We are now continuing on Sci's new found, somewhat relentless search into the relationship between eating disorders such as binge eating, bulimia, and anorexia, and reward systems that are usually associated with things like drug addiction.
And today I found a human study that looks a little...interesting. For a lot of reasons. Let's talk dopamine receptors, shall we?
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Frank et al. "Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride" Biological Psychiatry, 2005.
This one's going to require some background. Let's talk about dopamine and dopamine receptors.
Dopamine is in the news a lot these days, related to addiction and psychiatric disorders of all kinds, from cocaine and morphine to problems like attention deficit hyperactivity disorder and depression. Not to mention Parkinson's, or Huntington's, or schizophrenia...the list goes on.
So dopamine is a neurotransmitter. It is a small chemical that is released from one neuron, and binds to receptors on the next, transmitting a signal in the process. It looks like this:
At the top you can see the first neuron (we call that presynaptic), and at the bottom is the second (postsynaptic). The little orange things are dopamine getting released, and binding to receptors (in blue) on the other side.
But one of the most important things that a young neuroscientist has to keep in mind is that a molecule is only as good as its receptor. The actions produced by dopamine release, which result in behaviors and feelings and all that jazz, depend on the receptors that it binds to. Luckily for everyone studying dopamine, dopamine has only two main types of receptor, the D1 like and the D2 like.
The D1 like receptor is thought to be "stimulatory", it tends to stimulate the postsynaptic neuron to do something (of course if that neuron which is stimulated is itself an inhibitory neuron, all sorts of different stuff can take place. This will boggle your mind if you let it. Go ahead, be boggled. It's SCIENCE!)
And the D2 like receptors are thought to be "inhibitory", when they are stimulated (if you release dopamine on to them or you release a drug which hits them), they inhibit the actions of the neuron they are located on.
These sorts of actions can get very specific (people will spend entire portions of their LIVES investigating the actions of one type of receptor in one area of the brain under specific conditions), but there are a couple of things that scientists can say, very broadly, when we are talking about certain psychiatric conditions and dopamine.
For example, people who are addicted to drugs like cocaine, after using cocaine for a long time, will have LOW levels of D2 like receptors in the brain. The reason for this is that cocaine produces high levels of dopamine in the synapse (see the post linked here for details). When the dopamine continues to stimulate receptors over a long period of time, this overstimulation will actually DECREASE the number of receptors available. Very simply (very very), think of it as some of the receptors getting exhausted from overstimulation and going off to vacation in the cell. We call this receptor desensitization. What's really interesting is that, while cocaine addicts show these low levels of D2 receptors, people who naturally HAVE low levels of D2 receptors are more likely to use cocaine. So it appears to be something of a self-perpetuating cycle, if you have low D2, you're more likely to use cocaine, and the more cocaine you use, the fewer D2 receptors you have...
What's really cool about the brain is that this works the OTHER WAY as well. If you have low levels of dopamine around (as opposed to the high levels you see with cocaine), the receptors are understimulated, and you get more receptors available, a whole host of receptors waiting to catch the little dribbles of dopamine that are getting through.
And now we get to the question in this paper: if eating disorders are related to reward associated properties, then people with eating disorders might have changes in the dopamine system. The question is, what direction are those changes going in? Will people with eating disorders show increased D2 receptors (which are associated with low levels of dopamine) or will they show DECREASED D2 receptor (associated with addictive states and high levels of dopamine).
To find out, this group of scientists took a bunch of recovering (they specify recovered, though anorexia is something from which you are always recovering, rather than truly recovered) anorexic women and a bunch of control women (you want to use women for these studies because they are the most prevalent sufferers of the disorder), and put them in a PET scanner. They gave them a small amount of radioactive tracer specific for the D2 receptor, and looked at the resulting glow in the PET scanner. If the anorexic women had less glow than the controls, they probably have lower D2 receptor levels, and if they had MORE glow than the controls, they probably have higher D2 receptor levels. And this is what they saw:
The dots on the left are all the controls, and the dots on the right are the recovered anorexic patients. You can see the dots on the right are, on average, higher. For a pretty version of this:
In this picture the anorexic patient is on the left, and the D2-related glow is a lot stronger (there's more red) than the control patient on the right. So these results appear to show that recovered anorexics (and possibly people who are anorexic in general) have higher levels of D2 receptors. Since high levels of D2 receptors are often the result of LOW levels of dopamine, the authors hypothesize that these women have lower levels of dopamine, which would go along with their 'anhedonic' personality traits and their lack of reward associated with food.
It seems like a good story (and indeed it's a necessary study that needed to be done), but Sci's not so sure about their implications. And here's why.
1) First of all, for their group of women, they chose to work with recovered anorexics. Sci can certainly see WHY, because people who are anorexic and actively restricting their eating are going to have dopaminergic effects associated with that. But it's possible that the changes they saw in D2 receptors are actually a rebound effect associated with recovery, rather than the illness itself. Sci feels like you'd have to compare controls, anorexics, AND recovered anorexics to get a real idea of what the dopamine system may be doing here.
2) Their group of anorexics wasn't REALLY anorexics. It included anorexic restricting type (the anorexics who restrict what they eat drastically), anorexic binging type (anorexics who restrict most of the time and who often over exercise, but who also binge eat), and BULIMICS (who both binge eat and purge). Honestly, with this diverse group of different symptomatolgies, Sci's really amazed they got any result at all. I would certainly expect binge eaters to behave, and to show dopaminergic changes that are very different from anorexics who restrict all the time. For many of the studies on binge eating and bulimia that Sci has seen, she has seen DECREASES in the D2 receptor and changes in reward sensitivity associated with that, not increases like these authors saw. Sci doesn't think it was a good idea to include bulimics in this study at all, or at least they should have been analyzed separately. Who knows, if they had taken them out, their effects in anorexics might have been bigger.
3) The authors conclude that the increased levels of D2 binding could be associated with low dopamine, which they think explains the hyperactivity in anorexic women. A lot of people don't know this, but many anorexics either over-exercise or show other activities with are thought to be stereotypical (repeated movements). They are hyperactive. But hyperactivity is usually (and by usually Sci means almost all the time) associated with HIGH levels of dopamine. Not low levels. I don't feel like the authors adequately explain why they think low levels of D2 would be associated with hyperactivity (though they do hypothesis that D1 like receptors might be to blame, they don't measure those).
4) The authors were working with recovered anorexics (restricting and binging, and bulimics). How LONG were they recovered FOR? The study says for at least one year, but what about two? Or five? How would the length of time they have been in recovery affect their results?
Now, keep in mind, Sci's not saying this is a bad paper. It isn't. But it really does highlight how HARD it is do to a well controlled human study where you can really say something about your results. It's really hard to get a large group of recovering anorexic women, all at the same stage of recovery, and test them. It's harder to control for problems in people suffering under anorexia during testing. And it's even harder to restrict that to a certain kind of anorexia. And then, when you're looking at D2 receptors, how do you even know you're looking at the right thing? They mention in the discussion that D1 like receptors might provide a better explanation for some of the symptoms in anorexic women. But with humans, you can't just go get more data or try something different.
Sigh...Humans. The ultimate confound. 🙂
FRANK, G., BAILER, U., HENRY, S., DREVETS, W., MELTZER, C., PRICE, J., MATHIS, C., WAGNER, A., HOGE, J., & ZIOLKO, S. (2005). Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride Biological Psychiatry, 58 (11), 908-912 DOI: 10.1016/j.biopsych.2005.05.003