Anorexia, Dopamine, and Experimental Confounds

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?
Editor’s Selection IconThis post was chosen as an Editor's Selection for ResearchBlogging.org
ResearchBlogging.org 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:
dopamine synapse NIDA.gif
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…
Sucked Down Drain.jpeg
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:
anorexic d21.png
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:
anorexic d22.png
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

8 Responses

  1. Maybe they should start with anorexics and follow them through the recovery cycle.

  2. “But hyperactivity is usually (and by usually Sci means almost all the time) associated with HIGH levels of dopamine.”
    To be fair, primary hyperactivity (lone hyperactivity not directed to a particular goal) is practically diagnostic for low dopamine receptor stimulation: ADHD, restless legs syndrome, dopamine agonist withdrawal, and dopamine antagonist-associated akathisia. High dopamine can cause stereotypy that may or may not result in hyperactivity. (Secondary hyperactivity?)

  3. Hmmm…Nitpick first I guess…
    While I agree with you on the variety of symptomatolgies being problematic, anorexia nervosa does include people who binge eat and purge. The difference between anorexia and bulimia is body weight and to some degree body perception. That said, I think it is rather sad that they didn’t focus on a particular subset. While it is pretty nigh on impossible to get a diverse group of anorexics without any purging, it could have been narrower.
    I also would like to have seen current anorexics as well. Honestly, I think a significant confounding factor in this, is that a pretty large percentage of women never recover (men are far more inclined to survive it, as they almost always use extreme exercise – recovery is also far more likely). Although that one is rather impossible to compensate for, as it is impossible to measure the brain activity of someone who doesn’t exist.
    Ultimately though, I am happy to see this paper – flaws and all. I see eating disorders tend to share something else in common with substance use disorders – really shitty stigmas. There is a great deal of that moralizing about how “they did it to themselves” and “they are just extremely shallow.” I also think that people tend to equate anorexia especially, to supermodels. Of course the vast majority of anorexics have nothing to do with modeling at all. And indeed supremodels with anorexia nervosa may have no body image distortion driving anything – for them it is really the superficial and very real need to stay dangerously skinny for the cameras.
    The problem of course, is that this is a very real mental problem that has it’s roots in cultural perception and very real body perception problems. It isn’t being shallow that causes someone who is thirty percent underweight to see someone who is at least that percentage overweight.

  4. I have to agree with DuWayne, that I’m glad this paper is available, eve with its minor flaws. And AK makes a good point about following anorexics through the recovery process to see if they ever relapse, or if the treatment methods are effective. Dr. Julie O’toole of the Kartini Clinic recently wrote about long-term care for adolescents with eating disorders. I think you all might find her thoughts interesting: http://www.mditv.com/blog/?p=699

  5. Everyone’s comments are well taken. It is nice to see this paper, flaws and all. Personally, this is why I study rodents; to my mind the main handicap in this paper is the lack of control that you have with actual human beings (all that concern for their welfare and such – not that we aren’t concerned about animal welfare as well, of course, but we can do things in animal models that definitely can’t be done in humans). Of course this does mean that we have to make an anorexic rodent – hard to find out their opinions about body image, but, nonetheless can still be done to some extent. In fact one activity-based anorexia study (Gelegan, 2008, Genes, Brain and Behavior) found elevated D2 receptor mRNA in the striatum of “anorexic” mice, consistent with the present results. Some of the same issues remain – is that a predisposing effect, a consquence, a type of compensatory homeostatic mechanism, etc., etc.

  6. This is some facts for any scientists out there. I was anorexic in high school 1986-87. Then I became bulimic in college and seemingly suffered from ADD symptoms. When 26 I was placed in a 20k a month care facility, was placed on thorazine and stayed at this facility for four plus years. I was put on high levels of anti psychotic medicines on and off until I was 35.
    Then I married an eye surgeon. Now, relatively free, I am still eating disordered, have tardive dyskinesia, fibromyalgia and am considered bipolar II. FYI: for statistics, my biological family was upper middle class. I went to an ivy league school, yada yada. By the end of this over medication drill and my biological father’s losing his savings,I scored in the 8 percentile. Since I did not know I had become and idiot and had no way of coping, my child was taken away by DCFS.
    Recently, this past year 2009, I have worked with a program called Lumosity to get my scores back to 96 to the 99 percentile. I see a doctor who properly diagnosed me. I do not talk to my parents now, and I do hope to get my child back with prayer and work. I believe anorexia made me perceived as schizophrenic in addition to lack of social skills due to an eating disorder in combination to the typical neglected narcissism existent in the environment I describe.
    What does anyone else think as this relates to anorexia and dopamine level sensitivity (as well as doctor abuse of trusting families which is not the discussion but anyway)? Because I am not on that medicine anymore at that level and theoretically one cannot be cured from schizophrenia?

  7. This is some facts for any scientists out there. I was anorexic in high school 1986-87. Then I became bulimic in college and seemingly suffered from ADD symptoms. When 26 I was placed in a 20k a month care facility, was placed on thorazine and stayed at this facility for four plus years. I was put on high levels of anti psychotic medicines on and off until I was 35.
    Then I married an eye surgeon. Now, relatively free, I am still eating disordered, have tardive dyskinesia, fibromyalgia and am considered bipolar II. FYI: for statistics, my biological family was upper middle class. I went to an ivy league school, yada yada. By the end of this over medication drill and my biological father’s losing his savings,I scored in the 8 percentile. Since I did not know I had become and idiot and had no way of coping, my child was taken away by DCFS.
    Recently, this past year 2009, I have worked with a program called Lumosity to get my scores back to 96 to the 99 percentile. I see a doctor who properly diagnosed me. I do not talk to my parents now, and I do hope to get my child back with prayer and work. I believe anorexia made me perceived as schizophrenic in addition to lack of social skills due to an eating disorder in combination to the typical neglected narcissism existent in the environment I describe.
    What does anyone else think as this relates to anorexia and dopamine level sensitivity (as well as doctor abuse of trusting families which is not the discussion but anyway)? Because I am not on that medicine anymore at that level and theoretically one cannot be cured from schizophrenia?

  8. Eating disorders probably cause a “high” in sufferers. The feeling of satiety after a meal (especially a carbohydrate loaded one) will raise serotonin, a natural “tranquilizer”. But tranquility, for some, is not a pleasurable sensation. In fact, over time this feeling may be seen as a blunting/dulling of emotion and motivation.

    Dopamine agonists, like Wellbutrin and ADHD stimulants, are all known to suppress appetite and lead to weight loss. An excitatory reaction from a drug does make you lose your appetite. Some people even say they work better and focus more on an empty stomach.

    While anorexia is a serious health issue, I think part of the physiological reward system is a reduction in emotional flattening, which only works to reinforce the destructive behavior of extreme calorie restriction.

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