Anorexia nervosa is a serious eating disorder that may be linked to reduced release of a certain chemical in the brain, an animal study shows.
Male mice engineered to contain a rare genetic variant found in some people with eating disorders (as well as substance abuse) were found to be deficient in a neurotransmitter called acetylcholine in the striatum, a part of the brain involved in learned behavior, cravings and reward.
While further validation and human studies are needed, the work identifies “a mechanism and a potential treatment to alleviate these serious psychiatric disorders,” Mathieu Favier, a neuroscientist at McGill University in Montreal, and colleagues write in their published paper.
In short, restoring acetylcholine levels — using a drug already approved for Alzheimer’s — might help, but other types of therapies are likely still needed.
Favier and colleagues set out to confirm the link between the aforementioned genetic mutation and substance use disorders in a new cohort of patients, including some with eating disorders. The p.T8I variant of the SLC17A8 gene is rare, and was found in only 9 of 793 cases in this study. So keep in mind that the results may not apply to everyone with these disorders.
What these two disorders have in common are habits that are difficult to break, and compulsive behaviors that are driven by restrictions, in the case of eating disorders, and “rewards,” in the sense of addictive drugs. activate the brain’s reward systemwhich causes a boost of dopamine and other reward chemicals in the brain.
Treating the genetically engineered mice with donepezil, an Alzheimer’s drug that inhibits the enzyme that breaks down acetylcholine, had some striking effects: The animals began eating normally and lost weight less often, while previously they had exhibited behaviors resembling binge eating and restricting eating.
“We found that the anorexia-like behavior was completely reversed in mice and we think it could potentially provide the first mechanism-based treatment for anorexia nervosa,” said Salah El Mestikawy, a neuroscientist at McGill University and lead author of the study.
“In fact, we are already seeing its effects in some patients with the disease.”
Ten patients were treated with low doses of donepezil in a Canadian pilot study. Randomized controlled trials are planned to test whether this treatment is better than placebo in relieving anorexia nervosa.
It’s useful if existing drugs can be repurposed in this way to potentially treat other conditions. But until those trials are completed, we won’t know how well the findings from this animal study will work in humans, and whether restoring acetylcholine levels is an effective treatment strategy.
The study involved male mice, while eating disorders primarily affect women, so there may be some gender differences that aren’t taken into account there. Donepezil also has some known and serious side effects, so the clinical trials will only test low doses of the drug.
However, the results do offer some cautious hope that a drug may soon be available that could help treat anorexia, a disease that has one of the highest mortality rates of all serious psychiatric disorders.
As with many mental illnesses, research appears to be a tug-of-war between the biological factors underlying conditions such as anorexia or mood disorders such as depression, and the psychological aspects of each illness.
In 2019, scientists identified eight genetic markers linked to anorexia after analyzing DNA samples from nearly 17,000 patients with anorexia nervosa and about 55,000 people without it. Some of these genetic variants relate to the way people metabolize fats and sugars.
Finding those biological underpinnings can help reduce the stigma associated with mental illness. By showing that they have a physiological basis, it becomes clear that people can have a genetic or biological predisposition to develop a particular disorder.
However, there is always additional complexity from social, psychological, and environmental factors—over which people may or may not have control—that impact on those biological foundations.
Understanding the intersecting contributing factors of mental health problems has implications for treatment. For example, a chemical imbalance in serotonin, long thought to be the cause of depression, has led to the use of antidepressants that don’t work for many people, and now research suggests that theory may be slightly off the mark.
In the case of anorexia, the use of acetylcholine inhibitors to treat this and other obsessive-compulsive disorders can be controversial, as Favier and colleagues themselves note, and no single drug is a cure-all.
So the current standard of care, behavioral therapies, will still be part of the repertoire to help patients, even as new treatments are explored.
The research was published in Nature communication.