The pattern of 5-HTTLPR-associated differences in the functional dynamics of the amygdala and medial prefrontal cortex is echoed in structural measures within this same network. Specifically, the S allele has been associated with relatively decreased gray matter volume in the amygdala and medial prefrontal cortex (42, 57). The S allele has also been associated with alterations in the microstructure of the uncinate fasciculus, the white matter fiber bundle providing the majority of connections between the amygdala and medial prefrontal cortex (58). Individual differences in uncinate fasciculus microstructure correlate with trait anxiety (59). In addition, postmortem tissue analyses have associated the 5-HTTLPR S allele with relative enlargement of the pulvinar, which relays visual information to subcortical and higher cortical brain regions (60). Consistent with this, as well as with amygdala-mediated behavioral arousal, numerous studies have reported increased cortical activity in response to experimental provocation in S-carriers (61–66).
