Predicted DRD4 prefrontal gene expression moderates snack intake and stress perception in response to the environment in adolescents.
In plain language
Genes may influence responsiveness to both difficult and supportive environments
A genetic characteristic can be associated with different outcomes in different surroundings. This study explored that idea in adolescent eating behavior, asking whether predicted activity of a dopamine receptor gene changed the relationship between socioeconomic conditions and snack intake.
Testing environmental responsiveness. The study involved 76 adolescents aged fourteen to eighteen in Baltimore. Researchers used DNA data to predict expression of DRD4 in the prefrontal cortex, a brain region involved in regulating behavior. They combined household income, maternal education, food insecurity, perceived resources and receipt of public assistance into a measure of socioeconomic conditions. Adolescents could freely choose how much to eat during a laboratory meal containing several snack foods.
The design allowed the researchers to ask whether the same genetic prediction was associated with different eating patterns in more or less advantaged circumstances. Predicted gene expression was an indirect estimate, not a measurement taken from the adolescent brain.
The direction of the association depended on the environment. Adolescents with lower predicted DRD4 expression ate more snack food in the lower socioeconomic group, but less in the higher socioeconomic group. An exploratory analysis of perceived stress showed a similar pattern: the same lower-expression group reported more stress under less advantaged conditions and less stress under more advantaged conditions.
This crossover pattern is consistent with differential susceptibility, the idea that a biological characteristic can be associated with greater responsiveness to both adverse and supportive environments. It differs from a simple account in which a genetic feature always increases risk. The perceived-stress result raises the possibility that how an environment is experienced contributes to the eating pattern, although the study did not establish that stress mediated the effect.
The sample was small, so the findings need replication. They offer a concrete hypothesis for larger studies: dopamine-related biology may help explain why the same social environment is linked to different behavioral outcomes, and why a marker of vulnerability in one setting can be associated with benefit in another.
Original abstract
Body weight is substantially determined by eating behaviors, which are themselves driven by biological factors interacting with the environment. Previous studies in young children suggest that genetic influences on dopamine function may confer differential susceptibility to the environment in such a way that increases behavioral obesity risk in a lower socioeconomic status (SES) environment but decreases it in a higher SES environment. We aimed to test if this pattern of effect could also be observed in adolescence, another critical period for development in brain and behavior, using a novel measure of predicted expression of the dopamine receptor 4 (DRD4) gene in prefrontal cortex. In a sample of 76 adolescents (37 boys and 39 girls from Baltimore, Maryland/US, aged 14-18y), we estimated individual levels of DRD4 gene expression (PredDRD4) in prefrontal cortex from individual genomic data using PrediXcan, and tested interactions with a composite SES score derived from their annual household income, maternal education, food insecurity, perceived resource availability, and receipt of public assistance. Primary outcomes were snack intake during a multi-item ad libitum meal test, and food-related impulsivity assessed using a food-adapted go/no-go task. A linear regression model adjusted for sex, BMI z-score, and genetic ethnicity demonstrated a PredDRD4 by composite SES score interaction for snack intake (p = 0.009), such that adolescents who had lower PredDRD4 levels exhibited greater snack intake in the lower SES group, but lesser snack intake in the higher SES group. Exploratory analysis revealed a similar pattern for scores on the Perceived Stress Scale (p = 0.001) such that the low PredDRD4 group reported higher stress in the lower SES group, but less stress in the higher SES group, suggesting that PredDRD4 may act in part by affecting perceptions of the environment. These results are consistent with a differential susceptibility model in which genes influencing environmental responsiveness interact with environments varying in obesogenicity to confer behavioral obesity risk in a less favorable environment, but behavioral obesity protection in a favorable one.
Reproduced from the original publication under CC BY 4.0. Wording unchanged; layout and typography normalized.
Portella AK, Papantoni A, Paquet C, Moore S, Rosch KS, Mostofsky S, Lee RS, Smith KR, Levitan R, Silveira PP, Carnell S, Dube L. Predicted DRD4 prefrontal gene expression moderates snack intake and stress perception in response to the environment in adolescents. PloS one. 2020;15(6):e0234601.
Read the original publication and abstract