Neurological Consequences and Predisposition of
Anorexia Nervosa
Erica Metheny
Biobehavioral Health 468
Dr. Engeland
Spring 2015
April 28, 2015
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Up to 24 million people of all ages and genders suffer from an eating disorder
(anorexia, bulimia, and binge eating disorder) in the US (National Association of Anorexia
Nevosa and Associated Disorders, 2015). Furthermore, anorexia nervosa has the highest
mortality rate of all mental health disorders (National Association of Anorexia Nervosa and
Associated Disorders, 2015). Since there is such a high prevalence of these diseases in our
country it is cruicial to know the neurological side effects. Researchers have not found any
definitive biomarkers for a predisposition to eating disorders, but there is hope to learn
more on this. Not a lot of studies have focused on this area, so there is still a lot of possible
exploration on this topic. Multiple research studies using brain-imaging techniques show
that people with anorexia nervosa (AN) or bulimia nervosa (BN) have decreased brain
volume, but it normalizes during the recovery process. The volume loss typically is not
localized to one area of the brain, but there is cognitive impairment does indicate damage
to particular structures. Damage is most always in the basal ganglia structures and
prefrontal cortex, specifically the frontostriatal pathways. Studies have shown that people
with anorexia nervosa have impaired functioning in certain tasks most often relating to the
frontal lobe, but the impairments subside with recovery. Most studies were designed to
compare the brain activity and cognitive abilities of healthy controls to currently ill
participants and patients that were in different stages of recovery. The most cognitive
impairments were seen in patients still suffering from an anorexia nervosa and can be
attributed to starvation. The most common impairments included working memory,
decision-making, cognitive behavioral flexibility, and sequential learning (Seitz, J., &
Buhren, K., 2014). After patients had been in recovery for 1 year there was typically no
significant difference in cognitive abilities between them and the healthy controls (Firk, C.,
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& Mainz, V., 2015). Overall most experts agree that there is anatomical and functional
damage to the brain that occurs during eating disorders, but resolves once the patient is
recovered. This paper will look closely at the causes of these neurological changes. Recent
research has looked into the possible neurological predisposition to eating disorders,
specifically anorexia nervosa. The little research that has been done focuses on
predisposition due to faulty learning patterns and opioid peptides. I hypothesize that
people with anorexia nervosa have altered brain anatomy and functioning that causes
cognitive impairments due to the combination of starvation and mental distress their
bodies are experiencing and have a neurological predisposition to the disease.
Experts agree that individuals with anorexia nervosa experience loss of brain
volume. A recent meta-analysis compared MRI’s of currently ill AN patients and recovered
patients in order to determine the neuroanatomical effects of anorexia and how long they
last. The groups being compared in the study included currently ill AN patients, short-term
weight recovery (2-5 months of recovery), long term recovery (2-8 years of healthy eating
behaviors), and healthy controls. Meta-analysis concluded that currently ill AN patients
showed a 5.6% reduction in gray matter, 3.7% reduction in white matter, and 12.9%
increase in cerebral spinal fluid compared to healthy controls (Seitz et al., 2014). After
short-term recovery, gray matter loss was restored by 43%, white matter was restored
completely, and the increase in cerebral spinal fluid dropped 50% (Seitz et al, 2014). Longterm recovery patients showed slight, but insignificant reduction of gray matter and
increase in CSF (Seitz et al., 2014). These results indicate that although there is a loss of
global brain volume associated with anorexia nervosa it is resolved after long-term
treatment. A case study done on a severely anorexic patient gives similar results. The
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patient was a 20-year-old male that was admitted to a hospital weighing only 49% of his
ideal body weight (Shapiro, Davis, & Nguyen, 2014). After various other health problems
were attended to the patient underwent a head CT to assess structural damage. The CT
showed cortical atrophy seen by very prominent cortical sulci and cerebella folia that were
abnormal for his age (Shapiro et al., 2014). After eight months of treatment for
malnutrition and therapy for his eating disorder the patient had another CT that showed no
abnormalities. The results of both of these studies supports the notion that anorexia
nervosa does result in reversible cortical atrophy.
It is clear that eating disorders result in structural damage to the brain so it is
important to examine if there are any functional and/or cognitive impairments that
coincide with that damage. Researchers compared attentional control and working
memory of anorexic (AN) and bulimic (BN) patients through performance on n-Back tasks
and examined brain-activation patterns. n-Back tasks consists of participants responding
to a stimulus over multiple trials. The “n” stands for how many trials back the stimulus is
from. For example, if it is a 2-back test the participant is responding to a stimulus from two
trials back. Results indicate that the AN group performed significantly better than the BN
group across most levels of difficulty (Israel et al., 2015). Brain activation patterns only
differed in one of the n-back conditions. The AN group showed more activation than the
BN group in the dorsolateral prefrontal cortex, which is part of the frontostriatal circuit
(Israel et al., 2015). The neuroimaging results also seemed to go along with clinical
features of each disease. During rest the anorexia nervosa group showed a higher
activation of impulse control, which is a staple of the disease (Israel et al., 2015). This
study lacked a healthy comparison group so although the anorexia nervosa group
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performed significantly better than the bulimia nervosa group, it is unknown how they
would do versus healthy controls. Because this study was done on currently ill patients it
is hard to tell whether the cognitive impairments and brain activation differences are due
to side effects of the disease (i.e. starvation) or long term damage caused by eating
disorders. A longitudinal study that assessed decision-making abilities in eating disordered
patients before and after weight restoration is beneficial to look at because it addresses
some of the limitations of this study. It compares currently ill anorexic women with
healthy controls and also assesses the AN group after weight restoration. The study uses
the Iowa Gambling Task (IGT) to analyze decision-making abilities. “This task was
developed to simulate decision-making under conditions of uncertainty, reward, and
punishment” (Bodell et al., 2014). AN patients and healthy controls completed the IGT
along with an MRI and AN patients did this while currently ill and after weight restoration
(Bodell et al., 2014). Women with anorexia performed significantly worse on the IGT
compared to the control group (Bodell et al., 2014). Even after weight restoration the AN
group did not show a significant increase in performance from baseline on the IGT (Bodell,
2014). Although the overall group performance did not increase after weight restoration
some women did show significant improvement. After baseline, some AN women were put
in the subset of “poor performers” and that group did show a significant improvement in
performance after weight restoration (Bodell et al., 2014). Brain volume was calculated for
different brain regions from the MRI. Results show that baseline left orbitofrontal cortex
volume was significantly associated with decision-making performance at baseline, but not
after baseline even though volume increased (Boddell et al., 2014). Impaired decisionmaking during acute AN is logical due to the decreased volume of the OFC, which is very
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involved in decision-making. The restored OFC volume goes along with other research that
structural damage is resolved after weight restoration, but does not explain the
impairment in decision-making seen in this study after weight restoration. A possible
explanation for these findings could be that “decision-making in AN may represent a traitlike cognitive vulnerability that may influence eating behavior and the persistence of selfstarvation” (Bodell et al., 2014).
There is clearly cognitive impairment seen in anorexia, but is it reversible like the
neurological structural damage? An experimental design study examines the role that
hunger and satiety plays in motivation and cognitive control in recovered AN patients
compared to healthy controls. This study analyzes cognitive control in decision-making by
administering a delay discounting task to patients while they are in an fMRI machine.
Delay discounting assesses the participants’ ability to suppress the desire for smaller
rewards now in order to gain larger rewards in the future (Wierenga et al., 2015). This
study incorporated metabolic state by having participants complete the task when hungry
and when satiated. The structures involved in reward salience circuitry include the ventral
striatum, dorsal caudate, and the anterior cingulate cortex (Wierenga et al., 2015). The
venterolateral prefrontal cortex and the insula are active during cognitive control circuitry
(Wierenga et al., 2015). The remitted from anorexia group (RAN) and healthy controls
showed no significant difference in choice behavior in the task suggesting no cognitive
deficits in the RAN group. However, brain activation patterns did show a significant
difference between groups. The healthy control group had increased activation in the
reward salience circuitry when hungry, but increased activation of the cognitive control
circuitry when satiated (Wierenga et al., 2015). This means that the healthy control group
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had more cognitive control when satiated than when hungry. The response for the RAN
group did not significantly change between hunger and satiety. The lack of difference in
response suggests that these brain pathways involving motivation and cognitive control
are less sensitive to metabolic state in RAN individuals compared to healthy controls
(Wierenga et al., 2015). Although there is no cognitive impairment in recovered AN
patients, there seems to be a permanent functional change in their motivational pathways
in which they are less affected by hunger.
It is very difficult to study any possible predisposition to eating disorders. Anyone
can be affected by an eating disorder and although there are certain risk factors, doctors
don’t know why one person with similar risk factors will develop an eating disorder while
another person won’t. It is difficult, but researchers are looking for answers and they have
started by examining people that currently have or have had an eating disorder to see if
there are any neurological components that may have predisposed them. One study
examined the role of implicit sequence learning in adolescents and teens with anorexia.
Implicit learning sequence is a type of learning response in which the person is unaware of
the relationship between the stimulus and response. They chose to look at implicit
learning sequence because previous models suggested that “deficits in implicit learning in
the context of AN may contribute to the development of repetitive, explicit routines to
compensate for difficulties in implicit understanding and reduce anxiety” (Firk et al., 2015).
The implicit learning comes into play in that patients with AN have an intense, yet very
unnecessary fear of excessive weight gain, which is assumed to be partially contributed to
deficits in implicit learning (Firk et al., 2015). Results of the study show that implicit
sequence learning was impaired in acute AN, but after treatment there was no cognitive
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impairment. Because the impairment resolved after treatment it suggests that it was due
to starvation instead of a predisposition (Firk et al., 2015). There are still other
explanations such as an extremely small sample size in the study and the fact that the study
was done on adolescents and teens that are still developing. This study also used fMRI to
detect brain activation patterns. Similar to previous research they found a dysfunction in
the frontostriatal circuit in patients with anorexia (Firk et al., 2015). Although the findings
of this study can’t indicate a predisposition to anorexia nervosa based on deficits in implicit
learning it is a good starting point for future research on this topic. According to a review
by Hasan and Hasan, administering an opioid antagonist to anorexic patients resulted in
weight gain meaning that opioids could possibly mediate anorexic behavior. The review
also states that a significant amount of anorexic people in one study had an atypical
endogenous opioid system present, which would biologically predispose them to anorexia
nervosa (Hasan & Hasan, 2011). There has been very little research done that focuses on
the topic of predisposition to anorexia nervosa. If future research focuses on that then
health professionals can improve the prevention of the disease.
There has been a lot of research done on the neurological and cognitive effects of
anorexia nervosa that have consistent findings. A currently ill anorexic patient has
decreased white and gray matter and increased cerebral spinal fluid compared to healthy
controls. After recovery brain volume and cerebral spinal fluid normalizes and there is no
significant permanent volume loss (Seitz et al., 2014) (Shapiro et al., 2014). Studies that
examined brain activation patterns all found some type of dysfunction in the frontostriatal
circuit. The frontostriatal circuits are neural pathways that connects the frontal lobe to
basal ganglia structures that mediate behavioral, cognitive, and motor function within the
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brain. Patients with anorexia nervosa had cognitive impairments that were associated with
the dysfunctional activation of the frontostriatal circuits. The cognitive impairments seen
throughout various studies included decision-making, working memory,
cognitive/attentional control, and reward/motivation. Studies compared patients before
and after treatment and patients post-treatment with healthy controls and found that only
currently ill anorexic patients had cognitive deficits. Cognitive impairments and activation
patterns both seem to resolve after treatment, similar to the anatomical damage. One study
showed that certain pathways involving reward and motivation were permanently altered
in women that have recovered from anorexia only when metabolic state was involved.
That suggests that although most other brain functions and patterns are normalized after
treatment, they have trained their body to not respond to hunger and that it won’t change.
Unfortunately there are no definitive findings on any predispositions to anorexia nervosa,
but researchers have looked into implicit learning deficits as a possible predisposition to
anorexic behavior and opioid peptides as a biological predisposition. Overall there are
definite neurological effects of anorexia nervosa that involve structural issues and
functionality issues that result in cognitive defects and these issues resolve after treatment,
excluding motivation/reward during hunger.
Anorexia nervosa is a very serious mental illness that causes a lot of health
problems. The side effects of anorexia have been studied in depth, but what happens
before the disease presents has not been examined. It is important to know why two
people can have similar risk factors and only one of them develops anorexia nervosa. More
research needs to be done to determine if there is any type of predisposition to AN. If more
is known about a predisposition to anorexia then there can be a more specific target
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audience to increase prevention. It could also affect treatment options and make them
more effective. Studies could analyze if treatment outcome differed in patients with a
predisposition versus those that don’t have one. If different types of therapy is more
effective for each group then it will enhance treatment outcomes.
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