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Eating Disorders and Genetics: The Newfound Link
A new global study led by researchers from the University of North Carolina, published Monday in the journal Nature Genetics, offers the strongest evidence to date that anorexia nervosa not only has a genetic component, but that it is also associated with unique metabolic characteristics that make it more difficult for people with the disorder to gain and maintain weight, even after recovery.
Mainstream narratives about eating disorders like anorexia nervosa tend to focus on the psychological and social risk factors for the disease, and as a result, anorexia is generally viewed as a learned behavior or a response to environmental pressures. But often the disease can run in families. Experts have wondered if some people have a higher familial risk for the disorder, as someone might have a greater risk for breast cancer or Alzheimer’s disease.
Until now, research in the field of psychiatric genetics hadn’t found much evidence for a genetic basis for anorexia nervosa, in part because sample sizes were too small to conclude anything of significance. Anorexia nervosa affects an estimated 0.6% of the population in the U.S., making it difficult to gather enough DNA for statistical analysis that’s powerful enough to find subtle differences across thousands of genes. However, the disorder has one of the highest mortality rates of any psychiatric illness at around 6%, second only to substance use disorders for opioids, amphetamines, and cocaine with a 15% mortality rate, lending urgency to the research.
In the UNC study, researchers identified eight genetic markers in anorexia nervosa patients that may have contributed to their risk for developing the disease. Some of these genes were also linked to other psychiatric disorders like depression and obsessive compulsive disorder, which hints at a genetic factor for the reason that some people with the eating disorder also present with these additional illnesses as well.
But perhaps the most intriguing aspect of these genetic markers is that some of these genes are also associated with a low body mass index.
“This panel of genetic correlations suggests that we really need to be looking at two different realms of causal factors,” says psychiatry professor Cynthia Bulik, PhD, lead author of the paper and the founding director of the University of North Carolina Center of Excellence for Eating Disorders. “One being the psychiatric, and one being the metabolic.”
“For some people, it’s more genetic, and for some people, it’s more environmental. It’s way more complicated than we thought it was going to be.”
Most people have a tendency to gain weight over time, but people with anorexia nervosa are more likely to continue to have very low body weights, even after they are renourished and are in recovery for their illness. This makes treatment agonizing for patients, who may be trying their hardest to comply with healthier eating habits but aren’t seeing any results. It can also be worrying for loved ones, who might suspect that a relapse is imminent.
“We have been psychologizing this process forever by saying that it’s a psychologically-driven drive for fitness,” says Bulik. “Our results are saying that this might not be the only way to look at [anorexia], and there might be a metabolic component to this perplexing low weight as well.”
To conduct the study, Bulik and over 200 collaborators worldwide gathered a sample size of almost 17,000 people diagnosed with anorexia nervosa from five different countries: the U.S., Australia, New Zealand, Denmark, and Sweden — where Bulik splits her time as the director for the Centre for Eating Disorders Innovation at the Karolinska Institute in Stockholm.
Then the researchers compared these samples with a control group of over 55,000 people without the disease in order to identify any significant genetic differences between the two groups. This kind of research, known as a genome-wide association study, is part of a growing movement to analyze the genetic components for all different kinds of psychiatric illnesses.
Bulik hopes that a growing understanding of anorexia as a disease with metabolic factors could move health insurance companies to extend coverage for inpatient programs, as opposed to cutting off coverage once a patient hits a certain BMI number.
“When insurance companies kick [patients] out of the hospitals at BMIs like 17, the risk for relapse is high because your metabolism isn’t able to renormalize,” she says.
The study’s findings are a long way from identifying potential genetic risk factors and building the case for how they affect biological processes like brain circuitry or metabolism, says Dr. Walter Kaye, a psychiatry professor at the University of California, San Diego and founder of its Eating Disorders Program.
Kaye is one of Bulik’s more than 200 co-authors on the study because he contributed genetic samples and data to the research. He praised Bulik’s analysis as important to help understand the powerful biological forces that likely contribute to anorexia, but he points out that it’s difficult to distinguish between biological and psychosocial risk factors for any individual person. “For some people, it’s more genetic, and for some people, it’s more environmental,” he says. “It’s way more complicated than we thought it was going to be.”
Some of the anorexia data set Bulik used is part of a broader coalition known as the Psychiatric Genomics Consortium. Founded in 2007, this global collaboration unites scientists, clinicians, and genetic data sets from all over the world to learn more about ADHD, bipolar disorder, depression, schizophrenia, and other mental illnesses. Bulik hopes that if they continue to learn more about the biological pathways linking these genes to the development of anorexia nervosa and other eating disorders, researchers might one day be able to create a drug treatment to address the metabolic factors.
“We have no medications effective in the treatment of this illness, in part because we don’t understand the biology,” Bulik said. “Further down the line, hopefully what this will do is open a new door for drug discovery.”