Frontal-Limbic White Matter Pathway Associations with the Serotonin Transporter Gene Promoter Region (5-HTTLPR) Polymorphism

Abstract

Variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been associated with heightened neural activity in limbic and prefrontal regions in response to emotional stimuli. The current study examined whether the 5-HTTLPR polymorphism is also associated with alterations in microstructure of frontal-limbic white matter (WM) tracts. Thirty-seven (mean age, 20.51 years; range, 13-28) female participants were genotyped for the 5-HTTLPR polymorphism. Diffusion MRI was collected and a probabilistically defined tract of the uncinate fasciculus (UF), a WM pathway connecting the amygdala to medial and orbital prefrontal cortex, was used to generate fractional anisotropy (FA) values for participants. Regression analyses indicated a significant inverse association between number of low-expressing 5-HTTLPR alleles and FA values for the left frontal UF region, beta = - 0.42, p = 0.005. Furthermore, there was a positive association between age and FA values for bilateral frontal regions of the UF; these effects explained 39 and 20% of the variance in FA values for left and right frontal regions, respectively. 5-HTTLPR genotype and age appear to independently influence the WM microstructure of the UF. The observed reduction in FA values among low-expressing 5-HTTLPR allele carriers may contribute to biased regulation of emotional stimuli.