Anorexia nervosa has the highest mortality rate of any psychiatric illness. It is very difficult to treat: Relapses are likely, and no medications are approved to treat the eating disorder.

But hope is in sight. A breakthrough study published Monday in Nature Genetics both explains why it has been difficult to help anorexic patients and points the way toward stopping deaths in the future. Anorexia nervosa, the authors found, is more than just a psychiatric disorder, as it’s commonly characterized.

The team learned that there are eight genetic variants significantly associated with anorexia. Some of those DNA mutations are present in other psychiatric disorders, like anxiety, while others are linked to the process that controls metabolism.

"There is more to anorexia nervosa than just the psychological component."

This means that it’s very likely anorexia is a disorder that is both psychiatric and metabolic, and it’s important for physicians to consider both factors when creating a treatment plan for patients.

“The panel of genetic correlations that we reported strongly suggest that there is more to anorexia nervosa than just the psychological component,” co-author Cynthia Bulik, Ph.D. founding director of the Center of Excellence for Eating Disorders at the University of North Carolina at Chapel Hill, tells Inverse.

Bulik, who has studied eating disorders since 1982, says that one of the core missions of her career is to figure out the causes of this illness in order to improve treatment and prevent mortalities. The new study is a step towards that goal.

Not Just a Psychiatric Disorder

Eating disorders are complex and psychiatric illnesses. People with anorexia can misjudge their body size and not believe they are thin. Unsplash / Yuris Alhumaydy

She and a team of researchers from over 100 institutions worldwide conducted the new genome-wide association study of 16,992 individuals with anorexia and 55,525 control participants, a data set that represents people of European ancestry from 17 countries across North America, Europe, and Australasia.

The analysis that genetic factors contribute to the psychiatric traits that are implicated in anorexia nervosa as well as the metabolic traits demonstrated in populations of anorexic people.

This realization, says Bulik, could explain “some of the most perplexing aspects of anorexia nervosa.”

Having a low body mass index is commonly viewed as a consequence of the psychological features of the disorder, like a drive for thinness and body dissatisfaction. These are also thought to be factors involved in the difficulty people with anorexia face when trying to maintain a healthy body weight after treatment.

But the new study suggests that certain genetic markers allow people with anorexia to suppress hunger for longer periods than those without the genetic markers. This is consistent with previous research showing that people with anorexia have the physical capacity to tolerate extreme self-imposed weight loss. In this way, anorexia is not only a psychological issue but a metabolic one, though more research is needed to identify the specific metabolic mechanisms at play.

“This could explain why adequate re-nourishment is so critical to long term recovery,” Bulik says. “Stopping treatment before reaching and maintaining a healthy BMI may destine someone with anorexia nervosa to relapse because it does not give their bodies and their metabolism adequate time to equilibrate and reset.”

How The New Findings Can Improve Treatment

One of the reasons it’s been so difficult to treat anorexia is because, until now, its causes were not known. Previous hypotheses suggested the disorder was rooted in a combination of a person’s biology and life events, though the path of development is known to vary across individuals. Food restriction is only one of the practices used by patients to lose weight; some people also use overexercise and purging practices as well as repeated weighing and mirror-gazing. At times. anorexia begins as innocent dieting, and other times it is linked to trauma.

Right now, says Bulik, we have a “one size fits all” approach to treatment for anorexia that typically includes nutrition therapy and psychotherapy. The findings in the new study provide an opportunity to change that. Bulik is hopeful that “genetics could help us identify meaningful subtypes and more toward personalized interventions.”

Today, anorexia affects between 0.4 to 0.9 percent of women and 0.3 percent of men. It is more than twice as common in teenage girls compared to the rest of the population. For more than half of those afflicted, the condition can last decades; furthermore, up to 20 percent of people with anorexia die prematurely from the disorder and only 20 to 30 percent recover after using the available therapies.

Now what’s needed are further studies to evaluate how the metabolic features identified in the new study influence risk for disease, taking into account the possibility that some cases of anorexia will have more metabolic roots, while others can have psychiatric origins.

But research in the field is not as robust as it could be. Studies on anorexia, says Bulik, are insular compared to other science fields in part because of the misconception that the cause of anorexia is mostly sociocultural. She emphasizes that the genetics of anorexia aren’t just relevant to eating disorders but are also relevant to the study of obesity and other psychiatric disorders that commonly occur with anorexia, like obsessive-compulsive disorder and depression.

“Now I hope that other researchers will also become intrigued by this deadly disease,” Bulik says, “and engage their brainpower and expertise to eliminate deaths and improve treatment for anorexia nervosa.”

Abstract:

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders, and outcomes are unacceptably poor. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.