ANOREXIA may be a disorder more of the metabolism than the mind, according to a new paper that argues the disease is a sort of cousin of diabetes. But this theory of anorexia as a fundamentally biological disorder, rather than a psychological one, is untested, psychiatrists warn, and patients with the disease should not stray from proven treatments.
The review of past research on the topic, published in the June issue of the journal Molecular Psychiatry, finds that certain genetic and cellular processes get activated during starvation in organisms ranging from yeast to fruit flies to mice to humans. The idea, says study researcher Donard Dwyer, is that in people with a broken starvation response, a few initial rounds of dieting could trigger a metabolism gone haywire.
In this theory, it’s not stubbornness or a mental disorder that keeps anorexics from eating, it’s their own bodies. The theory could explain why it can be so difficult to convince anorexic patients that anything is wrong with them, says Dwyer. “Unless we conceive of it as more of a metabolic function, I don’t think we’ll get past the first stage of treatment with a lot of the real hard-core patients,” he says.
The diabetes of starvation
In the current understanding of anorexia nervosa, an eating disorder in which patients don’t maintain at least 85 percent of their normal body weight for their height, overachieving personality types attempt to control stress and emotion by restricting food and/or extreme exercising.
Dwyer sees the disease, instead, as a condition similar to diabetes. Someone who becomes obese and is genetically susceptible will develop insulin resistance, which then becomes diabetes. An initial trigger — the obesity — is required, but once the patient has diabetes, you can’t talk him or her out of the disease.
For anorexia, Dwyer says, the potential trigger is chronic undereating or dieting, and the messed-up molecular process could be any number of biological changes that happen during starvation. In the current review, he and his colleagues focus on a cascade of genetic and cellular events called the IGF-1/Akt/FOXO pathway. Organisms from yeasts to humans activate this pathway in response to starvation, triggering all sorts of biological changes, including a desire to look for food. If this pathway doesn’t work as it should, it could theoretically cause the warped approach to eating seen in anorexia. (The so-called epigenome, the supporting actor to our genes, is what helps determine which genes, or pathways, get switched on and off.)
If Dwyer is right, difficult-to-treat anorexic patients may need drugs to get their metabolisms back on track, much as diabetic patients have to take insulin shots. But so far, the idea has not been tested in humans.
“This is, at the moment, speculative,” says Timothy Walsh, a psychiatrist at Columbia University who was not involved in the research. “There’s no human data to support it, and it’s only part of the answer. It’s not proposed as the complete solution.”
Starvation and metabolism
Dwyer is careful to say that much more research is needed. But he says there is good reason to continue the work. Research on obesity has shown that being too heavy is more complex than simply calories in, calories out, he says. There are genetic and metabolic factors involved that make it hard for some people to shed weight. And obesity-related changes to the epigenome (our genes’ on-off switches) can even be passed down from mother to child. The same could be true on the flip side, with starvation, Dwyer says, adding, the genes linked to anorexia could be the same ones that regulate the metabolism during starvation.
Additionally, studies on starving people suggest that many of the supposed causes of anorexia, including food obsession and anxiety, may be symptoms of starvation. And starving people, like anorexics, often report that they’re doing much better than their physical condition would suggest.
“Here we have our anorexic patients who are not aware of how sick they are despite how thin they have gotten. … We’re not going to be able to convince them otherwise until we understand that better,” Dwyer says. “It’s probably not going to be something we can just talk them out of.”
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