BIOLOGICAL BASIS OF VARIABILITY IN DOPAMINE AVAILABILITY ON FRONTOSTRIATAL BRAIN FUNCTION IN ADOLESCENCE

Neurodevelopmental studies indicate a protracted development through adolescence of brain systems underlying incentive-driven behaviors including prefrontal cortex (PFC) and the striatum. These systems support the executive control of behavior as well as motivationally driven behaviors and may contribute to vulnerabilities in the emergence of psychopathology. The PFC and striatum may support cognition and motivation through the function of the neurotransmitter dopamine. Dopamine (DA) availability is increased during the adolescent period in human and animals and play an important role in mediating individual differences in risk-taking behaviors. This dissertation seeks to examine the moderating role of genetically mediated DA availability on frontostriatal brain function in adolescence. To this end, we genotyped individuals between the ages of 10 and 20 for common functional polymorphisms in three genes that have a direct influence on synaptic DA availability. In addition, we calculated a multilocus composite score in order to assess additive effects of our three genetic loci. We used functional magnetic resonance imaging (fMRI) to assess brain function. The purpose of our first study was to examine the integrity of frontostriatal networks using resting state functional connectivity. We then look more directly at the role of frontostriatal brain function on incentive-driven behaviors using a rewarded inhibitory control task that has a known developmental signature . Overall we found a moderating influence of DA availability on age-related changes in key frontostriatal circuitry suggesting that the maturation of brain function in adolescence may in part be mediated by inter-individual variability in DA signaling. Overall, the genotypes by age interactions highlight a unique DA-driven brain profile in adolescence. This suggests that a genetically mediated brain phenotype characterized in adolescence may differ significantly from that in adulthood. This has strong implications regarding the variability observed in adolescent risk-taking behaviors as well as predictions of later adult behavior.\u