Neuroimaging outcomes are promising new endophenotypes for addiction. Although current sample sizes are modest, primarily due to costs and burden of imaging technology, promising results have begun to emerge. For example, although not directly addressing functionality, Villafuerte et al.127 recently found that in families of alcoholics, rs279826 and rs279858 in the GABRA2 gene, previously associated with alcohol dependence (Table 1), were associated, not only with alcoholism and self-reported impulsivity but also with insula cortex activation in women during anticipation of monetary reward. The insula cortex has been implicated in cue-induced drug craving and addiction and thus, this study provides a potential neurobiological perspective on the link between GABRA2 and alcoholism. Capitalizing on polygenic variation in addiction, another recent study used a sum score created from frequently studied variants in dopamine pathways genes (DAT1 9-repeat, DRD4 7-repeat, DRD2 -141C Del, DRD2 Taq1A C (A2), and COMT Val(158)Met). Although no variant was statistically significant on its own, the sum score was associated with monetary reward-related activation in the ventral striatum, explaining 10.9% of variance.128
