Identification of a neurobiological dysfunction leading to anorexia

An international study, conducted by a team of researchers from Sorbonne University, Inserm, CNRS, and McGill University (Montreal, Canada), has identified a neurobiological dysfunction that can lead to anorexia in a rodent model.


This discovery paves the way for a potential treatment of this psychiatric disorder, which affects millions of people and has a very high mortality rate. These animal findings are currently being validated in humans, with more than ten patients responding positively to the treatment so far. This study is detailed in an article published in the journal Nature Communications.

Despite its high mortality rate, the neurobiological basis of anorexia nervosa remains poorly understood, which explains why there is no effective pharmacological treatment yet. According to a recent study, anorexia could be due to the excessive formation of habits, leading to a loss of control that results in the person ceasing to eat. The formation of habits is regulated by a brain structure called the dorsal striatum.

This study was conducted within the Neurosciences Paris Seine laboratory (Sorbonne University/Inserm/CNRS), led by neuroscience professor Stéphanie Daumas (Sorbonne University / Inserm / CNRS), and researcher Nicolas Pietrancosta (Sorbonne University / ENS / PSL University / CNRS) in collaboration with researcher Salah El Mestikawy (McGill University / Douglas Mental Health University Institute / CNRS emeritus / Sorbonne University).

They used a genetic mouse model expressing a mutation previously identified in human patients suffering from severe psychiatric disorders (eating disorders and addiction). The goal was to understand the neurobiological mechanisms underlying anorexia.

The researchers identified a deficit of acetylcholine, a neurotransmitter, in the dorsal striatum of mice expressing this mutation. These mice also developed an excessive tendency to form habits. This resulted in a drastic reduction in their food consumption within a behavioral model of anorexia used in rodents, called "activity-based anorexia" (ABA).

The mice were treated with a well-known acetylcholine stimulator, donepezil (Aricept). Donepezil stimulation blocks the degradation of acetylcholine, thereby increasing acetylcholine levels in the brain and body. Thanks to this treatment, the mice no longer exhibited anorexia-like behaviors in the ABA model.

In summary, this animal study confirms the importance of habits in anorexia nervosa and highlights a neurobiological mechanism, as well as a potential treatment for anorexia nervosa using donepezil.

To validate these findings in humans, an independent study is being conducted to evaluate the efficacy of donepezil in anorexia nervosa. Dr. Leora Pinhas (psychiatrist in Toronto) treated 10 patients suffering from severe anorexia nervosa with donepezil. Among these patients, three showed complete remission, while the remaining seven experienced a marked improvement in their condition. Placebo-controlled clinical trials will be conducted in 2024 at Sainte-Anne Hospital in Paris, the University of Denver, and Columbia University in New York.

This pioneering research has advanced understanding of the neuronal mechanisms that can lead to not only anorexia nervosa but also other compulsive disorders such as addiction or obsessive-compulsive disorders. The scientists of this study hope to pave the way for innovative treatments for other severe psychiatric diseases in the near future.