Genetically-predicted prefrontal DRD4 gene expression modulates differentiated brain responses to food cues in adolescent girls and boys

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.

The role of the genetic influence of DRD4 in Chinese adults in the context of the choice of tourist attractions

“…It is also necessary to improve the accounting and subsequent analysis of personal characteristics in the study that affect the motives of choice in a person, and it is desirable to use formalized scales with a rank assessment of a trait on a point basis (Molins et al, 2022). Portella et al (2021) studied that among the polymorphic variants of the DRD4 gene, the 7R allele appears to be a factor contributing to neurobiological mechanisms for attenuating the response to dopamine, and carriers of this polymorphism may be more likely to increase brain dopamine levels through aberrant eating behaviour or excessive consumption of stimulants in response to negative environmental stimuli, as genes involved in dopaminergic functions play an important role in reward and reinforcement processes. So, Gervasini et al (2018) found that DRD42R-type carriers showed higher rates of somatization, obsessive-compulsive disorder, phobic anxiety and paranoid patterns compared to DRD4R types.…”

Overweight/Obesity-related microstructural alterations of the fimbria-fornix in the ABCD study: The role of aerobic physical activity

“…For example, an increase in BMI in females may be related to more prominent alterations in core reward network regions associated with emotional regulation than in males [ 49 , 50 ]. Genetic contribution to the sex-dependent development in the reward circuit has also been reported [ 51 ]. These studies support that sex-specific brain alterations preceding weight gain may contribute to our results.…”