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This article is from the In-Depth Report New Insights into Obesity

The Goldilocks Principle of Obesity

For healthy body weight, the brain's reward system may need to be 'just right'



bluestocking

How pleasurable and desirable does this image of chocolate cake appear to you?

Research has shown that the more tempting this cake looks to you, the greater the chances you’ll take a bite of real cake, followed by another bite, and another. Before you know it, you may eventually find yourself like 34% of U.S. adults -- obese. But what if I told you that viewing this picture as not rewarding enough might also lead you down the path to obesity?

An exciting brain imaging and genetics study from the laboratory of Eric Stice at the Oregon Research Institute, recently published in the journal NeuroImage, has shown just that. Stice’s team had a group of adolescent girls imagine eating appetizing foods while viewing pictures of these foods. Over the following year, those whose brains showed less activation in areas known to respond to natural rewards like foods ended up gaining more weight -- though only if they had a particular genetic makeup.

Genetic factors
may play a large role in obesity. Some have estimated that 60-70% of the variability in a person’s  body mass index or BMI, which is a proxy measure for body fat based on weight and height,  is attributable to genetic factors. However, there has been a dramatic increase in the prevalence of obesity over the past 50 years, which is far too little time for changes in the genome to have occurred. What appears to account for this rise in obesity is a complex interaction between genetic and environmental factors. We now find ourselves in what some term an ‘obesogenic’ environment filled with cheap, easily accessible high-calorie foods served in large portions. Genetic risk factors may make some individuals more susceptible to these changes in the environment, and thus more prone to obesity.

Dopamine is an important neurotransmitter that is thought, in part, to mediate reward responses to foods, especially the drive to consume foods. When neuroscientists scanned the brains of obese individuals viewing images of desirable food, they found greater activity in brain regions rich in dopamine receptors. These are the same regions of the brain activated by addictive drugs and thought to lead to addiction. “Eureka!” said many brain scientists. “I bet people exhibiting greater activity in brain regions encoding food reward will be at increased risk for obesity!” The more rewarding the food, in other words, the more likely you are to eat too much of it and pack on the pounds.

But there was another camp of researchers who posited that there was decreased, not increased, reward activity in the brains of obese individuals. Following this hypothesis, overeating serves as a compensatory strategy to normalize this reward deficit. If you find food less rewarding, in other words, you eat too much in search of finding a ‘normal’ reward experience, and thus gain weight. This phenomenon is known as ‘reward deficiency syndrome’. Might there be radically different types of obesity? True, some obese people tend to show high reward activity when viewing food images. But some appear to have fewer dopamine D2 receptors in key reward regions of the brain than other people -- much like drug addicts. Fewer dopamine D2 receptors result in lower dopamine activity, which has been shown to lead to increased food consumption and weight gain. And our diet may be at least partly to blame: Gobbling down the delicious high-fat, high-sugar foods many of us enjoy appears to reduce the number of dopamine D2 receptors in the brain’s reward circuitry and leads to compulsive overeating.
 
So both increased and decreased reward sensitivity could lead to obesity? One lab reconciled these seemingly disparate ideas by focusing on sensitivity to reward, a psychobiological trait assumed to be rooted in the dopamine reward system. If you’re a healthy weight or somewhat overweight, the more sensitive you are to rewards, the heavier you tend to be. But if you’re obese, the less sensitive you are to rewards, the heavier you tend to be. This is especially true as obesity becomes more extreme. Thus, it is possible that the relationship between reward neurocircuitry and obesity follows the Goldilocks principle – too much or too little reward system activation may lead to weight gain. In order to maintain a healthy weight, reward system activation needs to be ‘just right.’  

Might there be some tipping point, at which higher reward sensitivity gets eroded too far, into lower sensitivity? There could be a transition in obesity, as has been suggested for addiction, where overconsumption of appetizing foods is initially driven by reward, but then becomes less reward driven and more automatic and compulsive over time. This is a very interesting idea that warrants further investigation.

Stice’s study seems to support the Goldilocks theory of obesity by providing rich brain imaging and genetics data in a prospective research design that allows us to begin teasing out the causes vs. consequences of obesity. Using fMRI, his team scanned the brains of adolescent girls with differing BMIs while they viewed pictures of appetizing foods and imagined eating what they saw. Stice’s group also genotyped these young women to determine whether or not they possessed variant alleles of two genes (DRD2 Taq1A A1 and DRD4-7+) that have been linked with lower dopamine activity and, in some studies, obesity. They then followed these young women for one year and measured changes in their BMI.

Overall, they found that adolescent girls with greater BMI showed increased reward region activation in response to food images. They also found that girls with greater reward activation gained more weight. A victory for the ‘increased reward activity’ camp! Not so fast. Remember the genetic testing? The study’s results suggested that girls whose brains showed less reward system activation to foods also gained more weight -- if they had the DRD2 Taq1AQ1 or the DRD4 7+ repeat alleles. So perhaps people whose genes incline them toward low dopamine activity are at particular risk for a subtype of obesity stemming from low food reward.  

It appears that both camps were right. Stice’s group has shown that viewing the cake above as too tempting or not tempting enough may lead you down the path to obesity…but your genes are key. This has enormous treatment implications, as we can try to develop patient-centered interventions that help normalize reward function in some obese individuals’ brains. We may eventually be able to figure out who needs their dopamine cranked up, and who needs it ratcheted down, to live well in our obesogenic world.

As with all research studies, these ideas need to be qualified with what scientists call the ‘caveats’ section. This study observed a somewhat small number of study participants with the dopamine variants (13 with DRD2 Taq1A A1 and 11 with DRD4-7+). There may be additional candidate brain regions and interesting effects that were not detected, and the findings should be verified with a larger group of participants. This study was also limited to adolescent young women of European American descent. It is possible that the relationship between genetics, brain function, and behavior differs by gender, age, and ethnicity. Future studies should consider investigating these relationships.

Finally, I leave you with something to ponder. The latest edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is scheduled to come out in May 2013. For the first time, it will include a diagnostic category for ‘behavioral addictions.’ A growing literature continues to build evidence showing neurobiological and behavioral parallels between addiction, pathological gambling, and obesity. Pathological gambling is just being introduced in the DSM-V as a ‘behavioral addiction’.

Is food addiction next?

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