Preliminary Evidence of White Matter Abnormality in the Uncinate Fasciculus in Generalized Social Anxiety Disorder
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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.
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Reduced grey matter volume in the mPFC and weaker integrity of the uncinate fasciculus have been reported in adults with anxious temperament and anxiety disorders.
“Structural abnormalities, such as reduced grey matter volume in the mPFC and weaker integrity of the uncinate fasciculus, have been reported in adults with anxious temperament and anxiety disorders24–28.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [27]
Weaker structural integrity of the uncinate fasciculus has been found in populations with anxious temperament, suggesting that this tract may play a crucial role in anxiety aetiology.
“Notably, weaker structural integrity of the uncinate fasciculus has been found in populations with anxious temperament24–27,32, suggesting that this tract may play a crucial role in anxiety aetiology.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [27]
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- Authors
- Phan, K. L., Orlichenko, A., Boyd, E., Angstadt, M., Coccaro, E. F., Liberzon, I., & Arfanakis, K.
- Affiliations
- University of Michigan (US)
- Illinois Institute of Technology (US)
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 66
- Issue
- 7
- Pages
- 691-694
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2743779
- OpenAlex
- W2049830989
- Cited by
- 226
- References
- 40
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 14 · 2021: 10 · 2020: 19 · 2019: 20 · 2018: 6 · 2017: 18 · 2016: 17 · 2015: 18 · 2014: 16 · 2013: 22 · 2012: 19
- FWCI
- 17.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K23MH076198)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- generalized social anxiety disorder, uncinate fasciculus, white matter microstructure, fractional anisotropy, amygdala-prefrontal connectivity, orbitofrontal cortex, limbic system, diffusion tensor imaging
- MeSH terms
- Adult, Brain Mapping, Female, Frontal Lobe, Humans, Limbic System, Male, Nerve Fibers, Myelinated, Neural Pathways, Neuropsychological Tests, Phobic Disorders, Psychiatric Status Rating Scales, Case-Control Studies, Anisotropy, Diffusion Magnetic Resonance Imaging, Young Adult
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