activation is influenced by SLC6A4 and MAOA. On the other hand, task-elicited activation of the prefrontal cortex accesses prefrontal cognitive function that is impaired in several psychiatric diseases including addictions and has been linked to genetic variation within COMT and MAOA. Activation of the ventral striatum and other brain areas during positive reward allows exploration of reward circuits55 enabling the observation that the OPRM1 Asn398Asp variant associated with altered naltrexone treatment response also modulates reward processes in the ventral striatum.56 Effect sizes of genetic variants on intermediate phenotypes appear to be larger than effects on complex disease phenotypes, potentially reflecting proximity to gene action, measurement properties, and specificity.43,57
