September 2, 2013 | 1
It’s food week here at SciAm! Make sure to check out all the posts!
For my food week post, I’m going at it a little differently. We spend a lot of time talking about food, thinking about whether it’s good for us, bad for us, which aspects of it are good or bad for us. We talk about why we crave some foods vs others, and we talk about why some foods taste disgusting. We talk about whether you’d want to replace your entire diet with a chalky fluid substance. Foodies spend a lot of time taking pictures of it, diet mags spend a lot of time talking about how to eat less of it. Food is surrounded by a culture that permeates almost everything we put in our mouths.
But food is more than what we like or don’t like. Food is more than a relationship between our stomach and our tongues and noses. There is a very strong relationship between food and your brain, and when it goes wrong, the results can be devastating. There is anorexia, where there is distorted body perception, huge fear of weight gain, and food restriction so severe it can kill. On the opposite end, there is binge eating, uncontrollable eating that people are unable to stop, despite health consequences and social stigma.
(Source. Side note: why are they keeping bananas in the fridge like that? Don’t they get all brown and weird flavored in there?)
Critical to both of these problems are issues with “reward”. Food needs to be rewarding, it needs to make you crave it, want more of it, seek it out, work to obtain it. We need to crave food because if we didn’t, we’d all starve to death due to lack of motivation. In binge eating, though, that craving becomes an obsession. And it’s a dangerous one. People who binge eat severely are at risk for obesity, heart problems, diabetes, and other health problems. There is also a lot of anxiety, depression, guilt, and other mental distress that goes along with binge eating. This is more than just a need for portion control or more exercise. It’s a serious compulsion and mental illness, and it shouldn’t be taken lightly.
Unfortunately, there are very few treatments out there for binge eating. Most involve therapy, some involve antidepressants or weight-loss programs. A lot of these are not very helpful. Scientists have been working in the meantime to try and understand WHY binge eating occurs, what makes it different or similar to other substance use disorders (such as drugs or alcohol), and how understanding might help treatment.
Halpern et al. “Amelioration of Binge Eating by Nucleus Accumbens Shell Deep Brain Stimulation in Mice Involves D2 Receptor Modulation” Journal of Neuroscience, 2013.
So food feels good. In binge eaters, it can often feel better than just about anything else. Problems like this are often linked to dysregulations in the “reward” systems of the brain. While “reward system” is a bit oversimplified (yes, the areas do respond to rewarding things, and yes, they keep responding to those things, but they also respond to NON rewarding things, and are also a measure of “salience”, a “pay attention to this”, that can be confused with reward), it is also a good target to look at when you’re trying to find way to treat disorders like binge eating.
The authors of this study were focused on an area called the nucleus accumbens, a big target of interest for things like drug addiction and binge eating. They wanted to see if deep brain stimulation might help stop binge eating, and if so, why it worked.
To do this, they used a mouse model of binge eating. You give a mouse access to high fat food for a limited period of time each day. This limited period of time for eating a super tasty substance makes the mice go to town on the high fat food, and soon they are eating over 25% of their daily calories in a single hour (though, considering that in a human, that’s about 500 calories…that like one Starbucks scone. I think we are the ones with the problem, here).
Once the mice have established a binge eating pattern, the authors implanted deep brain stimulating electrodes into the nucleus accumbens (a technique that is also being looked at for major depression, drug abuse, and obsessive-compulsive disorder). They gave small stimulations into the area…
…and the mice decreased their food intake. What you can see above are the control binge eating mice (white bars or circles), and the ones receiving deep brain brain stimulation (black bars or circles). You can see that at the higher stimulation intensity (top left), the mice getting deep brain stimulation reduced their high fat intake. In the points on the bottom, you can see that each day they tried deep brain stimulation (days 0 and 2), the high fat intake decreased.
Now the question is, how is this working. There are several ways that a scientist can test to see what the mechanism is behind an effect. Say, for example, you hypothesize that a chemical X at receptor Y is causing the effect of Z. You can try to add more of chemical X and see if you get Z. But that doesn’t prove that it was receptor Y, and it doesn’t really prove the effect. You can make a fake X to stimulate Y and get Z. That shows that Y and Z are connected. Then you can try and BLOCK receptor Y, say, with anti-X. Then give X. If you don’t get Z, you can conclude that the actions at receptor Y are necessary for Z.
So in this case, we have deep brain stimulation causing less binge eating. How? The hypothesis of the authors was that the chemical dopamine binding to D2 receptors might be responsible, that deep brain stimulation activates the D2 receptors and stops binge eating. So what the authors need to do here is block the D2 receptors. If that stops the deep brain stimulation from working, it suggests that the D2 receptors were indeed the way to go.
The authors used the D2 antagonist raclopride, which blocks D2 receptors and prevents them from functioning.
What you can see above is the normal deep brain stimulation (the white circles) which lowered the binge eating. Then you can see, after confirming that the deep brain stimulation was working, the authors added raclopride (the dark squares). Now, the mice continued to binge eat, even when they were getting deep brain stimulation. Since they were able to block the effect, they were able to conclude that the deep brain stimulation was working via the D2 receptors.
What does this mean for treatment? Well, for most people, not too much. Deep brain stimulation has been tested in humans for some conditions (most notably Parkinson’s), and is safe and doable. But it is extremely expensive, dangerous (we kind of have to put an electrode in your HEAD), and permanent. For people with Parkinson’s, these caveats are overruled by the need to move, and for some people with obsessive-compulsive disorder, it may be necessary just to function. But many people with binge eating disorder may not be able to reconcile themselves to an electrode in their brains. So a treatment like this may be one of last resort.
But that doesn’t meant it’s useless. Far from it. Studies like these show not only information about deep brain stimulation, but also the mechanism of the D2 receptor. And knowing about the mechanism gives us new targets to develop drugs, say, that might help the condition. Or ways to diagnose, by looking for changes in D2 receptors. So while we may not be putting electrodes into people’s brains immediately, we do have extra information that can help guide the development of future treatments. Because when our relationship to food goes this bad, a little portion control isn’t going to solve the problem.