Building a Bridge Between Research and Clinical Practice

At the International Conference on Eating Disorders in Seattle last May, nearly 1000 clinicians from around the world sampled a program packed with workshops, plenary sessions, and scientific presentations.

Keynote Address: Dialectical Behavioral Therapy

Keynote speaker Marcia Linehan, PhD, Director of the Behavioral Research and Therapy Clinics, University of Washington, Seattle, described the development of dialectical behavioral therapy (DBT), which combines cognitive behavioral therapy and eastern Zen practices. Dr. Linehan, who developed DBT, noted that the principle-driven approach was developed to treat patients with severe disorders and chronically difficult-to-treat patients with both Axis I and II disorders. DBT gradually evolved from problems that appeared when clinicians tried to apply standard treatments to these patients, she said. Often, as a result, the client shut down, withdrew, quit treatment, or attacked, she said. The solution was to apply a dialectical approach to balancing strategies for change and acceptance of change. Dr. Linehan noted that when all other treatment approaches had failed, DBT was effective for reducing suicidal ideation and attempts. She noted that often these patients have so much fear and anxiety that some clinicians may want to “dump” them on someone else; as a result, some addicts get dumped out of treatment and suicidal patients get dumped into hospitals, she said.

Dr. Linehan said that patients with extreme emotional dysfunction are good candidates for DBT. A good example is a patient with anorexia nervosa who is at her suggested healthy weight but fights it every day; these patients are dealing with quiet desperation, she said.

Dr. Linehan, who is the author of two DBT manuals, said that DBT challenges patients and clinicians with acceptance and change, and reaching the balance is a compassionate, dynamic process. The behavioral portion of DBT includes a structured set of agreements that clients and therapists must both agree to. A crucial part of this is that the patient must agree to the change.

Building bridges between research and clinical practice

In a plenary session, four eating disorders researchers addressed ways that laboratory research could be better related to clinical practice.

According to Evelyn Attia, MD, Clinical Professor of Psychiatry and Director of the Eating Disorders Research Program, New York State Psychiatric Institute, New York, NY, animal models enable researchers to identify biological mechanisms, and to narrowly target genetic and developmental factors that impact upon eating disorders. She added that research is racing to answer such questions as who develops an eating disorder, what can be done to change or treat it, and what modifies the course of an eating disorder.

Dr. Attia noted that well-designed epidemiologic studies can uncover important trends and can test the effectiveness of proposed interventions. Laboratory research can also help predict which eating disorders patients have the best chance for recovery. Dr. Attia urged clinicians and researchers to “interface and interact,” to work together to continue to improve the diagnosis and treatment of people with eating disorders. A recent event underscored just how essential it is for clinicians and researchers to work together, said Dr. Attia. As a result of the combined efforts of researchers, clinicians, and others in the eating disorders field, who worked together to lobby legislators and insurance companies for change, new and improved legislation is on the horizon that will be more protective for patients with anorexia nervosa (AN).

What lab animals can tell us about binge eating

Mary M. Boggiano, PhD, Associate Professor of Psychology at the University of Alabama, Birmingham, described results from her group’s laboratory model of binge eating. Dr. Boggiano, who specializes in the neurochemical bases for eating disorders, and her colleagues identified and studied five variables that affect binge eating among laboratory rats: a history of dieting, access to highly palatable foods, stress, environmental cues, and inherent (genetic) differences. “The beauty of studying animals is that we can isolate each component and see what the outcome is,” Dr. Boggiano said.

The researchers found that the most powerful elements that led to binge eating in laboratory rats was a history of dieting, plus the availability of palatable food, and the addition of stress. Dr. Boggiano also tied environmental cues to binge eating—rats exposed to palatable food in the form of cookies ate more when they were placed in a cage where cookies had been, even though they now only had plain laboratory rat chow as before. This is similar to settings that trigger overeating among humans, including watching TV, buffet restaurants, and even opening the refrigerator. Such environmental cues also occur in addictions, she said. A genetic component also seems to be in place with rats prone to binge-eat, and these animals overcome adversity and pain in the form of foot shock to overeat, in comparison to binge-eating-resistant rats, who will not overeat.

Weighty issues in AN

According to Dr. Johannes Hebebrand, Professor of Child and Adolescent Psychiatry at the University of Duisburg-Essen, Marburg, Germany, the current DSM-IV-R diagnostic criteria for AN need to be changed. Dr. Hebebrand explained that research shows that certain regulatory phenomena underlie the development of AN, and thus derail the idea that a patient “refuses to eat.”

Dr. Hebebrand cited several studies showing the role leptin plays in weight loss and weight gain. In people with AN, leptin levels are typically much below age-based reference weight ranges, and these levels go up rapidly with refeeding. In addition, an increase in leptin levels is required for normal follicle-stimulating hormone (FSH) levels and luteinizing hormone (LH) levels, he said. Otherwise, amenorrhea occurs.

In the future, treatment with leptin might be an option for some patients with AN, he said. He cited one 2004 study by Welt et al (N Engl J Med. 2004;351:987), one of the very few among humans. Among 8 women, leptin (r-metHuLeptin) treatment increased LH levels within 2 weeks, and increased the diameter of follicles, the size of ovaries and estrogen levels within 3 months, leading to ovulation among 3 women. The women had no significant weight loss, and no side effects beyond reduced appetite in the third month of treatment.

Dr. Hebebrand noted that science and clinicians need to find a better way of addressing the criteria of AN. Discussing whether or not a patient “refuses” to eat implies a willful and conscious psychological process, and a paternalistic approach to the problem. In fact, he added, evidence shows that underlying regulatory phenomena, such as leptin levels, contribute to both the somatic and psychopathological symptoms and the course of AN. He added that the course of weight loss is a nonrandom process; hypoleptinemia underlies amenorrhea: hypoleptinemia contributes to hyperactivity, and also predicts relapse. Then there is the element of genetics.

“We are conveying the wrong message to patients, families, clinicians and researchers,” he said. No study has shown that AN patients are refusing to maintain their body weight, he stressed. Patients with AN do seek help and, he pointed out that the word “refusal” is not used for any other psychiatric disorder or for obesity.

What is known about eating in eating disorders?

Dr. B. Timothy Walsh, Ruane Professor of Pediatric Psychopharmacology and founder of the Eating Disorders Research Unit at the New York State Psychiatric Institute, focused on several studies that help highlight eating behavior in patients with AN and binge eating disorder, or BED, and how this changes with treatment.

Based on clinical experience, Dr. Walsh said, people with AN are able to eat fewer calories in part by avoiding high-fat foods. In one study, when people were invited to the hospital and invited to select and eat whatever foods they wanted for 24 hours, researchers found that, compared with controls, AN patients ate half as many calories, and those calories came from foods with reduced fat content—these patients avoided fat. To see how this changed with treatment, Sysko and colleagues evaluated inpatients in a structured setting who were receiving nutritional rehabilitation and psychotherapy. The mean body mass indexes of the 123 patients rose by 5 points as they gained 25 lb. Nearly every parameter improved with weight gain: the psychopathological disorder improved, as did their depression, drive for thinness, and their weight was near normal.

Trends seen in other studies showed that the difference in diets between those who do well after discharge and those who do poorly involved energy intake and a higher percentage of energy derived from fat. Those who did better also had a larger variety of foods in their daily diets. Those who did less well were eating more bulk foods and foods less dense in energy, such as bran.

Dr. Walsh also noted that there is much laboratory data about eating behavior in people with BED and how such behavior changes with treatment. In laboratory studies, people with BED regularly consume nearly 50% more calories than do normal controls. People with BED eat more in binge- and non-binge settings as well, he said. Considering all this, he asked, why aren’t all BED patients overweight and gaining weight faster than others? Patients with BED eat fewer but larger meals than do non-BED controls. One reason may be that persons with BED may have difficulty sorting out what is a normal meal and what is overeating, he added.

A number of studies have shown that interventions are helpful and can dramatically reduce binge-eating episodes, said Dr Walsh. In addition, drug treatment with agents such as sibutramine has been very successful. The reasons for the success are still not completely known, but it may be that patients feel that they are more in control of their eating.

The continuing fashionable trend for extreme thinness among female and male models puts their physical and psychological health in jeopardy, according to three eating disorder experts at King’s College, London. It also is a reminder that the risk extends far beyond the modeling industry.

In an editorial in the British Journal of Psychiatry (192:243, 2008), Dr. Janet Treasure and colleagues turn a spotlight on the consequences of extreme underweight, both in the fashion industry and on general public health. They note that starvation affects all body organs, particularly the brain, and has more serious implications if food deprivation occurs during physical development. The second area of concern is that the overvaluation of extreme thinness, particularly in a society that judges individuals on the basis of weight, shape, and eating, increases the risk for eating disorders.

Health consequences of low weight

Restricting food affects many areas of the body, particularly the bones, the brain, and the reproductive system. As body weight falls, so does the level of leptin. This starts a cascade of actions, including irregular menstruation, amenorrhea, and diminished fertility. In addition, maternal starvation during pregnancy and in the neonatal period may lead to increased risk for the infant. Poor nutritional status stunts bone development and reduces bone turnover and repair, leading to osteoporosis. The authors also point out that, in humans, 20% of energy expenditure is for the brain, which also plays a key role in maintaining nutritional balance. In persons with anorexia nervosa, the brain shrinks, and it is still unknown if this is fully reversible with recovery. Starvation also changes drive, thoughts, feelings, and behavior, so those people who are starved become preoccupied with food.

The effects of ‘binge priming’

After a period of food restriction, when animals are exposed to highly palatable foods, they will overfeed to an excess. This pattern continues when their weight has recovered to pre-starvation levels, and has been termed “binge priming.” The underlying changes in behavior can be traced to an imbalance in chemical transmitters in the reward network, including dopamine, acetylcholine, and endogenous opiates. According to Dr. Treasure and her coauthors, the persistent priming of reward circuits by palatable foods bears some resemblance to the phenomenon of reward produced by drug misuse.

When the same patterns of behavior are extended to humans, the authors predict that binge priming from irregular dieting and/or extreme restriction of food, interspersed with a very common pattern of snacks and other highly palatable foods, might lead to permanent changes in our reward system. Two hypotheses are: (1) If binge priming occurs during adolescence when the developing brain is more susceptible to reward, persisting eating problems may follow; and (2) people exposed to binge priming will be more prone to develop substance abuse.

Some empirical evidence supports the first hypothesis. For example, people with eating disorders report eating more highly palatable foods (fast foods and snack foods) and also report having fewer regular mealtimes during childhood. Binge eating is persistent, and binge eating disorder is present for an average of 14 years and bulimia nervosa for 5.8 years. Abnormal eating patterns in early adolescence often precede substance abuse and alcohol use disorders often supersede clinical bulimic disorders.

Social factors

Fashion models are under constant pressure to remain thin, and their careers depend upon this. Body-related self-esteem is particularly important in their success. Since models are usually judged and evaluated based on thinness, they will be at ever-increasing risk of developing eating disorders, under the guise of professional development.

What can be done?

Efforts to better educate the public about the repercussions of extreme dieting are beginning to make some inroads. The progress made in dance and sports offers a model of successful intervention and a way to eliminate the binge-priming environment. In the U.S. and U.K., coaches and their athletes now have practical guidelines to reduce the prevalence of eating disorders, unhealthy weight loss, and unhealthy ways to maintain weight. This is at least a beginning.