A study led by researchers at King’s College London and the University of North Carolina at Chapel Hill has found that the eating disorder anorexia nervosa is not only a psychiatric condition but also has a physical element driven by metabolic differences between patients.
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Anorexia nervosa is typically perceived to be a serious psychiatric disorder. Now, a large-scale, international study has shown that some differences in the DNA of people with anorexia changed how they processed fats and sugars in ways that could make it easier for them to starve themselves.
The discovery, which the eating disorder charity Beat refers to as “ground-breaking,” may help to explain why doctors have had difficulty treating the illness and could pave the way for new treatment approaches to the devastating disorder. It may also lead to new ways of predicting who is most at risk of developing the condition.
What is anorexia nervosa?
Anorexia nervosa is a potentially life-threatening eating disorder, with a mortality rate that is the highest seen for any psychiatric disorder. It is more common among women than men, affecting between 1% and 4% of women and around 0.3% of men.
Disease outcomes include: a dangerously low body weight, a phobia of gaining any weight and a distorted body image.
While some sufferers may eat so little that they essentially starve themselves, others will follow a regular diet, but exercise to the extent that they burn off more calories than they have taken in. In the long term, the potentially fatal disorder can cause damage to muscles, bones, organs and fertility.
Common treatment approaches include psychological interventions such as cognitive behavioral therapy (CBT) and dietary plans that aim to restore a healthy weight, but these interventions often fail.
Testing for genetic changes common to anorexia
For the current study, more than 100 researchers worldwide assessed DNA data collected from the Anorexia Nervosa Genetics Initiative and the Eating Disorders Working Group for 16,992 anorexia sufferers and compared them with data for 55,525 individuals without the disease.
They then assessed the dataset, which covered 17 countries across North America, Europe, and Australasia, to look for genetic mutations that were more common to the anorexic individuals.
As reported in the journal Nature Genetics, the researchers found eight genetic variants that linked anorexia nervosa to depression, anxiety and obsessive-compulsive disorder – psychological disorders that would all be expected.
However, they also detected mutations that influenced the body’s metabolism of blood sugar and body fat, including calorie burning, physical activity and resistance to type 2 diabetes. "There is something in those systems that has gone awry," says Janet Treasure from the Institute of Psychiatry at King's College London.
What does this mean for patients?
"Metabolic abnormalities seen in patients with anorexia nervosa are most often attributed to starvation, but our study shows metabolic differences may also contribute to the development of the disorder,” says co-lead researcher and geneticist Gerome Breen. “Furthermore, our analyses indicate that the metabolic factors may play nearly or just as strong a role as purely psychiatric effects."
The authors suggest that anorexia now be regarded as "metabo-psychiatric disorder," referring to it as a disease of both the mind and the body.
What our study means is we can no longer treat anorexia, and perhaps other eating disorders, as purely psychiatric or psychological. Anorexia has the expected correlations with anxiety, depression and OCD, but it also has this set of apparently healthy metabolic correlations that we don’t see in any other psychiatric disorder.”
Gerome Breen, Co-author
Breen and colleagues have not yet fully investigated the role of the genetic changes they discovered, but they suspect that they make it easier for anorexic people to starve themselves because the signals that are usually triggered by weight loss to induce hunger no longer fuel the urge to restore a normal set-point.
How significant are the findings?
"It's very significant because there's been difficulty knowing what sort of disorder anorexia is… Over time there has been uncertainty about the framing of anorexia nervosa because of the mixture of physical and psychiatric features.
“Our results confirm this duality and suggest that integrating metabolic information may help clinicians to develop better ways to treat eating disorders,” says Treasure.
Chief Executive of the charity Beat, Andrew Radford, called the research ground-breaking, saying that it significantly increases understanding of the genetic origins underlying this serious disease.
Radford says the charity strongly encourages researchers to examine the findings and consider how they may contribute to the development of new therapies that may bring an end to the pain and suffering among people with eating disorders.
Next on the agenda: Predicting relapse for early intervention
The eight genes flagged up in this study only explain a small fraction of anorexia; there are probably hundreds or even thousands more genes that contribute overall to a person’s risk of developing the condition.
Breen is now calling for researchers to investigate the metabolism of people with anorexia and other eating disorders to see whether new metabolism-based therapies can be developed and whether it is possible to pinpoint sufferers who are at risk of relapse, which is a common problem in anorexia: “Predicting relapse is one of the most valuable things we could do.”
Consultant psychiatrist at the University of Oxford, Rebecca Park, says that, over time, such findings would not only hopefully lead to new treatment interventions, but also begin to shift a culture of blame where it is expected that sufferers should just be able to snap out of it.
We know we need more effective treatments for anorexia nervosa. A lot is based on trying to stop starvation in its tracks, but often that process doesn’t work. The most important message is intervening early on, right at the beginning.”
Rebecca Park, Consultant Psychiatrist
If you are struggling with an eating disorder or know someone who has been diagnosed with anorexia, you can contact the Beat hotline on +448088010677 or visit the website by clicking here. For families and friends, we also have a dedicated support page.
Watson, H. J., et al. (2019). Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics. https://www.nature.com/articles/s41588-019-0439-2