Team of International Scientists Finds Genetic Pattern Associated with Poor Recovery from Eating Disorders

By Christine Crane

A consortium of scientists from around the globe has identified a genetic pattern associated with poor recovery from eating disorders. The findings hint that a novel course of treatment for anorexia nervosa and bulimia might be possible, perhaps even using available drugs.

The research was published recently in the journal Neuropsychpharmacology.

"The study sheds light on what genes might actually be involved in a anorexia and bulimia, and they differ somewhat from what the research community might have previously thought to mediate anorexia and bulimia," said Nicholas J. Schork, professor at The Scripps Research Institute and director of bioinformatics and biostatistics at Scripps Translational Science Institute (STSI), who was senior author of the new study with Walter H. Kaye, professor of psychiatry and director of the Eating Disorder Treatment and Research Program at the University of California, San Diego (UCSD). "This research provides a new angle."

"Anorexia and bulimia likely stem from many different causes, such as culture, family, life changes, and personality traits," said first author Cinnamon Bloss, assistant professor at STSI, which is a collaboration of Scripps Research, Scripps Health, and other institutions. "But we know biology and genetics are highly relevant in terms of cause and can also play a role in how people respond to treatment. Understanding the genetics behind these conditions is important, because it could eventually help us tailor treatment based on the person's genetic makeup, with the goal of more personalized and effective treatments."

The Highest Mortality Rate of Mental Health Diseases

Anorexia nervosa is an inability (or refusal) to maintain a healthy body weight by severe caloric restriction or starvation, often coupled with excessive exercise. Bulimia nervosa is categorized as excessive binge eating followed by vomiting or abuse of laxatives.

According to the South Carolina Department of Mental Health an estimated 8 million Americans suffer from eating disorders, seven million of whom are women.

Eating disorders have the highest mortality rate of any mental health disease. According to the National Association of Anorexia Nervosa and Associated Disorders, 5 to 10 percent of anorexics die within 10 years of contracting the disease; 18 to 20 percent die after 20 years. Alarmingly, only 30 to 40 percent fully recover.

While skeptics have questioned whether anorexia and bulimia have any underlying genetic cause, the study's authors forged ahead to address the question of the genetic underpinnings of eating disorders in the new study.

"Individuals with anorexia in particular are often resistant to treatment and lack awareness of the medical consequences of their behavior, which can result in chronic, protracted illness and even death," said Kaye. "The question for us became, 'Are there prognostic factors that might help clinicians identify good versus poor outcomes for treatments including medication or psychotherapies?'"

The Science

To perform the research, the scientists looked for the frequency of specific genetic variations (inherited factors) in different groups of women with eating disorders, including those with anorexia who did not show signs of recovery for long time periods. A total of 1,878 women participated in the study.

Among the genetic patterns the scientists identified, they found that the women who did not recover over the long term exhibited a higher frequency of genetic variations in a family of genes that code for the GABA receptors.

GABA is an acronym for a neurotransmitter—a chemical substance that regulates brain chemistry or the central nervous system—called gamma-aminobutyric acid. Previously, the genes encoding the GABA receptors were not thought to be involved in behavioral disorders, but rather responsible for other brain functions.

Typically, behavioral disorders are genetically linked to two other infamous neurotransmitter receptors, serotonin and dopamine. Interestingly, in this study, no genetic variations in the serotonin or dopamine receptor gene families were found.

"In this case, among the women who did not recover from an eating disorder, there was an observable inherited pattern of variations in the GABA receptors," said Schork. "The frequency of these variations of the GABA receptors is different from those who did recover. The physiological aspects of this variation still need to be figured out, however."

Implications

Intriguingly, the discovery suggests that a course of treatment geared toward the GABA receptors, rather than serotonin or dopamine uptake, may provide an alternate pathway for treatment in patients with eating disorders.

"If variations in the GABA receptors are the cause for a person's inability to recover from an eating disorder, then further study and manipulation of those variations—anomalies in the receptor or the regulation of those receptors—may provide an alternate course of therapy," Schork, who noted that drugs targeting GABA are already on the market.

Schork was enthusiastic about conducting future studies to compare the effectiveness of selective serotonin reuptake inhibitor (SSRI) and GABA receptor treatments in patients with eating disorders.

In addition to Schork, Bloss, and Kaye, other contributors to the study include Wade Berrettini, University of Pennsylvania, Philadelphia; Andrew W. Bergen, Center for Health Sciences, SRI International; Pierre Magistretti, University of Lausanne Medical School, Switzerland; Vikas Duvvuri and Enrica Marzola, UCSD School of Medicine; Michael Strober, UCLA David Geffen School of Medicine; Harry Brandt and Steve Crawford, University of Maryland School of Medicine; Scott Crow, University of Minnesota; Manfred M. Fichter, Roseneck Hospital for Behavioral Medicine, Prien, Germany and University of Munich; Katherine A. Halmi, New York Presbyterian Hospital, Weill Medical College of Cornell University; Craig Johnson, Laureate Psychiatric Clinic and Hospital; Allan S. Kaplan and D. Blake Woodside, University of Toronto; Pamela Keel, Florida State University; Kelly L. Klump, Michigan State University; James Mitchell, University of North Dakota School of Medicine; and Janet Treasure, King's College, University of London. See http://www.nature.com/npp/journal/vaop/ncurrent/abs/npp2011113a.html.

The study was funded by the Price Foundation, a Swiss philanthropic organization interested in solving the mystery of severe eating disorders, and the U.S. National Institutes of Health.

Send comments to: mikaono[at]scripps.edu

"This research provides a new angle [on anorexia and bulimia]," says Scripps Research Professor Nicholas Schork. (Phot by Dana Neibert.)