Elsevier

Biological Psychiatry

Volume 66, Issue 7, 1 October 2009, Pages 691-694
Biological Psychiatry

Research Report
Preliminary Evidence of White Matter Abnormality in the Uncinate Fasciculus in Generalized Social Anxiety Disorder

https://doi.org/10.1016/j.biopsych.2009.02.028Get rights and content

Background

Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala's response to threat. The goal of this study was to investigate brain frontal WM abnormalities using diffusion tensor imaging (DTI) in patients with social anxiety disorder.

Methods

A Turboprop DTI sequence was used to acquire diffusion tensor images in 30 patients with GSAD and 30 matched healthy control subjects. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects, and an automated voxel-based, whole-brain method was used to analyze group differences.

Results

Compared with healthy control subjects, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls.

Conclusions

These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD, which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.

Section snippets

Subjects

Sixty subjects (30 with GSAD and 30 age-, sex-, education-matched healthy control subjects [HC]) participated in this study. Demographic and clinical characteristics of the subjects are presented in Table 1. GSAD diagnosis was established using the Structured Clinical Interview for DSM-IV (SCID) with additional probes from the Social Phobia Interview (13) conducted by trained, master's-level clinical assessors, and the self-administered Liebowitz Social Anxiety Scale (LSAS) (14). None of the

MRI Protocol

Subjects were scanned with Turboprop DTI (12, 15) on a 3-T GE MRI scanner (General Electric, Waukesha, Wisconsin) using the following parameters: repetition time (TR) = 5000 msec, echo time (TE) = 94 msec, 8 spin-echoes per TR/blade, 5 k-space lines acquired per spin-echo (40 lines per blade), 128 samples per line, 16 k-space blades per image, field-of-view = 24 cm × 24 cm, 36 contiguous axial slices, slice thickness = 3 mm, 256 × 256 final image matrix. Diffusion-weighted images with b = 900

DTI Image Processing and Analysis

Details for image processing and analysis have been described elsewhere (16). In brief, the diffusion tensor model was fit to each voxel to create FA images for each subject. The Brain Extraction Tool of the software package FSL (Oxford Centre for functional MRI of the Brain, Oxford, United Kingdom) was applied on all b = 0 sec/mm2 volumes to remove the skull and noise outside of the brain. The resulting binary brain masks were then applied on the FA maps. The FA images from all subjects were

Results

Relative to HCs, subjects with GSAD exhibited significantly lower FA nearby the OFC localized (by Talairach coordinates, x = right, y = anterior, z = superior) to right uncinate fasciculus (UF; 18, 18, −15; 383 voxels; t = 2.88, p = .003, uncorrected; Figure 1A). No other areas of reduced WM FA were identified in the GSAD group. Extracted FA values (mean ± SD) from the UF cluster are shown in Figure 1B to show individual variability (HC: .32 ± .02 vs. GSAD: .31 ± .02; t58 = 2.41, p = .02,

Discussion

In this Turboprop DTI study, as predicted, we observed lower prefrontal fractional anisotropy localized to right UF WM in the area adjacent to the orbitofrontal cortex in individuals with GSAD compared with matched HC subjects. Anatomically, the UF is the major WM fiber tract that connects the inferofrontal and anterotemporal cortices, and it travels over the lateral nuclei of the amygdala, terminating in the OFC (Brodmann area 11–12) and subcallosal area (Brodmann area 25) (9). Thus, lower FA

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