2550 words

Abstract

Researchers have tried to manage those with Prader-Willi’s Syndrome for multiple decades. Though they have greatly curbed some of the implications of the disease, there are still numerous ways in which we can better use our knowledge of how the disease manifests in order to better help those suffering from PWS. Looking at research into how the extra chromosome 15 is linked to low IQ; IQ and its relationship to obesity; how the ability to delay gratification leads to obesity; growth hormone treatment to better treat low muscle mass and higher body fat; and finally using reinforcement theory to punish a response, where doing so will greatly diminish the probability of that response occurring again in the future; all of these factors can be used in conjunction to better mitigate problems from the disease. By examining all of these variables and thinking of better ways to handle them, we can then think of other, better ways to manage those with PWS. In doing so, we can better increase the quality of life of those suffering from PWS, as well as have less of a strain on healthcare workers who care for them. With new advances in technology with CRISPR Cas9, we can then edit the genomes and chromosomes of those suffering from this disease.

How to Use Current Knowledge to Effectively Treat and Manage the Symptoms of PWS Patients

How can we use the research on chromosomal differences, research on their IQ differences and their lack of ability to delay gratification that, in turn, would help those individuals with the disease?  Seventy percent of PWS cases are attributed to the deletion of chromosome 15 (Ledbetter et al, 1981). Maternal uniparental disomy, which involves receiving an extra chromosome 15 from the mother, is yet another cause of PWS (Wang, 2004).

Whittington, Holland and Webb (2009) found that there was variation between families in deletion of chromosome 15. They found that the PWS and sibling IQ correlation was .3, a modest correlation.  What was also noticed was that there were subtype differences which manifested itself in the familial differences in IQ. As they expected, the correlation with normal siblings and those with PWS was .5 in those who suffered from PWS due to unilateral disomy. But in the second subset (the chromosomal deletion subset), the correlation was negative at -0.07. Their research shows great promise in the role of chromosome 15 and IQ. They end up concluding that there needs to be an explanation for the small genetic differences between them. How can we use these differences in IQ to help people with PWS and what does this suggest for other symptoms of their disease?

Kanazawa (2014), reviewed the data on the research between obesity and IQ. What he found was that those studies that concluded that obesity causes lowered intelligence only observed cross-sectional studies. Longitudinal studies that looked into the link between obesity and intelligence found that those who had low IQs since childhood then became obese later in life and that obesity does not lead to low IQ.  The average IQ for an individual suffering from PWS is 65 (Butler, Lee and Whitman 2006, p. 13), so that is one reason they have a tendency to be obese. He states that those with IQs below 74 gained 5.19 BMI points, whereas those with IQs over above 126 gained 3.73 BMI points in 22 years, which is a statistically significant difference. Also noted, was that those at age 7 who had IQs above 125 had a 13.5 percent chance of being obese at age 51, whereas those with IQs below 74 at age 7 had a 31.9 percent chance of being obese. This data makes it clear: low IQ is correlated with obesity, so we, therefore, need to find sufficient measures to help those with lower IQs who also suffer from PWS to better maintain their good health. Since we can better identify those PWS individuals who have lower IQs based on how they got the disease, we can then show them more attention in an effort to have them manage their gratification better. Moreover, the lack of ability to delay gratification is also correlated with low IQ (Mischel, Ebbeson, and Zeiss, 1972).

Schlam et al. (2013) observed in a follow-up study to the Marshmallow Experiment that found in a longitudinal study of individuals they found forty years later from the original Marshmallow Experiment, due to inability to delay gratification forty years previously, that was one cause of becoming obese forty years later. Due to PWS sufferers having lower average IQs, and, therefore, a lack of ability to delay their gratification, this is direct evidence that those PWS sufferers with low IQs need more stringent measures to be taken on them, which would then be helpful to those individuals who have a hard time delaying their gratification, which is partially caused by the drop in IQ due to the additional chromosome 15. We can see how those with PWS act; they want their gratification now and do not want to wait for it. This is why, when unsupervised, that those with PWS gorge on the food they understand they should not have, but do so, nevertheless, since their low IQ is correlated with lack of ability to delay gratification, which manifests itself in their obesity. We clearly need to find better methods in which to help those with low ability to delay gratification, which would strongly help those suffering from PWS.

Dykens et al (1997) note that those with PWS have hyperphagia, which correlates with their insatiable want for food. They state that the lack of fullness is due to an altered function of the hypothalamus, which is the part of the brain that is in control of feelings of satiety. Certain States gave restrictions to homes that take care of those with PWS and have come under fire because of this, mainly due to human rights violations. We must ask, then, should we limit their access to food if it will prolong their lives? Will doing so inhibit their freedom to do as they choose? PWS sufferers also have coronary heart problems; one could argue that given their free ability to choose what they want to do unfettered will lead to premature death due to obesity-related complications. Does their disease truly not allow them to learn the consequences of their behavior? Do they have the intellect to really understand the consequences of their actions of consuming too much food? There is no established or known way to control those with insatiable eating habits due to hyperphagia. So would the best course of action to take with those with PWS actually be to constantly monitor them and to lock access to easily attainable food? My answer is yes, however, there is a clear fine line in whether restricting access to food and constantly monitoring those with PWS infringes on their human rights, or that doing so actually will help them live better, healthier lives since they would have the constant supervision around them to better control their out of control eating habits. When negative actions occur, one idea that can be shown to them is constant positive reinforcement so that they may be better able to understand that what they are doing is harmful to their bodies. We can then use positive reinforcement when they do reach a healthy weight, so, in turn, they will have a higher chance of keeping a healthy weight. They may reap the benefits of positive reinforcement, and stick more closely to their program, and therefore, stay healthy.

The hormone ghrelin is secreted from the hypothalamus. With an altered hypothalamus, this would cause ghrelin levels to overload; then the individual suffering from PWS would feel the need to insatiably gorge on food due to this chemical imbalance in the brain. Ghrelin increased feeding in rats and ghrelin is the physiological mediator of feeding and probably has a function in growth regulation by stimulating feeding and release of growth hormone (Nakazato et al, 2001). There is a correlation between want of food, ghrelin release and growth hormone production. By attempting to mediate these variables, those who suffer from PWS will be able to better control their eating habits through positive reinforcement and better, more sustainable habits. Since whenever we eat we get a release of ghrelin that makes us hungry, people pretty much set their own eating times by eating multiple times a day. This affects PWS patients the same way. They can’t stop eating, due in part to constantly eating which constantly releases ghrelin in their body.

PWS sufferers have low muscle tone and, conversely, more body fat. Growth hormones may be a valid way of alleviating that problem, which in turn will give them a slightly higher resting metabolic rate so that they may burn slightly more calories, in an effort to stay healthier. Growth hormone therapy is great for those with PWS though they are largely inactive and lead a sedentary lifestyle, the growth hormone will allow them to have less body fat and more muscle mass. As noted earlier in my paper, those suffering from PWS have altered function in their hypothalamus, which is also where growth hormone is secreted. Aycan and Bas (2014) state that treatment with growth hormones should be strongly considered for those with PWS.

PWS sufferers are also quick to anger, which can be correlated with their sub-average IQ. They may, for instance, become irate at the fact that they do not have constant access to food, and may turn to emotional, angry and infantile outbursts in an attempt to receive what they want. This is one way that it’s tricky to treat those with the disease. How do you tell an individual with PWS who wants something “No”? Measures should be taken to show those with the disease what they are doing to their bodies in the simplest way possible as to better get the point across to them. We can help those sufferers of PWS who are quick to anger with by allowing them to discern between right and wrong ways to handle times when they don’t get what they want with positive reinforcement.

Since those who suffer from PWS have behavioral problems, there are better measures we can take to assure that they don’t have their violent outbursts. When positive reinforcement is consistently shown to an individual who has PWS, he will have more success with his program. When they do something wrong, they can then be shown positive reinforcement, and through being shown positive things with reinforcement theory, they can better learn that certain actions they take are dangerous and shouldn’t be done again, as Rushton (1980) states: “If one rewards a response, it will increase the probability of the future occurrence of that response. If one punishes a response, it will decrease the future probability of the occurrence of that response.” (p. 90).

Discussion

In this paper, I have presented causes for PWS as well as effective ways to manage the disease. To look at how IQ affects individuals in regards to obesity and because it is highly correlated with other measures as well, we can then better help those with the disease. By seeing which individuals have the parental disomy version of PWS, we can then monitor them and give them better care because of their lowered IQ and make sure they stay at a healthy weight. One of the best measures to take is to heavily restrict food, i.e., make sure ability to access food at all hours of the day is restricted along with constant supervision. Though, there are rights groups fighting for them saying that their human rights are being infringed on. In allowing them to have free reign over what, how and when they eat, they will gorge themselves to obesity, as well as lead themselves to horrible complications that come along with increased food consumption. When one is caught consuming food he or she shouldn’t be consuming, punishing them and letting them understand that the behavior they took was wrong will lead to better choices and outcomes from those choices, due in part to the main facet of reinforcement theory, that punishing a response will lead to a reduced outcome in that response that was punished happening in the future. Also, with the advent of CRISPR Cas9, we will be able to edit genomes, and therefore, eventually, put an end to PWS. It will enable us to fix the chromosomal deletion and uniparental disomy, which will eradicate this disease.

Conclusion

There are better, more helpful ways in which to help those suffering from PWS. By identifying and attempting to correct these abnormalities, those who suffer from the disease can, therefore, have a better quality of life due in part to the extra measures taken. By understanding that their lower average IQs lead to a lot of the problems associated with the disease, we can better structure methods for them to keep on a healthy track and reinforce positive behavior through reinforcement theory. Since obesity is correlated highly with low IQ, we can, therefore, use this information to better help those who suffer from PWS that have low IQs. Locking up food instead of providing free access, as well as understanding they do not have the ability to delay gratification, would be a big start to find better ways to treat sufferers of PWS. Treating negative actions with positive reinforcement through reinforcement theory will lead to better and increased prosocial behavior. It’s been shown that if you punish a response, then it will decrease the future probability of that response occurring. The advent of CRISPR Cas9 will then allow us to edit the chromosomes of those with this disease in the future. Should we use genome editing on individuals with this disease, as well as several other chromosomal/genetic diseases? I believe we should, in doing so, we will greatly increase the quality of life of those with the disease.

References

Aycan, Z., & Baş, V. N. (2014). Prader-Willi Syndrome and Growth Hormone Deficiency. Journal of Clinical Research in Pediatric Endocrinology Jcrpe, 62-67.

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Dykens, E. M., Goff, B. J., Hodapp, R. M., Davis, L., Devanzo P., Moss, F. . . King, B. (1997). Eating Themselves to Death: Have “Personal Rights” Gone Too Far in Treating People With Prader-Willi Syndrome? Mental Retardation, 35(4), 312-314.

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Ledbetter, D. H., Riccardi, V. M., Airhart, S. D., Strobel, R. J., Keenan, B. S., & Crawford, J. D. (1981). Deletions of Chromosome 15 as a Cause of the Prader–Willi Syndrome. New England Journal of Medicine N Engl J Med, 304(6), 325-329.

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Rushton, J. P. (1980). Altruism, socialization, and society. Englewood Cliffs, NJ: Prentice-Hall.

Schlam, T. R., Wilson, N. L., Shoda, Y., Mischel, W., & Ayduk, O. (2013). Preschoolers’ Delay of Gratification Predicts their Body Mass 30 Years Later. The Journal of Pediatrics, 162(1), 90-93.

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YM Wang, L Chuang, BT Wang, et al. Maternal uniparental disomy in a patient with Prader-Willi syndrome with an additional small inv dup(15) chromosome. J Formos Med Assoc, 103 (2004), pp. 943–947