Paradoxical Decrease in Striatal Activation on an fMRI Reward Task Following Treatment in Youth with Co-morbid Cannabis Dependence/Major Depression.

Reward behavior, including reward behavior involving drugs, has been shown to be mediated by the ventral striatum and related structures of the reward system. The aim of this study was to assess reward-related activity as shown by fMRI before and after treatment among youth with comorbid cannabis dependence and major depression. We hypothesized that the reward task (Delgado et al., 2003) would elicit activation in the reward system, and that the level of activation in response to reward would increase from the beginning to the end of the 12-week treatment study as levels of depressive symptoms and cannabis use decreased. Six subjects were recruited from a larger treatment study in which all received Cognitive Behavioral Therapy/Motivational Enhancement Therapy (CBT/MET), and also were randomized to receive either fluoxetine or placebo. Each of the six subjects completed an fMRI card- guessing/reward task both before and after the 12-week treatment study. As hypothesized, the expected activation was noted for the reward task in the insula, prefrontal, and striatal areas, both before and after treatment. However, the participants showed lower reward-related activation after treatment relative to pre-treatment, which is opposite of what would be expected in depressed subjects who did not demonstrate a comorbid substance use disorder. These paradoxical findings suggest that the expected increase in activity for reward associated with treatment for depression was overshadowed by a decrease in reward-related activation associated with treatment of pathological cannabis use in these comorbid youth. These findings emphasize the importance of comorbid disorders in fMRI studies.