Feature

Public misunderstanding of mental health disorders is nothing new. But for eating disorders in particular, misinformation abounds.

"You still read more about anorexia in the celebrity section of publications than in health sections," says Nancy Zucker, PhD, a professor of psychology and neuroscience at Duke University. "The emphasis is on it being a culturally guided phenomenon."

Even medical definitions of eating disorders have often focused on external factors, including cultural pressures, parents' attitudes toward weight and diet, and stressful or traumatic events that might trigger disordered eating habits.

While the environment certainly plays a part in shaping the behaviors, evidence is mounting that eating disorders begin in the brain.

"Lots of people diet or want to lose weight, but relatively few of them end up with anorexia nervosa or bulimia nervosa," says Walter Kaye, MD, director of the Eating Disorders Treatment and Research Program at the University of California, San Diego (UCSD) School of Medicine.

In fact, fewer than 1 percent of women develop anorexia, the more severe of those two diseases. "Culture plays some role — but maybe less so than we thought in the past," Kaye says.

Now, researchers including Kaye are beginning to sort out the brain regions and neural circuits that underlie the illnesses. For the millions of Americans who suffer from anorexia and bulimia, it's a welcome step toward better interventions for the notoriously hard-to-treat illnesses.

"People die from these disorders," Kaye says. "It's critical that we understand the contributing factors and develop new treatment approaches."

Circuits gone awry

Broadly speaking, eating disorders are any illnesses that cause serious disturbances to one's diet. These disorders include the relatively well-known anorexia, characterized by extreme food restriction and emaciation, and bulimia, marked by episodes of binge eating followed by purging, fasting or excessive exercise. At the opposite end of the spectrum from anorexia is binge-eating disorder, in which people experience insatiable cravings that cause them to eat large amounts of food beyond mere "overeating." Still other eating disorders fall into a catchall category known as "eating disorders not otherwise specified."

What all of these disorders share is a dangerously maladaptive approach to food.

Unsurprisingly, binge-eating disorder is often associated with obesity. People with anorexia and bulimia, on the other hand, fear gaining weight. Anorexia and bulimia often arise during the teen or early adult years, and are more common among women than men. According to a study by James Hudson, MD, ScD, and colleagues, 0.9 percent of women and 0.3 percent of U.S. men develop anorexia during their lifetime, while 1.5 percent of women and 0.5 percent of men develop bulimia (Biological Psychology, 2007).

Untreated, bulimia can lead to serious illnesses including gastrointestinal problems, electrolyte imbalance and cardiovascular disease. Anorexia can cause muscle wasting, heart and brain damage, and multiorgan failure. Indeed, anorexia has been reported to have one of the highest mortality rates of any psychiatric disorder.

"There are many disorders that are maladaptive, but in anorexia, individuals are basically starving themselves to death," Zucker says. "You don't have to be a scientist to step back and say there's something horribly wrong here."

While anorexia and bulimia both have distinct features, the disorders appear to share some biological underpinnings. Both are highly heritable, for example. But while one family member might develop anorexia, another will experience bulimia. And it's not uncommon for someone with one of the disorders to later develop the other. "That points to some common vulnerability — possibly neurological vulnerabilities," Zucker says.

People with anorexia and bulimia also tend to have relatively similar temperaments.

"When they're children, before the onset of an eating disorder, these tend to be kids [who] are anxious, obsessive, perfectionistic and achievement-oriented," Kaye says.

Yet eating disorders are more complicated than a perfectionist temperament gone awry. A faulty reward-processing system seems to be an important feature of the diseases. Learning from rewards is an ancient ability across the animal kingdom, and the process is particularly potent in guiding eating behaviors. When we eat a bite of chocolate cake, we're rewarded with the pleasure of its taste, and want to take another.

That basic process breaks down in anorexia, Kaye says. "There's an altered balance in people with anorexia where they have difficulty coding reward, and they're oversensitive to punishment."

In one demonstration of this breakdown, Kaye and colleagues scanned the brains of healthy women and women with anorexia as they played a monetary betting game. In women with anorexia, brain circuits involved in reward processing were less active when they won, but more active when they lost (Psychiatry Research: Neuroimaging, 2013).

An important piece of the altered reward system seems to be dopamine, the neurotransmitter that motivates us to cut a second helping of that chocolate cake. Dopamine activity is altered in both bulimia and anorexia — but in opposite ways, according to research by Guido Frank, MD, a professor of psychiatry at the University of Colorado Anschutz Medical Campus.

Women with bulimia have a weaker-than-normal response in brain regions that are part of the dopamine-related reward circuitry, while the reward circuits in women with anorexia are overly sensitive to food-related stimuli, as Frank described in a recent review (CNS Spectrums, 2015).

For most people, eating is an enjoyable activity. People with anorexia, though, often report that sitting down to a meal makes them feel worried — and there appears to be a biological reason for that reaction. Kaye and colleagues have found that in people with anorexia, the release of dopamine in the dorsal striatum triggers anxiety rather than pleasure (International Journal of Eating Disorders, 2012).

Body signals

As scientists delve into the faulty reward system, they've identified several brain regions that are possible perpetrators. One is the orbitofrontal cortex, which is involved in signaling us when to stop eating. Research has found that people with anorexia and bulimia have structural and functional differences in this area, Frank says.

Women with anorexia also appear to have more activity in the dorsal striatum, the brain area linked to habitual behavior, according to New York University psychologist Karin Foerde, PhD, and colleagues who scanned the brains of anorexic and healthy women as they decided what to eat. (Because anorexia is much less common in men, most research focuses on women.)

Traditionally, people with anorexia have often been thought of as having formidable willpower, allowing them to avoid food even when they're starving. Foerde's study suggests maladaptive eating behaviors may have more to do with habit than with willpower, the authors say (Nature Neuroscience, 2015).

The brain region known as the right insula also seems to be altered in people with anorexia. That bit of brain helps to process taste sensations, but it's also involved in interoception, the ability to sense one's own bodily signals.

Those skewed body signals are the subjects of Zucker's research at Duke. Most people only notice their bodies' clicks and rumbles when something's amiss, she says — when their stomachs rumble with hunger or their hearts skip a beat. But according to a concept known as visceral hypersensitivity, people with anorexia might pick up on bodily "noise" that the rest of us tune out.

"The theory is that they are hypersensitive to changing body sensations," Zucker says. "The input from their physiology is constantly interfering with their ability to focus."

Extreme food restriction might be a coping response to that hypersensitivity, Zucker believes. In response to starvation, the body slows down. Heart rate declines, menstrual cycles stop. "The whole body becomes muted," Zucker says.

Recently, she tested this idea as part of a team led by W. Kyle Simmons, PhD, at the Laureat Institute for Brain Research. The scientists scanned the brains of healthy women and women who had been treated for anorexia as they focused on sensations in their hearts, stomachs or bladders. They found abnormal insula activity in the women with anorexia. Interestingly, a particular subregion of the insula also showed increased activity when the women with anorexia were asked to think about situations that worried them. That finding suggests that altered interoception might contribute to their anxious temperament, Zucker says (Neuropsychopharmacology, 2016).

Traits and scars

While researchers are beginning to see patterns of brain abnormalities in eating disorders, the literature has been inconsistent, Frank says. Being severely malnourished can cause changes to the brain — many of which return to normal after a person begins eating again. Study results can vary dramatically depending on whether participants are actively restricting food, undergoing treatment or have recovered to a normal weight. For that reason, Frank favors studying women in highly controlled treatment programs so that he knows exactly how long, and how much, they have been eating.

Still, it can be difficult to know whether certain brain differences are the cause or the consequence of an eating disorder — in neurobiology terms, a "trait" or a "scar." Most likely, says Frank, some pre-existing features of the brain put a person at risk for developing an eating disorder, while other changes develop in response to one's eating habits.

Yet neurobiology can inform treatments even before it answers the question of trait-versus-scar. "If we can go in and directly and precisely intervene on a circuit that seems to be associated with illness severity, the chicken-or-the-egg question doesn't have to forestall intervening immediately," she says.

And better interventions are sorely needed. Approximately half of people with anorexia have the illness for five years or more, yet there is no FDA-approved medication nor a go-to psychotherapeutic approach proven to reverse the symptoms.

"Treatments for eating disorders are not very effective," says Christina Wierenga, PhD, a clinical neuropsychologist and associate professor of psychiatry at UCSD who works closely with Kaye. "Relapse rates are high, and that's because treatments have not been guided by an understanding of the etiology of the disorder."

Wierenga and other researchers are optimistic that neuroscience will point the way to new medications and therapeutic tools. She and Kaye have already begun testing new treatment programs that stem from neurobiology. Presenting brain-based findings can be helpful for motivating patients in recovery, Wierenga says. "One thing that makes these patients very difficult to treat is that they often lack an awareness of the severity of the disorder, and many times they lack a motivation to change," she says.

In light of the findings implicating defective reward circuits in eating disorders, Kaye and Wierenga are developing a treatment model that emphasizes negative consequences over rewards. Those consequences aren't intended to punish patients, Wierenga says, but rather to help guide patients toward positive behavior. A patient who refuses to drink her nutritional supplement might be moved into a more controlled level of inpatient care, for instance.

"Sometimes [the negative consequences we use are] as basic as not being allowed to wear makeup or your favorite pair of jeans," Wierenga says. "Those are privileges that you have to earn back."

Emphasizing the neurobiology of the disorders also reduces stigma, Zucker says, and helps parents better understand how to support their children during treatment.

"Eating disorders seem very behavioral. Sometimes it even seems oppositional when a child refuses to eat," she says. "Showing there are brain circuits that are not functioning effectively gives parents some pause, and helps them understand their child's illness."

There's a lot left to learn about the neurobiology of eating disorders, including whether the neurobiological risk factors are similar across racial and ethnic groups, and how those physical factors might interact with cultural messages about weight and body image. In the meantime, using neuroscience insights to motivate and educate patients and their families is a great place to start in treating eating disorders, Zucker says. Hopefully, that's just the beginning. She and her colleagues in the field are beginning to develop potential new interventions, ranging from deep brain stimulation to cognitive training exercises, that could reformat a faulty brain circuit.

Further reading

  • Foerde, K., Steinglass, J. E., Shohamy, D., & Walsh, B. T. (2015). Neural mechanisms supporting maladaptive food choices in anorexia nervosa. Nature Neuroscience, 18, 1571–1573.
  • Frank, G. K. W. (2015). Advances from neuroimaging studies in eating disorders. CNS Spectrums, 20, 391–400. doi:10.1017/S1092852915000012
  • Kaye, W. H., Wierenga, C. E., Bailer, U. F., Simmons, A. N., & Bischoff-Grethe, A. (2013). Nothing tastes as good as skinny feels: The neurobiology of anorexia nervosa. Trends in Neuroscience, 36(2), 110–120. doi:10.1016/j.tins.2013.01.003
  • Kaye, W. H., Wierenga, C. E., Knatz, S., Liang, J., Boutelle, K., Hill, L., & Eisler, I. (2014). Temperament-based treatment for anorexia nervosa. European Eating Disorders Review. doi: 10.1002/erv.2330