Unlocking the mysteries of eating disorders through brain imaging and hormone analyses

For patients with eating disorders, eating too little or too much can be a daily battle, taking a physical and emotional toll.  But what if researchers and doctors could better treat these patients by having an enhanced understanding of their brain activity and hormone levels?  Laura Holsen, PhD, and Elizabeth Lawson, MD, researchers at Brigham and Women’s and Massachusetts General Hospitals respectively, are jointly studying patients, their brain scans, and their hormones to create a clearer picture of what makes a person prone to having an eating disorder and how hormone and brain function may affect that.

Two researchers in front of an MRI“We know that losing and gaining weight is a huge struggle for many people, especially those with eating disorders,” says Holsen, Associate Psychologist at the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital (BWH) and Assistant Professor of Psychiatry at Harvard Medical School. “Part of the big question mark in the variability and change in weight over time is what’s going on in the brain, which is what drives a lot of our behavior and thus our eating patterns. So how does this play out over a long period of time in terms of body weight?”

Holsen, a developmental psychologist at BWH with expertise in functional neuroimaging and affective neuroscience, and Lawson, a neuroendocrinologist at Massachusetts General Hospital (MGH) and Assistant Professor of Medicine at Harvard Medical School, have collaborated for years, building on the ongoing 20-year National Institutes of Health (NIH)-funded program in the neuroendocrinology of anorexia nervosa at MGH. Their overlapping interests have facilitated their study to understand the differing levels of hormones in people with eating disorders, as well as their abnormal brain activity, and the possibility for developing treatments that target specific hormone pathways and areas of the brain.

“Combining hormone and brain imaging approaches to study this disorder is a new concept,” says Lawson. “It’s very novel and has the potential to uncover pathways that contribute to or make it more difficult to recover from eating disorders. It’s one of the things that makes this research so interesting.”

The two have been studying women with and recovering from anorexia nervosa with the goals of being able to more accurately treat these women, prevent relapses, and identify pathways that can lead to the development of the disorder.

“Anorexia nervosa actually has the highest mortality rate of any psychiatric disorder. So although the prevalence is not as high as other disorders, such as depression, the severity is quite striking,” says Holsen.

Study Design

One of Lawson and Holsen’s earlier studies involved using functional MRI, or fMRI, to measure brain activity while participants are in the machine, says Lawson. Participants came from three groups: patients with active anorexia nervosa, weight-recovered patients with anorexia nervosa, and a control group. Holsen and Lawson showed the participants images of food and images unrelated to food while they were in the fMRI. The fMRI was performed on fasting participants and after they had eaten a standardized meal. The researchers analyzed both blood samples to measure hormone levels and brain images to see what areas of the brain were or were not activated before and after a meal.

“What we have found is that activity in brain regions associated with reward and hunger are underactive in individuals with anorexia nervosa,” says Holsen. “What’s really interesting is that, even after they have recovered and are eating more typically for someone of their weight and frame size, they still are showing deficits, which suggests that having had a lengthy period of not eating can affect the brain and that weight recovery doesn’t mean that the brain completely goes back to ‘normal’.”

A particularly exciting finding is the discovery that abnormal secretion of hormones involved in appetite regulation is related to these deficits in brain activity, says Lawson.

Potential treatment for the future

Although their research has not yet turned to treatment of eating disorders, Lawson and Holsen say that it may not be too far off. Targeted therapies could potentially be used to treat patients with various types of eating disorders, including patients with binge eating disorders, as well as those with anorexia nervosa.

“If you can show that there are hormonal pathways for appetite that are abnormal, then you could potentially normalize or intervene in these abnormal pathways,” says Lawson. But how? Replacing a hormone that is deficient or using an agonist or antagonist — drugs that promote or inhibit the activity of a particular hormone — may be the key to modulating a hormonal pathway that regulates food motivation, says Lawson. She is currently investigating whether oxytocin, a hormone that has been shown to inhibit food intake in animals, could be used to fight obesity. The results of that study are still pending.

Both women have received funding to continue their research. Lawson has received an NIH K-23 Award to study the relationship between hormone secretion and brain imaging in patients with anorexia nervosa. Holsen has received an NIH K01 award to study the role of hormones and the neural circuitry of food motivation and reward in the context of obesity and depression, which occurs more frequently in women (as does anorexia nervosa). These NIH K awards are designed to develop the independent research careers of junior faculty, especially clinical researchers involved in patient-oriented research.

Lawson and Holsen’s research was aided by Thomas Weigel, MD, a psychiatrist at McLean Hospital, who helped recruit patients with eating disorders for their study.  They cite identifying subjects who fit their requirements as one of the largest challenges to performing this research. In addition, coordinating all of the staff, analyzing data efficiently, and organizing the logistics of handling a study involving the brain and hormones all added to the complexity. But being able to work together, across three Partners institutions, allowed both researchers to take advantage of resources and expertise that would not have been available had they worked alone.

“The resources here are so incredible. The expertise represented across the institutions, you don’t find that everywhere. It’s really enriched my research to have access to all of these functional resources and the people involved,” says Holsen.

 
 
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