Lecture 17; November 12, 2013

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Eating disorders

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Eating disorders
In theory, eating should be a simple process designed
to maintain homeostasis of energy and nutrient levels.
As we learned in the last lecture, the homeostatic
component of feeding is just one part of the picture.
Eating, as it turns out, is regulated by numerous higherlevel brain processes as well.

Given that it is regulated by higher-level brain

processes, there is plenty of room for the development
of disordered patterns of feeding.
This phenomenon reaches its peak in humans, among
whom feeding behavior is the most complex.
The eating disorders exist at a very fascinating
intersection of biology and culture; perhaps more so
than any other disorder discussed in this class.
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Cultural issues
The eating disorders are very tied to culture, and
understanding this is critical in appreciating their complexity.
It is impossible to become obese or develop a binge eating
disorder if one lives in a poor country where food is scarce.
Similarly, it is rare to see individuals voluntarily self-restricting
their food intake if they live in places where food is expensive.
This is probably not due to genetic differences.
A study in the late 80s looked at Egyptian women going to
university either in Egypt or London. There were no cases of
eating disorders among women in Cairo, but 12% of Egyptian
women in England had developed an eating disorder (Nasser,
1988).

The rate of eating disorders seems to be increasing

worldwide, as other nations begin importing Western culture
and beauty ideals.
While the role of culture cannot be denied, eating disorders
(particularly anorexia nervosa) are so disruptive that there
must be a large neurobiological component
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Bulimia nervosa
Though rarely discussed in the open, bulimia nervosa is one
of the most common disorders found on university
campuses.
The word bulimia comes from the Ancient Greek words bous
ox and lmos hunger. It implies a ravenous, ox-like hunger
(caused by nervous mechanisms).

The hallmarks of bulimia include:

Eating a larger amount of food than most people would typically
consume under similar circumstances (binging).
Attempting to compensate for excess food intake either through
purging or exercise.

Bulimia is categorized into purging and nonpurging

subtypes.

In the purging subtype, individuals attempt to rid their digestive

systems of excess food either by vomiting, or though laxatives
and diuretics.
In the nonpurging subtype, individuals attempt to compensate
for excess food by exercising, or by fasting.

The nonpurging subtype is quite rare, accounting for only 6-8% of patients.

Most patients with bulimia nervosa are of a normal weight.

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Bulimia nervosa purging methods

Self-induced vomiting is the most common means of
purging following a binge.
This is initially done for the sake of relief from the physical
discomfort of having over-eaten, and to guard against
weight gain.
As the disorder progresses, vomiting may become a goal
in itself.
Vomiting reduces around 50% of the calories consumed,
less if there is a delay between eating and vomiting.

The misuse of laxatives and diuretics is also quite

common, though very misguided.

Diuretics simply rid the body of water.

Laxatives do not substantially impact calorie absorption,
because by the time food reaches the large intestine, most
of the nutrients have already been absorbed.

Individuals with bulimia may also seek prescription

thyroid hormones in an attempt to artificially raise their
metabolism.
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Patients with a history of self-induced

vomiting often show Russells Sign:
characteristic callouses on the knuckles
caused by repeated scraping against
the teeth.

Bulimia nervosa DSM5

The behaviors associated with

bulimia nervosa are ego-dystonic.
This means that they are seen as
invasive and pathological, even by
the patient.

For this reason, patients with bulimia
tend to hide their symptoms.

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Anorexia Nervosa
Anorexia nervosa (AN) is less common than
bulimia, but quite a bit more dangerous.

The word anorexia comes from Greek, an

without, orexis appetite. On its own, the word
anorexia simply means a lack of appetite (which is
why leptin is called an anorectic hormone). The
word nervosa implies that it is caused by a nervous
disorder.

The core feature of AN is dramatic, dangerous

levels of weight loss that are not explainable by a
particular medical condition.
Individuals with AN also show an intense fear of
obesity, and a relentless pursuit of thinness.

This is accompanied by distortions in body image.

Anorexics seem to see a different version of
themselves in the mirror than the rest of society.

The disorder most commonly begins in

adolescence.
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Brazilian model Ana Caroline Reston

suffered from AN, and died in 2006
weighing 88lbs.

Prevalence and features of AN

The prevalence of AN is could be as low as
0.5%, which makes it less common than
bulimia nervosa.
It is apparently much less common in men a
10:1 female-to-male ratio is the figure usually
given.

Interestingly, anorexics deny themselves not

only food, but also other pleasures in life. They
show decreased rates of drug and alcohol
abuse.
This condition is called asceticism, from a Greek
word meaning monk or hermit.

Anorexics show unusual alterations in feeding

behavior. They chose odd food combinations
(cabbage and ketchup, for example), and eat in
a highly ritualized manner.
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Anorexia nervosa
Individuals with AN may fixate on one or another
specific body part (insisting, for example that their
abdomen buttucks or thighs are too fat).
Self-esteem in individuals with AN is closely tied to
their body weight. They perceive weight loss as an
extraordinary feat of self-discipline, and weight gain
as an unacceptable failure.
For this reason, they tend to habitually weigh
themselves and inspect various parts of their body in
mirrors.

Anorexics may acknowledge being thin, but usually

do not acknowledge the associated health
problems.
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In later stages of AN, the

individual becomes emaciated
and frail, yet continues to insist
that they need to lose weight.

Other consequences of starvation

Aside from starvation itself, AN is associated with
several other clinical markers:
Dry skin, brittle hair or nails, sensitivity to cold
temperatures, and lanugo the growth of downy hair
on the limbs and cheeks.
Prolonged starvation also leads to wasting of the
muscle and bone, eventually resulting in an extremely
frail physique.

Cessation of the menstrual cycle (amenorrhea) is

common among post-pubertal anorexic women.
This occurs due an interesting interaction between
leptin signaling and the reproductive system.
Leptin is a signal of adiposity, and hypothalamic
regions involved in reproduction use it as a measure of
how ready a woman is to be pregnant.
It is not safe to be pregnant without a certain amount
of fat stored up (since the nutritional demands of
pregnancy and lactation can be extreme). If body fat
and leptin levels fall below a certain threshold, the
menstrual cycle is stopped.
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Individuals with AN often develop

lanugo - downy baby hair on the
face and body.

Anorexia nervosa DSM5

The behaviors associated with
anorexia nervosa are ego-syntonic.
This means that they are consistent
with the individuals self image.

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Treatment of AN
Because AN is usually ego-syntonic, it is quite dicult to
get patients to accept treatment.
The most important goal in treating AN is restoring the
patients body weight to a healthy level (at least within the
low-normal range).

Restoring weight is probably the easiest part of the treatment

if patients can be made to eat (and fully digest) food, they will
invariably gain weight.

Weight regain, however, is not a good predictor of treatment

success. Relapse is extremely common.
Psychological treatments involve addressing dysfunctional
attitudes about body shape, as well as interpersonal
disruptions.
Only about 30% of patients make a full recovery in their
lifetimes. Roughly 10% eventually die of starvation related
complications or suicide.
The mortality rate of AN is the highest of any mental illness.

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Neural basis of body image distortions

Distorted body image is an extremely
common symptom of eating disorders in
general individuals counterfactually insist that
they are fat.
This manifests itself in some interesting
endophenotypes in anorexic patients.

In one experiment, patients with AN and

healthy controls were asked to estimate
whether they could fit through various sized
doors without turning sideways.
Healthy controls invariably rate doors 1.15 times
wider than their shoulder widths as passable.
Patients with AN, consistently overestimated
their size. They believed they required doors
1.33 times wider than their shoulder width.
They only applied this overestimation to
themselves they could accurately size up other
people.
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Feeding circuitry and AN

Circulating ghrelin levels are very high in
patients with AN. This is an expected
consequence of their perpetual state of
starvation, but individuals with AN appear
to be ghrelin-resistant.
Injections of ghrelin into patients with AN do
not produce hunger or any of the expected
hormonal effects.
This could be either a cause or consequence
of the disorder.

Unsurprisingly, patients with AN have very

low levels of leptin.
For reasons that are not well understood, this
also does not trigger a feeding response in
anorexic patients.
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Neural basis of body image distortions

Certain regions of the parietal lobe seem to
be involved in body image.
Patients with damage to this region can
develop a number of unusual conditions
including: denial of paralysis, misattribution of a
paralyzed limb to another person
(somatoparaphrenia), and unilateral neglect.
Dysfunction in the right parietal lobe has been
associated with hatred of the left side of the
body, and a desire to amputate healthy limbs
on that side (really!)

Brain areas activated by viewing

self pictures in healthy individuals.

Seeing pictures of ones own body causes

increased activity in the parietal lobe.
Specifically the precuneus and inferior parietal
lobule.

This eect is missing in individuals with AN.

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Brain areas activated by viewing

self pictures in anorexic patients.

Neural basis of taste

Anorexics apparently do not receive a great
deal of enjoyment from palatable food.
This appears to be due, in part, to altered
activity in the insula, a region of the frontal
lobe hidden behind the temporal lobe that is
involved in gustatory (taste) perception.
Healthy people show activation of the insula
when consuming an enjoyable sugar water
drink.
This spike in neural activity, as well as
subjective enjoyment of the drink, is attenuated
in women with AN.

Interestingly, the neural response to tasty food

among anorexics is reminiscent of what is
seen in healthy people who are not hungry at
the moment.
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Frontal lobe!
Insula!

Neural basis of altered reward processing

Anhedonia and asceticism are well-known traits in AN. It
seems that individuals with this disorder do not react
appropriately either to reward or disappointment.
Anorexics may produce less dopamine than healthy
people, and this persists even after recovery.

This is evidenced by reduced dopamine metabolites in CSF

samples from anorexics.

Healthy people, but not recovered anorexics showed

increased activity in the anterior ventral striatum when
they won a guessing game.

Caudate/striatal activation in
healthy women.

This region is involved in processing the real or perceived

value of a reward, suggesting that anorexics may be unable
to identify the rewarding value of stimuli.

In contrast, women recovered from AN had increased

activation in the caudate nucleus, a region involved in
planning when there is an uncertain connection between
stimulus and reward.

This suggests that anorexics may utilize strategic responses

as opposed to hedonic ones.

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Caudate/striatal activation in
recovered anorexic women.

Developmental roots of AN
It seems reasonable to suspect that sex hormones are
involved with AN, after all the disease aects so many
more women than men.
It is quite rare for AN to develop in girls until they reach
puberty and begin their menstrual cycles.
Before puberty, estrogen and progesterone levels are
very low.

Despite the obvious correlation between the pubertal

spike in estrogen secretion and the onset of AN, very
little is known about whether this relationship actually
causes AN.
Estrogen modulates serotonin and HPA axis function,
and is an anorectic hormone in its own right, but it is not
known if this has anything to do with AN.

The onset of puberty is a time of massive social

change as well. These influences cannot be ignored.
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Estradiol is the main hormone

in the estrogen family.

The uterine hormonal environment

Development of the brain and body during
prenatal life is very sensitive to the hormonal
environment.
Studying prenatal hormone levels is quite
dicult in humans, but opposite sex twins are
a reasonable proxy.
Females with a male twin are exposed to more
testosterone in-utero.

The ratio of the lengths of the 2nd and 4th

fingers (the digit ratio) is a reliable indicator of
prenatal testosterone exposure.
This ratio is higher (~0.965) in females than in
males (~0.947).
The digit ratio in females can be masculinized
by exposure to testosterone, either through a
male twin, or some kind of hormonal disorder.
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You can measure your own digit ratio.

Measure the index and ring fingers from
the basal crease to the tip, then divide
the index finger by the ring finger (2D/4D).

Developmental roots of AN
Perhaps something happens during
development that makes certain women
more likely to develop AN in adulthood
A recent study showed that females with a
male twin were less at risk of developing
an eating disorder than females with a
female twin.
The authors postulated that testosterone is
responsible for the reduced incidence of
eating disorders among males, and that
early-life exposure to testosterone is
protective against eating disorders in
females.

Another study showed that a masculinized

digit ratio was protective against eating
disorders in females.
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Females with a female twin (dashed line)

have the highest rates of disordered
eating. The rate is lower among females
with a male twin, and of course lowest
among males in general.