Today's Disorder: Prader Willi Syndrome

According to the Prader-Willi Syndrome Association (UK):

Prader-Willi Syndrome (PWS) was first described in 1956 by Swiss doctors, Prof. A Prader, Dr A Labhart and Dr H Willi, who recognised the condition as having unique and clearly definable features. These features are:

* Hypotonia: weak muscle tone, and floppiness at birth.
* Hypogonadism: immature development of sexual organs and other sexual characteristics.
* Obesity: caused by excessive appetite and overeating (hyperphagia), and a decreased calorific requirement owing to low energy expenditure levels. (Obesity is not normally a feature of those whose food intake is strictly controlled.)
* Central nervous system and endocrine gland dysfunction: causing varying degrees of learning disability, short stature, hyperphagia, somnolence, and poor emotional and social development.

image from Tokyo Medical University
It's a genetic disorder resulting from a deletion on chromosome 15 (15q11-13) in 70% of the cases. Another 25% are from a maternal uniparental disomy of chromosome 15, and the remainder are due to imprinting defects (Miller et al., 2006).

But it's most known for the symptom of insatiable appetite, and was even featured in an episode of CSI:, in which the dead body of

Jerry Gable (30), a short baby-faced man with an enormous potbelly, is found in a dumpster in back of a popular restaurant, covered in food remnants. Not a happy way to spend Thanksgiving. So why is there a smile on Jerry's face? There are no visible injuries or wounds other than some pasty white marking on his right wrist, and chipped and inflamed fingernails. There's also a trace of silver-metallic residue on his cheek. A wrapper belonging to Aunt Jackpot's Pretzel Stand is found in his back pocket. In autopsy, Dr. Robbins empties an enormous amount of food content. The victim's stomach was distended to six liters in volume: normal capacity is one, with a maximum load of about four. Jerry died from ASPHYXIA due to mechanical compression of the lungs. In other words, he ate himself to death.

It turns out this character had Prader Willi and was a contestant in a hot dog eating contest. Anyway, a new neuroimaging study examined brain activity when participants with Prader Willi and controls viewed pictures of food (and animals and tools) in the scanner.

Miller JL, James GA, Goldstone AP, Couch JA, He G, Driscoll DJ, Liu Y. (2006). Enhanced activation of reward-mediating prefrontal regions in response to food stimuli in prader-willi syndrome. J Neurol Neurosurg Psychiatry. 2006 Dec 8; [Epub ahead of print]

BACKGROUND: Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances of appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food, and eating of non-food substances. Brain pathways involved in control of appetite in humans are thought to include the hypothalamus, frontal cortex (including orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal, and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesized that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. METHODS: We compared functional MRI (fMRI) blood-oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. RESULTS: Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose, or triglyceride levels between the groups at the time of the scan. CONCLUSIONS: Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared to normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward-related behavior in modulating the response to food in humans.

The paper is very short, and seems to have minimal analyses, primarily FOOD vs. REST (looking at a fixation point), and the other categories vs. REST. They didn't correct for multiple comparisons because

...the Bonferonni corrections performed by BrainVoyager 2000 tend to be too conservative for functional neuroimaging analyses.

from Miller et al. (2006)

At any rate, the figure above shows greater activation of visual cortex in controls, and greater activation in the ventromedial prefrontal cortex (VMPFC) in the PWS participants. However, the PWS group also showed substantial activity in the PFC (more dorsally) for the TOOLS vs. REST comparison, unlike the controls. So it's not exactly appropriate to conclude that

increased reward value for food may underlie the excessive hunger in PWS...

since the TOOL stimulus set included both nonfood tools (e.g. hammers, hairdryers) and food-related tools (e.g. spoons, cups) . The authors' suggestion that the ANIMALS vs. REST comparison served as a check against any tool-related reward activity raises the issue of, um, whether chickens and pigs and cows appeared as stimuli.

Read more about PWS.