa Johnson1, Jennifer L Miller2
1Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.
Insights
Children with Prader-Willi syndrome (PWS) have significantly higher orexin A levels compared to healthy siblings. This suggests orexin A dysregulation may contribute to PWS behavioral issues and hyperphagia.
Area of Science:
- Neuroendocrinology
- Genetics
- Metabolic Disorders
Background:
- Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by behavioral issues, hyperphagia, and obesity.
- Orexin A, a neuropeptide, regulates feeding behavior and energy metabolism, with potential links to PWS symptoms.
Purpose of the Study:
- To investigate and compare plasma orexin A levels in children with PWS versus healthy controls.
- To explore the potential association between orexin A dysregulation and the characteristic behaviors of PWS.
Main Methods:
- Plasma orexin A levels were measured in 23 children with PWS and 18 healthy siblings using multiplex immune assays.
- Statistical analysis involved general linear models, adjusting for diagnosis, gender, age, body fat, and BMI.
Main Results:
- Children with PWS exhibited significantly higher fasting plasma orexin A levels compared to their healthy siblings (P < 0.006).
- Orexin A levels showed a correlation with age in females and remained elevated in PWS after controlling for covariates.
Conclusions:
- Elevated orexin A levels in PWS support the hypothesis of orexin signaling dysregulation contributing to hyperphagia and behavioral problems.
- Further research is needed to elucidate the complex relationship between orexin A and PWS-associated behaviors.
Abstract:
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia, and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat and body mass index (BMI). Plasma orexin A levels were significantly higher (P < 0.006) in children with PWS (average ±SD = 1028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc.
