Human neuroimaging research suggests that relatively increased amygdala reactivity associated with the 5-HT-TLPR S allele is likely to reflect both the functional and structural architecture of a distributed network of brain regions. Research suggests that this network communicates information about the environment to the amygdala and relays signals between the amygdala and regulatory circuits in the medial prefrontal cortex. This putative mechanism is further underscored by the significant role serotonin signaling plays in the general development and function of this extended neural network (56). The S allele has been associated with altered functional coupling (as indexed by correlated fMRI signal strength) between the amygdala and regions of the medial prefrontal cortex (40, 57). These medial prefrontal regions integrate amygdala-mediated arousal and down regulate amygdala reactivity. Medial prefrontal regions are also involved in the extinction of conditioned fear responses, which are dependent on amygdala circuitry.
