In 2002, a synergy emerged between research in human affective neuroscience and genetic research into the 5-HTTLPR. Specifically, noninvasive functional MRI (fMRI), which assays information processing within distinct neuronal circuits, revealed relatively exaggerated threat-related amygdala reactivity in carriers of the 5-HT-TLPR S allele (2). This initial finding has since been replicated in independent samples of both healthy volunteers and psychiatric patients, using a multitude of threatening stimuli and neuroimaging modalities (39–49). This effect on the magnitude of amygdala reactivity has recently been extended, with S-carriers also exhibiting a relatively faster response than L-allele homozygotes (50). Consistent with the heightened sensitivity to environmental threat documented in S-carriers, recent work suggests that the effects of the S allele on amygdala function may be unique to stimulus-provoked amygdala reactivity and not elevated baseline levels of activation (51–53).
