Cognitive and Affective FunctionResearch PaperGenetic contributions to avoidance-based decisions: striatal D2 receptor polymorphisms
Section snippets
Sample
The sample is the same as that reported in Frank et al. (2007a). There were 69 healthy participants (30 females, 39 males), between the ages of 18 and 35 (M=21). The majority of participants were white, with three participants categorizing themselves as “more than one race.” We were unable to obtain genotypes for one subject for rs2283265/rs1076560, and two subjects for rs12364283.
All SNPs were in Hardy Weinberg equilibrium (P's>0.2). The minor allele frequencies were as follows: rs12364283:
Results
There were no effects of any SNP on overall accuracy during the training phase (P's>0.1). The following analysis focuses on test phase reward and avoidance accuracy, as indicators of whether positive or negative aspects of stimuli drive their choices (Frank et al 2004, Frank et al 2005, Frank et al 2007a, Klein et al 2007).
Discussion
Taken together the above findings suggest multiple functional effects of DRD2 genes on brain D2 receptor function, which in turn contributes to probabilistic avoidance (Table 1). First, we find that the previously reported gene–dose effects of the C957T polymorphism (Frank et al., 2007a) continued to hold even when controlling for other DRD2 SNPs. These results imply a functional effect of C957T, consistent with observations that this SNP influences postsynaptic striatal D2 receptor density (
Conclusion
In sum, we show multiple genetic mechanisms associated with probabilistic avoidance learning, all linked to factors controlling striatal D2 receptor function. These effects contrast with those of other DA-related genes, such as COMT and DARPP-32 which affect other aspects of reinforcement learning. This specificity therefore supports a role for striatal D2 receptors in NoGo learning. It remains to be seen whether these genetic mechanisms generalize to other cognitive functions thought to depend
Acknowledgments
We thank Marilee Morgan and Melynda Byers for help with DNA analysis. This research was supported by NIMH grant R01 MH080066-01.
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