Neural Insensitivity to Effects of Hunger Contributes to Anorexia

Researchers at University of California San Diego School of Medicine have discovered differences in brain circuitry that contribute to starvation and weight loss in people with anorexia nervosa (AN). The findings, published yesterday in The American Journal of Psychiatry, shed new light on the neurobiology of starvation and emaciation.

"It has long been puzzling how people with anorexia are able to starve themselves and become emaciated, when most people struggle to lose just a few pounds," said Walter Kaye, M.D., lead author. "Because we lack effective treatments that normalize eating in AN, this illness is often chronic and has the highest death rate of any behavioral disorder."

In their latest study, Kaye and colleagues compared brain responses of two groups of female participants who received tastes of sugar water and plain water after either fasting or after a standardized meal. One group of women had been diagnosed with AN, but were in remission (RAN); the other group did not have AN. Neural responses were observed and measured by functional magnetic resonance imaging.

Hunger in people and animals makes food more rewarding because hunger activates brain circuits that motivate eating. The major finding in this study, said Kaye, was that hunger failed to activate this food reward circuit in people with AN, which raises the possibility that the trait underlies restrictive eating and severe weight loss in persons with a history of AN.

Specifically, data showed that the brain's ventral caudal putamen produced varied responses to hunger within the two study groups. RAN participants and the control group both displayed similar responses to food stimulation when sated, but in the RAN group, response to hunger was abnormal. In addition, the RAN group showed reduced neural activation to taste stimulation in the brain's anterior insula and reduced connectivity between the right anterior and mid-dorsal insula and ventral caudal putamen.

"These findings highlight the specific brain circuitry that may play a key role in unhealthy eating in anorexia," said Kaye. "In part, this circuitry involves connected regions that are important for recognizing the feeling of hunger, motivating us to want to eat when we are deprived of food, and helping to initiate actual eating or to decide to avoid it. This same circuitry has been implicated in appetite changes associated with major depression. The distortion of signals in the brain in both depression and anorexia impact the awareness of hunger, the motivation to eat and food avoidance."

"These data open the door to potential new ways of treating this disorder," said co-author Christina E. Wierenga, Ph.D. "For example, developing behavioral strategies for enhancing initiation to eat or compensating for altered motivational drives may be helpful. In addition, the brain circuitry implicated in these findings have also been highlighted in other studies and support a fresh look at medications acting on the dopamine system."