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Elevated reward region responsivity predicts future substance use onset but not overweight/obesity onset.

ABSTRACT: We tested the hypotheses that adolescents who show elevated reward region responsivity are at increased risk for initial onset of overweight/obesity and substance use, which is important because there have been no such prospective tests of the reward surfeit model of these motivated behaviors.One hundred sixty-two adolescents (mean age = 15.3±1.06 years) with healthy weights (mean body mass index = 20.8±1.90) completed functional magnetic resonance imaging paradigms that assessed neural activation in response to receipt and anticipated receipt of palatable food and monetary reward; body fat and substance use were assessed at baseline and 1-year follow-up.Elevated caudate (r = .31, p<.001) and putamen (r = .28, p<.001) response to monetary reward predicted substance use onset over 1-year follow-up, but reward circuitry responsivity did not predict future overweight/obesity onset. Adolescents who reported substance use versus abstinence at baseline also showed less caudate (r =-.31, p<.001) response to monetary reward.Results show that hyper-responsivity of reward circuitry increases risk for future substance use onset, providing novel support for the reward surfeit model. Results also imply that even a limited substance use history was associated with reduced reward region responsivity, extending results from studies that compared substance-dependent individuals with healthy control subjects and suggesting that substance use downregulates reward circuitry. However, aberrant reward region responsivity did not predict initial unhealthy weight gain.

SUBMITTER: Stice E

PROVIDER: S-EPMC3774523 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Elevated reward region responsivity predicts future substance use onset but not overweight/obesity onset.

Stice Eric E Stice Eric E Yokum Sonja S Burger Kyle S KS

Biological psychiatry 20130108 9

<h4>Background</h4>We tested the hypotheses that adolescents who show elevated reward region responsivity are at increased risk for initial onset of overweight/obesity and substance use, which is important because there have been no such prospective tests of the reward surfeit model of these motivated behaviors.<h4>Methods</h4>One hundred sixty-two adolescents (mean age = 15.3±1.06 years) with healthy weights (mean body mass index = 20.8±1.90) completed functional magnetic resonance imaging para ...[more]

PMID: 23312561

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Project description: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.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.

Project description:BACKGROUND:The association between obesity and cardiovascular disease (CVD) is proven, but why some adults with obesity develop CVD while others remain disease-free is poorly understood. Here, we investigated whether mitochondrial DNA (mtDNA) methylation in platelets is altered prior to CVD development in a population of adults with overweight and obesity. METHODS:We devised a nested case-control study of 200 adults with overweight or obesity who were CVD-free at baseline, of whom 84 developed CVD within 5 years, while 116 remained CVD-free. Platelet mtDNA was isolated from plasma samples at baseline, and mtDNA methylation was quantified in mitochondrially encoded cytochrome-C-oxidase I (MT-CO1; nt6797 and nt6807), II (MT-CO2; nt8113 and nt8117), and III (MT-CO3; nt9444 and nt9449); tRNA leucine 1 (MT-TL1; nt3247 and nt3254); D-loop (nt16383); tRNA phenylalanine (MT-TF; nt624); and light-strand-origin-of-replication (MT-OLR; nt5737, nt5740, and nt5743) by bisulfite-pyrosequencing. Logistic regression was used to estimate the contribution of mtDNA methylation to future CVD risk. ROC curve analysis was used to identify the optimal mtDNA methylation threshold for future CVD risk prediction. A model was generated incorporating methylation at three loci (score 0, 1, or 2 according to 0, 1, or 2-3 hypermethylated loci, respectively), adjusted for potential confounders, such as diastolic and systolic blood pressure, fasting blood glucose, and cholesterol ratio. mtDNA methylation at MT-CO1 nt6807 (OR = 1.08, 95% CI 1.02-1.16; P = 0.014), MT-CO3 nt9444 (OR = 1.22, 95% CI 1.02-1.46, P = 0.042), and MT-TL1 nt3254 (OR = 1.30, 95% CI 1.05-1.61, P = 0.008) was higher at baseline in those who developed CVD by follow-up, compared with those who remained CVD-free. Combined use of the three loci significantly enhanced risk prediction, with hazard ratios of 1.38 (95% CI 0.68-2.78) and 2.68 (95% CI 1.41-5.08) for individuals with score 1 or 2, respectively (P = 0.003). Methylation at these sites was independent of conventional CVD risk factors, including inflammation markers, fasting blood glucose concentration, and blood pressure. CONCLUSIONS:Methylations of MT-CO1, MT-CO3, and MT-TL1 are, together, strong predictors of future CVD incidence. Since methylation of these mtDNA domains was independent of conventional CVD risk factors, these markers may represent a novel intrinsic predictor of CVD risk in adults with overweight and obesity.

Project description:Background: Both an elevated brain-reward-region response to palatable food and elevated weight variability have been shown to predict future weight gain.Objective: We examined whether the brain-reward response to food is related to future weight variability.Design: A total of 162 healthy-weight adolescents, who were aged 14-18 y at baseline, were enrolled in the study and were assessed annually over a 3-y follow-up period with 127 participants completing the final 3-y follow-up assessment. With the use of functional magnetic resonance imaging, we tested whether the neural responses to a cue that signaled an impending milkshake receipt and the receipt of the milkshake predicted weight variability over the follow-up period. Weight variability was modeled with a root mean squared error method to reflect fluctuations in weight independent of the net weight change.Results: Elevated activation in the medial prefrontal cortex and supplementary motor area, cingulate gyrus, cuneus and occipital gyrus, and insula in response to milkshake receipt predicted greater weight variability. Greater activation in the precuneus and middle temporal gyrus predicted lower weight variability.Conclusions: From our study data, we suggest that the elevated activation of reward and emotional-regulation brain regions (medial prefrontal cortex, cingulate cortex, and insula) and lower activation in self-reference regions (precuneus) in response to milkshake receipt predict weight variability over 3 y of follow-up. The fact that the reward response in the current study emerged in response to high-calorie palatable food receipt suggests that weight variability may be a measure of propensity periods of a positive energy balance and should be examined in addition to measures of the net weight change. With our collective results, we suggest that weight variability and its brain correlates should be added to other variables that are predictive of weight gain to inform the design of obesity-preventive programs in adolescents. This trial was registered at clinicaltrials.gov as NCT01807572.

Dataset Information

Elevated reward region responsivity predicts future substance use onset but not overweight/obesity onset.

Publications

Elevated reward region responsivity predicts future substance use onset but not overweight/obesity onset.

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