The Neurobiology of Eating Disorders
By Kate Jackson
Social Work Today
Vol. 18 No. 4 P. 14

New brain research is pointing the way toward more effective treatment for anorexia and bulimia.

We are bombarded with messages telling us we can never be thin enough. Size-one celebrities, stick-thin runway models, and glossy magazine images of the current ideal set an unattainable standard. We get the message that thin will always be in, not only from the media but also from observing peers who are equally manipulated by the media and may turn from one diet to another. Increasingly, these environmental factors are blamed for the development of eating disorders such as anorexia and bulimia. Of course they play a role, but could there be something else influencing these behaviors?

"Given that most of us are exposed to similar cultural and social influences, yet less than 1% of individuals develop anorexia or bulimia, there must be something different about those individuals who develop an eating disorder," says Christina E. Wierenga, PhD, an associate professor of psychiatry at University of California San Diego (UCSD), codirector of research for the UCSD eating disorders treatment and research program, and research psychologist for the VA San Diego Healthcare System. Research, she says, suggests that the difference is encoded in our neurobiology.

As researchers learn more about the neural circuitry that may underlie the eating disordered behaviors that can result in devastating complications and high rates of mortality, they're laying the groundwork for new ways of treating these disorders, preventing comorbidities, and potentially saving lives.

According to Henry Cheng, MD, northeast regional medical director at The Renfrew Center, "Although the findings have not been entirely consistent, there's increasing evidence of neurobiological differences in the brains of individuals struggling with eating disorders. It's known that the gut and mechanisms in the hypothalamus contribute to regulating eating behaviors and metabolism. More recent studies suggest that the corticolimbic system plays a role in eating disorders. These systems can affect eating behaviors and override feelings of hunger or fullness," he adds.

Research on human behavior, explains Walter Kaye, MD, founder and executive director of the eating disorders program at UCSD, has lagged behind that in other fields of medicine because the subject of interest has long been hidden inside the skull. Over the last 20 years, he says, new technologies have increased understanding of how the brain works. "The brain is so complicated and the techniques are still limited enough that we can begin to understand something about gross circuitry, but we don't really understand the underlying molecular biology."

Some of the most significant recent findings about the role of neurobiology in anorexia nervosa and bulimia nervosa have come from MRI studies of brain function, Wierenga says. "These studies show that neural circuits involved in the motivation to eat are altered in individuals with anorexia and bulimia, which may help explain disordered eating behaviors." Her research previously showed that women with a history of anorexia have decreased brain reward response. "Our more recent work shows this sensitivity to reward differs when one is hungry or full. For example, we found that when hungry, individuals with anorexia have an even more blunted brain response to rewards, suggesting that hunger does not motivate eating, which may explain how individuals with anorexia can avoid food even when hungry." In contrast, she explains, "women with bulimia showed increased brain responses to pleasant taste when full, suggesting that their brains fail to devalue food after a meal, which might contribute to the tendency to binge eat or eat beyond fullness.

"In addition," Wierenga continues, "genome-wide association studies and studies of rare damaging genetic variants are beginning to identify specific genetic contributions to eating disorders. Together, genetic and imaging studies provide strong support for a powerful neurobiology underlying eating disorders."

The evidence for the role of neurobiology has been uniform, though the significance is not entirely clear. "The brain circuitry and cognitive domains implicated in eating disorders have been relatively consistent across studies," Wierenga says. "Differences between studies usually result from methodological differences in study design and participant characteristics," she adds.

According to Kaye, while most researchers would agree that reward processing is altered in people with eating disorders, there's little agreement about the underlying mechanisms or exactly how this works. "There's still a lot of controversy about what 'altered reward' means," he says.

Neurobiological Underpinnings
"Eating disorders are very complex with puzzling symptoms, and there's a lot that we don't yet know," Wierenga says.

What's clear, however, is that genetics influence the neurobiology. "When you do twin studies to try to tease apart how much is environment and how much is genetics, the studies pretty consistently show that genetics play a powerful role," Kaye says. What's often found, he adds, is that children, before they develop eating disorders, tend to have these certain personality and temperament traits that run in families."

Wierenga further explains that several key premorbid childhood traits and cognitive functions as well as hormone and peptide signaling are becoming recognized as significant factors in the emergence of eating disorders. Research, she says, "supports a neurobiologically based temperament that influences the development and maintenance of eating disorders, particularly anorexia nervosa." This temperament, which often is present before the development of the disorder and may remain after recovery, is characterized by anxiety, reward insensitivity, achievement orientation, sensitivity to criticism, perfectionism, harm avoidance, and cognitive inflexibility. "Similarly, cognitive functions related to the motivation to eat and associated neural circuit activity are also implicated in eating disorders. These functions include altered reward processing and reward learning, inhibitory or self-regulatory control, interoception (i.e., experience of one's physical state), habit, and social cognition," Wierenga says.

Kaye points out that many people have these traits, but, for reasons not fully understood, not all develop eating disorders. "Although there is agreement that alterations in these functions may contribute to eating disorders," Wierenga says, "it's not clear whether an individual must have disturbances in one or more of these functions to develop an eating disorder, and it is likely that multiple functions are implicated, and in different ways, depending on the eating disorder symptoms (e.g., binge-purge episodes, food restriction)."

It may be that genetics influences neurobiology, creating a predisposition, while culture and environment trigger the development of the disorders. "Biosocial models of eating disorders acknowledge the interplay between culture, environment, and neurobiology," Wierenga adds. "Although this is a hotly debated and controversial model, it proposes that neurobiological processes make an individual susceptible to developing an eating disorder, and culture and environmental factors may trigger its onset and maintain the disorder," she says.

The role of neurobiology may extend beyond anorexia and bulimia, experts say. "There's emerging evidence that similar neurobiological factors play a role in other eating disorders, such as binge eating disorder and avoidant-restrictive food intake disorder. Because these classifications were recently introduced with the newest version of the Diagnostic and Statistical Manual of Mental Disorders, they have not been as well researched," Wierenga says.

Similarly, Cheng believes research eventually will indicate that neurobiology plays a role in all psychiatric disorders.

Environment and Culture
Although genetic studies point to the power of biological factors, Cheng suggests that it's premature to dismiss the role played by culture and environment. For example, he notes, "Identical twins don't always exhibit identical problems and this is likely due to differences in environmental influences." He points, as an example of other factors, to emerging research about the role the microbiome plays in many disorders, including eating disorders. "We are learning that the makeup of the microorganisms living in our gut can have a tremendous impact on our health and even our behavior. This really hits home the idea that even within our bodies, we are perhaps not individuals but communities," Cheng says. "It would stand to reason that an individual's relationship with their world, including culture and environment, must play an important role in the development of the disorder." What's being learned about genetics and neurobiology, he says, "teaches us about vulnerabilities and tendencies. But the environment, which includes culture, still has a very substantial role in whether a vulnerability turns into an illness."

Effects of New Research on Diagnosis and Treatment
It's too soon to predict the impact the latest research will have on treatment for eating disorders. "Unfortunately, while our knowledge is certainly growing, we're not at the point where it has significantly changed the way we identify or treat these problems," Cheng says. "We identify subtypes now based on symptoms. In the future, we may do so based on an actual assessment of a patient's neurobiology." For now, he says, there are still many unanswered questions. "While differences have been noted, it's still not precisely clear how eating disorders develop in an individual nor how best to treat them. Future research will need to further outline neurobiological differences and, hopefully, develop more targeted treatments." It may also become possible, he says, to distinguish subtypes that benefit from different treatment approaches.

Nevertheless, Wierenga says, this new knowledge is beginning to change treatment of anorexia and bulimia. "For example, psychosocial behavioral interventions that focus on 'treating the trait' are being developed and tested in Europe and in America. These approaches recognize that the same traits that predispose and maintain disordered eating are also traits that set someone up for success, so they focus on educating patients and their families about the neurobiology of eating disorders and teach skills to redirect destructive traits toward being productive," she says.

Kaye and his team, for example, have been using a new treatment approach for adults with anorexia that takes into account the personality and temperament traits and is more carefully tailored to each person, an approach described in a recent paper accepted by the International Journal of Eating Disorders. People with anorexia, for example, he explains, "tend to be insensitive to reward but oversensitive to punishment—to things going wrong and making mistakes. They're also sensitive to and respond in an anxious way to change, uncertainty, and novelty." The treatment, therefore, is designed to help people with anorexia and their caregivers understand the underlying temperament and to give them strategies to better deal with and manage it. "We've shown that people accept this treatment and even have had a certain amount of weight gain in months after completing it, suggesting that there may be some tools that begin to move the ball and that people with anorexia who better understand why they behave the way they do get better."

New understanding of the role of neurobiology is influencing other areas of research as well. "Other techniques, such as neuromodulatory approaches, which directly influence brain function and are FDA approved for other psychiatric disorders like depression, are also being tested in eating disorders," Wierenga says. "Neurobiological knowledge offers the potential to inform drug discovery and new psychopharmacological interventions, as there are currently no FDA-approved medications for anorexia or bulimia."

There is great potential, Wierenga says, for knowledge of neurobiology to be a game-changer in treatment development by guiding experimental therapeutics and precision medicine. "In other words, neurobiology can help identify treatment targets and guide development of treatments to engage those targets to improve clinical outcome. By identifying individualized neurobiological profiles, we can become one step closer to personalized or precision medicine." Wierenga observes that most people with anorexia or bulimia don't receive treatment and that for those who do, treatment is often inadequate and followed by relapse. "New, more effective treatments are critical for this often chronic and sometimes fatal disorder, and we are using neurobiological knowledge to inform, develop, and test what we expect will be more effective treatments."

The Future
Making an impact on the field and altering the direction of treatment, Kaye says, requires a critical mass of information. He notes that the field of eating disorders has fewer researchers and less funding than do other areas of medicine. "In other fields, such as schizophrenia, there are a lot of funds and there's been a lot of progress made in understanding why people have schizophrenia—the molecular biology," he says. "But that only comes about when you have lots of studies and some things are replicated and some are not," he adds. Still, he's optimistic that the critical mass of information concerning neurobiology will gather.

"We still do not know why one person develops an eating disorder and another person develops a different psychiatric disorder, such as an anxiety disorder, or no disorder at all," Wierenga says. "Future work is needed to identify what is specific to eating disorders and how to predict who will develop an eating disorder. This is critical in order to guide early intervention so that these serious disorders can be prevented."

Cheng is also optimistic. "As we learn more about the biology of eating disorders, we will undoubtedly be able to develop treatments that target key factors in the neurobiological basis of these illnesses. Perhaps we will also be able to evaluate how well treatments are working by assessing neurobiological markers," he says.

Growing knowledge of the microbiome and gut-brain axis, brain circuitry, and peripheral physiological and genetic markers, according to Wierenga, will likely engender more appreciation for neurobiology's role in eating disorders.

If you look back 20 years, Kaye says, people considered disorders such as autism and schizophrenia as psychosocial in nature. Now, he says, it's clear that there are neurobiological causes for those conditions. "We're still getting there in eating disorders. As we do more neurobiological studies, we'll get to understanding exactly what that means." It's important, he stresses, for social workers and other health care professionals to realize how difficult it is for people with these eating disorders to change or respond to therapy. The field, he says, is evolving, and data support new concepts that can lead to more individualized treatment approaches.

— Kate Jackson is an editor and freelance writer based in Milford, PA, and a frequent contributor to Social Work Today.