People with anorexia are overly anxious about gaining weight and severely restricting their diet, exercising excessively, and experiencing significant weight loss. “Anorexia has the highest mortality rate of any psychiatric illness,” said lead author Dr. Yong Xu, a professor of pediatrics, nutrition and molecular and cell biology at Baylor. Anorexia is more common in women than in men, but this difference in prevalence remains poorly understood. This team not only identifies abnormal activity in a brain circuit, associated with anorexia, but also shows that genetic and pharmacological restoration of the activity of the brain circuit in question reduces the symptoms of the condition.
“The condition has no approved treatment and the underlying cause remains misunderstood,” the author adds. In this study, we identify on an animal model of anorexia brain circuit alterations that appear to be involved in this ADD.
The in vivo study: lThe team has been working on ADD for years and has already shown that dysfunction of dopaminergic and serotonergic neurons, which regulate diet, is associated with anorexia. However, how these 2 groups of neurons in the brain contribute to anorexia remained poorly understood. This animal study reveals that:
- under normal conditions, dopaminergic neurons communicate with serotonergic neurons, and this interaction regulates supply;
- the strength of the signal transmitted along the brain circuit dopamine-serotonin determines the importance of food intake;
- when dopaminergic neurons emit a low frequency signal, for example between 2 and 10 Hertz, the result is the inhibition of serotonergic neurons and supercharging behavior;
- when dopaminergic neurons are activated at a higher frequency between 10 and 30 Hertz, serotonergic neurons are activated, which causes the supply to stop.
The dopamine-serotonin circuit in the development or persistence of anorexia: in mice, this brain circuit appears super activated in case of lack of appetite and excessive exercise. Finally, the DRD1 dopamine receptor is identified as a key mediator of the hyperactivity of this circuit. Inactivation of the DRD1 gene partially restores normal eating behavior in animals;
What are the implications? This work suggests that targeting and inhibiting the DRD1 receptor may help reduce circuit hyperactivity and thus anorexic behavior. In fact, the team shows that a drug that interferes with the activity of the DRD1 receptor can also be used to prevent anorexia and weight loss.
These very promising first results will lead to future clinical trials.