The Chocolate Study

Obese vs lean humans show greater gustatory/oral somatosensory and reward region responsivity
to palatable food images/cues and this predicts future weight gain (Yokum et al., 2011; Stice
et al., 2008, 2010b; Stoeckel et al., 2008), in line with reward surfeit and incentive
sensitization models of obesity (Berridge, 2009; Davis et al., 2004). Yet, obese vs lean
humans have fewer dopamine (DA) receptors in striatal reward regions, show reduced striatal
response to palatable food intake, and low striatal response predicts future weight gain in
those at genetic risk for reduced DA signaling (Felsted et al., 2010; Stice et al., 2008;
Wang et al., 2001; Volkow et al., 2008), in line with the reward deficit model of obesity
(Wang et al., 2002b). One explanation for the mixed findings is that some of these findings
reflect initial risk factors and others result from overeating. Firing of DA neurons in
reward regions shifts from food intake to cues that predict food intake after conditioning
(Kiyatkin et al., 1994; Schultz et al., 1993) and overeating leads to reduced D2 receptor
density, D2 sensitivity, and reward sensitivity in rats (Alsio et al., 2010; Kelley et al.,
2003; Johnson & Kenny, 2010) and striatal response to food in humans (Stice et al., 2010a),
implying that overeating leads to increased incentive sensitization and down-regulation of
reward regions. Further, reduced inhibitory region response to food images/cues predicts
future overeating and weight gain (Cornier et al., 2010). Data imply that youth at risk for
obesity initially show greater responsivity of regions that encode the reward value of food
cues, coupled with greater responsivity of gustatory/oral somatosensory regions that encode
the sugar and fat content of foods, and with reduced inhibitory region responsivity, which
lead to overeating/weight gain that produces blunted striatal DA signaling, increased
responsivity of reward valuation regions to food cues, and reduced inhibitory activation in
response to food stimuli, increasing risk for further overeating/weight gain. We propose to
conduct a rigorous test of this dynamic-vulnerability model using a novel repeated measures
fMRI design in which teens complete scans annually over 4 years. Aim 1: test whether elevated
gustatory/oral somatosensory and reward region responsivity and reduced inhibitory region
responsivity to palatable food images, cues, and intake of food varying in sugar/fat content,
and behavioral inhibitory control deficits/immediate reward bias predict initial increases in
% body fat in 130 lean teens. Aim 2: use growth curve models to test whether initial
increases in % body fat and energy dense food intake predict future decreases in striatal
response to palatable food receipt, increases in reward circuitry response to palatable food
images/cues, decreased inhibitory region response to food images/cues, and increased
behavioral inhibitory control deficits/immediate reward bias. Aim 3: test whether decreased
striatal response to palatable food, increased reward region response to food images/cues,
reduced inhibitory region response to food images/cues, behavioral inhibitory control
deficits/immediate reward bias predict further escalation in % body fat.

Inclusion Criteria:

- between 14-16 years old

- BMI between 25th and 75th percentile

Exclusion Criteria:

- contraindicators of functional magnetic resonance imaging (fMRI)

1. metal implants

2. braces

3. pregnancy

- symptoms of major psychiatric disorders (substance use disorders, conduct disorder,
attention deficit hyperactive disorder, major depression, bipolar disorder, panic
disorder, agoraphobia, generalized anxiety disorder)

- binge eating

- use of pyschoactive drugs

- serious medical conditions (diabetes, brain injury)

- smoking

- dietary allergy to dairy