Neurocognitive investigation of immediate reward selection bias, a putative intermediate phenotype for alcohol use disorders Public Deposited

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  • March 22, 2019
  • Smith, Christopher Thomas
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
  • Immediate reward selection (or Now) bias is defined as the tendency for individuals to preferentially select a smaller, sooner reward over a larger, later reward in a delay discounting task. This behavior has been suggested as an intermediate behavioral phenotype for alcohol use disorders (AUDs). While Now bias has been shown to be elevated in individuals with AUDs, we provide additional support for Now bias as an intermediate phenotype for AUDs by showing it is enhanced in heavy drinking adults (ages 26-40) with no reported AUDs. Furthermore, we found that Now bias is elevated in light drinking adults with at least one first degree relative with an AUD, a key criterion in categorizing a behavior as an intermediate phenotype. Prior work has provided insight onto the genetic basis of Now bias with two studies reporting a role for a polymorphism associated with prefrontal cortex (PFC) dopamine (DA) tone: the Val158Met single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene. One study in adolescent males (Paloyelis et al., 2010) found Now bias to be heightened in COMT Met/Met individuals while another in adult males and females found Now bias was elevated in Val/Val individuals. We sought to further investigate the role of COMT Val158Met genotype in Now bias behavior to resolve the discrepancy between these previous studies. Here, we report data showing that variables that putatively affect frontal DA tone (age, estradiol, and COMT genotype) can explain differences in Now bias according to an inverted-U function--in other words, those with low or high PFC DA display greater Now bias than do individuals with intermediate levels. Furthermore, we found that individuals with lower tonic DA (COMT Val allele carriers) benefited most from putative increases in DA signaling (associated with increasing estradiol levels). While, the neural bases of Now bias and the role of DA in this behavior remain to be studied in further detail, our data suggests that considering individual differences in DA signaling according to an inverted-U model may be critical in any future treatments aimed at reducing Now bias with dopaminergic drugs or other interventions targeted at PFC function.
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  • In Copyright
  • Boettiger, Charlotte
  • Doctor of Philosophy
Graduation year
  • 2014

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