Earlier Help for Anorexia

The most life-threatening of all psychiatric disorders is anorexia nervosa. Caltech neuroscientist Cindy Hagan is searching for detectable differences in brain structure and function that could help doctors identify early warning signs of the disorder, and help patients sustain or regain health.

Anorexia affects about one percent of Americans. The eating disorder typically emerges in adolescence and is characterized by low body-mass index and an intense fear of weight gain. Anorexia damages the heart, sometimes fatally, and can injure the brain and other organs, weaken bones and muscles, impair fertility, and increase the likelihood of suicide or substance abuse, especially in those who engage in eating binges followed by purging behaviors. While the disorder is difficult to treat and may recur over decades, recovery is achievable.

In work that may one day help clinicians prevent and treat the disorder, Hagan seeks to identify potential differences in the mental processes and brains of people who have and have not experienced anorexia.

Neuroscience studies like hers complement medical professionals’ in-depth patient expertise. “Scientists can characterize large groups of individuals for the benefit of many people,” she says.

“As we move toward personalized medicine, knowledge of the pathways that these disorders take will be a critical part of understanding which treatment approaches best support each individual. ”
- Cindy Hagan

The Path to Anorexia

Our brains rely on our senses for information about the world. When a person’s eyes relay an image of an angry face, or nerves relay hunger pangs, the person’s brain processes those signals and directs a behavioral response. Each individual brain interprets and acts on sensory information differently. Hagan explores these differences by studying disorders in which the brain’s responses lead to extreme behaviors.

As a postdoctoral researcher at Cambridge, she joined a collaboration that helped change views about conduct disorder, a disruptive behavior disorder in childhood and adolescence which spurs antisocial behavior in adulthood. Scientists had thought that abnormal brain development led to the childhood variety of this disorder, while social mimicry caused the adolescent variation.

However, through brain imaging studies, the collaborators found abnormal brain development in both age groups with the disorder. The structures of areas of the brain linked to socioemotional processing, reward, and empathy were atypical, as were neural responses in these regions when presented with images of angry and sad faces. As these findings help clinicians reconsider the causes of conduct disorder in teenagers, earlier and more successful interventions may be possible.

Then, in 2016, Hagan joined the laboratory of Ralph Adolphs, Caltech’s Bren Professor of Psychology, Neuroscience, and Biology; the Allen V. C. Davis and Lenabelle Davis Leadership Chair of the Caltech Brain Imaging Center; and a member of the leadership team of the Tianqiao and Chrissy Chen Institute for Neuroscience, which was established during Break Through: The Caltech Campaign. Among Adolphs’s many collaborators are two members of the UCLA Eating Disorders Progam, psychiatrist Jamie Feusner and psychologist Michael Strober.

In this link, Hagan saw an opportunity to search for neural differences associated with anorexia, as she had done with conduct disorder. She teamed up with the UCLA researchers and Caltech psychology professor John O’Doherty, whose studies had begun to reveal the role of a brain region called the orbitofrontal cortex in assessments of the nutritional value of food that guide dietary decisions.

Food, through the Looking Glass

The team aims to compare the relative nutritional values assigned to fat, carbohydrates, and protein by the brains of people who have or have not experienced anorexia. Then, the researchers will compare those assigned values to the actual nutritional values, and find any associated differences in neural structure and function.

After the collaborators completed the necessary ethical reviews for the study to commence, COVID-19 safety precautions curbed in-person research. When her study resumes, Hagan will conduct scans of participants’ orbitofrontal cortices as images of different foods are presented.

If the team’s hypothesis is correct, they may find differences in neural signals about nutrition values that make food choices more difficult for those who have or have had anorexia. Such differences might one day allow clinicians to use brain scans in the diagnosis and treatment of anorexia. The researchers also hope to find commonalities in the histories of study participants whose assessment of nutritional values differ markedly from others. Commanilities might point to factors in the development of anorexia that could be used in diagnosis.

The project attracted a 2018 grant from the Brain & Behavior Research Foundation, and a 2019 T&C Chen Center for Social and Decision Neuroscience Award.

Hagan says she hopes that this research ultimately will contribute to the detection and individualized treatment of anorexia in its earliest stages, before the disorder can take root.

“The trajectory an individual takes to anorexia is important, and we know that it relates to the brain’s development,” she says. “There may be some clearly observable phenomena associated with the illness.”

To support Caltech neuroscience research, email or call Joe Shea at jshea@caltech.edu or (626) 395-4643.

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