Anorexia’s Complex Etiology Opens Path to New Treatments

Though anorexia nervosa remains one of the most challenging of psychiatric disorders to treat, evolving research and new treatment approaches are offering hope to sufferers of the illness, their families, and the mental health professionals who treat them.

Once considered a psychosocial disorder, anorexia nervosa is now the focus of increasing numbers of studies examining genetic anomalies that not only may play a role in the susceptibility of adolescents and young adults to develop anorexia, but might also impede therapeutic efforts to cure the disorder.

The subject of what really causes anorexia nervosa has long been debated, said Walter Kaye, M.D., in an interview with Psychiatric News. “Are there vulnerabilities that predispose one to having an eating disorder?” asked Kaye, a board member of the National Eating Disorders Association and director of the UC San Diego Medical Center Eating Disorder Treatment and Research Program. “Nobody really knows for sure, but if we can understand the mechanism, we can come up with a better treatment approach.”

A study led by Guido Frank, M.D., and published on February 24, in AJP in Advance, examined 21 female adolescents before and after treatment for anorexia. Frank, an associate professor of psychiatry and neuroscience at the University of Colorado School of Medicine, found that the disease fundamentally changes the brain response to stimuli in the environment, in addition to causing widespread changes to parts of the brain like the insula, which processes taste along with other functions such as body self-awareness.

“The more severely altered the brain was, the harder it was to treat the illness, or in other words, the more severely altered the brain, the more difficult it was for the patients to gain weight in treatment,” researchers reported.

In a larger, international study led by the University of North Carolina (UNC) School of Medicine and published in the American Journal of Psychiatry in September, a whole-genome analysis of 3,500 people with anorexia found that genetic anomalies on chromosome 12 contribute toward an increased risk of developing the disease.

The study, led by Cynthia Bulik, Ph.D., F.A.E.D., founding director of the UNC Center of Excellence for Eating Disorders and a professor at Karolinska Institutet in Stockholm, Sweden, also revealed that the anomalies on chromosome 12 were associated with type 1 diabetes and autoimmune disorders, as well as insulin metabolism. In addition, researchers reported that genetic correlations were found between anorexia nervosa, neuroticism, and schizophrenia.

One current treatment approach is focusing more on a family therapy model, often referred to as the Maudsley Approach after the U.K. hospital at which it was developed, according to a history of the treatment on the website Maudsley Parents.

The Maudsley Approach, which has been adopted worldwide, is an intensive three-phase outpatient treatment program that usually takes place over the course of six to 12 months. Phase I focuses on helping parents assume control of weight restoration in their child. The therapist assesses the interactions and eating habits of the family, and a family meal is typically conducted so that the therapist can assist the parents in encouraging their child to eat a little more than she would like (young women make up the majority of patients affected by anorexia).

Once the patient has increased her food intake and experiences a steady weight gain, phase II returns control of eating to the adolescent, while other family issues begin to be addressed. Phase III involves helping the family shift back to discussing adolescent issues without anorexia nervosa at the center of their concern.

“While older treatments have focused on family dynamics, family-based therapy takes an agnostic approach,” Melissa Nishawala, M.D., told Psychiatric News. “Nobody is at fault.”

Nishawala, a clinical assistant professor in the Department of Child and Adolescent Psychiatry and clinical director of the Eating Disorders Service at NYU Langone Health, observed that the initial focus of anorexia treatment must be on nutrition. “When the body is in starvation mode, the brain can’t reason, so using cognitive-behavioral therapy to begin with won’t do much good,” she said.

While psychiatric comorbidity (for example, anxiety, depression, obsessive-compulsive disorder, body image disturbance) is common among people with anorexia, Jamie Feusner, M.D., echoed Nishawala’s statement that the priority of both the therapist and the patient’s family must be on feeding.

“The primary risk of anorexia is death from malnutrition,” Feusner said in an interview. Feusner, who heads the UCLA Eating Disorders and Body Dysmorphic Disorder Research Program, added that feeding the patient “trumps any other treatment efforts at first. Once the patient is physically healthier, you can engage in other therapy.”

Because newer research shows that anorexia can alter brain responses to motivation, specialists in the treatment of anorexia are also looking at different motivation models that lean more toward a system of “consequences”—such as taking away something the child values, be it a cell phone or going to school—than “rewards”—such as getting a new car.

“Most young people with anorexia are perfectionistic and driven to perform well,” said Harry Brandt, M.D., co-director of the Center for Eating Disorders at Sheppard Pratt, in an interview with Psychiatric News. “Losing the privilege of going to school would matter more to them than gaining the reward of a material item.”

Despite strides being made in research and treatment, anorexia nervosa continues to be a complex psychiatric disorder that confounds mental health professionals. “It’s an intriguing, evolving, and complex field,” said Brandt. “There is no magic bullet.” ■

Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa” can be accessed here. “Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa” is available here.