Integrating behavioral economics and behavioral genetics: delayed reward discounting as an endophenotype for addictive disorders.
- Authors
- MacKillop, James
- Year
- 2013
- Journal
- Journal of the experimental analysis of behavior
- PMID
- 23344986
- DOI
- 10.1002/jeab.4
- PMCID
- PMC3881595
Delayed reward discounting is a behavioral economic index of impulsivity, referring to how much an individual devalues a reward based on its delay in time. As a behavioral process that varies considerably across individuals, delay discounting has been studied extensively as a model for self-control, both in the general population and in clinical samples. There is growing interest in genetic influences on discounting and, in particular, the prospect of discounting as an endophenotype for addictive disorders (i.e., a heritable mechanism partially responsible for conferring genetic risk). This review assembles and critiques the evidence supporting this hypothesis. Via numerous cross-sectional studies and a small number of longitudinal studies, there is considerable evidence that impulsive discounting is associated with addictive behavior and appears to play an etiological role. Moreover, there is increasing evidence from diverse methodologies that impulsive delay discounting is temporally stable, heritable, and that elevated levels are present in nonaffected family members. These findings suggest that impulsive discounting meets the criteria for being considered an endophenotype. In addition, recent findings suggest that genetic variation related to dopamine neurotransmission is significantly associated with variability in discounting preferences. A significant caveat, however, is that the literature is modest in some domains and, in others, not all the findings have been supportive or consistent. In addition, important methodological considerations are necessary in future studies. Taken together, although not definitive, there is accumulating support for the hypothesis of impulsive discounting as an endophenotype for addictive behavior and a need for further systematic investigation.
Prototypic hyperbolic delayed reward discounting curves reflecting the discounted subjective value of $100 delayed from 1 day to 1 year (curves reflect the immediate discounted value). At 100 days, $100 has lost ~50% of its nominal value for the less impulsive profile and ~90% of its nominal value for the high impulsivity profile.
Aggregated differences between criterion groups comprising individuals exhibiting various forms of addictive behavior and control participants in units of effect size (Cohenβs d); data from MacKillop et al. (2011).
The endophenotype approach in psychiatric genetics and delay discounting as an endophenotype. Panel A presents the conceptual premise, that for heritable polygenic conditions such as addictive disorders, alternative mechanistic phenotypes are necessary to map the relationship from genetic factors to risk for the condition. These phenotypes are defined as stable and heritable features of the individual that predate the onset of the condition, are independent of the condition itself, but are probabilistically related to the development of the condition. Panel B provides the elaborated endophenotype model that includes the additional relevant levels of analysis, including the direct effects of genetic variation on protein transcription, those effects on larger biological systems, the proximal endophenotype, and, ultimately, disorder liability. For both panels, the number of spaces in the arrows reflecting relationships reflects the putative strength of the relationship, with fewer spaces reflecting stronger relationship and vice versa.
Delay discounting as an endophenotype for addictive disorders. Genetic variation related to dopamine neurotransmission is hypothesized to affect the neuroanatomical and neurochemical substrates responsible for variation intertemporal choice. Variants associated with more impulsive discounting as a trait are hypothesized to constitute a risk factor for addictive disorders. The number of spaces in the arrows reflecting relationships reflects the putative strength of the relationship, with fewer spaces reflecting stronger relationship and vice versa.
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| Title | Year | PMID |
|---|---|---|
| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | 2015 | 26236574 |
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