The Neurobiological Underpinnings of Anorexia Nervosa

        The gaunt frame, the lifeless skin and hair, the fidgeting with what little food there is on the plate, these

trademark symptoms alert most people to the fact that someone they know might have anorexia. However,

no one seems to know exactly what causes anorexia or how to treat it. This has been the subject of much

scientific debate recently, and there is evidence that neurobiology plays a part in this disease.

        Anorexia nervosa (AN) is one of the main types of eating disorders. It is a chronic psychological

disorder that most commonly affects women and often begins during adolescence. According to the DSM-

IV the following are the criteria for a diagnosis of AN:         

        “1. Refusal to maintain a body weight at or above a minimally normal weight for age and height

         2. Intense fear of gaining weight or becoming fat, even though underweight

         3. Disturbance in the way in which one’s body weight or shape is experienced,undue influence of body

         weight or shape on self-evaluation, or denial of the seriousness of the current low body weight

         4. In postmenarcheal females, amenorrhea, i.e. the absence of at least three consecutivemenstrual

         cycles”  (Kaye).

AN can lead to starvation and other serious health problems, such as osteoporosis, kidney damage, and

heart problems. Due to the various potential health complications and the chronic nature of the disorder AN

can be fatal, with the most common causes of death being cardiac arrest, electrolyte imbalances, and suicide

AN has a mortality rate of about six percent, the highest mortality rate of all the psychiatric disorders 

(Stoppler).           

        Due to the very high mortality rate of AN, there is much interest in the development of programs to

prevent and treat AN. However, the cause of AN is unknown, making prevention and treatment difficult and

mostly ineffective. The most common theory is that society’s views on thinness and beauty, and the intense

pressure on females to conform to society’s standards are the primary causes of AN. However, this theory

raises some unanswered questions. For example, in developed countries the majority of females, if not all

females, are constantly exposed to societal pressures to be thin. However, only about 0.3% to 0.7% of

females in the United States have AN  (Kaye). If societal pressures were the only factor involved then a

much greater percentage of females would be affected. In addition, there is evidence from various historical

sources that AN existed several centuries ago, when society tended to favor heavier individuals because

weight was a sign of wealth  (Kaye). Obviously, several centuries ago there would not have been as great a

pressure to be thin as there is today, so society can not be the only cause of AN.

        There is compelling evidence that AN has biological and genetic components to it. Individuals who have

an anorexic parent are more likely to suffer from AN themselves. In addition, individuals with AN are more

likely to suffer from anxiety disorders, affective disorders, and other psychiatric disorders such as OCD than

the general population, even before they exhibit any signs of AN  (Kaye). Studies have shown that these

disorders persist in long-term recovered anorexics, demonstrating that these disorders are not brought on by

the AN, but rather are pre-existing conditions  (Kaye). Also, anorexics tend to have family histories that

include affective disorders, anxiety disorders, personality disorders, and OCD (Stoppler). Therefore, anxiety

disorders, OCD, and other psychiatric disorders may make people vulnerable to developing AN  (Kaye).

Finally, the onset of AN tends to be during adolescence. During adolescence significant biological changes

related to puberty occur which may increase one’s risk for AN. These changes are different for males and

females, which may contribute to the large difference in incidence of AN between the two sexes. “The

substantial hereditability… the developmentally significant age-of-onset distribution” (Kaye) and the

relationship between AN and other psychiatric disorders demonstrates that there are biological factors

involved in the development of AN.

        The discovery of the particular neurobiological underpinnings of AN will hopefully lead to affective

treatment options. Recent research has uncovered several possible neurobiological causes. One possibility is

that dysfunction of the hypothalamus, which regulates metabolic functions, causes AN. However, people

with AN experience “over control” in most aspects of their life, not just eating, so it is likely that there is

dysfunction in multiple systems of the nervous system, not just the hypothalamus  (Kaye). One theory is that

imbalances in certain neurotransmitters may be responsible for the dysfunction in these systems  (Stoppler).

The two main neurotransmitters of interest in current research are serotonin (5-HT) and dopamine (DA).

Recent studies reveal that both ill and recovered anorexics have reduced levels of DA in their cerebral-spinal

fluid  (Kaye). DA is active in the limbic and executive systems. Thus, “DA dysfunction might contribute to

altered reward and affect, decision-making, and executive control in AN”  (Kaye).

        One aspect of 5-HT systems implicated in AN are the 5-HT1A and 5-HT2A receptors. When 5-HT is

released into the synapse by the presynaptic neuron some of it binds to the presynaptic 5-HT1A receptor,

which then inhibits the release of 5-HT. Meanwhile, 5-HT also binds to the postsynaptic 5-HT2A receptor,

which affects the level of depolarization in the postsynaptic neuron  (Kaye). In a study of recovered

anorexics it was discovered that they have an increase in 5-HT1A activity compared to 5-HT2A activity, and

this could be partly responsible for the behavioral “over control” characteristic of AN  (Kaye).

        In addition to the roles of 5-HT receptors, actual levels of 5-HT may be involved in the development of

AN. As noted earlier, anorexics often suffer from anxiety disorders. It is believed, although not proven, that

hyperactivity of the 5-HT systems causes anxiety. The amino acid tryptophan (TRP) is the precursor of 5-

HT, so eating can lead to an increase in 5-HT levels in the brain. Restricted diets, such as the ones followed

by anorexics, reduce the levels of TRP in blood plasma, which reduces the levels of TRP available to the

brain. This leads to a decrease in brain 5-HT levels, thereby reducing the anxiety caused by the hyperactivity

of 5-HT  (Kaye). This may explain why anorexics claim that not eating or greatly restricting their diet has a

calming effect on them and gives them a sense of control.It is clear that there are biological factors that put an

individual at risk for developing AN.

        Correlations between family histories of certain psychological disorders and the development of AN

demonstrate that there are genetic factors involved. Also, studies reveal relationships between DA levels, 5-

HT levels, and certain 5-HT receptors and AN. These relationships may help explain the altered reward and

decision making systems in anorexics, as well as their characteristic behavioral over control, and the fact that

not eating relieves their anxiety. However, the roles of DA and 5-HT in AN have not been fully discovered

and much more research is still needed before any real conclusions can be made. Hopefully these preliminary

results will gain the topic more interest and funding, so that more research will be done. Perhaps future

research will yield effective preventative techniques and/or treatments, and AN will no longer be the world’s

deadliest psychiatric disorder.

Works Cited

Kaye, Walter. “Neurobiology of Anorexia and Bulimia Nervosa”. Physiology and Behavior 22 April 2008:

        121 to 135. Science Direct. Elsevier B. B. Bryn Mawr College, Bryn Mawr PA. 21 March 2009  

        http://trixie.brynmawr.edu:9003/brynm?sid=Entrez:PubMed&id=pmid:18164737.

Stoppler, Melissa Conrad. “Anorexia Nervosa”. MedicineNet.com. MedicineNet, Inc. 21 March 2009 

        http://www.medicinenet.com/anorexia_nervosa/article.htm.