[Abstract Title]. - Society for Neuroscience

Title: Frontolimbic white matter pathway differences associated with a serotonin transporter
polymorphism (5-HTTLPR): Prospective analyses of soldiers deploying to Iraq
Authors: *M. T. SATHISHKUMAR 1 , D. L. STOTE 2 , J. PACHECO 2 , R. E. FERRELL 3 , A.
HARIRI 4 , D. M. SCHNYER 2 , M. J. TELCH 2 ;
1 Imaging Res. Ctr., Univ. Texas Austin, Austin, TX; 2 Dept. of Psychology, Univ. of Texas,
Austin, Austin, TX; 3 Dept. of Human Genet., 4 Dept. of Psychiatry, Univ. of Pittsburg, Pittsburg,
PA
Abstract: Previous studies show that the low-expressing(S) polymorphism of the serotonin
transporter gene (5-HTTLPR) correlates with vulnerability to anxiety disorders and stressinduced
depression. This polymorphism has been linked to heightened fear and anxiety,
vulnerability to posttraumatic stress disorder, greater amygdala activation in response to fearful
faces, diminished volume in anterior cingulate (ACC), and functional uncoupling between the
ACC and amygdala (Lesch et al., 1996; Hariri et al 2002, 2005; Lee et al., 2005; Pezawas et al.,
2005).
The goal of the current study is to examine the relationship between 5-HTTLPR status and
frontolimbic fiber tracts (left and right uncinate fasciculus, UF). Prior to deploying to Iraq, 160
United States Army soldiers underwent MRI and were genotyped for the 5-HTTLPR. A random
subset of data (n = 54) was used in the current analysis. Diffusion tensor imaging data were
collected in a GE 3T magnet using single shot echo planar imaging, and a twice-refocused spin
echo pulse sequence, optimized to minimize eddy current (TR = 12000 ms, TE = 71.1 ms, FOV
= 24, slice thickness = 3mm, 0 gap, B = 1000, 128 x128 matrix, 1 T2 + 25 DWI, 47 slices).
Diffusion tensor and fractional anisotropy (FA) were calculated on a voxel by voxel basis using
standard reconstruction methods in FSL. A probabilistically defined track of the left and right UF
was subdivided into temporal and frontal sections. Data were sorted by genotype as either
containing a low-expressing allele (S/S and S/L; n=40) or not (L/L; n=14). Mean FA values were
computed for the UF from each section and hemisphere, and were submitted to statistical
analysis.
There was a significant effect of group, reflecting overall lower FA values for the individuals
with at least one short allele relative to those with none. This effect interacted with location and
hemisphere reflecting a reliable between-group difference in the left frontal UF pathway. FA
values were also extracted from 2 left hemisphere control regions, the posterior forceps and the
longitudinal fasciculus. These data are consistent with preliminary results in college-aged
females (Pacheco, et al., 2008) indicating a correspondence between the presence of a short
allele of the 5-HTTLPR promoter region and the white matter integrity of frontolimbic circuits,
which have been shown to play a critical role in the regulation of fear, anxiety, and mood.
Disclosures: M.T. Sathishkumar , None; J. Pacheco, None; R.E. Ferrell, None; A. Hariri,
None; D.M. Schnyer, None; D.L. Stote, None; M.J. Telch, None.
Poster