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May 20, 2022

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Anorexia: Does it depend on a gene?

Elimination of the DRD1 gene restores normal feeding behaviors in animals. A confirmation on humans will change the approach to anorexia.

Gianluca Ricciodi Gianluca Riccio
in Medicine
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POST FP 700X500 2022 05 08T153615.803
May 8, 2022
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An animal study by Baylor College of Medicine, Louisiana State University and other institutes may have made a breakthrough in the study of anorexia. The results show that anorexia would be caused by the malfunction of a gene, which would produce abnormal activity in a specific brain circuit.

Genetic and pharmacological restoration of normal brain circuit activity improved the condition. If confirmed in humans, this dynamic opens up great possibilities for treatment for those suffering from anorexia.

The study appears on Nature Neuroscience, and I'll put it here.

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Anorexia, a study also reveals genetic causes

Anorexia, the first killer

"Anorexia has the highest mortality rate of all psychiatric diseases," says the study's lead author, the Dr. Yong Xu, professor of pediatrics, nutrition, and molecular and cellular biology at Baylor College of Medicine. And he is right.

In addition to being the deadliest of psychiatric conditions, anorexia still has no real approved treatment, nor clarity about the causes.

Previous work in Xu's lab and other groups has shown that anorexia is linked to a dysfunction of the dopamine and serotonin neurons, which regulate nutrition. However, it wasn't clear how these two populations of neurons in the brain contributed to the condition.

This latest study analyzed an animal model to find the exact dynamics

anorexia
anorexia

"First, we found that under normal conditions dopamine neurons communicate with serotonin neurons, and we studied this interaction to determine how nutrition regulates," Xu said.

The researchers found that the strength of the signal transmitted along the dopamine-serotonin brain circuit determined how much the animals would eat.

"When the dopamine neurons emitted a low-frequency signal, for example between 2 and 10 Hertz, the result was inhibition of the serotonin neurons and overeating behavior," explained Xu. "When the dopamine neurons were activated at a higher frequency (between 10 and 30 Hertz), however, the serotonin neurons were activated and this led to a lack of power."

In summary, the dopamine-serotonin circuit plays a role in the development or persistence of anorexia. 

The DRD1 gene may be the key

The research team identified the dopamine receptor DRD1 as a key mediator of this dynamic: deleting this gene partially restored normal eating and exercise behaviors in the animals.

We need to understand more, to calibrate this possible approach. In particular, one factor, which is currently completely unknown: why is anorexia more common in females than in males? “In future work we plan to look at what mediates the differences between males and females and try to understand the mechanism,” Xu said. Either way, gene work improves the condition in both.

Indeed, we found that a drug that interferes with DRD1 receptor activity can effectively prevent anorexia and weight loss in the animal model. 

A discovery that can lead, if confirmed in humans, to pharmacological treatments for anorexia. A total turnaround.

tags: Anorexia
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