Genetic associations with neural reward responsivity to food cues in children.

Objective: To test associations of candidate obesity-related single nucleotide polymorphisms (SNPs) and obesity polygenic risk scores (PRS) with neural reward reactivity to food cues. Methods: After consuming a pre-load meal, 9-12-year-old children completed a functional magnetic resonance imaging (fMRI) paradigm with exposure to food and non-food commercials. Genetic exposures included FTO rs9939609, MC4R rs571312, and a pediatric-specific obesity PRS. A targeted region-of-interest (ROI) analysis for 7 bilateral reward regions and a whole-brain analysis were conducted. Independent associations between each genetic factor and reward responsivity to food cues in each ROI were evaluated using linear models. Results: Analyses included 151 children (M = 10.9 years). Each FTO rs9939609 obesity risk allele was related to a higher food-cue-related response in the right lateral hypothalamus after controlling for covariates including the current BMI Z-score (p < 0.01), however, the association did not remain significant after applying the multiple testing correction. MC4R rs571312 and the PRS were not related to heightened food-cue-related reward responsivity in any examined regions. The whole-brain analysis did not identify additional regions of food-cue-related response related to the examined genetic factors. Conclusion: Children genetically at risk for obesity, as indicated by the FTO genotype, may be predisposed to higher food-cue-related reward responsivity in the lateral hypothalamus in the sated state, which, in turn, could contribute to overconsumption. Clinical trial registration: https://clinicaltrials.gov/study/NCT03766191, identifier NCT03766191.

Genetic associations with consumption of palatable foods in the absence of hunger in response to food cues in children.

OBJECTIVE: The objective of this study is to evaluate obesity-related genetic factors in relation to excess consumption and assess if food cues modify associations. METHODS: Children (9-12 years) completed a randomized crossover experiment. During two visits, children ate a preload and then snacks ad libitum while watching television, embedded with food or non-food advertisements to assess eating in the absence of hunger (EAH). Primary exposures were obesity-associated genotypes, FTO rs9939609 and MC4R rs571312, and a paediatric-specific polygenic risk score (PRS). Outcomes included consumption of all snacks (total EAH) and gummy candy only (gummy candy EAH). Linear mixed-effects models tested whether genetic exposures related to EAH outcomes. We tested for effect modification by food cues using multiplicative interaction terms. RESULTS: Among 177 children, each FTO risk allele was associated with a 30% increase in gummy candy EAH (p = 0.025) in adjusted models. Food cue exposure exacerbated associations between the FTO variant with gummy candy EAH (p = 0.046). No statistically significant associations were found between MC4R and EAH. CONCLUSION: The results suggest children with the FTO rs9939609 risk allele may be predisposed to excess consumption of candy and that this association may be exacerbated by food cues.

Elucidating pathways to pediatric obesity: a study evaluating obesity polygenic risk scores related to appetitive traits in children.

BACKGROUND/OBJECTIVES: Obesity polygenic risk scores (PRS) explain substantial variation in body mass index (BMI), yet associations between PRSs and appetitive traits in children remain unclear. To better understand pathways leading to pediatric obesity, this study aimed to assess the association of obesity PRSs and appetitive traits. SUBJECTS/METHODS: This study included 248 unrelated children aged 9-12 years. DNA from the children was genotyped (236 met quality control thresholds) and four weighted polygenic risk scores from previous studies were computed and standardized: a 97 SNP PRS, 266 SNP pediatric-specific PRS, 466 SNP adult-specific PRS, and ~2 million SNP PRS. Appetitive traits were assessed using a parent-completed Child Eating Behavior Questionnaire, which evaluated food approach/avoidance traits and a composite obesogenic appetite score. BMI was directly measured and standardized by age and sex. Three associations were evaluated with linear regression: (1) appetitive traits and BMI, (2) PRSs and BMI, and (3) PRSs and appetitive traits, the primary association of interest. RESULTS: Expected positive associations were observed between obesogenic appetitive traits and BMI and all four PRSs and BMI. Examining the association between PRSs and appetitive traits, all PRSs except for the 466 SNP adult PRS were significantly associated with the obesogenic appetite score. Each standard deviation increase in the 266 SNP pediatric PRS was associated with an adjusted 2.1% increase in obesogenic appetite score (95% CI: 0.6%, 3.7%, p = 0.006). Significant partial mediation of the PRS-BMI association by obesogenic appetite score was found for these PRSs; for example, 21.3% of the association between the 266 SNP pediatric PRS and BMI was explained by the obesogenic appetite score. CONCLUSIONS: Genetic obesity risk significantly predicted appetitive traits, which partially mediated the association between genetic obesity risk and BMI in children. These findings build a clearer picture of pathways leading to pediatric obesity.

Associations between behavioral self-regulation and external food cue responsiveness (EFCR) in preschool-age children and evidence of modification by parenting style.

Decreased behavioral regulation is hypothesized to be a risk factor for excess weight gain among children, possibly via reduced appetite-specific regulation. Little research has specifically focused on behavioral regulation and food cue responsiveness, a conditioned precursor to eating, at a young age. This study examined the association between behavioral regulation and external food cue responsiveness among preschool-age children and explored if a more structured parenting style moderated that association. Baseline data from a prospective study on media use among preschool-age children (n = 83) in Northern New England were used. Parents reported on three domains of children's behavioral regulation (attentional focusing, inhibitory control, and emotional self-regulation), the children's external food cue responsiveness (EFCR), and their parenting styles (authoritative and permissive) via validated questionnaires. Mean age among children was 4.31 (SD 0.91) years, 57% of children were male, 89% were non-Hispanic white, and 26.2% had overweight or obesity. In a series of adjusted linear regression models, lower attentional focusing (standardized ß, ßs = -0.35, p = 0.001), inhibitory control (ßs = -0.30, p = 0.008), and emotional self-regulation (standardized beta, ßs = -0.38, p < 0.001) were each significantly associated with greater EFCR. In exploratory analyses, a more structured parenting style (more authoritative or less permissive) mitigated the associations between inhibitory control and EFCR (Bonferroni-adjusted p-interaction < 0.017). Findings support that lower attentional focusing, inhibitory control, and emotional self-regulation relate to greater ECFR in preschool-age children. The association between inhibitory control and EFCR may be modified by parenting style. Further research is needed to understand if children's responsiveness to external food cues may account for reported associations between lower behavioral regulation and adiposity gain over time.

Corrigendum: Differential neural reward reactivity in response to food advertising medium in children.

[This corrects the article DOI: 10.3389/fnins.2023.1052384.].

Differential neural reward reactivity in response to food advertising medium in children.

Introduction: Food cues including food advertisements (ads) activate brain regions related to motivation and reward. These responses are known to correlate with eating behaviors and future weight gain. The objective of this study was to compare brain responses to food ads by different types of ad mediums, dynamic (video) and static (images), to better understand how medium type impacts food cue response. Methods: Children aged 9-12 years old were recruited to complete a functional magnetic resonance imaging (fMRI) paradigm that included both food and non-food dynamic and static ads. Anatomical and functional images were preprocessed using the fMRIPrep pipeline. A whole-brain analysis and a targeted region-of-interest (ROI) analysis for reward regions (nucleus accumbens, orbitofrontal cortex, amygdala, insula, hypothalamus, ventral tegmental area, substantia nigra) were conducted. Individual neural responses to dynamic and static conditions were compared using a paired t-test. Linear mixed-effects models were then constructed to test the differential response by ad condition after controlling for age, sex, BMI-z, physical activity, and % of kcal consumed of a participant's estimated energy expenditure in the pre-load prior to the MRI scan. Results: A total of 115 children (mean=10.9 years) completed the fMRI paradigm. From the ROI analyses, the right and left hemispheres of the amygdala and insula, and the right hemisphere of the ventral tegmental area and substantia nigra showed significantly higher responses for the dynamic food ad medium after controlling for covariates and a false discovery rate correction. From the whole-brain analysis, 21 clusters showed significant differential responses between food ad medium including the precuneus, middle temporal gyrus, superior temporal gyrus, and inferior frontal gyrus, and all regions remained significant after controlling for covariates. Discussion: Advertising medium has unique effects on neural response to food cues. Further research is needed to understand how this differential activation by ad medium ultimately affects eating behaviors and weight outcomes.