Environmental factors may trigger anorexia
Anorexia is the third most common chronic illness among adolescents in the US, with a lifetime prevalence ranging from 0.3 to 0.9 percent in females and 0.1 to 0.3 percent in males. The disorder has a mortality rate of 8 to 15 percent, the highest of any psychiatric disease. In it, people struggle to eat healthily and develop distorted beliefs about healthy weight.
Researchers have suspected that the risk of anorexia is raised by a combination of genetic, biological, psychological and sociocultural variables, but a major obstacle to the development of new treatments has been the lack of animal models that recap the pattern of disease onset in humans.
However, a recent study, led by Lori Zeltser, PhD, from CUMC, says that although previous animal models of anorexia have included some variables, there were not any that were able to incorporate the social stress and genetic components of anxiety and anorexia that likely contribute to the development of this illness in humans.
For the new mouse model, the researchers exposed adolescent mice with at least one copy of a variant of the BDNF gene, which has been associated with anorexia and anxiety in mice and humans, to social stress and caloric restriction.
"One driver of anorexia in humans is peer pressure, specifically, the desire to be thin," said Dr. Zeltser. "People assumed that you couldn't replicate that in a mouse. We decided to take peer pressure out of the equation and focus on social stress, which can be accomplished by housing mice alone, instead of in groups."
The mice were placed on a calorie-restricted diet, which usually precedes the development of anorexia in adolescent humans and may act as a trigger for eating disorders. In the study, the impact of dieting was simulated by reducing the mice's caloric intake by 20 to 30 percent, roughly equivalent to the caloric reduction of a typical human dieter.
The researchers found that adolescent mice with the gene variant, when exposed to both social isolation stress and caloric restriction, were much more likely than controls to avoid eating. Changes in feeding behavior did not occur when the environmental variables were imposed during adulthood. When the researchers subjected adolescent mice with the gene mutation to either social stress or caloric restriction, but not both, the animals exhibited little change in feeding behavior.
"People do not develop eating disorders because they are weak-willed, but because they carry measurable susceptibilities that may or may not be activated by various pressures in the environment," Zeltser explains. "These can be early-life pressures, stress, and ultimately dieting.” he says. "For some people, dieting can be really dangerous behaviour. The reduction in certain nutrients can alter gene expression."
Because the study was conducted in mice and not humans, the researchers note that "there will always be questions about the extent to which a mouse model can fully capture a disorder as complex as anorexia nervosa."
However, they say that there are many key components of their model that "accurately reflect the conditions thought to promote eating disorders." These include the interactions between early life stress and the BDNF variant, increasing susceptibility; dieting often precedes the onset of anorexia, and its peak incidence is in adolescence.
The researchers are presently using the new mouse model to investigate signaling pathways in the brain that may contribute to anorexic behavior. They hope to find therapeutic targets in the near future.