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Reward, decision-making brain regions altered in teens with obesity



Adolescents with obesity show brain changes consistent with degradation of circuitry controlling appetite, reward, and decision making, according to a Brazilian study that used MRI to detect these changes.

Pamela Bertolazzi, of the University of Sao Paulo Kari Oakes

Pamela Bertolazzi

Brain changes were significantly correlated with increased levels of insulin, leptin, and other appetite- and diet-related hormones and neurohormones, as well as with inflammatory markers.

In an interview at the annual meeting of the Radiological Society of North America, Pamela Bertolazzi, a PhD student at the University of São Paulo, explained that childhood obesity in Brazil is estimated to have climbed by up to 40% in recent years, with almost one-third of Brazilian children and adolescents experiencing obesity. Epidemiologists estimate that there’s the potential for 2.6 million premature deaths from this level of overweight and obesity, she said. Brazil has over 211 million residents.

Previous studies have established diffusion tensor imaging as an MRI technique to assess white-matter integrity and architecture. Fractional anisotropy (FA) is a measure of brain tract integrity, and decreased FA can indicate demyelination or axonal degeneration.

Ms. Bertolazzi and colleagues compared 60 healthy weight adolescents with 57 adolescents with obesity to see how cerebral connectivity differed, and further correlated MRI findings with a serum assay of 57 analytes including inflammatory markers, neuropeptides, and hormones.

Adolescents aged 12-16 years were included if they met World Health Organization criteria for obesity or for healthy weight. The z score for the participants with obesity was 2.74, and 0.25 for the healthy-weight participants (P less than .001). Individuals who were underweight or overweight (but not obese) were excluded. Those with known significant psychiatric diagnoses or prior traumatic brain injury or neurosurgery also were excluded.

The mean age of participants was 14 years, and 29 of the 57 (51%) participants with obesity were female, as were 33 of 60 (55%) healthy weight participants. There was no significant difference in socioeconomic status between the two groups.

When participants’ brain MRI results were reviewed, Ms. Bertolazzi and associates saw several regions that had decreased FA only in the adolescents with obesity. In general terms, these brain areas are known to be concerned with appetite and reward.

Decreased FA – indicating demyelination or axonal degeneration – was seen particularly on the left-hand side of the corpus callosum, “the largest association pathway in the human brain,” said Ms. Bertolazzi. Looking at the interaction between decreased FA in this area and levels of various analytes, leptin, insulin, C-peptide, and total glucagonlike peptide–1 levels all were negatively associated with FA levels. A ratio of leptin to the anti-inflammatory cytokine interleukin-10 also had a negative correlation with FA levels. All of these associations were statistically significant.

Decreased FA also was seen in the orbitofrontal gyrus, an area of the prefrontal cortex that links decision making with emotions and reward. Here, significant negative associations were seen with C-peptide, amylin, and the ratios of several other inflammatory markers to IL-10.


“Obesity was associated with a reduction of cerebral integrity in obese adolescents,” said Ms. Bertolazzi. The clinical significance of these findings is not yet known. However, she said that the disruption in regulation of reward and appetite circuitry her study found may set up adolescents with excess body mass for a maladaptive positive feedback loop: elevated insulin, leptin, and inflammatory cytokine levels may be contributing to disrupted appetite, which in turn contributes to ongoing increases in body mass index.

She and her colleagues are planning to enroll adolescents with obesity and their families in nutritional education and exercise programs, hoping to interrupt the cycle. They plan to obtain a baseline serum assay and MRI scan with diffusion tensor imaging and FA, and to repeat the studies about 3 months into an intensive intervention, to test the hypothesis that increased exercise and improved diet will result in reversal of the brain changes they found in this exploratory study. In particular, said Ms. Bertolazzi, they hope that encouraging physical activity will boost levels of HDL cholesterol, which may have a neuroprotective effect.

Ms. Bertolazzi reported no outside sources of funding and no conflicts of interest.

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