This is indeed an interesting study. The authors have combined fMRI analysis with detailed assessment of learning and DRD2 genotype. It is intriguing that only avoidance learning is affected, not other processes. This points to the importance of choosing the proper outcome measure (phenotype) when studying genetic influence on behavior. The authors further conclude that the results support a central role of dopamine in learning processes—not entirely new𔃀and suggest that this could also affect susceptibility to addiction where the perception and learning from negative cues may play a key role.

There are rather strong conclusions considering that the allele used in this study (TAQ1A) is not even located within the DRD2 gene locus but resides at some distance downstream within another gene. Therefore it is unclear how TAQ1A could affect D2 receptor functions, and this would weaken their conclusions that dopamine is germane to avoidance learning. Yet, our recent study in PNAS (Zhang et...  Read more

This is indeed an interesting study. The authors have combined fMRI analysis with detailed assessment of learning and DRD2 genotype. It is intriguing that only avoidance learning is affected, not other processes. This points to the importance of choosing the proper outcome measure (phenotype) when studying genetic influence on behavior. The authors further conclude that the results support a central role of dopamine in learning processes—not entirely new𔃀and suggest that this could also affect susceptibility to addiction where the perception and learning from negative cues may play a key role.

There are rather strong conclusions considering that the allele used in this study (TAQ1A) is not even located within the DRD2 gene locus but resides at some distance downstream within another gene. Therefore it is unclear how TAQ1A could affect D2 receptor functions, and this would weaken their conclusions that dopamine is germane to avoidance learning. Yet, our recent study in PNAS (Zhang et al., 2007) has established a possible mechanistic explanation for the apparent effect of TAQ1A on D2 receptors, namely, a strong linkage disequilibrium (D'=0.855) to the intronic SNPs flanking exon6 of DRD2, that affect the relative expression of the two isoforms of the D2 receptor with or without exon 6 in the mature protein. While the authors have speculated that the differences in D2 receptor content might be underlying the observed differences in learning, our results indicate that the relative ratios of the S and L forms of D2 may be more important. It will be of particular interest to genotype these subjects for the intronic SNPs identified in our study.