ReviewLooking on the Bright Side of Serotonin Transporter Gene Variation
Section snippets
5-HTTLPR and Emotionality
There is general consensus—although there are also a considerable number of replication failures—that the s-allele is associated with emotionality or stress sensitivity, as has previously been described in comprehensive reviews (2, 5, 6, 7). In summary, Hariri et al. (8), as well as others (for review, see [5]), revealed that s-allele carriers displayed relatively exaggerated reactivity in the amygdala to pictures of fearful faces. Further, s-allele carriers show increased startle responses (9
5-HTTLPR and (Social) Cognition
More recently, researchers turned their attention to the role of 5-HTTLPR in cognitive functions. In 2007, Roiser et al. (51) demonstrated that s-allele carriers showed superior performance in the affective go/no-go task, an attentional test that measures the ability to withhold an intentional motor response based on the emotional valence of words. This finding may be in accord with increased memory recall, as observed in the recall stage of the affective directed forgetting test (51). Further,
5-HTTLPR and Brain Function
Noninvasive psychophysiological and morphofunctional neuroimaging studies have provided important insights in the neural circuits that bias behavioral responses in association with the 5-HTTLPR s-allele. Kickoff for imaging of genetic variation was in 1999 when Fallgatter et al. (65) linked the s variant to increased activity of the prefrontal cortex (PFC) during a response inhibition task. In 2002, Hariri et al. (8) reported that s-allele carriers exhibited increased amygdala reactivity during
Lessons from Serotonin Transporter Knockout Rodents
Serotonin transporter knockout (5-HTT−/−) mice were generated in 1998 by deleting a critical region of the gene via homologous recombination (82). In 2007, the 5-HTT−/− rat was introduced, generated by chemical mutagenesis that resulted in a premature stop codon in the 5-HTT gene (83). Using microdialysis, it is well established that 5-HTT−/− mice and rats exhibit increased extracellular serotonin levels in various brain regions (84). This could contribute to neurodevelopmental alterations (73)
Conclusion and Outlook
Evidence accumulated from studies in humans, nonhuman primates, and rodent models suggests a link between the neurobehavioral effects of the 5-HTTLPR s-variant and hypervigilance, an enhanced sensitivity to motivationally relevant environmental stimuli (Figure 1). This hypervigilance leads to enhanced emotional responses when environmental conditions are stable or uncontrollable, that is, when there are no explicit stimuli or conditions that draw attention away from stimuli predicting adversity
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