Tim Klucken, Jan Schweckendiek, Carlo Blecker, Bertram Walter, Yvonne Kuepper, Juergen Hennig, Rudolf Stark

Strong evidence links the 5-HTTLPR genotype to the modulation of amygdala reactivity, which is considered to convey the increased vulnerability for anxiety disorders in s-allele carriers. In addition to amygdala reactivity, the 5-HTTLPR has been shown to be related to alterations in structural and effective connectivity. The aim of this study was to investigate the effects of 5-HTTLPR genotype on amygdala reactivity and effective connectivity during fear conditioning, as well as structural connectivity (as measured by diffusion tensor imaging). In order to integrate different classification strategies, we used the bi-allelic (s-allele vs. l/l-allele group) as well as the tri-allelic (low-functioning vs. high-functioning) classification approach. S-allele carriers showed exaggerated amygdala reactivity and elevated amygdala-insula coupling during fear conditioning (CS+ > CS-) compared with the l/l-allele group. In addition, DTI analysis showed increased FA-values in s-allele carriers within the uncinate fasciculus. approach, increased amygdala reactivity and amygdala insula coupling were observed in the low-functioning compared the high-functioning group. No significant differences between the two groups were found in structural connectivity. The present results add to the current debate on the influence of the 5-HTTLPR on brain functioning. These differences between s-allele and l/l-allele carriers may CONTRIBUTE: to altered vulnerability for psychiatric disorders.