Cynthia Bulik began her scientific career studying childhood depression. But while she was working as a research assistant at the University of Pittsburgh in the 1980s, psychiatrist David Kupfer asked her to help write a book chapter comparing electroencephalography studies in depression and anorexia. As preparation, she shadowed a psychiatrist at a hospital inpatient unit for people with eating disorders.
Bulik was intrigued by what she witnessed there. “These people were my age, my sex, and weighed half as much as I did,” she says. “They seemed very eloquent and interactive, but at the same time, in this one area of their psychology and biology, they occupied a completely different space.”
Now the founding director of the Center of Excellence for Eating Disorders at the University of North Carolina at Chapel Hill, Bulik has been unraveling the biology behind eating disorders such as anorexia nervosa (AN) ever since. Characterized by extreme caloric restriction resulting in weight loss, an intense fear of gaining weight, and a distorted body image, anorexia has the highest mortality rate of any psychiatric disorder. Death can be a result of various risks associated with the condition, from suicide to heart failure. While many AN sufferers go undiagnosed, making incidence rates hard to pin down, some researchers estimate that up to 2 percent of women and 0.3 percent of men are affected globally.
Through studying twins, Bulik and other researchers have established that AN is 50 percent to 60 percent heritable. Bulik and colleagues have also been involved in multiple projects aiming to identify possible genetic bases of AN and other eating disorders. In 2017, for example, a genome-wide association study (GWAS) conducted by UNC researchers and other members of the Psychiatric Genetics Consortium Eating Disorders Working Group (PGC-ED) turned up a connection between AN and a locus overlapping six genes on chromosome 12 (Am J Psychiatry, 174:850–58). Researchers had previously linked that same region to various autoimmune disorders, including type 1 diabetes and rheumatoid arthritis.
The 2017 study also confirmed strong genetic correlations between AN and neuroticism, schizophrenia, and, less expectedly, various metabolic features including body mass index (BMI) and insulin-glucose metabolism. Bulik says that the finding of a possible genetic basis for the condition has been well-received by families and patients, who have long sought recognition that AN is a serious medical disorder, not a dieting choice, as was historically believed. She views the study as the “first step to rewriting the book on AN.”
In the coming months, Bulik also expects to publish the results of the largest genetic study on eating disorders to date. Funded by the Klarman Family Foundation, a charitable organization that donates to medical and other causes, the Anorexia Nervosa Genetics Initiative (ANGI) connected researchers in the US, Sweden, Australia, and Denmark, who collected clinical information and blood samples from 13,363 individuals with AN alongside ancestrally matched controls with no eating-disorder history. The results will be combined with the 2017 samples and others to look for genetic loci associated with the condition.
We must change how every physician and therapist learns about eating disorders.—Cynthia Bulik
University of North Carolina at Chapel Hill
But it’s not just AN that the team is focusing on. UNC’s Binge Eating Genetics INitiative (BEGIN) aims to understand genetic factors associated with binge-eating disorder, a condition characterized by frequent episodes of uncontrollable eating coupled with negative emotions, and bulimia nervosa, which involves episodes of binge eating and subsequent action to eliminate consumed calories. Over the next few months, approximately 5,000 participants in the US and Sweden will provide both genetic and microbiome data, which researchers will analyze in partnership with the consumer microbiome company uBiome to determine if changes in the microbiota are associated with clinical features of the disorders.
In addition to influencing how eating disorders develop, genetic factors could play a part in determining why some people experience chronic illness while others recover, notes Walter Kaye, director of the Eating Disorder Treatment and Research Program at the University of California, San Diego. For example, a study that he and his colleagues carried out on almost 2,000 women with eating disorders, including AN and bulimia, found single-nucleotide polymorphisms (SNPs) within GABRG genes—which code for receptors involved in neural signaling—that were associated with whether patients recovered.
Studies such as these are revealing that, like many psychiatric conditions, eating disorders are influenced by many biological pathways, says Kaye. “There was a hope that behavioral disorders would be related to relatively few genes,” he says. “But it doesn’t turn out to be that way. There seems to be many genes involved, each with relatively small effect.” Nevertheless, he notes, “We have learned an awful lot about traits and vulnerability for people who develop eating disorders”—traits that often include anxiety, perfectionism, and harm avoidance.
Although results from genetic research have yet to be translated into therapies, just understanding that anorexia runs in a family could be beneficial in treatment, says Jehannine Austin, a neuropsychiatric geneticist at the University of British Columbia and psychiatric genetic counselor. “Psychiatric genetic counseling is about using the evidence base we’ve accumulated in terms of our understanding about what actually contributes to the development of [psychiatric] illnesses,” she says, noting that the service can be provided even without a patient undergoing genetic testing. Counselors work “to get at that guilt, shame, fear, and blame and stigma and try to mitigate some of it for people by helping them better understand” the biological roots of their conditions.
Bulik underlines the importance of this science-based approach to treatment. “We must change how every physician and therapist learns about eating disorders and erase past false theories and hypotheses,” she says. While she acknowledges the role of environmental and sociocultural influences on the development of eating disorders, “we must anchor that in a clear understanding of the biology of these illnesses,” she says.
“The continuation of this research is so important,” agrees Sarah Blake, an eating disorder therapist who works with patients in Maryland. “When I started in this field, genetics wasn’t even being looked at. It’s interesting to see how far we’ve come and how far we might be able to go.”