Consider this thought experiment:

Drop a person in a blender (since it's all hypothetical, go ahead and make it someone you don't like. Feel better? I bet you do!). Then, count all the total number of cells that are produced. Only one in ten of these cells will be human. The other 90%? Those are all microbes. If you look at the total number of genes in your human smoothie (NOT coming soon to a Jamba Juice near you), the numbers are even more skewed: only one in 100 genes are human. The rest are, again, bacterial. The total collection of all of these bacteria living in and on our bodies is known as the microbiome.

The idea isn't to gross out the card-carrying germophobes among us. But let's face it: we're just as much bacterial as we are human. Plenty of these microbes live on our skin, in our lungs and genital tracts. The mother lode of microbes, however, live in our gut. They are crucial to extracting energy from food, and these microbes are extremely sensitive to what we eat. Starving mice for just one day dramatically alters the composition of their gut microbes. Specifically, it decreases a type of bacteria known as Firmicutes. When researchers transplanted Firmicutes into the guts of lean mice, they rapidly gained weight (Crawford et al., 2009)

When it comes to eating disorders, there isn't much talk of microbes. There are the occasional papers from researchers like Sergei Fetissov about potential auto-immune responses in people with eating disorders, and some work on PANS (pediatric auto-immune neuropsychiatric syndrome) and anorexia, but generally, researchers haven't looked at the role of the microbiome in triggering or perpetuating an eating disorder.

Much work has been done in obesity research. Scientists have consistently found that people with a BMI >30 have different gut microbes than people with BMIs in the "normal" range. As well, bariatric surgery also significantly changes gut microbes as people lose weight, making them look more similar to the bacterial profiles seen in "normal weight" individuals. A more recent study in The ISME Journal proposed a microbiome diet: eating foods that would eliminate a type of bacteria called Enterobacter helped a person lose drastic amounts of weight in a short period of time (Fei & Zhao, 2012).

So how are microbes involved in eating disorders? No one really knows. Cindy Bulik has begun a study looking at this relationship, but the results still aren't in. Based on the studies above, it's reasonable to assume that ED behaviors (starving, binge eating, and/or purging) will have a significant effect on a person's microbiota. It still has to be measured, but I would bet a lot of money on it. The question is what do these microbial changes have to do with ED symptoms?

Imbalances in gut microbes in mice and rats have been found to alter patterns of risk-taking and anxious behaviors--something that also happens in people with EDs. They could also, perhaps, explain weight loss seen in anorexia and EDNOS. Maybe the initial restricting triggered a significant change in gut microbes that amplified the effects of malnutrition. Maybe they lacked a group of microbes that produced an important hormone regulating hunger and satiety. No one really knows.

One hint to the potential role of microbes in EDs comes from a study published today in the journal Science (Smith et al., 2013). The scientists studied the relationship between gut microbes and kwashiorkor, a form of severe malnutrition that occurs when a person doesn't eat enough protein. Of the 317 twin pairs from Malawi that the researchers followed for three years, half became significantly malnourished and 7% developed signs of kwashiorkor. Obviously, a lack of protein is crucial to the development of this disease but it's not the only factor as not everyone with a severely protein-deficient diet will develop kwashiorkor. Something else had to be going on.

First, the researchers treated twin pairs discordant for kwashiorkor (that is, one twin had it, whereas the other didn't) with "ready-to-use therapeutic food"- basically peanut butter on steroids. Twins with kwashiorkor had significantly different from nearby twins who (presumably) at pretty close to the same diet. The researchers found significant changes to the gut microbes in the ill children with the use therapeutic food. Discontinuing the therapeutic food caused a regression in the functioning of the gut microbes.

The kicker is this: when the researchers fed mice a standard Malawian diet and inoculated them with microbes from the guts of malnourished children, they rapidly lost weight and also developed kwashiorkor. This happened despite the fact that their diets contained adequate calories. One of the reasons that the researchers believed the therapeutic food is so effective at treating kwashiorkor is that it helped restore normal gut microbes.

To say what effect restoring normal gut flora will have on ED symptoms remains to be seen. Probiotics are a hot item, but much of the research is fairly overblown. There's definitely still potential there, and we need to know more about which populations of people are likely to benefit and which aren't. But it's an interesting idea, and I think we need to know a lot more about the role of the microbiome in the development and perpetuation of EDs.

In closing, a quote from scientist John Rawls in an interview with Scientific American:

“We are in the midst of a revolution of our ability to describe the composition and physiological potential of these bacterial communities...What we can begin to speculate on, though, are the different types of relationships that might be taking place. We know gut microbiota enhance our ability to extract calories from complex carbohydrates, which is clearly a mutually beneficial relationship. But it’s thought that all vertebrates have the capacity to digest and absorb other types of nutrients, such as lipids, proteins and simple carbohydrates, so it’s not readily clear how we could enter into a mutually beneficial relationship with bacteria with regard to those nutrients."

Obsessive-compulsive disorder (OCD) is one of the most frequently diagnosed psychiatric disorders in people with eating disorders. It is known to make eating disorders more severe and harder to treat, leading to a longer time until remission is achieved. Recently, more and more researchers are beginning to recognize the significance of the overlap between EDs and OCD, and are trying to develop specific treatments targeted at this population.

A 2004 study by Walter Kaye and colleagues in the American Journal of Psychiatry measured how frequently anxiety disorders (OCD is a type of anxiety disorder) occurred in people with anorexia and bulimia. They found that two-thirds of the ED sufferers had been diagnosed with an anxiety disorder at some point in their life. In general, the onset of the anxiety disorder pre-dated the ED by several years. Of the people with an anxiety disorder, 41% had OCD and 20% had social phobia (social anxiety). The problem, then, is very significant.

The gold standard in treating OCD is a form of cognitive-behavioral therapy known as exposure and response prevention (ERP). You can read more about ERP here. The idea is relatively straightforward: You create a hierarchy of the things you're afraid of that would normally provoke a compulsion. For someone who is afraid of germs, something lower on the list would be touching an unused surgical mask. Higher up might be touching a doorknob at a doctor's office or being coughed on by someone with a cold. Together with a therapist, you would begin to expose yourself to these anxiety-provoking situations and then not engage in any compulsions (like hand-washing) to relieve the anxiety. The point of this is to learn to tolerate the anxiety and that you're not going to die if you happen to inhale a few germs.

Some researchers are beginning to use components of ERP to treat food fears in EDs, especially anorexia nervosa. In a 2011 study in the International Journal of Eating Disorders, researchers at Columbia University first outline a behavioral model for AN that is driven by anxiety and obsessionality (see figure below; the caption is copied from the paper).

Figure 1. Model of Anorexia Nervosa. Traits of high baseline anxiety and obsessionality interact with environmental factors such that patients develop maladaptive behaviors, including food avoidance, and rigid eating patterns (or dieting practices), and they experience high levels of anxiety around eating. These behaviors are interrelated in that rigid dieting leads to increased anxiety about food and vice versa. These behaviors result in a diet that is low fat (low energy density) and limited in variety. This, in turn, promotes weight loss. The low weight state feeds back on the baseline traits and leads to increased levels of anxiety and obsessionality.

Anxiety about eating more and gaining weight consistently interferes with weight gain in AN and with interrupting the binge/purge cycle in BN. The idea is that recovery cannot and will not occur unless these fears are addressed. In a 2012 review article in the European Eating Disorders Review, psychologists hypothesize that one of the reasons family-based treatment is successful for many adolescents is that it forces these exposures. Since the patients can't (theoretically) choose what to eat, they can't choose to avoid "scary" foods. Parents are also coached on how to help stop other food-related rituals

A study published earlier this week addressed the issue of treating OCD and EDs, this time in a residential setting. Published in Cognitive Behaviour Therapy, the researchers treated 56 individuals with AN, BN, or EDNOS in an eating disorder program specific for individuals with co-occurring OCD. Of these patients, 41% were diagnosed with AN, 25% with BN, and 34% with EDNOS. Rates and levels of depression and OCD did not appear to vary by diagnosis. After treatment, the researchers found a significant improvement on scores for OCD, depression, and eating disorders, as assessed by a variety of surveys and self-reports. Patients with AN also significantly increased their body weight.

Which is all well and good, but the problem is that this study (nor any others that I'm aware of) compared the treatment group to anything. Other studies have shown that treating an ED generally improves levels of depression and OCD. Was the improvement seen in this study due to regular eating and the prevention of binge eating and purging? What effect did being in a structured environment have? Would these results have been different if the patients weren't treated for OCD? What about if their OCD was treated and not their ED? I realize that actually conducting a research study in that last scenario would be unethical, especially in a group that qualifies for residential treatment, but it's something that should at least be considered in the discussion.

Another question the researchers didn't factor in was the use of psychotropic medication. Eighty-nine percent of patients were on some type of psychiatric medication; the authors said they didn't control for this in their analysis since only 7% started on medication during their treatment. But they didn't mention how many patients' medication was adjusted, increasing or decreasing dose, or changing types and brands of medication. These things can have a significant effect on OCD and depression symptoms (although a recent study indicated that no psychotropic medications appear to be effective for AN)

As well, one of the researchers is the medical director of the treatment center where the research was carried out. This makes me a little skeptical of the results as a matter of course.

The researchers concluded that "Simultaneous treatment of OCD and eating disorders using a multimodal approach that emphasizes ERP techniques for both OCD and eating disorders can be an effective treatment strategy for these complex cases." But how effective? Is it better? How much better? How long did the results last for? There was no follow-up on any of these patients. Improving in a program is great, but the rubber doesn't really hit the road until after discharge.

This study is a start, but it's a small start. Co-occurring EDs and OCD can be very difficult to treat, but many people do go on to develop healthy and productive lives. We desperately need more resarch into the subject, but we need to start making comparisons to help develop the best, most effective treatment possible.

I don't know if you've seen the headlines (the story has been making the rounds in the psychology circles for the past day or two), but a study just came out that looked at the relationship between body dysmorphic disorder and nose jobs. The study found that one-third of people who wanted a nose job for cosmetic reasons had moderate to severe symptoms of BDD. Of those who wanted a nose job for medical reasons (to improve breathing, etc), 2% had been diagnosed with BDD.

Except that's not how the study was reported. Instead, headlines like "Nose job patients often mentally ill, study says." An excerpt from this piece below:

Of patients who were seeking the procedure to correct a breathing problem, only about 2 percent showed symptoms of BDD. But of those who wanted a nose job for cosmetic reasons, 43 percent showed symtoms of the disorder.


BDD was especially common among people with a history of mental illness, as well as those who had already had a nose job and were seeking “revision” surgery.

The problem, as John Grohol pointed out on the World of Psychology blog, is that "symptoms of BDD" aren't the same as being diagnosed with BDD. It's a subtle difference in words, yes. But it's a major difference in what we're actually talking about.

I had symptoms of the flu several winters ago. High fever, muscle aches, chills, feeling utterly crap, all with a sudden onset. Classic flu symptoms. Except a flu test revealed that whatever I had wasn't the flu. It looked a lot like the flu, it had the same symptoms as the flu, but it wasn't caused by the influenza virus.

Someone can have symptoms of depression (low mood, feeling hopeless), but not actually have clinical depression. Same with BDD. Same with EDs, too. The scales and questionnaires used in research aren't diagnostic tools. They can give you an idea whether you should see an actual living, breathing professional for evaluation and a potential diagnosis, but they don't say whether you actually have the condition.

It's not the public's job to know this. I'm not saying scientists shouldn't use these measures simply because they are so frequently misinterpreted by laypeople and journalists alike. But I am saying that journalists and editors need to know the difference. It's responsible reporting.

It happens with eating disorder stories all the time. Most commonly, it happens when people conflate disordered eating with eating disorders, or the scores on a survey with an actual diagnosis. The problem is that most people don't know there's a difference between these two things, or that the difference really matters.

Of course we would expect that people seeking nose jobs have higher concern and focus on their appearance. They are, after all, dropping thousands of dollars in an attempt to, you know, look better. But focus on your appearance isn't the same as BDD, and it's offensive to those who are suffering to make the two things equivocal. It's like saying someone who is obsessed with their weight has an eating disorder. They're not the same. At all.

We need to start distinguishing between these two things so that we stop trivializing deadly mental illnesses as little more than cultural fads.

Last week, the American Medical Association released a policy statement about Photoshopping models and eating disorder prevention.

The statement:

Advertisers commonly alter photographs to enhance the appearance of models' bodies, and such alterations can contribute to unrealistic expectations of appropriate body image – especially among impressionable children and adolescents. A large body of literature links exposure to media-propagated images of unrealistic body image to eating disorders and other child and adolescent health problems.


The AMA adopted new policy to encourage advertising associations to work with public and private sector organizations concerned with child and adolescent health to develop guidelines for advertisements, especially those appearing in teen-oriented publications, that would discourage the altering of photographs in a manner that could promote unrealistic expectations of appropriate body image.


"The appearance of advertisements with extremely altered models can create unrealistic expectations of appropriate body image. In one image, a model's waist was slimmed so severely, her head appeared to be wider than her waist," said Dr. McAneny. "We must stop exposing impressionable children and teenagers to advertisements portraying models with body types only attainable with the help of photo editing software."

And if the AMA had left out the mention of "eating disorders" at the end of the first paragraph, I wouldn't have had anything to say except to nod my head in agreement.  Because the alteration of images is appalling and imappropriate and, indeed, harmful.  The problem is the link to eating disorders.  The AMA said there was a "large body of research" linking media exposure to eating disorders.

So I went looking to see if I could find this large body of research.  I went to PubMed and searched for "eating disorders media" and indeed, I pulled up 264 studies on the subject.  But if you read the studies more closely, you'll see that there's lots of links between "disordered eating" and "eating pathology" and "body image dissatisfaction" and media exposure, but there's very little mention of linkage to outright, diagnosable eating disorders as spelled out by the DSM-IV.  One study did actually say that "media contributes to the development of eating disorders," but when I looked at the studies cited, all I saw were examples that linked media exposure to disordered eating.

A lot of the media coverage of the story has said that Photoshopped images "promote anorexia."  I'm not entirely sure I understand what that means.  I think I know what they're getting at--that looking at these images make you more likely to develop anorexia--but there's no actual evidence that this is true (at least, none that I could find).  We don't think ads for disinfectant somehow promote OCD.  We also don't think that those Bluetooth headsets promote schizophrenia because it looks like you're talking to yourself.

I think the big difference is that people don't think they know what it's like to have schizophrenia because they've been paranoid at one time or another, or that they've had a rather animated conversation with themselves.  But people do think they know what it's like to have an eating disorder because they've dieted and asked their husbands if these jeans make their butts look big. 

It's a common mistake, confusing disordered eating and eating disorders.  Many men and women are unhappy with their bodies and are on a diet.  People with eating disorders also often express extreme body dysmorphia and restrict their food intake.  They do look alike on the outside, but the internal experience is very different.  Dr. Sarah Ravin summarizes the difference between disordered eating and eating disorders as follows:

Disordered eating is very widespread in our country, especially among women. I define disordered eating as a persistent pattern of unhealthy or overly rigid eating behavior – chronic dieting, yo-yo dieting, binge-restrict cycles, eliminating essential nutrients such as fat or carbohydrates, obsession with organic or “healthy” eating – coupled with a preoccupation with food, weight, or body shape.


By this definition, I think well over half of the women in America (and many men as well) are disordered eaters.


The way I see it, disordered eating “comes from the outside” whereas eating disorders “come from the inside.” What I mean is this: environment plays a huge role in the onset of disordered eating, such that the majority of people who live in our disordered culture (where thinness is overvalued, dieting is the norm, portion sizes are huge, etc) will develop some degree of disordered eating, regardless of their underlying biology or psychopathology.


In contrast, the development of an eating disorder is influenced very heavily by genetics, neurobiology, individual personality traits, and co-morbid disorders. Environment clearly plays a role in the development of eating disorders, but environment alone is not sufficient to cause them. The majority of American women will develop disordered eating at some point, but less than 1% will fall into anorexia nervosa and 3% into bulimia nervosa.

I think it's great that the AMA is trying to protect children and adolescents from companies that would turn actual women into bobblehead models (the woman in the Ralph Lauren ad looks a bit like a bobblehead since her head is so disproportionately large compared to her body).  Our ideas of what "normal" and "healthy" look like are disorted and it is harmful.  On that subject, the research is clear.

As I have promised, I'm going to do a few posts on some of the things I learned while at the AED conference last weekend.

The best session I went to was called "Who's Who in the Brain?" and it looked at what neural systems malfunction in anorexia.  To try and summarize the talk would be ludicrous, especially since the best part was interactive.  Basically, session leaders Bryan Lask and Ken Nunn had us get into groups of 8 (since most of the participants were MDs or PhDs, there was a little bit of eye rolling at this suggestion) and we each took on a role of one of the neural systems profiled, from the nucleus accumbens (the pleasure center) to the prefrontal cortex (PFC, the "executive" or decision-making part of the brain).

We were given the task of trying to decide where to meet for dinner.  We each had to play the part of the brain part we were assigned (I was the basal ganglia, which is involved in movement/exercise, precision, and also malfunctions during OCD. I'm pretty tight with my basal ganglia...) in deciding where to meet for dinner.  As the basal ganglia, I needed to know exactly where and when to meet, like give me some GPS coordinates, people, and exactly how much money did we have to spend?  So perhaps a little neurotic, but I was bound and determined to get us there on time.

The other five group members also provided their feedback, and the insula carried all of our messages to the prefrontal cortex, who made the final decision.  We were going to meet at the hip Asian joint down the street at 6:45 pm for drinks and sushi. Ta-da! Decision made.

Then, we had to make the same decision in a malfunctioning anorexic brain.  As the basal ganglia, I couldn't find the "perfect" restaurant or the "perfect" entree or be sure that everyone else in the group would agree.  The prefontal cortex was also malfunctioning, and pretty much left the five brain parts to rule in anarchy.  The insula was simply missing in action and none of the brain parts could talk to anyone else.

Our decision?

Skip dinner.  All around the room, the groups returned with the same verdict: no dinner.  With a malfunctioning brain, the decision was just too complicated, and so the "brains" defaulted on not eating.

Our group decided we'd get tattoos instead (there was some sort of inside joke there--it was tremendously funny at the time, but I can't exactly remember why). Another group went to the gym.  Mostly, people retreated to their rooms and spent a socially isolated evening on their own.

Sound familiar?

Lask and Nunn referred to this conundrum--an endless shouting by the various parts of the brain while the prefrontal cortex merely shrugged its shoulders and the insula had long since left the building--as analysis paralysis.  Wikipedia defines it as:

over-analyzing (or over-thinking) a situation, so that a decision or action is never taken, in effect paralyzing the outcome. A decision can be treated as over-complicated, with too many detailed options, so that a choice is never made, rather than try something and change if a major problem arises. A person might be seeking the optimal or "perfect" solution upfront, and fear making any decision which could lead to erroneous results, when on the way to a better solution.

Figuring out where to go for dinner seems like a pretty simple decision.  It's not like figuring out where to move or whether to take that job or how much to invest in your 401(k).  It's just dinner.  Yet the decision making process, though it can happen lightning fast, is also very complicated.  If the brain can't share and process information--if the insula isn't working properly--the brain gets stuck on the simplest of decisions, like a scratched record or CD.

The insula is known to malfunction in anorexia.  Starvation reduces blood flow to the brain, which makes other areas of the brain malfunction as well.  Soon, the simplest questions cause paralysis and the brain defaults to a simple answer: no.  I already ate. I'm not hungry. I'm busy. No thanks. I'd rather not. No. No. No.

It's our way of avoiding analysis paralysis.  Our brains, Nunn said, are rather like Congress.  Lots of bickering, lots of going back and forth, and without strong leadership, nothing gets done. Actually, even with strong leadership, things don't always get done in Congress, but I digress.  Even if the insula alone isn't working properly, the entire brain is affected, and it gets stuck in analysis paralysis.

The solution is for other people to step in and act as the insula and prefrontal cortex of the person suffering from anorexia, whether it's parents, caregivers, friends, or therapists.  It's often too complicated to decide what to eat, and so it helps for someone else to do a bit of the decision making, sometimes in the form of making all food choices, or giving guidelines in others.  Eventually, the brain regains enough function to begin to take over those decisions, and being able to easily make decisions is a sign of recovery.

So this whole life-size Barbie doll created a spark of discussion not just on my blog, but also on the Today show.  Take a look at a clip from this morning's show via Hulu:



Did you notice that one word was absent from this discussion of eating disorders? One aspect of the discussion that is so frequently ignored, here and elsewhere?

Biology.

I'm not trying to ignore culture and the ins and outs of people's lives that can have a significant effect on the development of an eating disorder. I'm not trying to say that an eating disorder is "just" biology, because the idea that anything is either biological or cultural is pretty ludicrous.

But biology is pretty much absent from our discussions about eating disorders in the mass media. Sure, people will mention that genetics influence eating disorders, but the discussion stops there. Of course, biology is being mentioned, which it wasn't just a few short years ago. Still, the notion that eating disorders are rooted in biology and have an actual neurological basis is rarely mentioned in most stories about eating disorders.

So often, media stories file eating disorders under one or two major causes: unrealistic beauty images and control issues. There might be lip service to ideas about neuroscience and genetics and biology, but it doesn't get much discussion. And that bugs me. I don't want a slew of cookie cutter stories on eating disorders, blathering on and on about DNA and nothing else. Eating disorders are very complicated and biology is one aspect of the story.

But it's a big aspect. It explains so much about why people get sick and why they have such a hard time getting better. And we (as a community, as a culture) basically ignore it.

It's something that continues to baffle me.  We talk about biology in lots of other contexts--why are eating disorders so different?  Why are we so resistant to bringing up the biology factor?

As much as my inner feminist hates to admit it, I had a Barbie doll when I was younger. I had several of them, in fact. And I even had the Ferrari. And a token Ken doll.

The point of this post isn't to wax nostalgic about toys gone by. It has to do with a recent blog in the Huffington Post about using a life-size Barbie to help raise awareness about eating disorders and body image issues.

Forgive me, but I'm not exactly sure I see the connection between a mental illness and Barbie. We don't connect Baby Cries A Lot and major depression. Or Furbies and animal hoarding. It's a plastic toy. And let's remember that eating disorders and even body image issues existed long before Barbie hit the scene in the 1950's.

I get that Barbie is probably not the best role model for pretty much anything other than reinforcing gender stereotypes.  I get that she is an exaggeration of what some people feel is the "ideal body type."  That being said, so was the Venus of Willendorf, and my body doesn't look a thing like either Venus OR Barbie.  Most women don't.

Our culture has some seriously warped ideas about beauty, especially feminine beauty.  Most of us buy into them, in one form or another.  Most of us don't have eating disorders.


I find blaming Barbie and the like (models, etc) for eating disorders pedantic and not just a little offensive.  I wasn't unable to eat and at death's door because I was over-idealizing a plastic doll with blonde hair.  I was unable to eat because my brain was broken and it needed to be fixed.  The suggestion that I nearly died because I was somehow society's dupe strikes me as a little bizarre.

I'm not saying that cultural body image stuff is irrelevant or totally unrelated.  It isn't.  It forms a backdrop against which eating disorders form and emerge.  Many in the fashion industry have frank eating disorders themselves, so there's definitely some overlap.  But it's not a cause, and I kind of resent it being made to look that way.

A college girl who learns that Barbie has an unrealistic body will be more informed and hopefully a better consumer of media and its messages.  The problem is that knowing these things--that models are Photoshopped, that eating disorders are dangerous, that Barbie is a total fake (the bitch!)--don't prevent eating disorders.  EDs aren't decisions.  They aren't under conscious control--if they were, they wouldn't be an actual mental illness.  I knew plenty about anorexia and Barbie dolls before I got sick, and here's the kicker: I still got sick.

I think stuff like this--however well-intentioned and well-executed it might be--almost trivializes eating disorders.  It makes me feel like a supercilious brat, when that's not the case at all.  Lots of things influenced my eating disorder, and I'm happy to take a good, hard look at any of them.  But, please, leave Barbie out of this one.

I'll plead guilty--I've thrown around the phrase "brain disorder" in my time, even here on this blog.

But what the hell does this term even MEAN?!?

Here's the problem: there's no consensus.  Not in the field of eating disorders, not in the field of psychiatry, not in mental health.  Obviously, the idea of "brain disorder" means that biology is involved, which, for this trained biochemist anyways, is pretty darn obvious.

In a recent email, my friend Sarah Ravin said this:

I conceptualize a brain disorder as a disease or disorder that originates in the brain and influences mood, thinking, learning, and/or behavior. So EDs, autism, bipolar disorder, OCD, Alzheimers, and most of the DSM would fall under this category.

To me, “brain disorder” does NOT mean:

• Environment does not play a role in its development
• Environment does not play a role in recovery
• It is 100% biologically based
• It can only be treated by physician or with a pill
• Psychological interventions won’t help
• The patient can’t do anything to influence the outcome

In fact, I don’t know of any physical disease or medical condition in which any of the above is true.

I think this is, bar none, the best explaination of what a "brain disorder" is that I have ever read.  I think that if professionals can be more clear about what they mean when they say "brain disorder" then people can start understanding and integrating biology into their picture of what eating disorders actually are.  Understanding the biology of EDs has actually left me far more hopeful than any other explanation.  No, biology doesn't mean that I'm hopelessly f*cked, but it does help me approach recovery from a more realistic standpoint.  Even if/when I resolve all of my ED issues, I will remain vulnerable to relapse.  That doesn't mean I will be tortured by AN thoughts, or even have them at all, but that it's also smart to be cautious.

I got some wonderful replies to yesterday post In Defense of Biology.  I was responding to one of these comments, when I realized that what I was saying was a post in and of itself.  So I moved it to an actual post.

First of all, here's the comment:

We're on a slippery slope, as patients, when considering the role of biology and the disease process. On the one hand, acknowledging a biological root to a disorder allows us to let go of some guilty, feeling (appropriately) that something else contributed to this condition or caused it.


On the other hand, it seems we often view biology as simply medical, that someone medical will need to fix for us, taking away our responsibility to also help ourselves.

The more the medical community seems to learn about most diseases, the more it appears they are more complex than we originally believed, combining genetic predisposition, an environmental trigger and then support of the disease process.

It's the middle paragraph that intrigued me the most.  I'm not entirely sure I see how viewing eating disorders as biological and/or medical takes away our responsibility to help ourselves.  Yes, newer treatments like Family-Based Treatment do take away the sufferer's responsibility to feed themselves.  But the goal of FBT is ultimately to give these responsibilities back.

Part of treating a broken ankle is resting the injury and putting any weight on the ankle.  It's temporarily relieving the ankle of its responsibility to help you walk, yes.  It's also a medical treatment.  But the point of using crutches for months is to let your ankle heal so that you can walk properly again.

One of the most frequent reasons I've heard against understanding the neurobiology of eating disorders (besides the fact that our culture equates biological with "I'm screwed, so why bother.") is that it makes people into passive, helpless victims.  But is that really true, or is that just a faulty assumption on our part?  I bet if you asked, say, a breast cancer survivor, you would hear that a cell in her breast couldn't stop dividing, but then she got treatment.  That treatment isn't entirely passive.  She had to show up.  She had to get her mammogram or do her self-exam.  She had to have the scans and the biopsies and the surgery and the chemo.  All very medical things.  None of which relieved her of responsibility for managing her illness.

It did say that she couldn't stop that cell from dividing.  She couldn't ask the cell if it had issues with its mother, and hope that if she gave the cell some control, it would stop dividing.  No, the cell was going to keep dividing and keep making that tumor bigger because that's just what cancer cells do.  With an eating disorder, the life-threatening behaviors aren't going to go away on their own.  After a while, biology takes over, and ain't nobody messes with Mother Nature.  The sufferer needs help and support to be able to stop.  Viewing this as a medical issue doesn't mean the patient is helpless. Nor does the medical view discount the fact that things that happened during this woman's life may have increased the chance she ultimately got cancer.

Doctors never viewed my broken ankle as anything more than a broken ankle.  They did realize that osteoporosis had ravaged my bones.  They did ask questions like "You broke your ankle doing what?" (I slipped on a patch of black ice in front of my apartment.  I still get panic attacks when I have to walk on ice).  But the surgery to repair the break and the rehab and all were essentially medical.

Other than occasional soreness and swelling and two nasty scars, my ankle is fine.

People use the word medicalization like it's some sort of cuss word.  And yes, medicalizing things (such as grief) can be unnecessary and rather harmful and counterproductive.  A grieving person doesn't need a pill.  They need neighbors to bring them casseroles, friends to listen to them cry, and time to heal.  There are lots of examples of making normal things medical conditions--I won't deny it.

But we medicalize cancer.  We medicalize tuberculosis and diabetes and Alzheimer's disease.  I'm not entirely sure I understand how mental illness in general and eating disorders in particular are different.  I, for one, am glad the medicalized broken ankles so I didn't have some BO-laden guy laying his hands all over me and telling me the Lord Commanded It!  I'm glad they no longer think of epilepsy and seizures as being the mark of the devil and instead give you EEGs, medication, and one of those little alert bracelets. 

If someone offered me a pill that would make my eating disorder go away, you better fucking believe I would take it.  I don't need to spill my guts to a therapist for $100 each week to create meaning to an illness.  I go to therapy because it's the only thing I've got.  Creating something metaphysical out of an illness doesn't create a cure.  Honestly, giving meaning to my suffering and illness is nice, but really?  Cancer patients don't need to do it in order to get better. Nor do diabetics.  Nor do people with schizophrenia.

I don't know--maybe I'm just bitter.  I would love to be able to take a pill for my eating disorder.  That might make me lazy or unwilling to do the hard work of recovery.  Maybe that is true.  But it would be nice nonetheless.

The influence and importance of biology is an interesting and controversial topic in the field of eating disorders.  When I was first diagnosed with anorexia ten years ago, the debate centered more on if biology was involved.  Now, it's pretty widely accepted that biology is a factor in eating disorders. The question that remains is how important is biology.

We don't have percentages.  No one can say that biology is 75% important, and environment is 25%.  Every person I have met with an eating disorder has at least one (and often several) tick marks in each category.  For me, in the biology category, I have

• impaired set-shifting
• anxiety
• perfectionism
• depression
• loss of appetite under stress
• temperament traits of harm avoidance, low novelty-seeking, high persistence

In the environment category, I have

• thin-is-in culture
• tried to lose weight
• teased (weight was among those topics, but not always the focus)
• achievement-oriented culture
• fat phobic environment

So, yeah.  It's not an either/or question, and it frustrates me to no end that so many people think that it is.  This isn't a game of Red Rover, Red Rover.  You don't need to pick sides.  In fact, you can't pick sides because you can't separate genes and environment.  It doesn't work that way.  Environment affects what your genes do, and your genes affect what environments you seek out.

Even the researchers who specifically study the neurobiology of anorexia don't say that culture is irrelevant.  They say (and I would agree) that culture doesn't cause eating disorders.  But that's far from some sort of robotic, reductionist view that life is just some biochemical soup.  The study of biology in relation to eating disorders has added volumes to our knowledge about the subject.  Biology is a powerful thing.  We shouldn't take it for granted, nor should we scoff at it as an easy way out.  If it's biology, you're either stuck with it, or you just take a pill and All Better!

Which is really funny because none of the researchers I know think anything even close to that.

This is why I was really chagrined to read this article on addiction and eating disorders.  It starts as follows:

These days researchers and writers like to boil all maladies down to the biochemical level. The medicalization of all things sure makes life simple: if it’s just faulty brain chemistry, then there’s eventually going to be a pill for it.


But there is no pill to erase the feelings that grip Katherine’s gut when she walks into her childhood home for Thanksgiving. The Marlboro stench of the old curtains, the worn areas on the carpet, the heaviness on her mother’s hips and in her voice, the back bedroom filled with unopened boxes from QVC shopping binges, her father’s palpable misery about his job, the bathroom where she first learned to throw up…

I will say that when neurobiological studies were first published maybe 20 or 30 years ago, people probably did hope that we could take a pill and cure all of our mental ills.  We've gotten a lot older and a lot wiser since then.  No one remotely believes that you take a pill and bye-bye eating disorder (or depression or anxiety or whatever).  Medications can help, but they're not a cure-all.

Secondly, there's a growing body of research related to PTSD of what happens to the brain during stress and during traumatic events.  Psychologists have long known that environmental cues are a huge factor in relapse in drug addiction.  It's environmental (you see or hear something that reminds you have your drug use) AND it's also biological (this triggers memories and cravings and dopamine and what have you).

Memories are powerful.  One of the times I was most powerfully triggered was when I spoke with the boss I had from when I was most acutely ill.  I was shaking when I hung up the phone.  I wanted to throw up.  I never wanted to eat again.  Her voice immediately took me back to that place.  It's another reason I avoid the gym.  Memories of my exercise addiction trigger cravings for more exercise.

Researchers are looking for ways to help the brain unlearn the traumatic response to an event, and some of these methods may involve pills.  But a pill isn't going to cure PTSD, it's not going to cure anxiety and depression, and it's not going to cure eating disorders.

Walter Kaye is probably the top neurobiologist in the eating disorder field.  And he doesn't give out pills at this San Diego clinic.  He delivers therapy.  Therapy changes the brain.

Biology isn't a dirty word.  It's not the lazy way out, and it's not ignoring or neglecting environmental influences.  And it is important.

Writer Naomi Wolf was the keynote speaker at NEDA this year, and I honestly wasn't sure I was going to hear her speak.  Not because I'm anti-feminist (I'm not) but because I've read her book "The Beauty Myth" and I didn't find it that relevant to my own experience of an eating disorder.  I'm glad I went as a) it wasn't as bad as I feared and b) I found that many people had a similar response to what Wolf had to say.

I've heard Wolf speak before, and she is a phenomenal, engaging speaker.  She's super-articulate, very intelligent, and she knows her stuff.  I very much respect her and what she has to say.

However...

Although I think our cultural ideas and beauty obsessions and diet mentality are absolutely toxic, I don't think that if you eliminated them, you would eliminate eating disorders.  Most women feel bad when they're looking at Photoshopped models.  Most women diet at some point.  Most women don't have eating disorders.

(Not to mention, what about men?  What about people who live in cultures when thin isn't overvalued?  What about people with non fat-phobic anorexia?)

It's not uncommon for an eating disorder to start with an effort to "tone up" or "lose a few."    Yet once the disease process starts--once it kicks in--appearance is the last stinking thing most people with EDs are really thinking about.  People told me that my ED was making me look atrocious.  I was aware, on some level, that they were right.  By that point, the ED had a life of its own.  I was terrified of eating.  Even if it didn't have calories and exercising didn't burn any of them off, I would have still felt compelled to starve and exercise.  I couldn't stop.  That's why it's an illness.

I'm aware that the only evidence based prevention programs for eating disorders have focused on improving body image, and I'm not saying they don't work.  The research literature shows they do work.  But in a survey of 6000 eating disorder sufferers, no one said that their eating disorder had anything to do with vanity or cultural ideas (I heard this in a presentation by Susan Ringwood, the CEO of the UK charity B-EAT).  They did say that cultural ideals made it harder to recover, something I definitely endorse.

Eating disorders existed before thin was in, and they will probably exist after Size Zero seems as antiquated and misguided as chastity belts and foot binding.  The cultural language of fat and thin and dieting are what we have to put our experience into words.  They are how we frame what is happening to us.  People in the Middle Ages framed anorexia has an effort to be more spiritual.  Now, we look at it as an effort to be thinner or look like some supermodel.  But the way we make sense of an illness is different than the illness itself.

It just fundamentally bothers me that fighting eating disorders is seem as (in large part) fighting the fashion and cosmetics industry.  They use our obsession with being thin and such to sell products, it's true.  They make lots of women feel insecure about their looks, and then go on whackjob diets.  The body dysmorphia that accompanies an eating disorder isn't just a really bad version of wondering if these pants make your thighs look fat.  Being beheaded isn't just like a really bad paper cut, either.  An eating disorder isn't a really extreme diet.  It might look like that, but it's fundamentally different.

Wolf mentioned nothing about underlying vulnerabilities like anxiety and depression to eating disorders.  She did say that restricting in and of itself is crazy making, which is good.  Although she said that "parents don't cause eating disorders," she also said that her own mother's bitching about her thighs primed her for anorexia.  None of her other siblings developed an eating disorder, yet I'm sure they all heard the kvetching and comparing.  Why Naomi?  Why only her?  It's fundamentally not okay if your mother is diet-obsessed and tells you you're too fat.  Not okay.  And that sort of environment is certainly conducive to the development of an ED, but it's impossible to say that had this person grown up in a different environment, they never would have developed an eating disorder.

It was...frustrating at times to hear no mention of science and biology.  My friend Sarah Ravin asked Wolf afterwards why there was no mention, and Wolf said "I don't really do that science stuff."  I understand that science might not be everyone's little pet, but seriously?

The emphasis on beauty images only reinforces the idea that EDs are an expression of vanity, or just a bunch of beauty-obsessed kids who need to stop reading magazines.  And they're not.  Our focus on this does everyone a disservice.

In attending many presentations and talks about eating disorders, one of the more fascinating topics I've heard mentioned was interoceptive awareness. Interoceptive awareness (IA), as a research article on the subject succinctly put it in the title, is "the sense of the physiological condition of the body." What this means is that when you sense things like "pain, temperature, itch, sensual touch, muscular and visceral sensations, vasomotor activity, hunger, thirst, and 'air hunger,'" you are using IA. The input is internal, unlike other senses that are more external. Visual input comes from outside your body; a sense of exhaustion is more internal. Furthermore, an ability to recognize your emotions is also considered part of IA, and all of these IA tasks occur in an area of the brain known as the insula. Wikipedia tells us that the functions of the insula "include perception, motor control, self-awareness, cognitive functioning, and interpersonal experience."

Scientists have long speculated that people with eating disorders have impaired IA. A recent research review article by Walter Kaye examines the evidence of dysfunction in both the insula and in IA as one of the drivers of ED behaviors (Kaye, Fudge, and Paulus, 2009). Research on the relationship between EDs and IA dates back to this paper from 1978 by Garfinkel et al. Impaired IA would help explain how a person with AN might be able to continue to starve themselves--their hunger cues might be impaired. Or how someone with BN might be able to continue to binge--their satiety cues might be impaired. Furthermore, people with eating disorders often struggle with identifying emotions, body size and shape, and fulfilling other biological needs (such as sleep). Poorer IA is also associated with poorer ED outcome (Lilienfeld et al, 2006). I've blogged on my own (mis)adventures with IA here.

I'm still not very talented at figuring out whether I'm hungry or full, whether I'm tired and need a nap or just need to stretch my legs. Some of the hunger/satiety issues were probably thrown off by the eating disorder, but some of it may just be the way I'm wired. I've been in the midst of several full-blown hypoglycemic episodes (feeling faint, shaking, sweating, vomiting) and thinking "How could that be? I don't feel hungry." Obviously. I wasn't trying to delude myself- I've had ED-induced hypoglycemic episodes where I knew damn well it was because I hadn't eaten and I played the green-eyed ingenue. But there were plenty of times where I delayed a meal because I didn't feel hungry and then WHAM! Which is a great example of impaired IA, if nothing else.

A new study published this week found that levels of Brain Derived Neurotropic Factor (BDNF; which encourages the growth of new neurons and helps existing ones thrive) were correlated with interoceptive awareness and maturity fears in people with anorexia and/or bulimia (Mercader et al, 2010). Specifically, the researchers found that higher levels of BDNF were correlated with lower interoceptive awareness and higher maturity fears. The authors suggest that BDNF levels may play a role in regulating ED psychopathology via impaired IA.

Previous research has explored a link between BDNF and both anorexia nervosa and bulimia nervosa.

I'm not thinking that testing BDNF levels are going to become standard of care anytime soon--BDNF is associated with impaired IA but that doesn't tell us much. Does BDNF have an affect on IA or is it just a bystander? How might BDNF affect IA? Does decreasing BDNF levels increase IA?

Like so much research, this paper raises more questions than it really answers. Still, I find it all very interesting.

Our data suggest that BDNF levels may influence the severity of the ED by modulating the associated psychopathology, in particular through the impairment of interoceptive awareness.

A new post on the "You Must Be Hungry" blog at Psychology Today looked at the relationship between eating disorders and autoimmune diseases, as well as potential treatments in the form of probiotics (healthy bacteria, like the kind in yogurt). Writes author Shelia Himmel:

Enter NuBiome, a company founded in 2009 to develop therapies, including probiotics (beneficial bacteria) that interfere with disease-causing bacteria found in the gastrointestinal tract, focusing on autoimmune conditions. The company founders all have seen or had family members who got sick with autoimmune diseases. That includes bulimia and anorexia.

"The paradigm's got to change," said Brian Lue, a NuBiome researcher. In a paper he delivered recently, Lue explained how people used to think that stomach ulcers were caused by stress and dietary choices.

...Lue explains, "A normal person with a normal immune system may have a rare event in their intestine and this changes the way the normal bacteria in their gut die and break up into fragments. Their immune system then finds a specific piece of the bacteria that looks like a piece of the insulation on their nerves. Now, when the immune cells find that piece of insulation on the nerves, bad things start to happen. The body's immune system turns against nerve insulation because it "thinks" that they are foreign bits of bacteria. In the process it ends up destroying its own tissue because it confuses body tissue with that of the bacteria. This is what an autoimmune disease is. In the case of multiple sclerosis, the insulation on the nerves is attacked by the person's own immune system."

How does all this relate to eating disorders?

Lue refers to a 2005 paper in the Proceedings of the National Academy of Sciences by Serguei Fetissov, who identified specific antibodies in people with anorexia and bulimia nervosa. These antibodies disrupted the normal hormonal systems of the brain, particularly the part of the brain that is responsible for appetite control and the stress response.

Lue writes, "This seems to correlate with the changes in eating habits that defines bulimia and anorexia. The authors of the study suggested that the autoimmune response could be triggered by pieces of several types of bacteria in the gut mimicking the brain hormones. Pieces of H. pylori, the stomach ulcer bacteria, and E. coli are some of the likely suspects."

I'm a long way from saying that yogurt is some magical cure-all for eating disorders (though I do loves me some yogurt), but the research is interesting.

I had previously downloaded the 2005 Fetissov paper that Himmel mentioned in her blog post, titled "Autoantibodies against neuropeptides are associated with psychological traits in eating disorders," and re-read it for this post. The researchers knew from previous research that people with AN and BN had antibodies to α-melanocyte stimulating hormone (Fetissov et al, 2002), known as auto-antibodies because they were antibodies against "self" proteins, and the authors of the 2005 study note that:

melanocortin peptides involved in appetite control and the stress response. In this work, we studied the relevance of such [auto-antibodies] to AN and BN. In addition to previously identified neuropeptide autoAbs, the current study revealed the presence of [auto-antibodies] reacting with oxytocin (OT) or vasopressin (VP) in both patients and controls.

Which is interesting, when you look at the roles of both oxytocin and vasopressin and consider that difficulties with social relationships and stress, respectively, are pretty common in eating disorders. What is also interesting from this study are the differences in auto-antibody levels in AN and BN. In AN, higher levels of auto-antibodies were correlated with higher scores on the Eating Disorder Inventory-2 (meaning higher levels of ED psychopathology), while in BN the opposite was true: higher levels of auto-antibodies meant lower levels of ED psychopathology, and vice versa. (If I'm reading the statistics wrong, please someone let me know- it's been a long time since I had to puzzle through dense biostatistics jargon.) What this difference ultimately means is beyond me, although I hope more research will look into the subject.

At the end of Himmel's blog post, she mentioned that a NuBiome researcher asked about her daughter's (who had anorexia and bulimia) childhood exposure to antibiotics, and Himmel recalled that her daughter had frequent doses of antibiotics. Granted, so did I, for frequent lung infections aggravated by asthma that left me with a 10-pack-a-day smoker's cough at the age of 6. However, antibiotics were peddled like candy when I was younger, and furthermore, EDs existed long before penicillin. Nor was I able to find any research indicating a link between antibiotics and the onset of eating disorders.

Still, the research is interesting and thought-provoking, and I'm curious to see more. I'm also getting a strange urge to hit the dairy case, so if you'll excuse me...

Earlier this week on Twitter (do you follow ED Bites on Twitter? You know you want to...), I ran across an interesting article about why some antidepressants don't work in some patients. The article was published last week in the research journal Neuron and is titled "5-HT1A Autoreceptor Levels Determine Vulnerability to Stress and Response to Antidepressants." (Clicking the link will take you to the free full-text of the article.) I'll let the opening of the article's Science Daily press release explain the research for me:

An excess of one type of serotonin receptor in the center of the brain may explain why antidepressants fail to relieve symptoms of depression for 50 percent of patients, a new study from researchers at Columbia University Medical Center shows.

...Most antidepressants -- including the popular SSRIs -- work by increasing the amount of serotonin made by cells -- called raphe neurons -- deep in the middle of the brain. Serotonin relieves symptoms of depression when it is shipped to other brain regions.

But too many serotonin receptors of the 1A type on the raphe neurons sets up a negative feedback loop that reduces the production of serotonin, Dr. Hen and his colleagues discovered. "The more antidepressants try to increase serotonin production, the less serotonin the neurons actually produce, and behavior in mice does not change," Dr. Hen says.

Seeing as anti-depressant therapy hasn't shown much promise in the treatment of anorexia nervosa (although it does appear to help treat co-morbid conditions like depression and anxiety), this research could help with the development of new treatments for AN. It also seemed like a good a time as any to discuss the links between serotonin levels and eating disorders. In a 2005 review article, titled "Serotonin alterations in anorexia and bulimia nervosa," Walter Kaye wrote that people with either anorexia and/or bulimia showed alterations of brain functioning in specific neural areas:

Importantly, such disturbances are present when subjects are ill and persist after recovery, suggesting that these may be traits that are independent of the state of the illness. Emerging data point to a dysregulation of serotonin pathways in cortical and limbic structures that may be related to anxiety, behavioral inhibition, and body image distortions...Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.

The serotonin/anorexia connection has been researched over the years (searching PubMed for "serotonin anorexia" gives you over 700 results), and the most recent thinking goes something like this. People with anorexia are generally thought to have unusually high levels of serotonin in their brains, and high levels of brain serotonin have been linked to anxiety and obsessionality. An old BBC article titled "Genetic clues to eating disorders" has a quote from Janet Treasure that explains some of the link:

People with high levels of serotonin are prone to anxiety. Dr Janet Treasure, director of the eating disorders unit at the Maudsley, believes this could be behind anorexic patients' ability to suppress appetite. She said: "In anorexia nervosa the drive to eat can be inhibited, but we know that in normal people who are starved they will kill each other and do all sorts of morally repugnant things, and eat all sorts of foodstuffs that you wouldn't normally touch.

"Yet that doesn't happen in anorexia nervosa, so there's some aspect of the appetite system that isn't working."

The unit looked at the biology of stress mechanisms, in particular the fight or flight response. This is where the body prepares itself for action when confronted by a stressful situation. Heart rate and blood pressure rise and two of what are usually humans' highest priorities, eating and reproducing, are put on hold. It is possible that anorexic people are chronically in an acute state of stress reaction - they are constantly in a fight or flight state of mind.

And by restricting food intake, people with anorexia can lower the amount of serotonin their bodies can make (serotonin is ultimately derived from the essential amino acid tryptophan). This actually makes people with anorexia feel better. However, the brain begins to sense the decreased serotonin production and tries to maintain homeostasis by increasing the number of serotonin receptors. Thus the brain is back at Square One, as it is producing less serotonin but is using the decreased amount much more efficiently. So restricting doesn't feel as good, and the (obvious!) solution is to eat even less. And thus that negative cycle is born and the anorexic becomes trapped by their own brain chemistry.

Refeeding would then increase the amount of serotonin in the brain before the brain has a chance to decrease the number of serotonin receptors. This could be the neurological equivalent of All Hell Breaking Loose and could very well explain why refeeding is so distressing, although I don't think there has been any formal research done on the subject.

In bulimia, the serotonin problem is reversed. People with BN appear to have much lower than average levels of serotonin in the brain, which may be temporarily increased by binge eating.* Purging increases levels of vasopressin, which can have a euphoric and sedating effect, thus making the binge/purge cycle addictive much in the same way that starvation becomes addictive in AN. The chronic low levels of serotonin in BN also explain why SSRIs can be effective at reducing the urges to binge and purge.

Of course, plenty of people cross over from anorexia to bulimia, and I haven't the slightest idea of how serotonin might affect that crossover. So many brain systems are thrown out of whack during an ED that I don't know an exact answer will ever be found.

*The story is, as usual, a little more complicated than this, but the basic idea is the same.

A post on the DANA Foundation blog, titled "Wired for Hunger," looks at obesity, how the body regulates hunger and satiety, and what happens when these systems malfunction. But that's not the real interesting part. The interesting part was the sidebar on anorexia. It was both interesting and scientifically astute, with some testable hypotheses and potential interventions for anorexia. I'm copying it in its entirety here because I really think its worth reading.

Anorexia Nervosa: A Mortal Clash between Reward and Hunger

Few disorders reveal the power of the brain’s cognitive circuitry more clearly than anorexia nervosa, a psychiatric disorder characterized by extreme undereating, loss of body weight, hyperactivity and hypothermia. Compared with other psychiatric conditions, this disorder has the highest mortality rate. We theorize that, in cases of anorexia nervosa, the brain’s ancient evolutionary wiring for adapting happily to low food availability is inappropriately activated and finds itself in a life-threatening battle with other brain signals demanding action to obtain nourishment.

One clue to the intensity of this clash is the elevated level of physical activity in patients with anorexia nervosa, a symptom that people have reported for more than 100 years. Several studies have established a relationship between obsessive-compulsive characteristics and exercise frequency in women with strenuous daily exercise routines and in hospitalized female patients with anorexia nervosa.16 In the patient group, preoccupation with weight was associated with both the frequency of exercise and pathological attitudes toward it. Addictive and obsessive-compulsive personalities contributed to excessive exercise because of their obligatory, pathological thoughts promoting it. Among anorexia nervosa patients, those who exercise excessively have more bulimic symptoms, higher levels of general psychopathology about eating and a greater degree of body dissatisfaction, anxiety, somatization (physical symptoms with a psychological origin), depression and irritability.

Scientists view the tendencies toward mental alertness and continued normal-to-high activity levels (despite insufficient nutrition and weight loss) as being relatively unique to anorexia nervosa patients, versus individuals who experience semi-starvation due to causes such as illness, chemotherapy or famine. For both of these tendencies, the most plausible explanation is activation of evolutionarily old circuitry leading to reward upon reduced energy intake.

A final clue is another characteristic of anorexia nervosa patients: 90 percent are women, mainly in their late teens. This leads us to propose that a cellular mechanism, in association with the changing hormonal milieu that is characteristic of anorexia nervosa patients, unifies and orchestrates activation of key brain circuits, which in turn leads to the behavioral and endocrine manifestation of anorexia nervosa. Our hypothesis is that anorexia nervosa occurs following shifts in the circulating hormones ghrelin, leptin and estradiol, which alter key groups of neurons. These alterations bring about sex-specific structural and functional changes in particular circuits of the midbrain that transmit the chemical dopamine to communicate. Dopamine then triggers a reward response in the prefrontal cortex and hypothalamus to undereating and overexercise.

We further hypothesize that rolling back this shift in reward response could reverse anorexia nervosa, and that either eliminating ghrelin signaling or suppressing the number of available long-chain free fatty acids in the brain could accomplish this. Neuronal cells normally activated by ghrelin use these acids for energy; thus, eliminating the fatty acids would silence the ghrelin-activated neuronal population. Patients who received controlled leptin and estrogen replacement therapy also might see their anorexic symptoms diminish. Moreover, we predict that if doctors help at-risk patients maintain estradiol and/or leptin levels during the initial phase of disease, the patients will be less likely to undergo the shift in reward responses that leads to anorexia nervosa.

Thoughts?

One of the most profound things I learned in treatment for anorexia was how much the symptoms of my eating disorder (obsession with food, increased anxiety and insomnia, agitation, hyperactivity) were as much symptoms of starvation as they were symptoms of anorexia. Not that this made eating any easier--it didn't--but it helped put a context to all of the frightening thoughts and compulsions I was having. Eating seemed to make them worse, but only after a while did eating make them somewhat better.

Undernutrition may actually be at the core of many of the traits and symptoms researchers initially thought were caused by anorexia. Many people with anorexia are probably more obsessive, anxious, and perfectionistic than average; since these traits existed before the eating disorder, they aren't caused by undernutrition, but they sure can be exaggerated. Even just a quick read of Keys' starvation study indicates that many of the behavior changes brought about by semi-starvation can be significant. Many brain imaging studies of anorexia are performed after weight restoration and a period of recovery and normal eating because starvation has such profound effects on the brain.

There have been numerous studies that have reported on psychological changes that occur during refeeding (Konrad et al 2007), but two interesting studies appeared within the past week that seemed to emphasize the role of refeeding in the psychological recovery from EDs.

The first article was from the French journal Encephale, which looked at the relationship between social phobia, anorexia, and the stage of treatment (Coulon, Jeammet, and Godart, 2009). Because the journal is in French, I'm going to have to stick with the abstract, but the results were still interesting. Social phobia has been loosely associated with AN, but the researchers were trying to figure out whether the social phobia might be a by-product of malnutrition rather than an actual trait of the anorexia sufferer. In this sense, it's kind of the proverbial chicken-and-egg question: which came first, the undernutrition or the symptoms of the eating disorder?

And what did the researchers say about how stage of treatment in anorexia affected social phobia? They found a correlation between social phobia and symptoms of AN as well as "total clinical picture" of the patient, but no relationship between social phobia and nutritional status (as measured by BMI). The researchers concluded that "We therefore feel that a diagnosis of social phobia can only be confirmed after an acute state of AN, thus allowing for preferential treatments. Other studies must be conducted in order to continue to explore the links between social phobia and AN."

This doesn't preclude the pre-illness onset of social phobia--in fact, a 2004 study found that approximately one in five ED sufferers met the diagnostic criteria for social phobia before the onset of their disorder (Kaye et al, 2004). However, due to the eating disorder, social phobia can appear in a person who had no previous symptoms of the disorder. So is that social phobia a true, independent disorder, or is it related to undernutrition? This study says that social phobia might be related to undernutrition, but we don't know for sure yet.

The second study looked at the hypothesized relationship between anorexia and autism spectrum disorders (ASDs; Time Magazine had a good article earlier this year on the issue that I blogged about here). Specifically, the study looked at the difficulties people with AN have with respect to the emotional Theory of Mind (eToM), with understanding and interpreting others' emotions (Oldershaw et al, 2009). People with ASDs often have difficulty understanding other people's emotions, and the fact that AN sufferers also had difficulty with this seemed to be a neurological link between the two disorders.

The researchers compared a group of currently ill AN patients with both recovered AN patients and healthy controls, and found that the emotional deficits seen in acutely ill AN patients had essentially disappeared in the recovered AN patients. Furthermore, there were few differences in emotional tasks in recovered AN patients and healthy controls, which indicates that the emotional deficits are more related to the current state of undernutrition than they are a person's temperament.

Conclude the researchers:

These findings indicate almost complete normalization of emotion recognition ability as well as the restoration of eToM in recovered patients, despite the observation of difficulties in both domains in currently ill patients. Findings suggest that similarities between AN and ASD in poor eToM are restricted to the currently ill AN state and such difficulties in AN may be a factor of starvation.

However, other similarities between AN and ASDs remain, such as difficulties with set-shifting and impaired central coherence (i.e., you can't see the forest because of the trees) that seem to extend long beyond recovery. That, however, is its own blog post that will hopefully be up soon.

Last month, I wrote on Part One of an article from the magazine Psychiatric Times titled "The Cellular and Molecular Substrates of Anorexia Nervosa, Part One." As I promised, I am writing on Part Two now that it has appeared (the original link I found was bad, and I had to hunt down the article, so I apologize for the delay, but here it is!).

The author, John Medina, summarized the first article as follows:

A testable hypothesis was outlined: AN was described as a conflict between an un-acquired biological need to have food and an acquired negative reaction to it. Patients with AN recruit cortical executive reactions in response to appetite cues, reactions that insert a top-down “food-negative” bias into the normal drives for fuel. These executive reactions are consistently overstimulated in AN patients, leading to high anticipatory behavior and obsessive concern with future events. Derived mostly from noninvasive imaging studies, this notion of conflicting priorities (complete with a dysfunctional reward/punishment system) has surprising empirical support.

But it is hardly the complete story of AN. Besides behavioral and cellular concerns, there are also molecular interactions to consider. It is to these efforts that we turn, focusing on the “usual regulatory suspects” of dopamine and serotonin neurotransmitter biology.

Medina first begins discussing the role of malfunctions in the dopamine system in people with AN, since many anorexics report varying levels of asceticism, anhedonia (the inability to find anything pleasurable), and the difficulties in finding something consistently rewarding. This is otherwise known as the Theme of My Life. These are considered trait features because they often exist before the onset of illness and persist after recovery. Other clues pointing to the dopamine system are difficulties with visual tasks (which can often signal a malfunction in the dopamine system), lower levels of dopamine metabolites in the cerebrospinal fluid even after recovery, variances in the genes of dopamine receptors in the brain, as well as brain imaging studies.

The other major neurotransmitter being studied with respect to anorexia is serotonin. Medina included a diagram (that I've copied here) that portrays the two hypotheses related to abnormalities in the serotonin system that may contribute to anorexia. The first hypothesis is that people with AN have increased levels of serotonin in the brain, which may contribute to the common traits of harm avoidance and anxiety, as well as the general lack of effectiveness of SSRIs in treating AN. The other hypothesis has to do with an imbalance in serotonin receptors which can be altered by both hormonal changes and stress. The evidence for this has to do with the usual onset of AN during puberty/adolescence, and many times the onset coincides with a particularly stressful time in the sufferer's life.


Writes Medina:

Starvation-induced reductions in levels of extracellular 5-HT, for example, might result in reduced stimulation of postsynaptic 5-HT1a and 5-HT2a receptors, leading to behavioral alteration. The resulting dysphoria, normal in unaffected individuals, might be exaggerated in patients with AN.

There are testable questions surrounding these ideas. Forcing AN patients to eat, for example, might stimulate postsynaptic 5-HT1a and 5-HT2a receptor activity. This stimulation would lead to an elevation in dysphoric mood, transforming eating and weight gain activities into traumatic stress-inducing experiences. This might explain the no-win behaviors so common in AN patients. If the patient were allowed to continue to starve herself, anorexigenic information related to neuropeptide alterations (reduced b-endorphins, elevation in stress-related metabolism such as elevated corticotropic-releasing hormone), might exacerbate AN symptoms by driving food-restricting behaviors. Whether eating or starving, the same dysfunctional circuitry would be stimulated, all leading to the symptoms.

... Persons with AN show unique anxiety-related 5-HIAA metabolic perturbations. The weight loss in these patients results in a reduction in 5-HIAA CSF levels. But they concomitantly show dramatically elevated 5-HIAA receptor binding in specific cortical and limbic structures—something not seen in healthy controls. Food might very well be anxiogenic in these individuals.

Which, really, explains both everything and nothing. As Medina says, there is no one neurological system that is both necessary and sufficient for the development of AN. And I hate to rain on anyone's parade, but I doubt it will be just one thing or just one system or just one factor. Human behavior is way too complicated. Still, we have made enormous strides in understanding the scientific basis of anorexia, and I'm looking forward to future research.

Last week, two interesting research papers were published that looked at the neurological origins of body image distortion in anorexia nervosa. And what researchers found was rather interesting.

The first article looked at not only how people with AN process body image, but it broke down that processing into two different steps: attitudes towards their body and how they experienced their own size (Mohr et al, 2009). Using fMRI, the researchers

"further demonstrated stronger activation of the insula and lateral prefrontal cortex during the satisfaction rating of thin self-images. This indicates a stronger emotional involvement when patients are presented with distorted images close to their own ideal body size. Patients also overestimated their own body size."

Furthermore, the researchers found a complex pattern of activation of the precuneus, an area of the brain that is thought to contain a sensory-based map of the body. Scientists hypothesized that people with AN have a deficit in their ability to pull up an accurate map of their bodies, leading to the body size overestimation so prevalent in AN.

I think it would be fascinating to compare fMRI scans of people with non-fat-phobic anorexia to those with AN and body dysmorphia. Perhaps this would help confirm that these different patterns are specific to body image and not related to anorexia in some other way.

The second paper looked at the role of the right parietal lobe in the formation of body image in people with AN (Nico et al, 2009). Part of the parietal lobe's job is to integrate sensory information from different points in the body, and stroke patients who have damaged right parietal lobes have difficulties with body representation and schema. Whereas people without AN and those with stroke damage to the left parietal lobe were able to estimate their bodies accurately, those with AN and stroke damage to the right parietal lobe were not. The researchers concluded that these results

"support the possibility for a neuropsychological component in the pathogenesis of anorexia, offering alternative approaches to treatment of the disorder."

Together, this research indicates that the body image difficulties in eating disorders go beyond seeing skinny models in magazines (though this doesn't help) and these neuropsychological differences play a role in the development of EDs.