PT  - JOURNAL ARTICLE
AU  - Eric Stice
AU  - Sonja Yokum
AU  - Kyle Burger
AU  - Leonard Epstein
AU  - Andy Smolen
TI  - Multilocus Genetic Composite Reflecting Dopamine Signaling Capacity Predicts Reward Circuitry Responsivity
AID  - 10.1523/JNEUROSCI.1506-12.2012
DP  - 2012 Jul 18
TA  - The Journal of Neuroscience
PG  - 10093--10100
VI  - 32
IP  - 29
4099  - http://www.jneurosci.org/content/32/29/10093.short
4100  - http://www.jneurosci.org/content/32/29/10093.full
SO  - J. Neurosci.2012 Jul 18; 32
AB  - The objective of the study was to test the hypotheses that humans with genotypes putatively associated with low dopamine (DA) signaling capacity, including the TaqIA A1 allele, DRD2-141C Ins/Ins genotype, DRD4 7-repeat or longer allele, DAT1 10-repeat allele, and the Met/Met COMT genotype, and with a greater number of these genotypes per a multilocus composite, show less responsivity of reward regions that primarily rely on DA signaling. Functional magnetic resonance imaging (fMRI) paradigms were used to investigate activation in response to receipt and anticipated receipt of palatable food and monetary reward. DNA was extracted from saliva using standard methods. Participants were 160 adolescents (mean age = 15.3 years, SD = 1.07 years; mean body mass index = 20.8, SD = 1.9). The main outcome was blood oxygenation level-dependent activation in the fMRI paradigms. Data confirmed that these fMRI paradigms activated reward, attention, somatosensory, and gustatory regions. Individuals with, versus without, these five genotypes did not show less activation of DA-based reward regions, but those with the Met/Met versus the Val/Val COMT genotype showed less middle temporal gyrus activation and those with the DRD4-L versus the DRD4-S genotype showed less middle occipital gyrus activation in response to monetary reward. Critically, the multilocus composite score revealed that those with a greater number of these genotypes showed less activation in reward regions, including the putamen, caudate, and insula, in response to monetary reward. The results suggest that the multilocus genetic composite is a more sensitive index of vulnerability for low reward region responsivity than individual genotypes.