Functional MRI establishes link between brain receptor activation and obesity

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Kathryn Madden, science administrator, Oregon Research Institute

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Using brain imaging and chocolate milkshakes, scientists have found that women with weakened "reward circuitry" in their brains are at increased risk of weight gain over time and potential obesity. The risk increases even more for women who also have a gene associated with compromised dopamine signaling in the brain.

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The results, drawn from two studies using functional MRI at the University of Oregon's Lewis Center for Neuroimaging, appear in the Oct. 17 issue of the journal Science. The first-of-its-kind approach unveiled blunted activation in the brain's dorsal stratium, which may reflect less-than-normal dopamine output, when subjects were given milkshakes.

Although recent findings have suggested that obese individuals may experience less pleasure when eating, and therefore eat more to compensate, this is the first prospective evidence for this relationship, according to lead author Eric Stice, Ph.D.

"The evidence of temporal precedence suggests it is a true vulnerability factor that predates obesity onset," he said. "In addition, the evidence that this relation is even stronger for individuals at genetic risk for compromised signaling in these brain regions points to an important biological factor that appears to increase risk for obesity onset."

Stice, a senior researcher at the Oregon Research Institute in Eugene, has studied eating disorders and obesity for 18 years. His collaborators in the fMRI study were researcher Sonja T.P. Spoor, Ph.D., Cara Bohon, a University of Oregon doctoral candidate in clinical psychology, and Dana M. Small, Ph.D., an associate professor of psychiatry at the Yale University School of Medicine.

Dopamine is the primary neurotransmitter in the brain's reward pathways. Food intake is associated with dopamine release, and pleasure from eating correlates with the amount of dopamine release. Previous studies have suggested that obese individuals have fewer dopamine receptors in the brain and have to eat more than lean people to be satisfied, but those studies were based on fMRI of subjects watching pictures of food.

In this latest fMRI experiment, imaging was performed while the subjects were actually eating. Stice and colleagues measured the extent to which the dorsal striatum was activated in response to an individual's receipt of a taste of chocolate milkshake or a tasteless solution.

One study involved 43 female college students ranging in age from 18 to 22 with a mean body mass index of 28.6. A second investigation examined 33 adolescent girls, ages 14 to 18, with a mean body mass index of 24.3. Most participants were tested for the presence of a genetic variation known as the Taq1A1 allele that is linked to a lower number of dopamine D2 receptors.

Researchers tracked changes in mean body index for a year. Results showed that participants with decreased striatal activation in response to receiving milkshake and those with the A1 allele were more likely to gain weight over time.

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"These results suggest that individuals with hypofunctioning reward circuitry are at increased risk for unhealthy weight gain," Stice said. "Thus, it is possible that behavioral or pharmacological interventions that correct this reward deficit may help prevent and treat obesity — an avenue we are currently pursuing in our research."

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The National Institutes of Health funded the study.

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Bohon noted that the results were drawn from the first prospective study using fMRI and genetic data to predict unhealthy weight gain.

"The findings suggest that certain biological factors may impact one's risk for weight gain, which is important in order to better understand how we can eventually intervene and prevent obesity," she said.