By far the largest genetic study to date of anorexia nervosa has identified eight areas in the human genome in which DNA variations are likely to contribute to risk for the illness. Even more important, potentially: the new research extends our understanding of this psychiatric illness by showing that genetic factors that influence metabolism also contribute to its origins.

“Our results encourage a reconceptualization of anorexia as a metabo-psychiatric disorder,” the researchers wrote.

The leader of the large multinational team that performed the genomic study, Cynthia M. Bulik, Ph.D., a 2017 BBRF Distinguished Investigator at the University of North Carolina (UNC) at Chapel Hill and Karolinska Institutet, commented on the new findings for the Wall Street Journal in July, after the study appeared in the journal Nature Genetics.

“Many of us have wondered for a long time if there is more to anorexia nervosa than the psychological component,” she said. Those afflicted seem to “override normal biology, override hunger signals. We’ve often wondered what it is that permits them to lose so much weight and stay down there. This new research might help explain why they get metabolically out of control.”

Anorexia nervosa affects up to 4% of women and less than 1% of men. People with anorexia nervosa may see themselves as overweight, even when they are dangerously underweight, according to the National Institute of Mental Health. They typically weigh themselves repeatedly, severely restrict the amount of food they eat, often exercise excessively, and/or may force themselves to vomit or use laxatives to lose weight. Anorexia nervosa has the highest mortality rate of any mental disorder.

Dr. Bulik, along with Patrick Sullivan, M.D., FRANZCP, a 2014 BBRF Lieber Prizewinner, of UNC and Karolinska Institutet, and their large team of colleagues assembled a sample of sufficient size to make headway on the genetics of anorexia nervosa. By combining 33 samples they were able to compare the genomes of 16,992 people with anorexia nervosa with 55,525 controls. In genomic studies, mathematically robust results generally depend upon large sample sizes. The team is hoping eventually to have genome readouts of 100,000 anorexia nervosa patients.

The sample of nearly 17,000 patients was sufficiently large to identify eight “loci,” or genomic locations, across the 23 human chromosomes, where DNA variations correspond with elevated risk for anorexia nervosa. At those locations—which together contain many genes—it is possible so far to say four genes in particular are likely involved in anorexia nervosa pathology. These genes tend to be active (“expressed”) in the brain, in neuronal cell types that are linked to feeding behaviors, including food motivation and reward.

The study revealed significant correlation between the genetics of anorexia nervosa and metabolic traits. One such component is the body mass index, or BMI. Although we know that low BMI in patients with anorexia nervosa is a result of restricting caloric intake and increasing energy expenditure, the new results open the possibility that a tendency to have low BMI may itself be a potential cause or contributing factor to developing anorexia nervosa. To put this another way, the processes in the body that normally regulate metabolism, including weight regulation, may be malfunctioning in anorexia nervosa patients, underlying some of the weight and feeding “symptoms” that have previously been explained as purely psychological.

The new study also revealed that anorexia nervosa shares genetic factors with other psychiatric disorders including obsessive-compulsive disorder, anxiety, major depressive disorder, and schizophrenia.

For this reason, the new results place the problem of severe stigma and misunderstanding, which often attaches to anorexia nervosa, in a new light. Dr. Bulik states, “Anorexia nervosa has been misunderstood for decades. Patients often say they want to eat and desperately want to get well, but they find it enormously difficult to do so.” The new results can help explain on a metabolic level why, even after hospital-based weight restoration, patients with anorexia nervosa rapidly lose weight again after discharge, often despite aftercare. These findings can help parents and loved ones understand that it is not just a matter of “deciding” to eat more. “Recovery from anorexia nervosa is fighting an uphill battle against their biology and patients need our support in doing so,” says Dr. Bulik.

The results therefore open a new chapter in efforts to find treatments that can more effectively help patients with anorexia nervosa recover. Current treatments are successful, typically, in only one-third of patients, the researchers point out.

If you enjoyed learning about this research, you might find this webinar on The Social Brain in Anorexia Nervosa: