Genetically-predicted prefrontal DRD4 gene expression modulates differentiated brain responses to food cues in adolescent girls and boys.
In plain language
Why food cues may engage adolescent brains differently
A picture of food can attract attention even after a meal. During adolescence, the brain systems that connect attention, motivation and behavioral control are still developing. This study asked whether inherited differences related to a dopamine receptor help explain how adolescent girls and boys respond to food cues when they are already full.
Linking genetic prediction with brain imaging. The researchers used participants’ DNA to estimate expression of DRD4, the gene for the dopamine D4 receptor, in prefrontal brain regions. Gene expression means the activity involved in producing a gene’s biological product. The estimates came from a statistical model trained on genetic and gene-expression data; the researchers did not take samples from participants’ brains.
Adolescents then viewed cues for foods with high or low energy density, as well as non-food cues, during functional MRI. This imaging method detects blood-oxygen changes associated with brain activity. Testing participants after eating helped focus the experiment on food responsiveness in a satiated state rather than on responses to an immediate energy deficit.
The pattern differed between girls and boys. Girls with lower predicted prefrontal DRD4 expression showed less activation to food cues in a distributed set of regions involved in attention and sensory or movement-related processing. For low-energy-density foods, differences also appeared in regions involved in evaluating reward and value, including the orbitofrontal and ventromedial prefrontal cortex. Boys showed fewer differences, with a more localized pattern in the inferior parietal region.
These results suggest that dopamine-related genetic variation may be associated with the way food information is processed, and that the association can depend on sex during adolescence. They do not mean that lower activation necessarily produces more eating, less self-control or a particular body weight. The contribution is more specific: a candidate genetic influence on food responsiveness was linked to measurable differences across brain networks, providing a bridge between genetic studies of eating behavior and studies of brain function.
Original abstract
The dopamine receptor 4 (DRD4) in the prefrontal cortex (PFC) acts to modulate behaviours including cognitive control and motivation, and has been implicated in behavioral inhibition and responsivity to food cues. Adolescence is a sensitive period for the development of habitual eating behaviors and obesity risk, with potential mediation by development of the PFC. We previously found that genetic variations influencing DRD4 function or expression were associated with measures of laboratory and real-world eating behavior in girls and boys. Here we investigated brain responses to high energy-density (ED) and low-ED food cues using an fMRI task conducted in the satiated state. We used the gene-based association method PrediXcan to estimate tissue-specific DRD4 gene expression in prefrontal brain areas from individual genotypes. Among girls, those with lower vs. higher predicted prefrontal DRD4 expression showed lesser activation to high-ED and low-ED vs. non-food cues in a distributed network of regions implicated in attention and sensorimotor processing including middle frontal gyrus, and lesser activation to low-ED vs non-food cues in key regions implicated in valuation including orbitofrontal cortex and ventromedial PFC. In contrast, males with lower vs. higher predicted prefrontal DRD4 expression showed minimal differences in food cue response, namely relatively greater activation to high-ED and low-ED vs. non-food cues in the inferior parietal lobule. Our data suggest sex-specific effects of prefrontal DRD4 on brain food responsiveness in adolescence, with modulation of distributed regions relevant to cognitive control and motivation observable in female adolescents.
Reproduced from the original publication under CC BY 4.0. Wording unchanged; layout and typography normalized.
Portella AK, Papantoni A, Joseph AT, Chen L, Lee RS, Silveira PP, Dube L, Carnell S. Genetically-predicted prefrontal DRD4 gene expression modulates differentiated brain responses to food cues in adolescent girls and boys. Sci Rep. 2021 Dec 16;11(1):24094. doi: 10.1038/s41598-021-02797-9. PMID: 34916545; PMCID: PMC8677785.
Read the original publication and abstract