Regain control over anorexia

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In the field of mental health, eating disorders are particularly difficult to treat. So far, there is no medicine that treats the problem at the source. But a Montreal researcher has found a lead that could change the situation.

Madelyn Eybergen has suffered from anorexia nervosa since her early teens.

Like many young women with anorexia, Madelyn Eybergen has struggled with the condition since her early teens. Last year, her symptoms became so severe that the 21-year-old almost had to end her sports career.

The young woman is a member of the team athletics at the University of Windsor, where she is also studying kinesiology. His discipline: the high jump. However, her eating disorder led her to severely restrict her diet, while training excessively, up to four hours a day, seven days a week. A rhythm that her body could no longer sustain.

“I was cold all the time. I was constantly hurting myself. I had a stress fracture in my femur from running too much. It started affecting my white blood cells, my kidneys and my liver. »

— Madelyn Eybergen, student and athlete at the University of Windsor

Madelyn Eybergen has suffered several physical consequences due to anorexia.

Over the past few years, the young athlete has been hospitalized several times. She also underwent psychotherapy, and was prescribed medication to treat her symptoms of anxiety and depression. However, this never solved the root of the problem.

When I'm given tools in therapy to try to reduce my anxiety, it doesn't work, she says. The only thing that helps reduce it is to do my usual behavior. Medications for anxiety and depression have helped improve my mood, but they don't change my behavior. I stay motivated to keep doing what I do, just by being in a better mood.

This illustrates the limitations of the usual treatments for eating disorders. We don't have drugs that directly treat the symptoms of eating disorders, such as depression, says Toronto psychiatrist Leora Pinhas, who has been following Madelyn Eybergen for two years.

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“Anorexia has one of the highest mortality rates in mental health, next to substance abuse disorders . Of those who do not recover, one in ten will die. »

— Dr. Leora Pinhas, psychiatrist specializing in eating disorders from Toronto

Psychiatrist Leora Pinhas specializes in treatment of eating disorders.

Madelyn Eybergen is well aware of the impact her eating disorder has had on her life. She wants to get out of it, but sheer willpower is not enough. My thoughts and emotions are always in conflict, she explains. For the past few years, I have wanted to get better, I want to be healthy. But my eating disorder works in the opposite direction.

Behind eating disorders are very stubborn habits, as Dr. Pinhas explains. There is a part of our brain that has a kind of autopilot and, in some, the autopilot can get stuck. So when they try to change something, they are overwhelmed with anxiety. You can have a discussion with a patient. He can understand why he needs to gain weight and eat. He is very reasonable. But two hours later, he may be in front of food and be overwhelmed with anxiety about changing his routine.

Neuroscience researcher Salah El Mestikawy, from the Douglas Mental Health University Institute in Montreal, became interested in this autopilot by studying the brains of genetically modified mice. These mice have a predisposition to develop compulsive behaviors. They lack flexibility, they are a bit psycho-rigid, he says. When they learn to do something, if we change instructions, they will have trouble doing something else.

Neuroscience researcher Salah El Mestikawy became interested in the cause of eating disorders.

“There are commonalities between addiction, anorexia, bulimia and obsessive-compulsive disorders, where there is this dimension of doing and redoing an action despite the negative consequences.

— Salah El Mestikawy, neuroscientist at the Douglas Mental Health University Institute

The mice he studies have been conditioned to develop a form of anorexia. By gradually depriving them of food during the day, the researcher leads them to prefer running around in their cage rather than eating. When food is offered to them again, some continue to run compulsively and hardly eat. When they lose more than 25% of their base weight, they are considered anorexic.

The researcher studied mice conditioned to become anorexic.

Salah El Mestikawy focused on the areas of the brain responsible for our behaviors. He studied the striatum, which includes the nucleus accumbens—part of the reward center—the caudate nucleus—which directs goal-directed behaviors—and the putamen, which is responsible for habit formation. /p>

The striatum is composed in particular of the caudate nucleus, the nucleus accumbens and the putamen.

The nucleus accumbens and the caudate nucleus are involved in learning new actions, such as driving a car. The putamen, on the other hand, makes it possible to transform this learning into a habit. You should know that this is a mode that makes us very efficient, a super-important mode, explains the researcher.

Each sub-region has a brake and an accelerator, something that will tell you, “There's a $100 bill, go get it”; or something that will tell you, “No, there's a poisonous poison there, a poisonous snake, don't go there”; or: “If you eat this, you will die”. Something that will make you do the action or block you from the action, he explains. Dopamine is the neurotransmitter that controls this mechanism. Dopamine, when it arrives in these structures, it will press on the accelerator and it will block the brake, the brake does not work anymore.

So when the rate of dopamine in the putamen is higher than in the nucleus accumbens and caudate nucleus, automatic behaviors take over. This is how disorders like anorexia manifest themselves, which become difficult to control.

To restore balance, Salah El Mestikawy identified another neurotransmitter, acetylcholine, which has the effect of increasing dopamine levels in the nucleus accumbens and in the caudate nucleus, but without affecting the putamen. This will allow a regain of control, since the other two regions will become more powerful than they were before, he explains.

Increase the Acetylcholine in the brain, however, was not an obvious task. To achieve this, the Douglas Institute researcher used a drug used to treat certain cognitive problems in Alzheimer's disease, donepezil.

In the brain, an enzyme called acetylcholinesterase breaks down acetylcholine. It's like a Pac-Man cutting acetylcholine into two pieces and then inactivating it, explains Professor El Mestikawy. And what donepezil does is it gets lodged in the active site of that enzyme, and it's going to block it. By doing this, it will prevent the breakdown of acetylcholine, and therefore it will prolong the action. It will increase the levels of acetylcholine outside the neurons.

By increasing the level of acetylcholine, it allows to increase the dopamine in the nucleus accumbens and in the caudate nucleus, and to reduce the influence of automatic behaviors.

Salah El Mestikawy and his colleague Erika Vigneault are studying neurotransmitters in the mouse brain.

The neuroscientist obtained good results by giving donepezil to his anorexic mice in the laboratory: their weight returned to normal. But what about humans? To find out, he turned to Dr. Leora Pinhas, who agreed to try it with some of her patients. As a precaution, the psychiatrist prescribed it in doses much lower than what is usually used for the treatment of Alzheimer's.

“I had told Leora that I thought donepezil would work relatively quickly on the flexibility and compulsiveness component. And that's exactly what she described to me. It's amazing because, even with extremely low doses, the anticompulsive effects are super-fast. »

— Salah El Mestikawy, neuroscientist at the Douglas Mental Health University Institute

I think I noticed the difference in a month, sometimes less. It's remarkable, confirms Dr. Pinhas, who has tried it on half a dozen of her patients so far.

Madelyn Eybergen is one of them. She was a patient who had tried everything and was really stuck in a condition that was affecting her life, notes the psychiatrist. For two years, we tried to get him to reduce his training time by 5 or 10 minutes a day, and we couldn't. A few weeks after starting the drug, she managed to increase the variety of what she ate and she was able to cut her workout time in half.

The young woman confirms that donepezil has helped her regain control of her behavior, where previous treatments had failed. Before, my goal was to take care of my health, but I didn't feel able to make those changes, she says.

” Along with the medication, it helps me overcome the anxiety I felt when I was trying to make these changes.

—Madelyn Eybergen, University of Windsor student and athlete

Madelyn Eybergen was able to resume high jumping after undergoing treatment.

However, donepezil has drawbacks: it increases blood pressure significantly, which can be dangerous for patients whose physical health is already fragile. To treat anorexic patients, the doctor and the researcher agreed to prescribe it at a tenth of the usual dose, which required special preparation.

To circumvent this problem, Salah El Mestikawy is currently working on developing a new molecule that will have the same effect as donepezil on the brain, but without its side effects. Until this drug is ready, donepezil remains a temporary solution, which the researcher now wishes to test with larger cohorts of patients.

As for Madelyn Eybergen, the treatment allowed her to return to a normal life. I was able to heal from the wounds I had last year, she says. I no longer have pain anywhere. I have more energy, and I don't feel cold all the time. Above all, she was able to resume the practice of her favorite sport. I'm much better, I run faster, I'm much stronger, and I hope I can compete this year, she says hopefully.

Read also :

  • Anorexia, a psychological and metabolic disease

  • Anorexia and hyperactivity have a common mechanism |

  • Treating anorexia with electrical impulses |

The report by Bouchra Ouatik and Sylvain Caron is broadcast on the program Découverte Sundays at 6:30 p.m. on ICI Radio-Canada Télé.

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