The relationship between serum brain-derived neurotrophic factor (BDNF) levels, BDNF haplotypes and neurocognitive performance in children with PWS

Prader-Willi Syndrome (PWS) is a genetic disease characterized by failure to thrive and low muscle tone during infancy, followed by food-seeking and severe obesity in childhood. Other manifestations include altered pain perception, cognitive impairment, maladaptive behaviors (obsessive compulsive, temper tantrums, skin picking, rigid thinking and repetitive speech) and language difficulties. These maladaptive behaviors may be related to deficits in executive function. Executive function refers to interrelated activities that enable an individual to deal successfully with novel situations, generate plans, inhibit inappropriate behaviors and effectively utilize working memory.

Brain-derived neurotrophic factor (BDNF) acting through its receptor, tropomyosin-related kinase B (TrkB), regulates the development, differentiation and survival of neurons. BDNF plays a key role in energy balance in mice and humans and is expressed in areas of the brain that are important in regulating energy homeostasis. Furthermore, BDNF is expressed in the prefrontal cortex, a key brain area implicated in executive function. Deficiency of BDNF in rodents and humans results in a syndrome characterized by early-onset obesity, hyperactivity, impaired cognition, memory and altered pain perception. Many of these clinical features overlap with characteristics found in PWS. We have novel data showing significantly decreased serum BDNF levels in PWS compared with obese controls. Circulating BDNF concentrations are believed to reflect cerebral output of BDNF. Therefore, the lowered peripheral BDNF concentrations may reflect insufficient central BDNF production, suggesting a potential cause for the disordered satiety, obesity, altered pain perception, and complex neurobehavioral phenotype (including specific deficits in executive function) in PWS.

Research Outcomes: Project Summary

Results of this pilot study might suggest further effective intervention strategies that increase BDNF expression in PWS, not only to control satiety, but also to enhance and maximize executive function performance.

Research Outcomes: Publications

Autism spectrum disorder in Prader-Willi syndrome: A systematic review. Bennett JA, Germani T, Haqq AM, Zwaigenbaum L. American Journal of Medical Genetics: Part A. 2015 Dec;167(12):2936-44. 

Autonomic nervous system dysfunction in obesity and Prader–Willi syndrome: current evidence and implications for future obesity therapiesHaqq AM, DeLorey DS, Sharma AM , Freemark M , Kreier F, Mackenzie ML, Richer LP. Clinical Obesity 1, 175–183, 2012.

Funded Year:


Awarded to:

Andrea Haqq, MD




University of Alberta, Canada

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