Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4

Abstract

Objective: To determine whether responsivity of reward circuitry to food predicts future increases in body mass and whether polymorphisms in DRD2 and DRD4 moderate these relations.

Design: The functional magnetic resonance imaging (fMRI) paradigm investigated blood oxygen level dependent activation in response to imagined intake of palatable foods, unpalatable foods, and glasses of water shown in pictures. DNA was extracted from saliva samples using standard salting-out and solvent precipitation methods.

Participants: Forty-four adolescent female high school students ranging from lean to obese.

Main outcome: Future increases in body mass index (BMI).

Results: Weaker activation of the frontal operculum, lateral orbitofrontal cortex, and striatum in response to imagined intake of palatable foods, versus imagined intake of unpalatable foods or water, predicted future increases in body mass for those with the DRD2 TaqIA A1 allele or the DRD4-7R allele. Data also suggest that for those lacking these alleles, greater responsivity of these food reward regions predicted future increases in body mass.

Discussion: This novel prospective fMRI study indicates that responsivity of reward circuitry to food increases risk for future weight gain, but that genes that impact dopamine signaling capacity moderate the predictive effects, suggesting two qualitatively distinct pathways to unhealthy weight gain based on genetic risk.

Figure 1

A. Coronal section of increased activation in a region of the putamen (−15, 6, 3, Z = 3.59, P < 0.05 FDR corrected) during appetizing food - unappetizing food as a function of BMI with B. the graph of parameter estimates (PE) from that region. C. Axial section of increased activation in the lateral OFC (33, 27, −12, Z = 4.01, P < 0.05 FDR corrected) during appetizing food – water as a function of BMI with D. the graph of PE from that region.

Figure 2

A1 allele of the DRD2 attenuates the relation between concurrent Body Mass Index (BMI) and response in a region of the OFC (36, 27, −15, Z = 3.27, P < 0.05 FDR corrected) during appetizing food – unappetizing food.

Figure 3

A. Activation in a region of the putamen (−15, 6, 3, Z = 3.59, P < 0.05 FDR corrected) during appetizing food - unappetizing food was negatively related to predicted values of future weight gain for participants with the A1 allele, but positively related to predicted values of future weight gain for participants without the A1 allele. B. Activation in the lateral OFC (36, 27, −15, Z = 3.27, P < 0.05 FDR corrected) during appetizing food – unappetizing food was negatively related to predicted values of future weight gain for participants with the A1 allele, but positively related to predicted values of future weight gain for participants without the A1 allele.

Figure 4

Activation in a region of the frontal operculum (33, 27, −12, Z = 4.01, P < 0.05 FDR corrected) was A negatively related to predicted values of future weight gain for participants with the A1 allele, but positively related to predicted values of future weight gain for participants without the A1allele and B negatively related to predicted values of future weight gain for participants with the 7-repeat allele of the DRD4, but positively related to predicted values of future weight gain for participants without the 7-repeat allele.