Reward Region Responsivity Predicts Future Weight Gain and Moderating Effects of the TaqIA Allele

Abstract

Because no large prospective study has investigated neural vulnerability factors that predict future weight gain, we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over a 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. A total of 153 adolescents completed fMRI paradigms assessing response to these events; body fat was assessed annually over follow-up. Elevated orbitofrontal cortex response to cues signaling impending milkshake receipt predicted future body fat gain (r = 0.32), which is a novel finding that provides support for the incentive sensitization theory of obesity. Neural response to receipt and anticipated receipt of monetary reward did not predict body fat gain, which has not been tested previously. Replicating an earlier finding (Stice et al., 2008a), elevated caudate response to milkshake receipt predicted body fat gain for adolescents with a genetic propensity for greater dopamine signaling by virtue of possessing the TaqIA A2/A2 allele, but lower caudate response predicted body fat gain for adolescents with a genetic propensity for less dopamine signaling by virtue of possessing a TaqIA A1 allele, though this interaction was only marginal [p-value <0.05 corrected using voxel-level familywise error rate (pFWE) = 0.06]. Parental obesity, which correlated with TaqIA allele status (odds ratio = 2.7), similarly moderated the relation of caudate response to milkshake receipt to future body fat gain, which is another novel finding. The former interaction implies that too much or too little dopamine signaling and reward region responsivity increases risk for overeating, suggesting qualitatively distinct reward surfeit and reward deficit pathways to obesity.

Significance statement: Because no large prospective study has investigated neural vulnerability factors that predict future weight gain we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. Elevated reward activation in response to food cues predicted future body fat gain. Elevated reward response to food receipt predicted body fat gain for adolescents with a TaqIA A2/A2 allele and lower reward response predicted body fat gain for those with a TaqIA A1 allele. Results imply that too much or too little dopamine signaling and reward region responsivity increases risk for overeating.

Keywords: obesity; prospective fMRI; reward sensitivity; weight gain.

Conflict of interest statement

The authors declare no competing financial interests.

Copyright © 2015 the authors 0270-6474/15/3510316-09$15.00/0.

Figures

Figure 1.

Example of timing and ordering of presentation of pictures and beverages during the food reward paradigm (A) and of presentation of images and notification of monetary reward during the monetary reward paradigm (B).

Figure 2.

Correlation between baseline body fat percentage and 3-year follow-up body fat percentage.

Figure 3.

Greater BOLD response and parameter estimates from the orbitofrontal cortex (circles; MNI coordinates: 33, 18, −21, Z = 3.9) and greater BOLD response in a region in the frontal pole (square; MNI coordinates: 24, 51, 21, Z = 3.3) in response to the anticipatory milkshake cue-predicted future body fat gain over 3-year follow-up.

Figure 4.

A, Greater BOLD response in the precuneus (MNI coordinates: 0, −60, 30, Z = 3.4, r = 0.28) in response to milkshake receipt predicted future body fat gain over 3-year follow-up. B, Lower BOLD response in the visual cortex, lingual gyrus and vmPFC (r values −0.40 to −0.32) predicted future body fat gain over 3-year follow-up. C, Greater BOLD response in the caudate during milkshake receipt predicted body fat gain for participants without an A1 allele, but lower caudate response predicted future body fat change for participants with the A1 allele (MNI coordinates: −18, 6, 21, Z = 3.0, r = 0.24). D, Greater BOLD response in the caudate during milkshake receipt predicted future body fat gain for participants without parental obesity, but lower caudate response predicted body fat gain for participants with parental obesity (MNI coordinates: 18, −3, 24, Z = 3.8, r = 0.31).