The few neurogenetic studies of GABRA2, CHRNA5-CHRNA3-CHRNB4, and CNR1 genotypes associated with addiction risk suggest that these polymorphisms may drive addiction risk via their effects on corticostriatal connectivity and reactivity to reward. Notably, while we concentrated on neurogenetic research investigating genetic polymorphisms that are believed to moderate the psychoactive effects of substances, new research suggests that this approach may also afford a remarkable opportunity to examine whether indices of metabolism exert an impact on neural systems. For instance, a revealing new study [106] found that normal metabolizers (defined by CYP2A6 genotype) have greater smoking cue-induced activation in the right amygdala, striatum, hippocampus, and cingulate cortex relative to reduced metabolizers. Such studies of metabolic-related polymorphisms may be particularly informative in the context of drug-challenge paradigms.
