A New Model For How Brain Reward Response May Impact Anorexia

Summary: Researchers report the brain’s response to taste stimuli is linked to higher anxiety and a drive for thinness in those with anorexia.

Source: University of Colorado.

Researchers at the University of Colorado Anschutz Medical Campus have found that the brain’s response to taste stimuli is linked to high anxiety and a drive for thinness that could play a role in driving anorexia nervosa.

The study was published last week in the journal JAMA Psychiatry.

The researchers, led by Dr. Guido Frank, MD, associate professor of psychiatry and neuroscience at the University of Colorado School of Medicine, monitored a large group of patients with anorexia nervosa as they tasted sugar during brain imaging.

They found their brain response was higher than those in the control group, representing a biological marker for the illness. At the same time, this brain response was related to high anxiety and less weight gain for those being treated for anorexia nervosa.

Frank found that as these patients restricted their diet, a brain reward circuit associated with the neurotransmitter dopamine becomes more active but also triggers anxiety. This makes food avoidance worse and perpetuates the often deadly disease.

“When you lose weight your brain reward response goes up,” said Frank. “But instead of driving eating, we believe it elevates anxiety in anorexia nervosa, which makes them want to restrict more. This becomes then a vicious cycle.”

Using brain scans, the researchers examined 56 female adolescent and young adults with anorexia nervosa between the ages of 11 and 21 and 52 healthy control participants of the same age. They all learned to associate colored shapes with either getting or not getting a sugary solution. Sometimes when they expected sugar they got nothing, and sometimes when they didn’t expect sugar they received it.

Those with the eating disorder responded more strongly to the unexpected getting or not getting of sugar water, perhaps due to the release of dopamine.

The researchers found that the higher the brain response, the higher the harm avoidance in those with anorexia nervosa was. Harm avoidance is an anxiety measure for excessive worrying and fearfulness. In these patients, it pushes the drive for thinness and furthers body dissatisfaction.

Frank discovered that the higher the brain response, the lower the weight gain during treatment.

This brain reward response acted on the hypothalamus, which stimulates eating, in the anorexia nervosa group. The researchers hypothesized that this could make it possible to override and fend off signals to eat.

“An enhanced dopamine reward system response is an adaptation to starvation,” the study said. “Individuals vulnerable to developing anorexia nervosa could be particularly sensitive to food restriction and adaptations of reward response during the [mid-adolescence] development period.”

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According to Frank, anorexia nervosa behavior could alter the brain circuits and impact its taste-reward processing mechanisms. Those who are already worried about shape and weight become even more concerned. And a strong response that says “feed me” might be overwhelming and trigger more food restriction instead of eating.

The study noted that while most people like sweet tasting things, those with eating disorders associate the taste with weight gain and try to avoid it. Frank found that the brain activation among the anorexia group was inversely connected with any pleasant experience of eating sugar.

“Our data raise the possibility that adolescents with anorexia nervosa in this study were negatively conditioned to sweet taste and may have developed an inverse association with dopamine release across the larger (brain) reward circuitry,” the study said.

Frank believes these insights could lead to new treatments for eating disorders.

“I hope we can use these findings to manipulate these biomarkers and design better treatments for this often-deadly disease,” he said.


Source: David Kelly – University of Colorado
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Association of Brain Reward Learning Response With Harm Avoidance, Weight Gain, and Hypothalamic Effective Connectivity in Adolescent Anorexia Nervosa” by Guido K. W. Frank, MD; Marisa C. DeGuzman, BA, BS; Megan E. Shott, BS; Mark L. Laudenslager, PhD; Brogan Rossi, BS; and Tamara Pryor, PhD in JAMA Psychiatry. Published July 19 2018.

University of Colorado”A New Model For How Brain Reward Response May Impact Anorexia.” NeuroscienceNews. NeuroscienceNews, 26 July 2018.


Association of Brain Reward Learning Response With Harm Avoidance, Weight Gain, and Hypothalamic Effective Connectivity in Adolescent Anorexia Nervosa

Anorexia nervosa (AN) is associated with adolescent onset, severe low body weight, and high mortality as well as high harm avoidance. The brain reward system could have an important role in the perplexing drive for thinness and food avoidance in AN.

To test whether brain reward learning response to taste in adolescent AN is altered and associated with treatment response, striatal-hypothalamic connectivity, and elevated harm avoidance.

Design, Setting, and Participants
In this cross-sectional multimodal brain imaging study, adolescents and young adults with AN were matched with healthy controls at a university brain imaging facility and eating disorder treatment program. During a sucrose taste classical conditioning paradigm, violations of learned associations between conditioned visual and unconditioned taste stimuli evoked the dopamine-related prediction error (PE). Dynamic effective connectivity during sweet taste receipt was studied to investigate hierarchical brain activation across the brain network that regulates eating. The study was conducted from July 2012 to May 2017, and data were analyzed from June 2017 to December 2017.

Main Outcomes and Measures
Prediction error brain reward response across the insula, caudate, and orbitofrontal cortex; dynamic effective connectivity between hypothalamus and ventral striatum; and treatment weight gain, harm avoidance scores, and salivary cortisol levels and their correlations with PE brain response.

Of 56 female participants with AN included in the study, the mean (SD) age was 16.6 (2.5) years, and the mean (SD) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 15.9 (0.9); of 52 matched female controls, the mean (SD) age was 16.0 (2.8) years, and the mean (SD) BMI was 20.9 (2.1). Prediction error response was elevated in participants with AN in the caudate head, nucleus accumbens, and insula (multivariate analysis of covariance: Wilks λ, 0.707; P = .02; partial η2 = 0.296), which correlated negatively with sucrose taste pleasantness. Bilateral AN orbitofrontal gyrus rectus PE response was positively correlated with harm avoidance (right ρ, 0.317; 95% CI, 0.091 to 0.539; P < .02; left ρ, 0.336; 95% CI, 0.112 to 0.550; P < .01) but negatively correlated with treatment BMI change (right ρ, −0.282; 95% CI, −0.534 to −0.014; P < .04; left ρ, −0.268; 95% CI, −0.509 to −0.018; P < .045). Participants with AN showed effective connectivity from ventral striatum to hypothalamus, and connectivity strength was positively correlated with insula and orbitofrontal PE response. Right frontal cortex PE response was associated with cortisol, which correlated with body dissatisfaction.

Conclusions and Relevance
These results further support elevated PE signal in AN and suggest a link between PE and elevated harm avoidance, brain connectivity, and weight gain in AN. Prediction error may have a central role in adolescent AN in driving anxiety and ventral striatal-hypothalamus circuit-controlled food avoidance.