The Thinkers
This monthly series will highlight people from Western Pennsylvania who are on the forefront of new ideas in their fields.

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Martha Rial, Post-Gazette Click photo for larger image. Dr. Walter Kaye, director of research at the Eating Disorders Program at the University of Pittsburgh School of Medicine, is in the forefront of research on the genetic role in anorexia and bulimia. Age: 61 Position: Research director, Eating Disorders Program, University of Pittsburgh School of Medicine; also, principal investigator of a 10-center, $12 million study of the genetics of anorexia funded by the National Institute of Mental Health. Education: Oberlin College, bachelor's degree in chemistry, 1966; Ohio State University College of Medicine, doctor of medicine degree, 1970; surgical and neuropathology residencies, University of Southern California, 1970 to 1972; psychiatry residency, University of California at Los Angeles, 1977. Professional honors: Price Family Lifetime Research Award, National Eating Disorders Association, 2004; National Institute of Mental Health senior scientist award, 2001-2006; Lifetime Research Award, Academy of Eating Disorders, 1998; and founding member, Academy of Eating Disorders. Publications: Author or co-author of nearly 180 refereed scientific articles, including "Neurobiology of anorexia nervosa," International Journal of Eating Disorders, 2005; "Serotonin alterations in anorexia and bulimia nervosa: New insights from imaging studies," Physiology & Behavior, 2005; and "Perfectionism and obsessive-compulsive symptoms in eating disorders," International Journal of Eating Disorders, in press. He also has authored more than 90 book chapters and reviews. The Series Click here to view other installments in this continuing series.

Karen Carpenter dies. Calista Flockhart denies. Sharply etched ribs. Jutting shoulder blades. Fingers down the throat. The perfect girl.

Most Americans are familiar by now with these hallmarks of anorexia nervosa and bulimia, and girls are increasingly being taught the dangers of succumbing to our culture's emphasis on the glory of thinness.

The University of Pittsburgh's Dr. Walter H. Kaye supports all that education, and he'd be the last to argue against preaching the benefits of a healthy body image.

But he is also in the forefront of a group of researchers who are convinced that genes contribute strongly to anorexia and bulimia, so that these disorders can't be prevented simply by enlightened education.

As the chief investigator of a study that is still under way in several nations, Kaye can say with confidence that anywhere from 50 percent to 80 percent of anorexia and bulimia is driven by a person's genes.

That doesn't mean these eating disorders can't be overcome.

But it does mean that the young women who have struggled for years with the self-starvation of anorexia or the binge-and-purge cycle of bulimia are probably wired differently from others.

And perhaps most importantly, it means that their mothers weren't to blame for causing their diseases.

In the not-so-distant past, mothers were accused of causing their daughters' eating disorders through poor parenting. It's not the first time that mothers have been chastised for what turned out to be genetic conditions.

"We could have been sitting here 20 years ago and have had the same conversation about autism or schizophrenia," Kaye said. "And people would have said of course schizophrenia and autism are caused by [the actions of] mothers."

Just as schizophrenia and autism are now understood to be biological disorders, so anorexia and bulimia deserve to join that group, Kaye says.

He is quick to acknowledge that scientists are just beginning to understand the genetic basis for the two eating disorders, and that they still do not know why nearly half of women who have anorexia recover, usually in their 20s, and the other half do not.

For those who don't turn the corner, the statistics are grim. Overall, 10 percent of those with anorexia and bulimia will die of the disease over a 20-year period -- the highest fatality figure for any major psychiatric disorder.

Why? Because women with severe anorexia and bulimia are convinced there is nothing wrong with them, and so "the homeostatic self-preservation the rest of us have isn't working."

"You try starving yourself to death," Kaye said. "It's like holding your breath. After a while, your physiology is going to scream, 'Breathe!' "

But for some reason, the usual compulsion to satisfy hunger doesn't kick in for anorexic women who are withering away. They do in fact starve themselves to death.

Yet there is real hope for those who can overcome their food denial.

Kaye and other researchers have found that some of the psychological attributes of anorexia and bulimia can end up being helpful.

"The people who recover actually do pretty well in life," Kaye said. "They have traits for achievement, drive and motivation that have beneficial effects if they get past the anorexia. People with anorexia, for example, are great at paying attention to detail," and many who recover are able to forge successful careers in fields where detail matters, such as engineering, research and medicine.

Research on the disorders has entered an exciting era, Kaye says, because brain imaging techniques promise to open new windows of understanding in coming years.

One of his group's most recent findings is that women who have had anorexia show heightened activity by brain receptors for a basic neurotransmitter known as dopamine.

Other studies have shown that anorexic women tend to have less dopamine in their systems than most people do, so the theory is that smaller amounts of the substance satisfy their brains' receptors.

Since dopamine is released by food, that may help explain why these women can feel "full" after eating only a small amount and be oblivious to the feelings of hunger that a normal eater would have.

Earlier studies showed bulimic women had a surplus of another neurotransmitter called serotonin. People with high serotonin levels are known to be anxious, which is also an iconic trait of women with eating disorders.

One of the main ways this heightened anxiety shows itself is an intense desire not to make mistakes.

"A certain amount of harm avoidance is a good thing. You want to worry about stuff. It keeps you alive," Kaye said. "But too much harm avoidance gets you into trouble; it makes you so paralyzed that you're dysfunctional.

"Instead of kind of learning from experience and seeing mistakes as a normal part of life, [anorexics are] freaked out when they make a mistake, and their strategy is to do the same thing over and over again" to try to avoid errors.

That can mean such repetitive behaviors as excessive cleaning or organizing, or double- and triple-checking work to make sure no mistakes were made.

It also shows up before the women actually get the eating disorder, when they are about 8 to 10 years old. At that stage, he says, these girls are painfully eager to please and obey instructions.

A study financed by the National Institute of Mental Health is helping uncover the genetic foundations of the disease by looking at more than 400 extended families with two or more members who have the disorder.

Kaye says researchers have found that many of these women have abnormalities in Chromosome 1, but since the key section of the chromosome involves hundreds of genes, there's still a long way to go in figuring out the full impact of the genetic problems.

It may turn out that even women who never get full-fledged anorexia, but who struggle with eating problems for a briefer period of their lives, have some of these genetic markers.

"I look at it very much like depression," Kaye said. "All of us can get depressed. If somebody dies in the family, and you don't get depressed, there's something wrong with you. But there's a small percentage of people who have major depressive disorders. It's the same kind of thing with bulimia and anorexia; it's a spectrum."

At the extreme end of that spectrum, anorexia and bulimia appear to involve between 1.25 percent and 3.5 percent of American women.

That's a tiny fraction, but it still could mean that up to 10 million women in the United States suffer from these disorders.

Walter Kaye has been studying these disorders for nearly 30 years.

He grew up in Cleveland, son of a salesman father and homemaker mother. His father had always wanted to be a doctor, but the Depression derailed his plans.

So both Kaye and his brother became physicians.

After getting out of medical school at Ohio State University and doing residencies in neurology and psychiatry in California, Kaye went to work as a brain researcher at the National Institutes of Health in Bethesda, Md., in the late 1970s.

He started out doing research on Parkinson's and Huntington's diseases, but when a colleague asked him to finish up an anorexia study, he said, "I became fascinated with how stereotypically good a model this was to understand how the brain works."

Pitt recruited Kaye in 1985.

What has kept him in this field, he says, is "that I have a lot of these same traits myself."

"While I don't suffer from eating disorders, I'm perfectionistic, I'm obsessional, I pay attention to detail, I can relate to these kinds of traits," he said. "I feel an emotional bond."

One of the biggest hurdles to get over in the future, he says, is the way that anorexic women resist change.

When people have a phobia like fear of flying, Kaye says, it's much easier to treat them because "they hate their phobias and want to get rid of them. But these women with anorexia simply think, 'This is the way we are.' "

Nothing shows this distorted thinking -- or the challenge still facing Kaye and his colleagues -- more than the way women with anorexia can accurately describe everyone else's body type and eating habits, but can't do that for themselves.

More than once, Kaye has taken two 70-pound anorexic women into a medical class and asked the first woman to describe how much she weighs and how she looks. The gaunt woman will say accurately that she is about 70 pounds and then say, "I'm too fat."

He then will ask her to look at the other anorexic woman and describe her.

"She'll say correctly that she's about 70 pounds, but she'll say that 'She looks terrible; she's so thin; she looks like she's going to die.'

"And you say, 'But look, you're 70 pounds and she's 70 pounds and you're the same height and weight. How do you put this together saying you're too fat and she's too thin?'

"And she just looks at you and says, 'I don't know -- but I feel too fat.' "