How biology trumps image as cause of anorexia
Scientists now believe genes account for up to 70 per cent of risk of developing the disease
April 13, 2008
The insidious voice of anorexia nervosa is the most deadly of psychiatric disorders.
It can make its sufferers, often astonishingly bright young women, shun food until their skin stretches taut across their skeletal frames. It can make looking in a mirror a dangerous act, or wearing jeans unbearable, since jutting hip bones get rubbed raw by the rough fabric. And, for some, it can make eating a plate of food more frightening than death.
Yet contrary to dominant thinking about the condition for the past two decades, this slow slide into starvation is not about aspiring to a cultural ideal and becoming supermodel skinny.
Other eating disorders, including bulimia nervosa, may be largely influenced by our culture's obsession with thinness. But scientists now say anorexia, which kills up to 15 per cent of those it afflicts, is likely rooted in a person's genes.
And though environment does play a role, researchers believe a genetic predisposition for anorexia outweighs any psychological or cultural factors, and can account for up to 70 per cent of the risk for developing the disorder.
Many people diet, they say, and almost everyone is bombarded with pressures to be thin, but only a very few – less than half a per cent of all women and a scant number of men – develop anorexia.
Experts also point to a long history of anorexia over the centuries, before strikingly thin models became cultural superstars and skinny became the ideal of feminine beauty.
But perhaps the biggest clue that biology trumps culture is the fact that the incidence of anorexia has not changed dramatically in the past 30 years. Rates of bulimia, on the other hand, have risen sharply over the same period, along with societal pressure to be thin.
Cynthia Bulik, a professor of nutrition and director of the eating disorders program at the University of North Carolina at Chapel Hill, says a core of researchers have long believed anorexia has genetic origins – even before scientific studies bore out their theory.
"These patients are not choosing this behaviour," says Bulik, who's considered an international expert on the disorder. "You could go to any eating disorder clinic around the world and the core clinical picture would be identical. There may be different cultural presentations or variations on the packaging, but the core signs of low body weight, an extreme drive for thinness, amenorrhea (absence of menstruation) and often hyperactivity and anxiety just jump out at you as saying this is biological in origin."
Results of the first genetic studies, released in the past five years, reveal that genetic vulnerability for anorexia nervosa lies on chromosome 1 of the 24 chromosomes that make up the human genome.
Researchers are now digging down to find the exact genes, proteins and pathways involved in the disorder. This could lead to new options for detection, treatment and even prevention of the illness.
Right now there is no effective drug protocol, and doctors mainly try to help patients gain – and maintain – weight, says Dr. Allan Kaplan, head of the eating disorders program at Toronto General Hospital, part of the University Health Network.
Developing new therapies based on genetic research will likely take years, but Kaplan says understanding the role of genes will help ease the guilt and stigma that afflict patients and their families. Sometimes parents feel responsible for their child's eating disorder or are accused of bad parenting.
"For whatever reason," he says, "it's easier for a parent to stand up and announce they are starting a fundraising campaign for schizophrenia than it is for a parent to do the same thing for their child with anorexia."
Patients, meanwhile, may blame themselves for their condition.
There is the long-held idea that anorexia is a self-imposed affliction, Kaplan observes – that people just need to "pull up their socks," to get better.
Many people – even some medical professionals – get angry over a child or young adult's refusal to eat, seeing the patient as "a manipulative, kind of, spoiled brat kid who is just acting out.
"When somebody says, `I'm not eating' and they're 80 pounds and it's obvious that if they don't eat, they are going to die, this gets people very angry.
"They think, `How hard is it to take food and put it on your fork and put it in your mouth.'"
Part of the problem is that anorexia research lags behind that into other psychiatric disorders, as do public awareness campaigns, notes Kaplan, who is also a professor of psychiatry at the University of Toronto. The media, he adds, also fuel the message that anorexia is driven by culture rather than by genes.
"Summer" (she asked the Star to use only her nickname), a 29-year-old graduate student at the University of Toronto, is in recovery from what she calls "her anorexia." And she says the shift to thinking anorexia is rooted in genetics will bring some peace to sufferers.
"The biggest myth is that anorexia is about being thin," she says. "We're surrounded by images of having to diet more or eat more or exercise more or buy more weight-loss drugs, and you look at someone with an eating disorder and think they are just buying into that. And it's not that at all ...
"If this new research can help alleviate feelings of blame – anything that can take that away is a good thing and will help in recovery."
Scientists first started to investigate whether biology was a factor in anorexia in the 1980s, after observing that identical twins, who share 100 per cent of their genes, were more likely to both get the disorder than non-identical – or fraternal – twins, who share only a portion of DNA.
That led to family studies in the 1990s, in which investigators found that a person is more likely to have anorexia if she has a close relative who's affected. But it was unclear whether the increased risk was due to genetic predisposition or environmental factors, such as a child watching a mother obsessively diet, says Bulik.
To tease out that critical difference, researchers turned back to studying identical twins in very large groups, and found the chance of both twins having anorexia if one is afflicted was close to 60 per cent. In fraternal twins, that chance dropped to 10 per cent.
In the mid-1990s, a private foundation in Europe financed research to locate the specific region on the human genome that gives rise to anorexia. That effort, from data collected across Canada, Germany, Italy and the U.S., pinpointed the hotspot on chromosome 1.
Another genetic-linkage study, this one funded by the U.S. National Institute of Mental Health (NIMH), is wrapping up this spring. The five-year, $10-million study brings together 11 research groups, including Kaplan's at Toronto General, to analyze DNA samples from families with two or more members with anorexia.
So far, two genes have been identified, one associated with serotonin (a neurotransmitter that controls mood and appetite) and the other with opioid receptors (which modulate pain), says Bulik, who was involved with the NIMH study.
However, most genetic research these days relies on genome-wide association studies, where whole genomes of thousands, rather than hundreds, of people are rapidly scanned looking for similarities and differences. Two weeks ago, for example, scientists reported the first strong genetic link to lung cancer using this method.
And that method, says Bulik, is where anorexia researchers need to go next – once they get the money.
"For the magnitude of severity of anorexia and for its mortality rate, we are grossly underfunded," she says. "It has the highest mortality rate of any psychiatric illness. The way I describe it to people is if there is a girl in the ninth grade who has anorexia nervosa, she is 10 times more likely to die than all of those kids who are sitting around her who are the same age."
Bulik attributes the lack of attention to "the plausibility (of) the socio-cultural explanation" for anorexia. "It's so easy to believe, because we're so surrounded by these cultural pressures for thinness, that these (people with anorexia) are just vain people who are trying to diet down to reach some societal ideal. That plausibility hits you in the face when you're in the checkout line in your supermarket."
Experts stress anorexia is a complex disorder that can't be entirely explained by genetics, and not by just one or two genes.
Unlike cystic fibrosis, for example, which is caused by a mutation on a single gene, anorexia is likely due to the interaction of a number of genes with a number of environmental factors.
Someone with a genetic predisposition for anorexia may be at higher risk for developing the disorder, much like someone with a family history of breast cancer. But that genetic risk does not guarantee a person will get anorexia, says Walter Kaye, the scientist who co-helmed both genetic studies of anorexia and who holds a joint professorship of psychiatry at the University of California at San Diego and the University of Pittsburgh.
Environmental factors, including pressure to be thin, can trigger the underlying risk, he believes.
Kaplan suggests parents who have a strong history of anorexia in their families take some preventive measures: they should avoid talking about people's weight or shape, having diet products in the house or labelling foods as either good or bad. Self-esteem, he adds, has to be kept separate from weight and appearance, and even from successes at school or in sports.
Kaplan even suggests that a young girl who, for example, has a mother with anorexia or a father with some of the temperamental traits of compulsivity or perfectionism should not participate in activities that focus on shape, including competitive gymnastics or ballet.
For Summer, anorexia has been a way of exercising some control over life and coping with stress. She says she spiralled into the disorder at 27 after a major crisis. "I became obsessive about food."
Summer compulsively counted calories, which almost landed her in hospital. Now that she's in recovery, she's counting calories again – but now it's to make sure she's getting enough.
"I'm learning that I'm important," she says, "that I need to eat and be healthy, that I have a lot of important things to say and important things to do. And that I'm important in myself."