Tony Holland, University of Cambridge
Most of us know what it feels like to be full, especially after Christmas dinner. Our bodies have a few different ways to tell our brains weíve had enough to eat. But in some people, this process doesnít work. Not being able to feel full is a serious problem and a symptom of the genetic disease, Prader-Willi syndrome. Professor Tony Holland from the University of Cambridge told Ginny Smith how we know when we're full...
Tony - The body has really developed a number of ways to, if you like, to inform the brain that youíve had enough to eat. So, as food enters the mouth, into the stomach and then is absorbed in the gut, there are really two major processes that are going on that feedback to the brain. One is, that there are changes in the blood, glucose and insulin. Well they have an effect on satiety, the sense of fullness. But also, there are other chemicals that are in the blood that actually influence the brain. The second way that this feedback mechanism is happening is through a nerve called the vagus nerve and the vagus nerve if you like, links the brain and the gut and there are messages in both directions Ė both the brain telling altering the gut and the gut telling the brain that food has entered the gut and is being absorbed. So, itís really quite a sophisticated feedback mechanism that helps change us from a sense of hunger to a sense of fullness.
Ginny - So, what happens if this system goes wrong?
Tony - The commonest example is severe obesity and where the system doesnít regulate well enough so that you continue to eat when in fact, youíve had enough calories that the body requires then of course, you will put on weight. There are conditions of course where you lose weight too.
Ginny - So, you work on Prader-Willi syndrome. Can you tell me a little bit about that? What exactly is it?
Tony - Prader-Willi syndrome is a genetic disorder. Itís often referred to as a neurodevelopmental syndrome and by that, what itís meant is that itís really apparent birth. So, a baby born with Prader-Willi syndrome will be characteristically very, very floppy. There's a certain irony really here because that baby usually can't feed very well and in fact, often needs assistance very early in childhood to make certain it has enough food. But from about 2, 3, 4 years of age, you begin to see a substantial change. In fact, the baby and the infant will eat and eat, and eat. And itís at that stage, severe obesity can arise if people aren't aware that you need to control access to food, you need to limit how much food you give. Thatís one of the characteristic features. There are a number of other features about Prader-Willi syndrome. They tend to have some learning disabilities. They are often of short stature because of low growth hormone. And also, they donít develop sexually normally because of low sex hormones. And as a psychiatrist, I've also been very interested in the fact that they have often some problem behaviours. They may have a quite high risk for mood disorder and other mental health problems.
Kat - Do we know why they eat so much? Is it that they're always feeling hungry and why is that?
Tony - These things of course are very difficult to assess because you can't readily get inside someoneís brain and decide, determine, what's actually happening. Our own work would suggest that that is probably the case. So, both in terms of Ėif you observe people with Prader-Willi eating and you ask them to rate how hungry or how full they are, or if you want to take now more sophisticated studies using some of the brain imaging techniques, it looks as if that the brain responds to conditions of hunger in much the same way as you or I do. But in fact, if people with Prader-Willi syndrome eat even substantial amounts of food, the brain doesnít change in the way that it does as it would if we had eaten the same amount of food. So, it looks as if there is a failure of this feedback mechanism in Prader-Willi syndrome.
Ginny - So keeping control of the food is a way of stopping them becoming obese, but it doesn't actually solve the problem if they are feeling hungry all the time. Is there anything you can do to change that?
Tony - that is obviously what I think all of us are working towards. The idea that whether it's mediciation or some other intervention might actually suthis feeling of hunger, and dramatically change the life of people with Prader-Willi syndrome. But one of the things we tried recently is something called vagus nerve stimulation and we had three people with Prader-Willi syndrome whoíve had one of these stimulators which is a bit like a cardiac pacemaker inserted. That then ran for many, many months in the hope that this would reduce the overeating behaviour.
Ginny - So, you're stimulating that nerve that connects the stomach to the brain, in the hopes that you might be able to change the messages.
Tony - The reason we thought we should try it is, theoritically, it seemed to us, if you, if you like, stimulated that nerve, you might increase this feeling of fullness. Thatís perhaps a bit naÔve. However, there is a good data to suggest that when people have vagus nerve stimulation for epilepsy for example and itís an approved treatment for epilepsy then a proportion of people who Ė particularly those who happen also to be obese, actually lose weight when they're on the vagus nerve stimulator. Again, this is over months or even years. So, there is some evidence to suggest that this treatment might actually result in weight loss.
Ginny - And did it work in your study?
Tony - Sadly, it didnít really result in very significant weight loss in the three people. One person in fact put on some weight and someone else lost some weight over time. However, there was an observation that particularly the parents and two of the three people with Prader-Willi syndrome themselves made. And that was, that whilst on the vagus nerve stimulator, that many of the other behaviours, particularly the temper outburst reduced dramatically. Now, these are behaviours that are very debilitating for people with Prader-Willi syndrome. They're often triggered by change in demands in peopleís lives. But they can be quite serious and sometimes lasts at their worse, for hours. And what the parents were telling us - that outbursts essentially stopped.
Ginny - So, if this was actually affecting their mood, would it be worth trying for perhaps other mood disorders Ė anxiety, depression, that sort of thing?
Tony - Yes, vagus nerve stimulation is used for treatment resistant depression. So, it is approved in many parts of the world for that. We donít actually think that itís having its effects through mood in Prader-Willi syndrome although we can't be certain about that. We think that itís having its effect through somehow increasing resilience if you like, reducing the arousal that people with Prader-Willi syndrome experience when there's something in the environment that they donít like. So you and I, by and large, weíre able to contain ourselves under those circumstances, but for someone with Prader-Willi syndrome, they have really quite a low threshold for and they might lose it under those occasions. Maybe itís just raising that threshold in some way.