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