Alain Dagher is a neurologist who specializes in movement disorders and functional brain imaging. He became interested in dopamine through his work in Parkinson’s, and began to study things like addiction and other dopamine-related problems.
You do research in the field of addiction and obesity. What are you looking at specifically in this field?
We’re basically trying to understand addictive phenomena, where an individual loses control of their behaviour. It has something to do with how we make decisions or fail to make decisions. We’re interested in understanding what brain regions are implicated in addiction and what they do specifically. What dysfunction leads to drug craving or the inability to resist smoking when you’re trying to quit? With respect to appetite, the basic idea is that brain regions involved in controlling of appetite are the same regions involved in addiction. That’s why addictive drugs are addictive, because they act on those structures.
The dopamine reward centre?
Dopamine plays a big role in it – it’s the main determinant of reward learning and motivation to obtain rewards. We’re doing a lot of research trying to measure vulnerability to addiction, why some people become addicted and others don’t. It’s partly genetic, partly environmental, and part of our research is aimed at looking for those things in the brain that predict that vulnerability.
What kind of studies are you doing?
We often do studies in healthy subjects to try and see decision making related to rewards and/or reward learning, that is, how you learn that something is rewarding, what parts of the brain are involved in that learning process, and how dopamine affects that process. That is one kind of research.
We’re looking also at the role of hunger signals, signals from the gut and from the rest of the body that act on the brain to change appetite. The reason you are hungry before lunch, for example, is that a bunch of hormones in the blood change their levels. The satiety hormone levels go down, and the hunger hormones, there is only one hunger hormone called ghrelin, it goes up. These hormones, which are secreted by the gut and by fat cells, and by the liver and pancreas, all act on the brain to make you desire food and make you willing to expend energy in order to obtain that food. And this is very interesting because we think that these hormones play a role in obesity – at the very least they play a role in the inability to lose weight. When you go on a diet you decrease caloric intake and the first thing that happens is you get hungrier. That, in part, is because of these hormonal signals that detect the reduction in caloric intake and tell the brain: “Hey something is going wrong, you’ve got to eat more.” Obviously this is of great interest in the treatment of obesity and diabetes, which is now the number one cause of disease in the Western world.
When we make a decision to eat a donut even though we’ve had a full meal - do these hormones play a role in that?
That’s what we’re trying to study. We’re trying to understand how ghrelin acts on the brain, how it’s involved in hunger, in making foods more rewarding, and in how we learn about food. One aspect of obesity in children is that being exposed to high calorie food, especially very sweet soft drinks, seems to create a process of conditioning, just like Pavlovian conditioning, where the reward value of the sweet food becomes higher and higher. Once that’s happened, it’s there for life, so we’re trying to study that process of conditioning to foods.
There’s also an interaction between these hunger hormones and stress, a complex interaction. Stress can enhance the activity of hunger hormones, and vice-versa, some of the hunger hormones can actually cause stress, at least I think they can. So, stress is also a major factor in weight gain and obesity.
We’re also looking at this from a standpoint of what’s called “neuroeconomics.” It’s clear that a major cause of the increase in obesity in the last 30 years is cheap food. The cost of food has gone way down, especially the cost of calories. When food is cheaper people eat more. There’s also a lot of evidence that obesity is becoming a disease of the poor. In this generation there’s a very weak association between socioeconomic status and body mass, but in children there’s a very strong association. In the next 20 to 30 years obesity is going to become a disease of the poor in the Western world, much like cigarette smoking. Even in the developing world, they’re going from famine to obesity in one generation. China, for example, is leading the world in the increased incidence of diabetes. Studying neuroeconomics, that is bringing in financial decision-making aspects to the research, we think is potentially very helpful.
We weren’t programmed to deal with abundance.
Well, presumably not. Abundance is something that we detect, but normally abundance is followed by winter, that is by lack of food. When food is abundant you eat more, when it is scarce, you save your energy. Now we’re in a situation where it’s always abundant.
How do you factor in neuroeconomics?
You can look at it in a simple way: how do hunger hormones change your willingness to pay money for food? In animals what that means is if an animal is very hungry, it may be willing to work harder for food. It may be willing to take more risks, to spend more time in the open, to risk being at the mercy of predators for example. Or, if you are a predator, you may be more willing to go and attack a large animal at risk to yourself. Not surprisingly, people are willing to pay more for food when they are hungry than when they are full. The brain systems that are involved with changing your degree of motivation to eat are also implicated in your degree of motivation to pay for food. By bringing in these neuroeconomic approaches, you can formally study these things using paradigms that have been used by economists for 40 – 50 years.
Obesity is also related to other aspects of decision-making; there’s some evidence that people who are overweight are more likely to be impulsive, that is, to make rapid decisions without due consideration of the consequences. They’re also more likely show what’s called “delayed discounting,” that is, they discount the value of future rewards. For example, if you offer someone $100 now, or $120 a month from now, they’ll take the $100 now, because the $120 is discounted, it’s worth less when it’s in the future. This delayed discounting goes along with impulsivity and the desire to have the immediate reward. It’s measured by financial paradigms but it’s actually associated with obesity. It’s a small association, but it’s there.
How does this understanding translate into treating problems like obesity?
If you understand how peptide hormones in the gut, or stress, or various patterns of decision-making can impact obesity, you can develop therapeutic approaches. For example, you might conclude that you shouldn’t go to the supermarket when you’re hungry—people know that already. You would also conclude that maybe you shouldn’t skip meals because if you skip meals your appetite hormones will be greater and you’ll eat more at the next meal, for example. That’s at the individual level. You might also use that research to develop drugs to reduce appetite or to test potential drugs. At the societal level, you could also [use the research] to make policy recommendations. You may not need the neuroscience to say that we should not subsidize unhealthy food, but the neuroscience helps to promote that idea and maybe to inform what kinds of policies we should be taking to reduce obesity in the general population. So there are two different approaches, the treatment of the individual person and the treatment of society, both of which I think will benefit from the neuroscience.
There’s no weight loss clinic in Quebec that’s funded by the government. It’s the thing that costs healthcare systems the most, and nothing’s done about it. Now, the success rate of weight loss programs is extremely low. Weight Watchers has the highest success rate and it’s about 1%.
What about drug treatments?
As for drugs for weight loss, the situation is not so good right now. There was one drug called rimonabant that was very effective but it caused mood side effects, it caused depression. It was taken off the market, and that has scared all the drug companies I think. The problem, of course, is if the drug acts on the reward system it risks having serious side effects. If you suppress the function of the reward system chances are you will cause depression or mood problems in most people. So one of the problems is to find a drug treatment that will not cause these side effects. Although if someone has diabetes and obesity, it’s going to kill them, so it’s worth risking depression, especially if you follow the patient and you monitor their mood. If they have problems you take them off the medication.
There’s a drug called bupropion that helps for quitting smoking but is also useful for weight loss. I think there’s a company that has a phase-3 trial with a bupropion plus something else. Again, it will have side effects but it might be acceptable to risk the side effects when you have obesity and diabetes.
Currently the only treatment for obesity that works is bariatric surgery, which is obviously reserved for very overweight people, morbidly obese people.
How does the surgery work? Does it affect ghrelin levels?
We don’t know. Some of the surgeries do appear to reduce ghrelin levels. Basically all of these surgeries restrict the stomach in some way, either by restricting the size, or removing part of the stomach. They have multiple effects and it is still not known how they work. Some effects clearly have to do with decreased food intake; you eat less because you feel full sooner. But there are other effects, for example, on the first day after the surgery, diabetes is cured. That can’t be due to weight loss, of course. It’s quite puzzling.
In terms of understanding impulsivity, what is considered normal?
There’s not necessarily a “normal,” but you can develop laboratory tests of impulsivity (there are several) and come up with average patterns of behaviour. You can decide that something is normal if it falls one or two standard deviations away from the average pattern, that’s the usual way we define normality in biology. A lot of the associations are weak, but there’s a very strong association between attention deficit disorder and obesity, for example. Attention deficit is a proto-type disease of impulsivity. It’s an inability to focus attention correctly, so things that grab your attention are hard to resist. It’s not attention deficit so much as an inability to properly regulate attention, and so people with ADHD tend to be very impulsive and have a much higher rate of obesity than people who don’t have ADHD. They also have a higher rate of addiction. And there are other diseases that predispose to obesity: depression, anxiety disorders, schizophrenia, almost any mental health disorder predisposes to obesity.
Why is that?
We don’t know. That’s one of the things we are studying. The study of the brain’s role in obesity is extremely new.
In terms of addictions, are you also looking at people who are addicted to gambling, drugs, etc?
I’ve done a couple of studies on gambling. And also a lot of studies on cigarette smoking, That’s the main drug that I have studied.
As an ex-smoker, it seems to me that the addiction never really goes away. I’ve quit, but I don’t feel as if I have unlearned the addiction, more as if I overruled it somehow.
That’s because the learning process has been hard wired. That’s what an addiction is, an aberrant learning process, where you learn to value the drug. We know that it involves the same brain areas that are involved in the control of eating. So just like eating is an extremely important behaviour, when a drug comes into that system, it sort of subverts the system into making your brain think that smoking is crucial to your survival. That’s one way to think about it. And some people can’t overrule it, and that relates back to this impulsivity issue. The more impulsive you are, the more likely it is that you can’t resist those urges.
Researchers in Robert Zatorre’s lab have shown that music can affect the dopamine system. Does this mean that we can become addicted to music?
No one has ever described music addiction, as far as I know. Usually an addictive behaviour has to be harmful, it’s very hard to see how listening to music could be harmful. I don’t know of any cases of people who listen to music at the expense of social activities—that’s one way behavioural addictions are defined. You don’t talk to your spouse or you don’t have friends because you spend all your time on the Internet, say. I’ve never heard of anything like this for music.
Behavioural addictions are difficult – the problem is that you spend too much time doing one thing and less time doing other things that you should be doing. That may not be enough, I think, to call something an addiction. For example, if a child would rather play video games than do their homework, you would not really call that an addiction, that would be silly.
Why is it that one thing that triggers the dopamine system might go into overdrive and another thing, like music, doesn’t?
The dopamine system is somewhat self-regulated but drugs act directly on the brain cells that release dopamine, and so they bypass any regulatory system. That’s always been the theory of why drugs can be addictive. Why gambling is addictive, I think is really not clear, although it’s clear that it is. In fact it’s probably one of the worse addictions you can have. It’s extremely damaging.
[This interview has been edited for clarity.]
posted by Maria Schamis Turner @ 3:34 PM
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