The face in the coffee beans

Howdy everyone. I realize that I've been a little lax at updating this blog- I've been launching my career as a freelance science writer, and that was a giant time suck, to say the least. But now I've gotten established and I'm looking forward to blogging regularly here about the latest ED research. To get you back in the swing of things, I'm starting off with a little brain teaser.

Do you see the face in the coffee beans?

This is one of the neuropsychological tests that researchers have used at the Institute of Psychiatry in London. People with EDs, especially anorexia, are really good at finding the face in the coffee beans. They find it easy to focus on the details and ignore the bigger picture. Essentially, they embody the phrase "can't see the forest for the trees."

These tests aren't diagnostic of anorexia, but they do indicate a detail-orientation, a tendency to lose sight of the big picture (the coffee beans) and focus in on tiny little details that ultimately reveal a face. The "Where's Waldo" books are something similar. For someone with an eating disorder, they will focus on the fact that a Hass avocado has 300 calories rather than focusing on the good fats and oils in the fruit, the buttery taste of guacamole, that California burger they had at a backyard cookout. Or even the need to eat such fats to think better and have shiny, smooth hair. No, an avocado only means 300 calories. Period.

Kara Fitzpatrick at Stanford University gives a talk about the latest eating disorder neuroscience research. It's a series of 3 videos that last slightly over 20 minutes. You can easily just listen to the talk--the visuals aren't utterly crucial.

Part One

Part Two

Part Three

I hope you enjoy!

Bone health and eating disorders

A recent study from the Journal of Bone and Mineral Research found that women with anorexia had much higher levels of fat in their bone marrow than women without AN (Ecklund et al, 2010). The study was generally publicized as "OMG! Anorexics have FAT on their bony bodies!" Which, as an interesting irony and news hook, I'll give you. But the story goes much deeper than that, which some of the news coverage touched on but really didn't delve into (they appeared to get stuck on the "WTF- could anorexics be fat?!?" part).

Eating disorders are associated with an increased risk for osteoporosis--and it ain't no joke. I've learned that the hard way, with three broken bones and several stress fractures. There are many hypotheses for this increased risk, including deficits in estrogen, high levels of cortisol, and high levels of leptin. I'm guessing each of these plays a role in the decrease in bone mass and density through either the metabolism of bone cells and/or a dramatic decrease in the formation of new bone cells during malnutrition.

This study points to a new mechanism for the dramatic bone density decrease seen in eating disorders in general and anorexia in particular. At the center of larger bones is the bone marrow, one type of which is the red bone marrow and produces new blood cells. The other type is the yellow bone marrow and contains fat cells that can be used as an energy source in cases of extreme starvation. Furthermore, the two types of bone marrow can be interchangeable--in cases of extreme blood loss, the yellow marrow can be converted to red marrow. What Ecklund et al found in this most recent study is that red marrow can be converted to yellow marrow if the body is profoundly starved, which can result in premature osteoporosis.

The study subjects with anorexia had much higher levels of yellow marrow than red marrow, and the researchers hypothesized that the body had prioritized the formation of extra fat for future energy needs at the expense of red blood cell formation (I'm wondering whether this also helps to explain the high levels of anemia seen in people with eating disorders). The innate intelligence of the body never ceases to astound me. In a starving person, fat (which is essentially energy) is much more useful than red blood cells. Without energy, the body shuts off. With fewer red blood cells, you may be more easily fatigued, but mild levels of anemia are rarely out-and-out life threatening.

It will be interesting to see if there is follow-up research done to see how weight restoration and recovery change the ratio of red and yellow marrow, and whether these changes persist for a long period of time after recovery.

Serotonin, antidepressants, and eating disorders

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.

Of Mice and Men (and Anxiety)

Two studies were published this week that made the connection between genetic variations and anxiety disorders in both humans and animals.

One study, published in the journal Science, found that mice and humans with the same mutation in an anxiety-related gene behave similarly. The study, titled "A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human," sounds almost deliberately obtuse, but the results are interesting. Lab rats (or in this case, lab mice) are often used in research for any number of reasons, which include the fact that they are small and relatively easy to handle, they reproduce quickly, and over a century of intense breeding and research has enabled researchers to know an animal's exact genetic profile. Many studies in behavioral neuroscience use mice and rats for these reasons, and also because it's generally difficult to get humans to participate in many of these experiments (which are often ended by autopsy so the brain can be examined). From a genetic standpoint, there aren't a whole lot of differences between a human and a mouse. Many of the tasks we both have to complete--digesting food, eliminating waste, maintaining homeostasis--are pretty darn similar, so researchers have hypothesized that the neural circuits controlling behavior in mice and people are actually similar.

This most recent study looked at a variation in the gene that makes Brain Derived Neurotropic Factor (BDNF), a protein responsible for brain growth and development. The interesting result was that the mice and humans who had this variation had similar behaviors. From a Science Daily press release:

To make their comparison, the researchers paired a harmless stimulus with an aversive one, which elicits an anxious-like response, known as conditioned fear. Following fear learning, exposure to numerous presentations of the harmless stimulus alone, in the absence of the aversive stimulus, normally leads to subjects extinguishing this fear response. That is, a subject should eventually stop having an anxious response towards the harmless stimulus.

"But both the mice and humans found to have the alternation in the BDNF gene took significantly longer to 'get over' the innocuous stimuli and stop having a conditioned fear response," explains Dr. Fatima Soliman...

...[Researchers] found that a circuit in the brain involving the frontal cortex and amygdala -- responsible for learning about cues that signal safety and danger -- was altered in people with the abnormality, when compared with control participants who did not have the abnormality.

"Testing for this gene may one day help doctors make more informed decisions for treatment of anxiety disorders," explains Dr. Francis S. Lee.

Specifically, it may help therapists tailor approaches to treating anxiety such as exposure therapy, which is an empirically supported treatment for a variety of anxiety disorders, such as phobias and PTSD.

"Exposure therapy may still work for patients with this gene abnormality, but a positive test for the BDNF genetic variant may let doctors know that exposure therapy may take longer, and that the use of newer drugs may be necessary to accelerate extinction learning," explains Dr. Soliman.

BDNF has also been associated with both anorexia nervosa and bulimia nervosa.

In a completely separate study, researchers have identified a genetic mutation that results in compulsive behaviors in a wide variety of animals. From a New York Times article on the study:

Researchers studied Doberman pinschers that curled up into balls, sucking their flanks for hours at a time, and found that the afflicted dogs shared a gene...the findings [have] broad implications for compulsive disorders in people and animals.

Dr. Dodman and his collaborators searched for a genetic source for this behavior by scanning and comparing the genomes of 94 Doberman pinschers that sucked their flanks, sucked on blankets or engaged in both behaviors with those of 73 Dobermans that did neither. They also studied the pedigrees of all the dogs for complex patterns of inheritance. The researchers identified a spot on canine chromosome 7 that contains the gene CDH2 (Cadherin 2), which showed variation in the genetic code when the sucking and nonsucking dogs were compared.

The statistical association led to further investigation to determine for which protein the gene contained instructions. It did for one of the proteins called cadherins, which are found throughout the animal kingdom and are apparently involved in cell alignment, adhesion and signaling.

Cadherins have also been recently associated with autism spectrum disorder, which includes repetitive and compulsive behaviors...

...“Stress and anxiety, as well as physical trauma and illness, can trigger repetitive behavior that then takes on a life of its own,” Dr. Ginns said.

But he believes that in many cases there is an underlying genetic predisposition that responds to environmental stimuli in such a way that once-normal behavior turns into something pathological. Those genetic dispositions may differ markedly between different behaviors.

Considering the links recently postulated between anorexia and autism as well as anorexia and OCD, these results may one day have an effect on our understanding of eating disorders.