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

• Published in: Biological psychiatry (1969) Vol. 66; no. 7; pp. 691 - 694
• Main Authors: Phan, K. Luan, Orlichenko, Anton, Boyd, Erin, Angstadt, Mike, Coccaro, Emil F., Liberzon, Israel, Arfanakis, Konstantinos
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2009; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Anisotropy; Anxiety disorders. Neuroses; Biological and medical sciences; Brain Mapping - methods; Case-Control Studies; Connectivity; Diffusion Magnetic Resonance Imaging - methods; diffusion tensor imaging; Female; fractional anistropy; Frontal Lobe - pathology; Humans; Limbic System - pathology; Male; Medical sciences; Miscellaneous; Nerve Fibers, Myelinated; Neural Pathways - pathology; Neuropsychological Tests; Phobia; Phobic Disorders - pathology; prefrontal; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; social phobia; uncinate fasciculus; white matter; Young Adult; uncinate fasciculus; white matter; prefrontal; social phobia; Connectivity; diffusion tensor imaging; fractional anistropy; Generalized anxiety disorder; Social phobia; Central nervous system; Anxiety disorder; Prefrontal cortex; White matter; Encephalon; Diffusion tensor imaging
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2009.02.028

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. 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. 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. 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.