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

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.