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Understanding Neurobiology

Why Is Understanding The Etiology Of Anorexia Nervosa (AN) And Bulimia Nervosa (BN) Important?

Until we understand what actually causes a disorder, treatments tend to be aimed at reducing symptoms. This can be a reasonable strategy, provided that we test to ensure that such symptom reduction treatments actually work, and change the course of the illness. Once the cause of an illness is understood, then specific therapies can be designed to prevent or cure the disease.

For example, leukemia is a disorder where the body makes too many white blood cells. Gleevec is a therapy that cures a type of leukemia (Chronic Myeloid Leukemia). In this illness, a genetic defect creates a signal that tells the body to make more and more abnormal white blood cells. Past treatments, aimed at reducing symptoms, attempted to cure this leukemia by poisoning the white blood cells and had varied degrees of success, however, treatment was usually un satisfactory. Gleevec works by interfering with the abnormal protein and blocking it from telling the body to keep making more and more abnormal white blood cells. This treatment, which is based on an understanding of the cause of this type of leukemia, “cures” this illness.

Do We Understand The Etiology Of Anorexia Nervosa And Bulimia Nervosa?

Many individuals in our culture are concerned with their weight and diet. Yet less than half of 1% of all women develop anorexia nervosa, indicating to us that societal pressure alone is not enough to cause someone to develop this disease. Recent research has found that genes seem to play a substantial role in determining who is vulnerable to developing an eating disorder. Genes regulate the chemicals that make up the pathways in the brain that regulate behavior. The past decade has brought about substantial progress in understanding how brain chemistry regulates behavior. Personality traits such as perfectionism, anxiety, and obsessionality, are often present in childhood before the eating disorder develops. Such traits may be caused by how certain genes change brain chemistry. In turn, these behaviors may contribute to the risk of developing this disorder. Societal pressure isn’t irrelevant; it may be the environmental trigger that releases a person’s genetic risk.

We have been frustrated in the past because the inaccessibility of the brain has made it difficult to understand how the brain modulates behavior. Now, new brain imaging technology allows us to safely and directly study brain pathways and behavior in people. These new brain imaging technologies, which include functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), are helping to identify the brain pathways that are involved in AN and BN.

The brain is the organ that allows us to interact with the world. We have to make many judgments and decisions everyday about what is good for us and what is bad for us. Dopamine D2 Receptor BindingScience is now starting to understand how the brain makes these types of decisions. A mechanism deep in the brain, in part related to the neurotransmitter dopamine, assesses information (e.g. stimuli) in the world, and compares it to our past memories of that information. The brain then processes this information and determines whether it is rewarding or harmful information, so we can make the right decision for the situation. New brain imaging technology now allows us to measure dopamine activity in humans, and watch how brain pathways modulating this system respond to rewards or harm. We are finding dopamine pathways are overactive in people with anorexia nervosa (see image). Consequently, they process rewarding stimuli differently. In fact, the way the dopamine system is wired appears to contribute to obsessing, over worry , and over exercise, in AN. We think that the dopamine system may be over sensitive to stimuli and/or stimuli is aversive. Food is one of these stimuli, and this may explain why eating may not be rewarding. Similarly, other stimuli may not be rewarding or overwhelming, and this may explain why there is often self-denial and restraint, as a way of controlling and reducing stimuli.

Temperament

Trying to understand what symptoms may contribute to causing these disorders and what symptoms may be a consequence of the illness is very difficult. When people are ill with anorexia and bulimia nervosa, it is difficult to disentangle cause and effect. But there are strategies that can be used to better understand the contributing factors.

Obsessive Compulsive Personality Traits One strategy is to ask the question about whether there are behaviors, particularly behaviors of temperament, that occurred in childhood before the onset of an eating disorder. If there are childhood evidence of temperament, this would be strong evidence that this was a pre-existing trait that might be a susceptibility for an eating disorder. For example a studied published in the American Journal of Psychiatry in 2003 by Anderluh of the Janet Treasure’s group in London, asked people with eating disorders for recollections of what they were like as children. They studied people with anorexia and with bulimia. They found that approximately 50-70% of people with eating disorders described themselves as perfectionistic as children, and roughly about the same percent described themselves as inflexible. Somewhat more people with anorexia than with bulimia that described these traits, but the traits were reasonably high in bulimia. Approximately 80% of people with anorexia described themselves as inflexible as children, about 60% of anorexics and bulimics described themselves as inflexible as children, and about 20% of bulimics described themselves as inflexible. This has been an important study because it clearly shows that these are likely to be traits that predate the onset of eating disorders : premorbid vulnerability factors.

In another group of studies, investigators began to ask questions about the rate of anxiety disorders. We know that anxiety and obsessive disorders are very common in people with ED, as well as their relatives. But what was not clear was whether these disorders occurred before the onset of the eating disorder, or were a consequence of starvation. The first study was done in our laboratory in 1995 and we found that approximately 68% of people described themselves as having a lifetime anxiety disorder. Importantly, for these people, about 60% of the time that anxiety disorder occurred before the onset of the eating disorder. So that meant that as children, people were developing anxiety disorders roughly around the age of 8 or 10 years old, well before they developed anorexia nervosa. This was followed by some studies by Cindy Bulik in New Zealand who found almost identical findings. She found roughly about 60% of people with anorexia and bulimia had lifetime anxiety disorders, and about 54% of the time, those occurred before eating disorders. Several years later, a study by Godart in France found somewhat higher rates for anxiety disorders, in the order 70-80%, and again 62% of the time, these anxiety disorders occurred before eating disorders.

Anxiety Disorders and EDFinally, these studies were relatively small. Altogether these studies encompassed about 300 subjects. More recently, a data set supported by the Price Foundation of Europe studied the genetics of ED. We had the opportunity to investigate 672 people with anorexia and bulimia nervosa. This was published by Kaye in the American Journal of Psychiatry in 2004. And again we found roughly the same thing, 64% of the time people had a lifetime anxiety disorder, that is sometime during their lifetime they had diagnosable anxiety disorder which was either generalized anxiety or social phobia. What was particularly interesting about this new study was that we finally had a large enough sample that we could actually begin to ask questions about which anxiety disorders were really occurring. Again, we found that 61% of the time these anxiety disorders occurred before the onset of the eating disorder. We found the most common anxiety disorder in childhood was obsessive compulsive disorder (OCD). Twenty three per cent of the time, people had OCD. This is much higher than the rate of OCD seen in children, probably ten to twenty times higher than would be seen in the general population, and we also saw a 13% rate of social phobia, that is kids being excessively shy and having difficulties dealing in social situations, avoid social situations, which is probably also much higher than the general population.

So in summary, these are studies that were done on three different continents, New Zealand, Europe and the United States. Despite that, the findings are amazingly consistent from study to study. That is, roughly about 60-70% of the time people have an anxiety disorder some time in their lifetime if they have an eating disorder, and of those people, two-thirds of the time that anxiety disorder will occur before the onset of the eating disorder. That is, it will occur in childhood, the most common anxiety disorder being OCD and then social phobia. This is strong evidence suggesting that these are vulnerability factors for developing an eating disorder.